what is covid 19 research article

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• Open access
• Published: 04 June 2021

Coronavirus disease (COVID-19) pandemic: an overview of systematic reviews

• Israel Júnior Borges do Nascimento 1 , 2 ,
• Dónal P. O’Mathúna 3 , 4 ,
• Thilo Caspar von Groote 5 ,
• Hebatullah Mohamed Abdulazeem 6 ,
• Ishanka Weerasekara 7 , 8 ,
• Ana Marusic 9 ,
• Livia Puljak   ORCID: orcid.org/0000-0002-8467-6061 10 ,
• Vinicius Tassoni Civile 11 ,
• Irena Zakarija-Grkovic 9 ,
• Tina Poklepovic Pericic 9 ,
• Alvaro Nagib Atallah 11 ,
• Santino Filoso 12 ,
• Nicola Luigi Bragazzi 13 &
• Milena Soriano Marcolino 1

On behalf of the International Network of Coronavirus Disease 2019 (InterNetCOVID-19)

BMC Infectious Diseases volume  21 , Article number:  525 ( 2021 ) Cite this article

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Navigating the rapidly growing body of scientific literature on the SARS-CoV-2 pandemic is challenging, and ongoing critical appraisal of this output is essential. We aimed to summarize and critically appraise systematic reviews of coronavirus disease (COVID-19) in humans that were available at the beginning of the pandemic.

Nine databases (Medline, EMBASE, Cochrane Library, CINAHL, Web of Sciences, PDQ-Evidence, WHO’s Global Research, LILACS, and Epistemonikos) were searched from December 1, 2019, to March 24, 2020. Systematic reviews analyzing primary studies of COVID-19 were included. Two authors independently undertook screening, selection, extraction (data on clinical symptoms, prevalence, pharmacological and non-pharmacological interventions, diagnostic test assessment, laboratory, and radiological findings), and quality assessment (AMSTAR 2). A meta-analysis was performed of the prevalence of clinical outcomes.

Eighteen systematic reviews were included; one was empty (did not identify any relevant study). Using AMSTAR 2, confidence in the results of all 18 reviews was rated as “critically low”. Identified symptoms of COVID-19 were (range values of point estimates): fever (82–95%), cough with or without sputum (58–72%), dyspnea (26–59%), myalgia or muscle fatigue (29–51%), sore throat (10–13%), headache (8–12%) and gastrointestinal complaints (5–9%). Severe symptoms were more common in men. Elevated C-reactive protein and lactate dehydrogenase, and slightly elevated aspartate and alanine aminotransferase, were commonly described. Thrombocytopenia and elevated levels of procalcitonin and cardiac troponin I were associated with severe disease. A frequent finding on chest imaging was uni- or bilateral multilobar ground-glass opacity. A single review investigated the impact of medication (chloroquine) but found no verifiable clinical data. All-cause mortality ranged from 0.3 to 13.9%.

Conclusions

In this overview of systematic reviews, we analyzed evidence from the first 18 systematic reviews that were published after the emergence of COVID-19. However, confidence in the results of all reviews was “critically low”. Thus, systematic reviews that were published early on in the pandemic were of questionable usefulness. Even during public health emergencies, studies and systematic reviews should adhere to established methodological standards.

Peer Review reports

The spread of the “Severe Acute Respiratory Coronavirus 2” (SARS-CoV-2), the causal agent of COVID-19, was characterized as a pandemic by the World Health Organization (WHO) in March 2020 and has triggered an international public health emergency [ 1 ]. The numbers of confirmed cases and deaths due to COVID-19 are rapidly escalating, counting in millions [ 2 ], causing massive economic strain, and escalating healthcare and public health expenses [ 3 , 4 ].

The research community has responded by publishing an impressive number of scientific reports related to COVID-19. The world was alerted to the new disease at the beginning of 2020 [ 1 ], and by mid-March 2020, more than 2000 articles had been published on COVID-19 in scholarly journals, with 25% of them containing original data [ 5 ]. The living map of COVID-19 evidence, curated by the Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre), contained more than 40,000 records by February 2021 [ 6 ]. More than 100,000 records on PubMed were labeled as “SARS-CoV-2 literature, sequence, and clinical content” by February 2021 [ 7 ].

Due to publication speed, the research community has voiced concerns regarding the quality and reproducibility of evidence produced during the COVID-19 pandemic, warning of the potential damaging approach of “publish first, retract later” [ 8 ]. It appears that these concerns are not unfounded, as it has been reported that COVID-19 articles were overrepresented in the pool of retracted articles in 2020 [ 9 ]. These concerns about inadequate evidence are of major importance because they can lead to poor clinical practice and inappropriate policies [ 10 ].

Systematic reviews are a cornerstone of today’s evidence-informed decision-making. By synthesizing all relevant evidence regarding a particular topic, systematic reviews reflect the current scientific knowledge. Systematic reviews are considered to be at the highest level in the hierarchy of evidence and should be used to make informed decisions. However, with high numbers of systematic reviews of different scope and methodological quality being published, overviews of multiple systematic reviews that assess their methodological quality are essential [ 11 , 12 , 13 ]. An overview of systematic reviews helps identify and organize the literature and highlights areas of priority in decision-making.

In this overview of systematic reviews, we aimed to summarize and critically appraise systematic reviews of coronavirus disease (COVID-19) in humans that were available at the beginning of the pandemic.

Methodology

Research question.

This overview’s primary objective was to summarize and critically appraise systematic reviews that assessed any type of primary clinical data from patients infected with SARS-CoV-2. Our research question was purposefully broad because we wanted to analyze as many systematic reviews as possible that were available early following the COVID-19 outbreak.

Study design

We conducted an overview of systematic reviews. The idea for this overview originated in a protocol for a systematic review submitted to PROSPERO (CRD42020170623), which indicated a plan to conduct an overview.

Overviews of systematic reviews use explicit and systematic methods for searching and identifying multiple systematic reviews addressing related research questions in the same field to extract and analyze evidence across important outcomes. Overviews of systematic reviews are in principle similar to systematic reviews of interventions, but the unit of analysis is a systematic review [ 14 , 15 , 16 ].

We used the overview methodology instead of other evidence synthesis methods to allow us to collate and appraise multiple systematic reviews on this topic, and to extract and analyze their results across relevant topics [ 17 ]. The overview and meta-analysis of systematic reviews allowed us to investigate the methodological quality of included studies, summarize results, and identify specific areas of available or limited evidence, thereby strengthening the current understanding of this novel disease and guiding future research [ 13 ].

A reporting guideline for overviews of reviews is currently under development, i.e., Preferred Reporting Items for Overviews of Reviews (PRIOR) [ 18 ]. As the PRIOR checklist is still not published, this study was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 statement [ 19 ]. The methodology used in this review was adapted from the Cochrane Handbook for Systematic Reviews of Interventions and also followed established methodological considerations for analyzing existing systematic reviews [ 14 ].

Approval of a research ethics committee was not necessary as the study analyzed only publicly available articles.

Eligibility criteria

Systematic reviews were included if they analyzed primary data from patients infected with SARS-CoV-2 as confirmed by RT-PCR or another pre-specified diagnostic technique. Eligible reviews covered all topics related to COVID-19 including, but not limited to, those that reported clinical symptoms, diagnostic methods, therapeutic interventions, laboratory findings, or radiological results. Both full manuscripts and abbreviated versions, such as letters, were eligible.

No restrictions were imposed on the design of the primary studies included within the systematic reviews, the last search date, whether the review included meta-analyses or language. Reviews related to SARS-CoV-2 and other coronaviruses were eligible, but from those reviews, we analyzed only data related to SARS-CoV-2.

No consensus definition exists for a systematic review [ 20 ], and debates continue about the defining characteristics of a systematic review [ 21 ]. Cochrane’s guidance for overviews of reviews recommends setting pre-established criteria for making decisions around inclusion [ 14 ]. That is supported by a recent scoping review about guidance for overviews of systematic reviews [ 22 ].

Thus, for this study, we defined a systematic review as a research report which searched for primary research studies on a specific topic using an explicit search strategy, had a detailed description of the methods with explicit inclusion criteria provided, and provided a summary of the included studies either in narrative or quantitative format (such as a meta-analysis). Cochrane and non-Cochrane systematic reviews were considered eligible for inclusion, with or without meta-analysis, and regardless of the study design, language restriction and methodology of the included primary studies. To be eligible for inclusion, reviews had to be clearly analyzing data related to SARS-CoV-2 (associated or not with other viruses). We excluded narrative reviews without those characteristics as these are less likely to be replicable and are more prone to bias.

Scoping reviews and rapid reviews were eligible for inclusion in this overview if they met our pre-defined inclusion criteria noted above. We included reviews that addressed SARS-CoV-2 and other coronaviruses if they reported separate data regarding SARS-CoV-2.

Information sources

Nine databases were searched for eligible records published between December 1, 2019, and March 24, 2020: Cochrane Database of Systematic Reviews via Cochrane Library, PubMed, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Web of Sciences, LILACS (Latin American and Caribbean Health Sciences Literature), PDQ-Evidence, WHO’s Global Research on Coronavirus Disease (COVID-19), and Epistemonikos.

The comprehensive search strategy for each database is provided in Additional file 1 and was designed and conducted in collaboration with an information specialist. All retrieved records were primarily processed in EndNote, where duplicates were removed, and records were then imported into the Covidence platform [ 23 ]. In addition to database searches, we screened reference lists of reviews included after screening records retrieved via databases.

Study selection

All searches, screening of titles and abstracts, and record selection, were performed independently by two investigators using the Covidence platform [ 23 ]. Articles deemed potentially eligible were retrieved for full-text screening carried out independently by two investigators. Discrepancies at all stages were resolved by consensus. During the screening, records published in languages other than English were translated by a native/fluent speaker.

Data collection process

We custom designed a data extraction table for this study, which was piloted by two authors independently. Data extraction was performed independently by two authors. Conflicts were resolved by consensus or by consulting a third researcher.

We extracted the following data: article identification data (authors’ name and journal of publication), search period, number of databases searched, population or settings considered, main results and outcomes observed, and number of participants. From Web of Science (Clarivate Analytics, Philadelphia, PA, USA), we extracted journal rank (quartile) and Journal Impact Factor (JIF).

We categorized the following as primary outcomes: all-cause mortality, need for and length of mechanical ventilation, length of hospitalization (in days), admission to intensive care unit (yes/no), and length of stay in the intensive care unit.

The following outcomes were categorized as exploratory: diagnostic methods used for detection of the virus, male to female ratio, clinical symptoms, pharmacological and non-pharmacological interventions, laboratory findings (full blood count, liver enzymes, C-reactive protein, d-dimer, albumin, lipid profile, serum electrolytes, blood vitamin levels, glucose levels, and any other important biomarkers), and radiological findings (using radiography, computed tomography, magnetic resonance imaging or ultrasound).

We also collected data on reporting guidelines and requirements for the publication of systematic reviews and meta-analyses from journal websites where included reviews were published.

Quality assessment in individual reviews

Two researchers independently assessed the reviews’ quality using the “A MeaSurement Tool to Assess Systematic Reviews 2 (AMSTAR 2)”. We acknowledge that the AMSTAR 2 was created as “a critical appraisal tool for systematic reviews that include randomized or non-randomized studies of healthcare interventions, or both” [ 24 ]. However, since AMSTAR 2 was designed for systematic reviews of intervention trials, and we included additional types of systematic reviews, we adjusted some AMSTAR 2 ratings and reported these in Additional file 2 .

Adherence to each item was rated as follows: yes, partial yes, no, or not applicable (such as when a meta-analysis was not conducted). The overall confidence in the results of the review is rated as “critically low”, “low”, “moderate” or “high”, according to the AMSTAR 2 guidance based on seven critical domains, which are items 2, 4, 7, 9, 11, 13, 15 as defined by AMSTAR 2 authors [ 24 ]. We reported our adherence ratings for transparency of our decision with accompanying explanations, for each item, in each included review.

One of the included systematic reviews was conducted by some members of this author team [ 25 ]. This review was initially assessed independently by two authors who were not co-authors of that review to prevent the risk of bias in assessing this study.

Synthesis of results

For data synthesis, we prepared a table summarizing each systematic review. Graphs illustrating the mortality rate and clinical symptoms were created. We then prepared a narrative summary of the methods, findings, study strengths, and limitations.

For analysis of the prevalence of clinical outcomes, we extracted data on the number of events and the total number of patients to perform proportional meta-analysis using RStudio© software, with the “meta” package (version 4.9–6), using the “metaprop” function for reviews that did not perform a meta-analysis, excluding case studies because of the absence of variance. For reviews that did not perform a meta-analysis, we presented pooled results of proportions with their respective confidence intervals (95%) by the inverse variance method with a random-effects model, using the DerSimonian-Laird estimator for τ 2 . We adjusted data using Freeman-Tukey double arcosen transformation. Confidence intervals were calculated using the Clopper-Pearson method for individual studies. We created forest plots using the RStudio© software, with the “metafor” package (version 2.1–0) and “forest” function.

Managing overlapping systematic reviews

Some of the included systematic reviews that address the same or similar research questions may include the same primary studies in overviews. Including such overlapping reviews may introduce bias when outcome data from the same primary study are included in the analyses of an overview multiple times. Thus, in summaries of evidence, multiple-counting of the same outcome data will give data from some primary studies too much influence [ 14 ]. In this overview, we did not exclude overlapping systematic reviews because, according to Cochrane’s guidance, it may be appropriate to include all relevant reviews’ results if the purpose of the overview is to present and describe the current body of evidence on a topic [ 14 ]. To avoid any bias in summary estimates associated with overlapping reviews, we generated forest plots showing data from individual systematic reviews, but the results were not pooled because some primary studies were included in multiple reviews.

Our search retrieved 1063 publications, of which 175 were duplicates. Most publications were excluded after the title and abstract analysis ( n = 860). Among the 28 studies selected for full-text screening, 10 were excluded for the reasons described in Additional file 3 , and 18 were included in the final analysis (Fig. 1 ) [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. Reference list screening did not retrieve any additional systematic reviews.

PRISMA flow diagram

Characteristics of included reviews

Summary features of 18 systematic reviews are presented in Table 1 . They were published in 14 different journals. Only four of these journals had specific requirements for systematic reviews (with or without meta-analysis): European Journal of Internal Medicine, Journal of Clinical Medicine, Ultrasound in Obstetrics and Gynecology, and Clinical Research in Cardiology . Two journals reported that they published only invited reviews ( Journal of Medical Virology and Clinica Chimica Acta ). Three systematic reviews in our study were published as letters; one was labeled as a scoping review and another as a rapid review (Table 2 ).

All reviews were published in English, in first quartile (Q1) journals, with JIF ranging from 1.692 to 6.062. One review was empty, meaning that its search did not identify any relevant studies; i.e., no primary studies were included [ 36 ]. The remaining 17 reviews included 269 unique studies; the majority ( N = 211; 78%) were included in only a single review included in our study (range: 1 to 12). Primary studies included in the reviews were published between December 2019 and March 18, 2020, and comprised case reports, case series, cohorts, and other observational studies. We found only one review that included randomized clinical trials [ 38 ]. In the included reviews, systematic literature searches were performed from 2019 (entire year) up to March 9, 2020. Ten systematic reviews included meta-analyses. The list of primary studies found in the included systematic reviews is shown in Additional file 4 , as well as the number of reviews in which each primary study was included.

Population and study designs

Most of the reviews analyzed data from patients with COVID-19 who developed pneumonia, acute respiratory distress syndrome (ARDS), or any other correlated complication. One review aimed to evaluate the effectiveness of using surgical masks on preventing transmission of the virus [ 36 ], one review was focused on pediatric patients [ 34 ], and one review investigated COVID-19 in pregnant women [ 37 ]. Most reviews assessed clinical symptoms, laboratory findings, or radiological results.

Systematic review findings

The summary of findings from individual reviews is shown in Table 2 . Overall, all-cause mortality ranged from 0.3 to 13.9% (Fig. 2 ).

A meta-analysis of the prevalence of mortality

Clinical symptoms

Seven reviews described the main clinical manifestations of COVID-19 [ 26 , 28 , 29 , 34 , 35 , 39 , 41 ]. Three of them provided only a narrative discussion of symptoms [ 26 , 34 , 35 ]. In the reviews that performed a statistical analysis of the incidence of different clinical symptoms, symptoms in patients with COVID-19 were (range values of point estimates): fever (82–95%), cough with or without sputum (58–72%), dyspnea (26–59%), myalgia or muscle fatigue (29–51%), sore throat (10–13%), headache (8–12%), gastrointestinal disorders, such as diarrhea, nausea or vomiting (5.0–9.0%), and others (including, in one study only: dizziness 12.1%) (Figs. 3 , 4 , 5 , 6 , 7 , 8 and 9 ). Three reviews assessed cough with and without sputum together; only one review assessed sputum production itself (28.5%).

A meta-analysis of the prevalence of fever

A meta-analysis of the prevalence of cough

A meta-analysis of the prevalence of dyspnea

A meta-analysis of the prevalence of fatigue or myalgia

A meta-analysis of the prevalence of headache

A meta-analysis of the prevalence of gastrointestinal disorders

A meta-analysis of the prevalence of sore throat

Diagnostic aspects

Three reviews described methodologies, protocols, and tools used for establishing the diagnosis of COVID-19 [ 26 , 34 , 38 ]. The use of respiratory swabs (nasal or pharyngeal) or blood specimens to assess the presence of SARS-CoV-2 nucleic acid using RT-PCR assays was the most commonly used diagnostic method mentioned in the included studies. These diagnostic tests have been widely used, but their precise sensitivity and specificity remain unknown. One review included a Chinese study with clinical diagnosis with no confirmation of SARS-CoV-2 infection (patients were diagnosed with COVID-19 if they presented with at least two symptoms suggestive of COVID-19, together with laboratory and chest radiography abnormalities) [ 34 ].

Therapeutic possibilities

Pharmacological and non-pharmacological interventions (supportive therapies) used in treating patients with COVID-19 were reported in five reviews [ 25 , 27 , 34 , 35 , 38 ]. Antivirals used empirically for COVID-19 treatment were reported in seven reviews [ 25 , 27 , 34 , 35 , 37 , 38 , 41 ]; most commonly used were protease inhibitors (lopinavir, ritonavir, darunavir), nucleoside reverse transcriptase inhibitor (tenofovir), nucleotide analogs (remdesivir, galidesivir, ganciclovir), and neuraminidase inhibitors (oseltamivir). Umifenovir, a membrane fusion inhibitor, was investigated in two studies [ 25 , 35 ]. Possible supportive interventions analyzed were different types of oxygen supplementation and breathing support (invasive or non-invasive ventilation) [ 25 ]. The use of antibiotics, both empirically and to treat secondary pneumonia, was reported in six studies [ 25 , 26 , 27 , 34 , 35 , 38 ]. One review specifically assessed evidence on the efficacy and safety of the anti-malaria drug chloroquine [ 27 ]. It identified 23 ongoing trials investigating the potential of chloroquine as a therapeutic option for COVID-19, but no verifiable clinical outcomes data. The use of mesenchymal stem cells, antifungals, and glucocorticoids were described in four reviews [ 25 , 34 , 35 , 38 ].

Laboratory and radiological findings

Of the 18 reviews included in this overview, eight analyzed laboratory parameters in patients with COVID-19 [ 25 , 29 , 30 , 32 , 33 , 34 , 35 , 39 ]; elevated C-reactive protein levels, associated with lymphocytopenia, elevated lactate dehydrogenase, as well as slightly elevated aspartate and alanine aminotransferase (AST, ALT) were commonly described in those eight reviews. Lippi et al. assessed cardiac troponin I (cTnI) [ 25 ], procalcitonin [ 32 ], and platelet count [ 33 ] in COVID-19 patients. Elevated levels of procalcitonin [ 32 ] and cTnI [ 30 ] were more likely to be associated with a severe disease course (requiring intensive care unit admission and intubation). Furthermore, thrombocytopenia was frequently observed in patients with complicated COVID-19 infections [ 33 ].

Chest imaging (chest radiography and/or computed tomography) features were assessed in six reviews, all of which described a frequent pattern of local or bilateral multilobar ground-glass opacity [ 25 , 34 , 35 , 39 , 40 , 41 ]. Those six reviews showed that septal thickening, bronchiectasis, pleural and cardiac effusions, halo signs, and pneumothorax were observed in patients suffering from COVID-19.

Quality of evidence in individual systematic reviews

Table 3 shows the detailed results of the quality assessment of 18 systematic reviews, including the assessment of individual items and summary assessment. A detailed explanation for each decision in each review is available in Additional file 5 .

Using AMSTAR 2 criteria, confidence in the results of all 18 reviews was rated as “critically low” (Table 3 ). Common methodological drawbacks were: omission of prospective protocol submission or publication; use of inappropriate search strategy: lack of independent and dual literature screening and data-extraction (or methodology unclear); absence of an explanation for heterogeneity among the studies included; lack of reasons for study exclusion (or rationale unclear).

Risk of bias assessment, based on a reported methodological tool, and quality of evidence appraisal, in line with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method, were reported only in one review [ 25 ]. Five reviews presented a table summarizing bias, using various risk of bias tools [ 25 , 29 , 39 , 40 , 41 ]. One review analyzed “study quality” [ 37 ]. One review mentioned the risk of bias assessment in the methodology but did not provide any related analysis [ 28 ].

This overview of systematic reviews analyzed the first 18 systematic reviews published after the onset of the COVID-19 pandemic, up to March 24, 2020, with primary studies involving more than 60,000 patients. Using AMSTAR-2, we judged that our confidence in all those reviews was “critically low”. Ten reviews included meta-analyses. The reviews presented data on clinical manifestations, laboratory and radiological findings, and interventions. We found no systematic reviews on the utility of diagnostic tests.

Symptoms were reported in seven reviews; most of the patients had a fever, cough, dyspnea, myalgia or muscle fatigue, and gastrointestinal disorders such as diarrhea, nausea, or vomiting. Olfactory dysfunction (anosmia or dysosmia) has been described in patients infected with COVID-19 [ 43 ]; however, this was not reported in any of the reviews included in this overview. During the SARS outbreak in 2002, there were reports of impairment of the sense of smell associated with the disease [ 44 , 45 ].

The reported mortality rates ranged from 0.3 to 14% in the included reviews. Mortality estimates are influenced by the transmissibility rate (basic reproduction number), availability of diagnostic tools, notification policies, asymptomatic presentations of the disease, resources for disease prevention and control, and treatment facilities; variability in the mortality rate fits the pattern of emerging infectious diseases [ 46 ]. Furthermore, the reported cases did not consider asymptomatic cases, mild cases where individuals have not sought medical treatment, and the fact that many countries had limited access to diagnostic tests or have implemented testing policies later than the others. Considering the lack of reviews assessing diagnostic testing (sensitivity, specificity, and predictive values of RT-PCT or immunoglobulin tests), and the preponderance of studies that assessed only symptomatic individuals, considerable imprecision around the calculated mortality rates existed in the early stage of the COVID-19 pandemic.

Few reviews included treatment data. Those reviews described studies considered to be at a very low level of evidence: usually small, retrospective studies with very heterogeneous populations. Seven reviews analyzed laboratory parameters; those reviews could have been useful for clinicians who attend patients suspected of COVID-19 in emergency services worldwide, such as assessing which patients need to be reassessed more frequently.

All systematic reviews scored poorly on the AMSTAR 2 critical appraisal tool for systematic reviews. Most of the original studies included in the reviews were case series and case reports, impacting the quality of evidence. Such evidence has major implications for clinical practice and the use of these reviews in evidence-based practice and policy. Clinicians, patients, and policymakers can only have the highest confidence in systematic review findings if high-quality systematic review methodologies are employed. The urgent need for information during a pandemic does not justify poor quality reporting.

We acknowledge that there are numerous challenges associated with analyzing COVID-19 data during a pandemic [ 47 ]. High-quality evidence syntheses are needed for decision-making, but each type of evidence syntheses is associated with its inherent challenges.

The creation of classic systematic reviews requires considerable time and effort; with massive research output, they quickly become outdated, and preparing updated versions also requires considerable time. A recent study showed that updates of non-Cochrane systematic reviews are published a median of 5 years after the publication of the previous version [ 48 ].

Authors may register a review and then abandon it [ 49 ], but the existence of a public record that is not updated may lead other authors to believe that the review is still ongoing. A quarter of Cochrane review protocols remains unpublished as completed systematic reviews 8 years after protocol publication [ 50 ].

Rapid reviews can be used to summarize the evidence, but they involve methodological sacrifices and simplifications to produce information promptly, with inconsistent methodological approaches [ 51 ]. However, rapid reviews are justified in times of public health emergencies, and even Cochrane has resorted to publishing rapid reviews in response to the COVID-19 crisis [ 52 ]. Rapid reviews were eligible for inclusion in this overview, but only one of the 18 reviews included in this study was labeled as a rapid review.

Ideally, COVID-19 evidence would be continually summarized in a series of high-quality living systematic reviews, types of evidence synthesis defined as “ a systematic review which is continually updated, incorporating relevant new evidence as it becomes available ” [ 53 ]. However, conducting living systematic reviews requires considerable resources, calling into question the sustainability of such evidence synthesis over long periods [ 54 ].

Research reports about COVID-19 will contribute to research waste if they are poorly designed, poorly reported, or simply not necessary. In principle, systematic reviews should help reduce research waste as they usually provide recommendations for further research that is needed or may advise that sufficient evidence exists on a particular topic [ 55 ]. However, systematic reviews can also contribute to growing research waste when they are not needed, or poorly conducted and reported. Our present study clearly shows that most of the systematic reviews that were published early on in the COVID-19 pandemic could be categorized as research waste, as our confidence in their results is critically low.

Our study has some limitations. One is that for AMSTAR 2 assessment we relied on information available in publications; we did not attempt to contact study authors for clarifications or additional data. In three reviews, the methodological quality appraisal was challenging because they were published as letters, or labeled as rapid communications. As a result, various details about their review process were not included, leading to AMSTAR 2 questions being answered as “not reported”, resulting in low confidence scores. Full manuscripts might have provided additional information that could have led to higher confidence in the results. In other words, low scores could reflect incomplete reporting, not necessarily low-quality review methods. To make their review available more rapidly and more concisely, the authors may have omitted methodological details. A general issue during a crisis is that speed and completeness must be balanced. However, maintaining high standards requires proper resourcing and commitment to ensure that the users of systematic reviews can have high confidence in the results.

Furthermore, we used adjusted AMSTAR 2 scoring, as the tool was designed for critical appraisal of reviews of interventions. Some reviews may have received lower scores than actually warranted in spite of these adjustments.

Another limitation of our study may be the inclusion of multiple overlapping reviews, as some included reviews included the same primary studies. According to the Cochrane Handbook, including overlapping reviews may be appropriate when the review’s aim is “ to present and describe the current body of systematic review evidence on a topic ” [ 12 ], which was our aim. To avoid bias with summarizing evidence from overlapping reviews, we presented the forest plots without summary estimates. The forest plots serve to inform readers about the effect sizes for outcomes that were reported in each review.

Several authors from this study have contributed to one of the reviews identified [ 25 ]. To reduce the risk of any bias, two authors who did not co-author the review in question initially assessed its quality and limitations.

Finally, we note that the systematic reviews included in our overview may have had issues that our analysis did not identify because we did not analyze their primary studies to verify the accuracy of the data and information they presented. We give two examples to substantiate this possibility. Lovato et al. wrote a commentary on the review of Sun et al. [ 41 ], in which they criticized the authors’ conclusion that sore throat is rare in COVID-19 patients [ 56 ]. Lovato et al. highlighted that multiple studies included in Sun et al. did not accurately describe participants’ clinical presentations, warning that only three studies clearly reported data on sore throat [ 56 ].

In another example, Leung [ 57 ] warned about the review of Li, L.Q. et al. [ 29 ]: “ it is possible that this statistic was computed using overlapped samples, therefore some patients were double counted ”. Li et al. responded to Leung that it is uncertain whether the data overlapped, as they used data from published articles and did not have access to the original data; they also reported that they requested original data and that they plan to re-do their analyses once they receive them; they also urged readers to treat the data with caution [ 58 ]. This points to the evolving nature of evidence during a crisis.

Our study’s strength is that this overview adds to the current knowledge by providing a comprehensive summary of all the evidence synthesis about COVID-19 available early after the onset of the pandemic. This overview followed strict methodological criteria, including a comprehensive and sensitive search strategy and a standard tool for methodological appraisal of systematic reviews.

In conclusion, in this overview of systematic reviews, we analyzed evidence from the first 18 systematic reviews that were published after the emergence of COVID-19. However, confidence in the results of all the reviews was “critically low”. Thus, systematic reviews that were published early on in the pandemic could be categorized as research waste. Even during public health emergencies, studies and systematic reviews should adhere to established methodological standards to provide patients, clinicians, and decision-makers trustworthy evidence.

Availability of data and materials

All data collected and analyzed within this study are available from the corresponding author on reasonable request.

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Acknowledgments

We thank Catherine Henderson DPhil from Swanscoe Communications for pro bono medical writing and editing support. We acknowledge support from the Covidence Team, specifically Anneliese Arno. We thank the whole International Network of Coronavirus Disease 2019 (InterNetCOVID-19) for their commitment and involvement. Members of the InterNetCOVID-19 are listed in Additional file 6 . We thank Pavel Cerny and Roger Crosthwaite for guiding the team supervisor (IJBN) on human resources management.

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Israel Júnior Borges do Nascimento & Milena Soriano Marcolino

Medical College of Wisconsin, Milwaukee, WI, USA

Israel Júnior Borges do Nascimento

Helene Fuld Health Trust National Institute for Evidence-based Practice in Nursing and Healthcare, College of Nursing, The Ohio State University, Columbus, OH, USA

Dónal P. O’Mathúna

School of Nursing, Psychotherapy and Community Health, Dublin City University, Dublin, Ireland

Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany

Thilo Caspar von Groote

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Hebatullah Mohamed Abdulazeem

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Center for Evidence-Based Medicine and Health Care, Catholic University of Croatia, Ilica 242, 10000, Zagreb, Croatia

Livia Puljak

Cochrane Brazil, Evidence-Based Health Program, Universidade Federal de São Paulo, São Paulo, Brazil

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Yorkville University, Fredericton, New Brunswick, Canada

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IJBN conceived the research idea and worked as a project coordinator. DPOM, TCVG, HMA, IW, AM, LP, VTC, IZG, TPP, ANA, SF, NLB and MSM were involved in data curation, formal analysis, investigation, methodology, and initial draft writing. All authors revised the manuscript critically for the content. The author(s) read and approved the final manuscript.

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Supplementary Information

Additional file 1: appendix 1..

Search strategies used in the study.

Additional file 2: Appendix 2.

Adjusted scoring of AMSTAR 2 used in this study for systematic reviews of studies that did not analyze interventions.

Additional file 3: Appendix 3.

List of excluded studies, with reasons.

Additional file 4: Appendix 4.

Table of overlapping studies, containing the list of primary studies included, their visual overlap in individual systematic reviews, and the number in how many reviews each primary study was included.

Additional file 5: Appendix 5.

A detailed explanation of AMSTAR scoring for each item in each review.

Additional file 6: Appendix 6.

List of members and affiliates of International Network of Coronavirus Disease 2019 (InterNetCOVID-19).

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Borges do Nascimento, I.J., O’Mathúna, D.P., von Groote, T.C. et al. Coronavirus disease (COVID-19) pandemic: an overview of systematic reviews. BMC Infect Dis 21 , 525 (2021). https://doi.org/10.1186/s12879-021-06214-4

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Rain, rain, go away, come again another day: do climate variations enhance the spread of COVID-19?

• Masha Menhat 1 ,
• Effi Helmy Ariffin   ORCID: orcid.org/0000-0002-8534-0113 2 ,
• Wan Shiao Dong 3 ,
• Junainah Zakaria 2 ,
• Aminah Ismailluddin 3 ,
• Hayrol Azril Mohamed Shafril 4 ,
• Mahazan Muhammad 5 ,
• Ahmad Rosli Othman 6 ,
• Thavamaran Kanesan 7 ,
• Suzana Pil Ramli 8 ,
• Mohd Fadzil Akhir 2 &
• Amila Sandaruwan Ratnayake 9  

Globalization and Health volume  20 , Article number:  43 ( 2024 ) Cite this article

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The spread of infectious diseases was further promoted due to busy cities, increased travel, and climate change, which led to outbreaks, epidemics, and even pandemics. The world experienced the severity of the 125 nm virus called the coronavirus disease 2019 (COVID-19), a pandemic declared by the World Health Organization (WHO) in 2019. Many investigations revealed a strong correlation between humidity and temperature relative to the kinetics of the virus’s spread into the hosts. This study aimed to solve the riddle of the correlation between environmental factors and COVID-19 by applying RepOrting standards for Systematic Evidence Syntheses (ROSES) with the designed research question. Five temperature and humidity-related themes were deduced via the review processes, namely 1) The link between solar activity and pandemic outbreaks, 2) Regional area, 3) Climate and weather, 4) Relationship between temperature and humidity, and 5) the Governmental disinfection actions and guidelines. A significant relationship between solar activities and pandemic outbreaks was reported throughout the review of past studies. The grand solar minima (1450-1830) and solar minima (1975-2020) coincided with the global pandemic. Meanwhile, the cooler, lower humidity, and low wind movement environment reported higher severity of cases. Moreover, COVID-19 confirmed cases and death cases were higher in countries located within the Northern Hemisphere. The Blackbox of COVID-19 was revealed through the work conducted in this paper that the virus thrives in cooler and low-humidity environments, with emphasis on potential treatments and government measures relative to temperature and humidity.

• The coronavirus disease 2019 (COIVD-19) is spreading faster in low temperatures and humid area.

• Weather and climate serve as environmental drivers in propagating COVID-19.

• Solar radiation influences the spreading of COVID-19.

• The correlation between weather and population as the factor in spreading of COVID-19.

Graphical abstract

Introduction

The revolution and rotation of the Earth and the Sun supply heat and create differential heating on earth. The movements and the 23.5° inclination of the Earth [ 1 ] separate the oblate-ellipsoid-shaped earth into northern and southern hemispheres. Consequently, the division results in various climatic zones at different latitudes and dissimilar local temperatures (see Fig.  1 ) and affects the seasons and length of a day and night in a particular region [ 2 ]. Global differential heating and climate variability occur due to varying solar radiation received by each region [ 3 ]. According to Trenberth and Fasullo [ 4 ] and Hauschild et al. [ 5 ] the new perspective on the issue of climate change can be affected relative to the changes in solar radiation patterns. Since the study by Trenberth and Fasullo [ 4 ] focused on climate model changes from 1950 to 2100, it was found that the role of changing clouds and trapped sunlight can lead to an opening of the aperture for solar radiation.

The annual average temperature data for 2021 in the northern and southern hemispheres ( Source: meteoblue.com ). Note: The black circles mark countries with high Coronavirus disease 2019 (COVID-19) infections

Furthermore, the heat from sunlight is essential to humans; several organisms could not survive without it. Conversely, the spread of any disease-carrying virus tends to increase with less sunlight exposure [ 6 ]. Historically, disease outbreaks that led to epidemic and pandemic eruptions were correlated to atmospheric changes. Pandemic diseases, such as the flu (1918), Asian flu (1956–1958), Hong Kong flu (1968), and recently, the coronavirus disease 2019 (COVID-19) (2019), recorded over a million death toll each during the winter season or minimum temperature conditions [ 7 ]. The total number of COVID-19 cases is illustrated in Fig.  2 .

A graphical representation of the total number of COVID-19 cases across various periods between 2020 and 2021. ( Source : www.worldometers.info ). Note: The black circles indicate countries with high numbers COVID-19-infections

In several previous outbreaks, investigations revealed a significant association between temperature and humidity with a particular focus on the transmission dynamics of the infection from the virus into the hosts [ 8 , 9 , 10 ]. Moreover, disease outbreaks tended to heighten in cold temperatures and low humidity [ 11 ]. Optimal temperature and sufficient relative humidity during evaporation are necessary for cloud formation, resulting in the precipitated liquid falling to the ground as rain, snow, or hail due to the activity of solar radiation balancing [ 4 ].

Consequently, the radiation balancing processes in the atmosphere are directly linked to the living beings on the earth, including plants and animals, and as well as viruses and bacterias. According to Carvalho et al. [ 12 ]‘s study, the survival rate of the Coronaviridae Family can decrease during summer seasons. Nevertheless, numerous diseases were also developed from specific viruses, such as influenza, malaria, and rubella, and in November 2019, a severe health threat originated from a 125 nm size of coronavirus, had resulted in numerous deaths worldwide.

Transmission and symptoms of COVID-19

The COVID-19, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an infectious disease caused by a newly discovered pathogenic virus from the coronavirus family, the novel coronavirus (2019-nCoV) [ 13 ]. The first case was recorded in Wuhan, China, in December 2019 [ 14 ]. The pathogenic virus is transmitted among humans when they breathe in air contaminated with droplets and tiny airborne particles containing the virus [ 14 , 15 , 16 , 17 , 18 ].

According to the World Health Organization (WHO), the most common symptoms of COVID-19 infection include fever, dry cough, and tiredness. Nevertheless, older people and individuals with underlying health problems (lung and heart problems, high blood pressure, diabetes, or cancer) are at higher risk of becoming seriously ill and developing difficulty breathing [ 19 ]. The COVID-19 was initially only predominant in China but rapidly spread to other countries globally. The remarkably swift acceleration of the number of infections and mortality forced WHO to declare COVID-19 a global public health emergency on the 30th of January 2020, which was later declared as a pandemic on the 11th of March 2020 [ 20 ].

Since no vaccine was available then, WHO introduced the COVID-19 preventative measures to reduce the chances of virus transmission. The guideline for individual preventative included practising hand and respiratory hygiene by regularly cleaning hands with soap and water or alcohol-based sanitisers, wear a facemask and always maintaining at least a one-meter physical distance [ 21 ]. Nevertheless, the worldwide transmission of COVID-19 has resulted in fear and forced numerous countries to impose restrictions rules, such as lockdown, travel bans, closed country borders, restrictions on shipping activities, and movement limitations, to diminish the spread of COVID-19 [ 22 ].

According to WHO, by the 2nd of December 2020, 63,379,338 confirmed cases and 1,476,676 mortalities were recorded globally. On the 3rd of December 2021, 263,655,612 confirmed cases and deaths were recorded, reflecting increased COVID-19 infections compared to the previous year. The American and European regions documented the highest COVID-19 patients with 97,341,769 and 88,248,591 cases, respectively (see Fig. 2 ), followed by Southeast Asia with 44,607,287, Eastern Mediterranean accounted 16,822,791, Western Pacific recorded 6,322,034, and Africa reported the lowest number of cases at 6,322,034 [ 19 ].

Recently, an increasing number of studies are investigating the association between environmental factors (temperature and humidity) and the viability, transmission, and survival of the coronavirus [ 23 , 24 , 25 , 26 ]. The results primarily demonstrated that temperature was more significantly associated with the transmission of COVID-19 [ 27 , 28 , 29 ] and its survival period on the surfaces of objects [ 30 ]. Consequently, the disease was predominant in countries with low temperature and humidity [ 31 ], which was also proven by Diao et al. [ 32 ]‘s study demonstrating higher rates of COVID-19 transmission in China, England, Germany, and Japan.

A comprehensive systematic literature review (SLR) is still lacking despite numerous research on environmental factors linked to coronavirus. Accordingly, this article aimed to fill the gap in understanding and identifying the correlation between environmental factors and COVID-19 by analysing existing reports. Systematically reviewing existing literature is essential to contribute to the body of knowledge and provide beneficial information for public health policymakers.

Methodology

The present study reviewed the protocols, formulation of research questions, selection of studies, appraisal of quality, and data abstraction and analysis.

The protocol review

The present SLR was performed according to the reporting standards for systematic evidence syntheses (ROSES) and followed or adapted the guidelines as closely as possible. Thus, in this study, a systematic literature review was guided by the ROSES review protocol (Fig.  3 ). Compared to preferred reporting items for systematic review and meta-analysis (PRISMA), ROSES is a review protocol specifically designed for a systematic review in the conservation or environment management fields [ 33 ]. Compared to PRISMA, ROSES offers several advantages, as it is tailored to environmental systematic review, which reduces emphasis on quantitative synthesis (e.g. meta-analysis etc.) that is only reliable when used with appropriate data [ 34 ].

The flow diagram guide by ROSES protocol and Thematical Analysis

The current SLR started by determining the appropriate research questions, followed by the selection criteria, including the review, specifically on the keywords employed and the selection of journals database. Subsequently, the appraisal quality process and data abstraction and analysis were conducted.

Formulation of research questions

The entire process of this SLR was guided by the specific research questions, while sources to be reviewed and data abstraction and analysis were in line with the determined research question [ 35 , 36 ]. In the present article, a total of five research questions were formed, namely:

What the link between solar activity and COVID-19 pandemic outbreaks?

Which regions were more prone to COVID-19?

What were the temporal and spatial variabilities of high temperature and humidity during the spread of COVID-19?

What is the relationship between temperature and humidity in propagating COVID-19?

How did the government’s disinfection actions and guidelines can be reducing the spread of COVID-19?

Systematic searching strategies

Selection of studies.

In this stage of the study, the appropriate keywords to be employed in the searching process were determined. After referring to existing literature, six main keywords were chosen for the searching process, namely COVID-19, coronavirus, temperature, humidity, solar radiation and population density. The current study also utilised the boolean operators (OR, AND, AND NOT) and phrase searching.

Scopus was employed as the main database during the searching process, in line with the suggestion by Gusenbauer and Haddaway [ 37 ], who noted the strength of the database in terms of quality control and search and filtering functions. Furthermore, Google Scholar was selected as the supporting database. Although Halevi et al. [ 38 ] expressed concerns about its quality, Haddaway et al. [ 39 ] reported that due to its quantity, Google Scholar was suitable as a supporting database in SLR studies.

In the first stage of the search, 2550 articles were retrieved, which were then screened. The suitable criteria were also determined to control the quality of the articles reviewed [ 40 ]. The criteria are: any documents published between 2000 to 2022, documents that consist previously determined keywords, published in English, and any environment-related studies that focused on COVID-19. Based on these criteria, 2372 articles were excluded and 178 articles were proceeded to the next step namely eligibility. In the eligibility process, the title and the abstract of the articles were examined to ensure its relevancy to the SLR and in this process a total of 120 articles were excluded and only 58 articles were processed in the next stage.

Appraisal of the quality

The study ensured the rigor of the chosen articles based on best evidence synthesis. In the process, predefined inclusion criteria for the review were appraised by the systematic review team based on previously established guidelines and the studies were then judged as being scientifically admissible or not [ 40 ]. Hence, by controlling the quality based on the best evidence synthesis, the present SLR controls its quality by including articles that are in line with the inclusion criteria. It means that any article published within the timeline (in the year 2000 and above), composed of predetermined keywords, in English medium, and environment-related investigations focusing on COVID-19 are included in the review. Based on this process, all 58 articles fulfilled all the inclusion criteria and are considered of good quality and included in the review.

Data abstraction and analysis

The data abstraction process in this study was performed based on five research questions (please refer to 2.2, formulation of research questions). The data that was able to answer the questions were abstracted and placed in a table to ease the data analysis process. The primary data analysis technique employed in the current study was qualitative and relied on thematic analysis.

The thematic technique is a descriptive method that combines data flexibly with other information evaluation methods [ 41 ], aiming to identify the patterns in studies. Any similarities and relationships within the abstracted data emerge as patterns. Subsequently, suitable themes and sub-themes would be developed based on obtained patterns [ 42 ]. Following the thematic process, five themes were selected in this study.

Background of the selected articles

The current study selected 58 articles for the SLR. Five themes were developed based on the thematic analysis from the predetermined research questions: the link between solar activity and pandemic outbreaks, regional area, climate and weather, the relationship between temperature and humidity, and government disinfection action guidelines. Among the articles retrieved between 2000 and 2022; two were published in 2010, one in 2011, four in 2013, three in 2014, two in 2015, six in 2016 and 2017, respectively, one in 2018, six in 2019, twelve in 2020, eight in 2021, and seven in 2022.

Temperature- and humidity-related themes

The link between solar activity and pandemic outbreaks.

Numerous scientists have investigated the relationship between solar activities and pandemic outbreaks over the years ([ 43 ]; A [ 27 , 44 , 45 ].). Nuclear fusions from solar activities have resulted in minimum and maximum solar sunspots. Maximum solar activities are characterised by a high number of sunspots and elevated solar flare frequency and coronal mass injections. Minimum solar sunspot occurrences are identified by low interplanetary magnetic field values entering the earth [ 1 ].

A diminished magnetic field was suggested to be conducive for viruses and bacteria to mutate, hence the onset of pandemics. Nonetheless, Hoyle and Wickramasinghe [ 46 ] reported that the link between solar activity and pandemic outbreaks is only speculative. The literature noted that the data recorded between 1930 and 1970 demonstrated that virus transmissions and pandemic occurrences were coincidental. Moreover, no pandemic cases were reported in 1979, when minimum solar activity was recorded [ 47 ].

Chandra Wickramasinghe et al. [ 48 ] suggested a significant relationship between pandemic outbreaks and solar activities as several grand solar minima, including Sporer (1450–1550 AD), Mounder (1650–1700 AD), and Dalton (1800–1830) minimums, were recorded coinciding with global pandemics of diseases, such as smallpox, the English sweat, plague, and cholera pandemics. Furthermore, since the Dalton minimum, which recorded minimum sunspots, studies from 2002 to 2015 have documented the reappearance of previous pandemics. For example, influenza subtype H1N1 1918/1919 episodically returned in 2009, especially in India, China, and other Asian countries. Zika virus, which first appeared in 1950, flared and became endemic in 2015, transmitted sporadically, specifically in African countries. Similarly, SARS-CoV was first recorded in China in 2002 and emerged as an outbreak, MERS-CoV, in middle east countries a decade later, in 2012.

In 2020, the World Data Centre Sunspot Index and Long-term Solar Observations ( http://sidc.be ) confirmed that a new solar activity was initiated in December 2019, during which a novel coronavirus pandemic also occurred, and present a same as the previous hypothesis. Nevertheless, a higher number of pandemic outbreaks were documented during low minimum solar activities, including Ebola (1976), H5N1 (Nipah) (1967–1968), H1N1 (2009), and COVID-19 (2019–current). Furthermore, Wickramasinghe and Qu [ 49 ] reported that since 1918 or 1919, more devastating and recurrent pandemics tend to occur, particularly after a century. Consequently, within 100 years, a sudden surge of influenza was recorded, and novel influenza was hypothesised to emerge.

Figure  4 demonstrates that low minimum solar activity significantly reduced before 2020, hence substantiating the claim that pandemic events are closely related to solar activities. Moreover, numerous studies (i.e. [ 43 ], Chandra [ 46 , 47 , 48 ]) reported that during solar minimums, new viruses could penetrate the surfaces of the earth and high solar radiation would result in lower infection rates, supporting the hypothesis mentioned above.

The number of sunspots in the last 13 years. Note : The yellow curve indicates the daily sunspot number and the 2010–2021 delineated curve illustrates the minimum solar activity recorded (source: http://sidc.be/silso )

Regional area

In early December 2019, Wuhan, China, was reported as the centre of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak [ 50 ]. Chinese health authorities immediately investigated and controlled the spread of the disease. Nevertheless, by late January 2020, the WHO announced that COVID-19 was a global public health emergency. The upgrade was due to the rapid rise in confirmed cases, which were no longer limited to Wuhan [ 28 ]. The disease had spread to 24 other countries, which were mainly in the northern hemisphere, particularly the European and Western Pacific regions, such as France, United Kingdom, Spain, South Korea, Japan, Malaysia, and Indonesia [ 51 , 52 ]. The migration or movement of humans was the leading agent in the spread of COVID-19, resulting in an almost worldwide COVID-19 pandemic [ 53 ].

The first hotspots of the epidemic outspread introduced by the Asian and Western Pacific regions possessed similar winter climates with an average temperature and humidity rate of 5–11 °C and 47–79%. Consequently, several publications reviewed in the current study associated the COVID-19 outbreak with regional climates (i.e. [ 1 , 29 , 54 , 55 ]) instead of its close connection to China. This review also discussed the effects of a range of specific climatological variables on the transmission and epidemiology of COVID-19 in regional climatic conditions.

America and Europe documented the highest COVID-19 cases, outnumbering the number reported in Asia [ 19 ] and on the 2nd of December 2020, the United States of America (USA) reported the highest number of confirmed COVID-19 infections, with over 13,234,551 cases and 264,808 mortalities (Da S [ 56 ].). The cases in the USA began emerging in March 2020 and peaked in late November 2020, during the wintertime in the northern hemisphere (December to March) [ 53 ]. Figure  5 demonstrates the evolution of the COVID-19 pandemic in several country which represent comparison two phase of summer and one phase of winter. Most of these countries tend to increase of COVID cases close to winter season. Then, it can be worsening on phase two of summer due to do not under control of human movement although the normal trend it is presenting during winter phase.

The evolution of the COVID-19 pandemic from the 15th of February 2020 to the 2nd of December 2020 ( Source: https://www.worldometers.info/coronavirus )

The coronavirus spread aggressively across the European region, which recorded the second highest COVID-19 confirmed cases after America. At the end of 2020, WHO reported 19,071,275 Covid-19 cases in the area, where France documented 2,183,275 cases, the European country with the highest number of confirmed cases, followed by the United Kingdom (1,629,661 cases) and Spain (1,652,801 cases) [ 19 ]. Europe is also located in the northern hemisphere and possesses a temperate climate.

The spatial and temporal transmission patterns of coronavirus infection in the European region were similar to America and the Eastern Mediterranean, where the winter season increased COVID-19 cases. Typically, winter in Europe occurs at the beginning of October and ends in March. Hardy et al. [ 57 ] also stated that temperature commonly drops below freezing (approximately − 1 °C) when snow accumulates between December to mid-March, resulting in an extreme environment. Figure 5 indicates that COVID-19 cases peaked in October when the temperature became colder [ 21 ]. Similarly, the cases were the highest in the middle of the year in Australia and South Asian countries, such as India, that experience winter and monsoon, respectively, during the period.

In African regions, the outbreak of COVID-19 escalated rapidly from June to October before falling from October to March, as summer in South Africa generally occurs from November to March, while winter from June to August. Nevertheless, heavy rainfall generally transpires during summer, hence the warm and humid conditions in South Africa and Namibia during summer, while the opposite happens during winter (cold and dry). Consequently, the outbreak in the region recorded an increasing trend during winter and subsided during the summer, supporting the report by Gunthe et al. [ 58 ]. Novel coronavirus disease presents unique and grave challenges in Africa, as it has for the rest of the world. However, the infrastructure and resources have limitations for Africa countries facing COVID-19 pandemic and the threat of other diseases [ 59 ].

Conclusively, seasonal and regional climate patterns were associated with COVID-19 outbreaks globally. According to Kraemer et al. [ 60 ], they used real-time mobility data in Wuhan and early measurement presented a positive correlation between human mobility and spread of COVID-19 cases. However, after the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases were still indicative of local chains of transmission outside of Wuhan.

Climate and weather

The term “weather” represents the changes in the environment that occur daily and in a short period, while “climate” is defined as atmospheric changes happening over a long time (over 3 months) in specific regions. Consequently, different locations would experience varying climates. Numerous reports suggested climate and weather variabilities as the main drivers that sped or slowed the transmission of SARS-CoV-2 worldwide [ 44 , 61 , 62 , 63 ].

From a meteorological perspective, a favourable environment has led to the continued existence of the COVID-19 virus in the atmosphere [ 64 ]. Studies demonstrated that various meteorological conditions, such as the rate of relative humidity (i.e. [ 28 ]), precipitation (i.e. [ 65 ]), temperature (i.e. [ 66 ]), and wind speed factors (i.e. [ 54 ]), were the crucial components that contributed to the dynamic response of the pandemic, influencing either the mitigation or exacerbation of novel coronavirus transmission. In other words, the environment was considered the medium for spreading the disease when other health considerations were put aside. Consequently, new opinions, knowledge, and findings are published and shared to increase awareness, thus encouraging preventive measures within the public.

The coronavirus could survive in temperatures under 30 °C with a relative humidity of less than 80% [ 67 ], suggesting that high temperatures and lower relative humidity contributed to the elicitation of COVID-19 cases [ 18 , 51 , 58 , 68 ]. Lagtayi et al. [ 7 ] highlighted temperature as a critical factor, evidently from the increased transmission rate of MERS-Cov in African states with a warm and dry climate. Similarly, the highest COVID-19 cases were recorded in dry temperate regions, especially in western Europe (France and Spain), China, and the USA, while the countries nearer to the equator were less affected. Nevertheless, the temperature factor relative to viral infections depends on the protein available in the viruses. According to Chen and Shakhnovich [ 69 ], there is a good correlation between decreasing temperature and the growth of proteins in virus. Consequently, preventive measures that take advantage of conducive environments for specific viruses are challenging.

Precipitation also correlates with influenza [ 43 ]. A report demonstrated that regions with at least 150 mm of monthly precipitation threshold level experienced fewer cases than regions with lower precipitation rates. According to Martins et al. [ 70 ], influenza and COVID-19 can be affected by climate, where virus can be spread through the respiratory especially during rainfall season. The daily spread of Covid-19 cases in tropical countries, which receive high precipitation levels, are far less than in temperate countries [ 27 ]. Likewise, high cases of COVID-19 were reported during the monsoon season (mid-year) in India during which high rainfall is recorded [ 71 ]. Moreover, the majority of the population in these regions has lower vitamin D levels, which may contribute to weakened immune responses during certain seasons [ 27 ].

Rainfall increases the relative atmospheric humidity, which is unfavourable to the coronaviruses as its transmission requires dry and cold weather. Moreover, several reports hypothesised that rain could wash away viruses on object surfaces, which is still questioned. Most people prefer staying home on rainy days, allowing less transmission or close contact. Conversely, [ 72 ] exhibited that precipitation did not significantly impact COVID-19 infectiousness in Oslo, Norway due the location in northern hemisphere which are during winter season presenting so cold.

Coşkun et al. [ 54 ] and Wu et al. [ 29 ] claimed that wind could strongly correlate with the rate of COVID-19 transmission. Atmospheric instability (turbulent occurrences) leads to increased wind speed and reduces the dispersion of particulate matter (PM 2.5 and PM 10 ) in the environment and among humans. An investigation performed in 55 cities in Italy during the COVID-19 outbreak proved that the areas with low wind movement (stable atmospheric conditions) possessed a higher correlation coefficient and exceeded the threshold value of the safe level of PM 2.5 and PM 10 . Resultantly, more individuals were recorded infected with the disease in the regions. As mentioned in Martins et al. [ 70 ] the COVID-19 can be affected by climate and the virus can be spread through respiratory which is the virus moving in the wind movement.

The relationship between temperature and humidity

Climatic parameters, such as temperature and humidity, were investigated as the crucial factors in the epidemiology of the respiratory virus survival and transmission of COVID-19 ([ 61 ]; S [ 73 , 74 ].). The rising number of confirmed cases indicated the strong transmission ability of COVID-19 and was related to meteorological parameters. Furthermore, several studies found that the disease transmission was associated with the temperature and humidity of the environment [ 55 , 64 , 68 , 75 ], while other investigations have examined and reviewed environmental factors that could influence the epidemiological aspects of Covid-19.

Generally, increased COVID-19 cases and deaths corresponded with temperature, humidity, and viral transmission and mortality. Various studies reported that colder and dryer environments favoured COVID-19 epidemiologically [ 45 , 76 , 77 ]. As example tropical region, the observations indicated that the summer (middle of year) and rainy seasons (end of the year) could effectively diminish the transmission and mortality from COVID-19. High precipitation statistically increases relative air humidity, which is unfavourable for the survival of coronavirus, which prefers dry and cold conditions [ 32 , 34 , 78 , 79 ]. Consequently, warmer conditions could reduce COVID-19 transmission. A 1 °C increase in the temperature recorded a decrease in confirmed cases by 8% increase [ 45 ].

Several reports established that the minimum, maximum, and average temperature and humidity correlated with COVID-19 occurrence and mortality [ 55 , 80 , 81 ]. The lowest and highest temperatures of 24 and 27.3 °C and a humidity between 76 and 91% were conducive to spreading the virulence agents. The propagation of the disease peaked at the average temperature of 26 °C and humidity of 55% before gradually decreasing with elevated temperature and humidity [ 78 ].

Researchers are still divided on the effects of temperature and humidity on coronavirus transmission. Xu et al. [ 26 ] confirmed that COVID-19 cases gradually increased with higher temperature and lower humidity, indicating that the virus was actively transmitted in warm and dry conditions. Nevertheless, several reports stated that the spread of COVID-19 was negatively correlated with temperature and humidity [ 10 , 29 , 63 ]. The conflicting findings require further investigation. Moreover, other factors, such as population density, elderly population, cultural aspects, and health interventions, might potentially influence the epidemiology of the disease and necessitate research.

Governmental disinfection actions and guidelines

The COVID-19 is a severe health threat that is still spreading worldwide. The epidemiology of the SAR-CoV-2 virus might be affected by several factors, including meteorological conditions (temperature and humidity), population density, and healthcare quality, that permit it to spread rapidly [ 16 , 17 ]. Nevertheless, in 2020, no effective pharmaceutical interventions or vaccines were available for the diagnosis, treatment, and epidemic prevention against COVID-19 [ 73 , 82 ]. Consequently, after 2020 the governments globally have designed and executed non-pharmacological public health measures, such as lockdown, travel bans, social distancing, quarantine, public place closure, and public health actions, to curb the spread of COVID-19 infections and several studies have reported on the effects of these plans [ 13 , 83 ].

The COVID-19 is mainly spread via respiratory droplets from an infected person’s mouth or nose to another in close contact [ 84 ]. Accordingly, WHO and most governments worldwide have recommended wearing facemasks in public areas to curb the transmission of COVID-19. The facemasks would prevent individuals from breathing COVID-19-contaminated air [ 85 ]. Furthermore, the masks could hinder the transmission of the virus from an infected person as the exhaled air is trapped in droplets collected on the masks, suspending it in the atmosphere for longer. The WHO also recommended adopting a proper hand hygiene routine to prevent transmission and employing protective equipment, such as gloves and body covers, especially for health workers [ 86 ].

Besides wearing protective equipment, social distancing was also employed to control the Covid-19 outbreak [ 74 , 87 ]. Social distancing hinders the human-to-human transmission of the coronavirus in the form of droplets from the mouth and nose, as evidenced by the report from Sun and Zhai [ 88 ]. Conversely, Nair & Selvaraj [ 89 ] demonstrated that social distancing was less effective in communities and cultures where gatherings are the norm. Nonetheless, the issue could be addressed by educating the public and implementing social distancing policies, such as working from home and any form of plague treatment.

Infected persons, individuals who had contact with confirmed or suspected COVID-19 patients, and persons living in areas with high transmission rates were recommended to undergo quarantine by WHO. The quarantine could be implemented voluntarily or legally enforced by authorities and applicable to individuals, groups, or communities (community containment) [ 90 ]. A person under mandatory quarantine must stay in a place for a recommended 14-day period, based on the estimated incubation period of the SARS-CoV-2 [ 19 , 91 ]. According to Stasi et al. [ 92 ], 14-days period for mandatory quarantine it is presenting a clinical improvement after they found 5-day group and 10-day group can be decrease number of patient whose getting effect of COVID-19 from 64 to 54% respectively. This also proven by Ahmadi et al. [ 43 ] and Foad et al. [ 93 ], quarantining could reduce the transmission of COVID-19.

Lockdown and travel bans, especially in China, the centre of the coronavirus outbreak, reduced the infection rate and the correlation of domestic air traffic with COVID-19 cases [ 17 ]. The observations were supported by Sun & Zhai [ 88 ] and Sun et al. [ 94 ], who noted that travel restrictions diminished the number of COVID-19 reports by 75.70% compared to baseline scenarios without restrictions. Furthermore, example in Malaysia, lockdowns improved the air quality of polluted areas especially in primarily at main cities [ 95 ]. As additional, Martins et al. [ 70 ] measure the Human Development Index (HDI) with the specific of socio-economic variables as income, education and health. In their study, the income and education levels are the main relevant factors that affect the socio-economic.

A mandatory lockdown is an area under movement control as a preventive measure to stop the coronavirus from spreading to other areas. Numerous governments worldwide enforced the policy to restrict public movements outside their homes during the pandemic. Resultantly, human-to-human transmission of the virus was effectively reduced. The lockdown and movement control order were also suggested for individuals aged 80 and above or with low or compromised immunities, as these groups possess a higher risk of contracting the disease [ 44 ].

Governments still enforced movement orders even after the introduction of vaccines by Pfizer, Moderna, and Sinovac, as the vaccines only protect high-risk individuals from the worst effects of COVID-19. Consequently, in most countries, after receiving the first vaccine dose, individuals were allowed to resume life as normal but were still required to follow the standard operating procedures (SOP) outlined by the government.

The government attempted to balance preventing COVID-19 spread and recovering economic activities, for example, local businesses, maritime traders, shipping activities, oil and gas production and economic trades [ 22 , 96 ]. Nonetheless, the COVID-19 cases demonstrated an increasing trend during the summer due to the higher number of people travelling and on vacation, primarily to alleviate stress from lockdowns. Several new variants were discovered, including the Delta and Omicron strains, which spread in countries such as the USA and the United Kingdom. The high number of COVID-19 cases prompted the WHO to suggest booster doses to ensure full protection.

As mentioned in this manuscript, the COVID-19 still uncertain for any kind factors that can be affected on spreading of this virus. However, regarding many sources of COVID-19 study, the further assessment on this factor need to be continue to be sure, that we ready to facing probably in 10 years projection of solar minimum phase can be held in same situation for another pandemic.

The sun has an eleven-year cycle known as the solar cycle, related to its magnetic field, which controls the activities on its surface through sunspots. When the magnetic fields are active, numerous sunspots are formed on its surface, hence the sun produces more radiation energy emitted to the earth. The condition is termed solar maximum (see Fig.  6 , denoted by the yellow boxes). Alternatively, as the magnetic field of the sun weakens, the number of sunspots decreases, resulting in less radiation energy being emitted to the earth. The phenomenon is known as the solar minimum (see Fig. 6 , represented by the blue boxes).

The emergence and recurrence of pandemics every 5 years in relation to solar activities ( Source: www.swpc.noaa.gov/ ). Note: The yellow boxes indicate the solar maximum, while the blue boxes represent the solar minimum

The magnetic field of the sun protects the earth from cosmic or galactic cosmic rays emitted by supernova explosions, stars, and gamma-ray bursts [ 97 ]. Nevertheless, galactic cosmic rays could still reach the earth during the solar minimum, the least solar radiation energy period. In the 20th and early 21st centuries, several outbreaks of viral diseases that affected the respiratory system (pneumonia or influenza), namely the Spanish (1918–1919), Asian (1957–1958) and Hong Kong (1968) flu, were documented. Interestingly, the diseases that claimed numerous lives worldwide occurred at the peak of the solar maximum.

Figure  6 illustrates the correlation between the number of sunspots and disease outbreaks from 1975 to 2021, including COVID-19, that began to escalate in December 2019. Under the solar minimum conditions, the spread of Ebola (1976), H5N1 (1997–1998), H1N1 (2009), and COVID-19 (2019-2020) were documented, while the solar maximum phenomenon recorded SARS (2002) and H7N9 (2012–2013) or MERS outbreaks. Nonetheless, solar activity through the production of solar sunspots began to decline since the 22nd solar cycle. Accordingly, further studies are necessary to investigate the influence such solar variations could impart or not on pandemic development.

Despite the findings mentioned above, the sun and cosmic radiations could influence the distribution or outspread of disease-spreading viruses. The rays could kill the viruses via DNA destruction or influence their genetic mutations, which encourage growth and viral evolution. Nevertheless, the connection between radiation and the evolutionary process requires further study by specialists in the field it is become true or not.

The spread of viral diseases transpires naturally in our surroundings and occurs unnoticed by humans. According to records, the spread of pandemic diseases, including the Black Death (fourteenth century) and the Spanish flu (1919), was significantly influenced by the decline and peak of solar activities. Furthermore, in the past 20 years, various diseases related to the influenza virus have been recorded. According to the pattern observed, if all diseases were related to the solar cycle (solar maximum and minimum), the viral diseases would reoccur every 5 to 6 years since they first appeared between 1995 and 2020. Accordingly, the next pandemic might occur around 2024 or 2025 and need to have a proper study for prove these statements. Nonetheless, the activities on the surface of the sun have been weakening since the 23rd solar cycle and it can be proven later after the proper study can be make it.

The beginning of the COVID-19 spread, only several countries with the same winter climate with an average temperature of 5–11 °C and an average humidity rate of 47–79% located at latitudes 30–50 N reported cases. The areas included Wuhan distribution centres in China, the United Kingdom, France, Spain, South Korea, Japan, and the USA (see Fig.  5 ). Other than biological aspects, the higher number of confirmed cases recorded in colder environments was due to the human body secreting less lymphoproliferative hormone, leading to decreased immunogenicity effects and increased risk of infection [ 24 ]. Consequently, the virus could attack and rapidly infect humans during the period [ 1 , 54 ].

The lymphoproliferative response is a protective immune response that plays a vital role in protecting and eradicating infections and diseases. On the other hand, staying in warm conditions or being exposed to more sunlight would lower the risks of infection. According to Asyary and Veruswati [ 98 ], sunlight triggers vitamin D, which increases immunity and increases the recovery rates of infected individuals.

Researchers believe that viruses could survive in the environment for up to 3 to 4 years or even longer. The survival rate of the microorganisms is relatively high, which is related to their biological structures, adaptability on any surfaces, and transmission medium to spread diseases. Viruses possess simple protein structures, namely the spike, membrane, and envelope protein; therefore, when they enter living organisms (such as through the respiratory system), the viruses are easily transmitted.

Once they have entered a host, the viruses duplicate exponentially and swarm the lungs. Subsequently, after the targeted organs, such as the lungs, are invaded, the viruses attack the immune system and create confusion in protective cells to destroy healthy cells. The situation is still considered safe in younger and healthy individuals as their immune systems could differentiate and counter-attack the viruses, curing them. Nonetheless, in elders and individuals with several chronic diseases, most of their protective cells are dead, hence their immune system is forced to work hard to overcome the infection. Pneumonia and death tend to occur when the situation is overwhelming [ 85 ]. Consequently, the viruses are harmful to humans as they could multiply in a short period, enter the blood, and overrun the body.

The coronavirus could attach to surfaces without a host, including door knobs and steel and plastic materials. The microorganisms could survive alone, but virologists have yet to determine how long. If someone touches any surface with the virus, the individual would then be infected. The situation would worsen if the infected person contacted numerous people and became a super spreader. A super spreader does not exhibit any symptoms and continuously transmits the virus without realising it. An infected individual transmits the coronavirus via droplets from coughs or sneezes. Nevertheless, scientists have yet to determine if coronavirus is spread via airborne or droplets, hence requiring thorough evaluation [ 99 ].

The COVID-19 virus mutates over time, and it can be changing any times. Mutations alter the behaviour and genetic structure of the virus, resulting in a new strain. Numerous research have been conducted to procure vaccines and anti-viral medications, but mutations have led to evolutionary disadvantages. The novel strains are more infectious than the original ones. As of November 2020, approximately six new coronavirus strains have been detected, each displaying different transmission behaviours [ 100 ].

Recent studies demonstrated that the mutated viruses exhibit little variability, allowing scientists to produce viable vaccines [ 71 ]. Furthermore, different types of vaccines are manufactured by different countries, which could be advantageous. Currently, most countries also recommend booster doses to attain extra protection after receiving the mandatory two vaccine doses. In same time, the social and physical interactions between humans also necessitate to be aware.

The COVID-19 virus is primarily transmitted through droplets produced by an infected person. Accordingly, physical distancing, a one-metre minimum distance between individuals [ 19 ], and following the SOP might prevent or avoid spreading the disease. Moreover, self-quarantine, school closures, working from home, cancelling large events, limiting gatherings, and avoiding spending long periods in crowded places are essential strategies in enforcing physical distancing at a community level. The policies are essential precautions that could reduce the further spreading of coronavirus and break the chain of transmission.

Government support also need to control the spread of COVID-19 with the strict SOP. The SOP enforcement in public places would enhance adherence to the new practice among the public and the community, aiding in curbing disease transmission. Practising limited meetings and social gatherings, avoiding crowded places, workplace distancing, preventing non-necessary travels of high-risk family members, especially those with chronic disease, and adhering to the recommended SOP could reduce coronavirus outbreaks. Nonetheless, individual awareness is also necessary to achieve COVID-19 spread prevention.

Many researchers are focused on identifying the primary drivers of pandemic outbreaks. Seasonal, temperature, and humidity differences significantly impacted COVID-19 growth rate variations. It is crucial to highlight the potential link between the recurrence of pandemics every 5 years and solar activities, which can influence temperature and humidity variations. Notable variations in COVID-19 mortality rates were observed between northern and southern hemisphere countries, with the former having higher rates. One hypothesis suggests that populations in the northern hemisphere may receive insufficient sunlight to maintain optimal vitamin D levels during winter, possibly leading to higher mortality rates.

The first COVID-19 case was detected in Wuhan, China, which is in the northern hemisphere. The number of cases rapidly propagated in December during the winter season. At the time, the temperature in Wuhan was recorded at 13–18 °C. Accordingly, one theory proposes that the survival and transmission of the coronavirus were due to meteorological conditions, namely temperatures between 13 and 18 °C and 50–80% humidity.

Daily rainfall directly impacts humidity levels. The coronavirus exhibited superior survival rates in cold and dry conditions. Furthermore, transmissible gastroenteritis (TGEV) suspensions and possibly other coronaviruses remain viable longer in their airborne states, which are more reliably collected in low relative humidity than in high humidity. Consequently, summer rains would effectively reduce COVID-19 transmission in southern hemisphere regions.

In southern hemisphere regions, the summer seasons are accompanied by a high average temperature at the end and beginning of the year. Countries with temperatures exceeding 24 °C reported fewer infections. As temperatures rise from winter to summer, virus transmission is expected to decline. Nonetheless, the activities and transmission of the virus were expected to decrease during winter to summer transitions, when the countries would be warmer. The peak intensity of infections strongly depends on the level of seasonal transmissions.

Social distancing plays a critical role in preventing the overload of healthcare systems. Many respiratory pathogens, including those causing mild common cold-like syndromes, show seasonal fluctuations, often peaking in winter. This trend can be attributed to increased indoor crowding, school reopening, and climatic changes during autumn.

The spread of COVID-19 to neighbouring regions can be attributed to population interactions. Migration patterns, such as the movement from northern to southern regions during the warmer months, have significant epidemiological impacts. This trend mirrors the behavior of influenza pandemics where minor outbreaks in spring or summer are often followed by major waves in autumn or winter.

Availability of data and materials

Not applicable.

Abbreviations

Novel coronavirus

Coronavirus disease 2019

Deoxyribonucleic acid

Swine influenza

Influenza A virus subtype H5N1

Asian Lineage Avian Influenza A(H7N9) Virus

Middle East respiratory syndrome

Middle East respiratory syndrome Coronavirus

Particulate matter

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

RepOrting standards for Systematic Evidence Syntheses

Severe Acute Respiratory Syndrome

Severe Acute Respiratory Syndrome Coronavirus

Syndrome coronavirus 2

Systematic literature review

Standard operating procedure

Transmissible gastroenteritis Virus

United States of America

World Health Organization

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The authors would also like to acknowledge the Editors and an anonymous reviewer, who contributed immensely to improving the quality of this publication and a special thanks to Muhammad Hafiy Nauwal Effi Helmy, that contributed an excellent idea through singing during the COVID-19 lockdown period.

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Menhat, M., Ariffin, E.H., Dong, W.S. et al. Rain, rain, go away, come again another day: do climate variations enhance the spread of COVID-19?. Global Health 20 , 43 (2024). https://doi.org/10.1186/s12992-024-01044-w

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Mortality in Patients Hospitalized for COVID-19 vs Influenza in Fall-Winter 2023-2024

• 1 Clinical Epidemiology Center, VA St Louis Health Care System, St Louis, Missouri

In the first year of the COVID-19 pandemic, risk of death in people hospitalized for COVID-19 was substantially higher than in people hospitalized for seasonal influenza. 1 , 2 The risk of death due to COVID-19 has since declined. In fall-winter 2022-2023, people hospitalized for COVID-19 had a 60% higher risk of death compared with those hospitalized for seasonal influenza. 3 New variants of SARS-CoV-2 have continued to appear, including the emergence of JN.1, the predominant variant in the US since December 24, 2023. 4 This study evaluated the risk of death in a cohort of people hospitalized for COVID-19 or seasonal influenza in fall-winter 2023-2024.

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Xie Y , Choi T , Al-Aly Z. Mortality in Patients Hospitalized for COVID-19 vs Influenza in Fall-Winter 2023-2024. JAMA. Published online May 15, 2024. doi:10.1001/jama.2024.7395

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There’s a New Covid Variant. What Will That Mean for Spring and Summer?

Experts are closely watching KP.2, now the leading variant.

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By Dani Blum

For most of this year, the JN.1 variant of the coronavirus accounted for an overwhelming majority of Covid cases . But now, an offshoot variant called KP.2 is taking off. The variant, which made up just one percent of cases in the United States in mid-March, now makes up over a quarter.

KP.2 belongs to a subset of Covid variants that scientists have cheekily nicknamed “FLiRT,” drawn from the letters in the names of their mutations. They are descendants of JN.1, and KP.2 is “very, very close” to JN.1, said Dr. David Ho, a virologist at Columbia University. But Dr. Ho has conducted early lab tests in cells that suggest that slight differences in KP.2’s spike protein might make it better at evading our immune defenses and slightly more infectious than JN.1.

While cases currently don’t appear to be on the rise, researchers and physicians are closely watching whether the variant will drive a summer surge.

“I don’t think anybody’s expecting things to change abruptly, necessarily,” said Dr. Marc Sala, co-director of the Northwestern Medicine Comprehensive Covid-19 Center in Chicago. But KP.2 will most likely “be our new norm,’” he said. Here’s what to know.

The current spread of Covid

Experts said it would take several weeks to see whether KP.2 might lead to a rise in Covid cases, and noted that we have only a limited understanding of how the virus is spreading. Since the public health emergency ended , there is less robust data available on cases, and doctors said fewer people were using Covid tests.

But what we do know is reassuring: Despite the shift in variants, data from the C.D.C. suggests there are only “minimal ” levels of the virus circulating in wastewater nationally, and emergency department visits and hospitalizations fell between early March and late April.

“I don’t want to say that we already know everything about KP.2,” said Dr. Ziyad Al-Aly, the chief of research and development at the Veterans Affairs St. Louis Healthcare System. “But at this time, I’m not seeing any major indications of anything ominous.”

Protection from vaccines and past infections

Experts said that even if you had JN.1, you may still get reinfected with KP.2 — particularly if it’s been several months or longer since your last bout of Covid.

KP.2 could infect even people who got the most updated vaccine, Dr. Ho said, since that shot targets XBB.1.5, a variant that is notably different from JN.1 and its descendants. An early version of a paper released in April by researchers in Japan suggested that KP.2 might be more adept than JN.1 at infecting people who received the most recent Covid vaccine. (The research has not yet been peer-reviewed or published.) A spokesperson for the C.D.C. said the agency was continuing to monitor how vaccines perform against KP.2.

Still, the shot does provide some protection, especially against severe disease, doctors said, as do previous infections. At this point, there isn’t reason to believe that KP.2 would cause more severe illness than other strains, the C.D.C. spokesperson said. But people who are 65 and older, pregnant or immunocompromised remain at higher risk of serious complications from Covid.

Those groups, in particular, may want to get the updated vaccine if they haven’t yet, said Dr. Peter Chin-Hong, an infectious disease specialist at the University of California, San Francisco. The C.D.C. has recommended t hat people 65 and older who already received one dose of the updated vaccine get an additional shot at least four months later.

“Even though it’s the lowest level of deaths and hospitalizations we’ve seen, I’m still taking care of sick people with Covid,” he said. “And they all have one unifying theme, which is that they’re older and they didn’t get the latest shot.”

The latest on symptoms and long Covid

Doctors said that the symptoms of both KP.2 and JN.1 — which now makes up around 16 percent of cases — are most likely similar to those seen with other variants . These include sore throat, runny nose, coughing, head and body aches, fever, congestion, fatigue and in severe cases, shortness of breath. Fewer people lose their sense of taste and smell now than did at the start of the pandemic, but some people will still experience those symptoms.

Dr. Chin-Hong said that patients were often surprised that diarrhea, nausea and vomiting could be Covid symptoms as well, and that they sometimes confused those issues as signs that they had norovirus .

For many people who’ve already had Covid, a reinfection is often as mild or milder than their first case. While new cases of long Covid are less common now than they were at the start of the pandemic, repeat infections do raise the risk of developing long Covid, said Fikadu Tafesse, a virologist at Oregon Health & Science University. But researchers are still trying to determine by how much — one of many issues scientists are trying to untangle as the pandemic continues to evolve.

“That’s the nature of the virus,” Dr. Tafesse said. “It keeps mutating.”

Dani Blum is a health reporter for The Times. More about Dani Blum

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"FLiRT" COVID variants are now more than a third of U.S. cases. Scientists share what we know about them so far.

By Alexander Tin

Edited By Paula Cohen

May 10, 2024 / 10:31 AM EDT / CBS News

More than a third of COVID-19 cases in the U.S. are now estimated to be from a new, fast-growing member of a group of so-called "FLiRT" variants, nicknamed for their small but distinctive changes relative to the JN.1 strain. JN.1 was the variant behind this past winter wave of infections.

The largest among them, called KP.2 by scientists, has quickly multiplied in recent weeks to become the now-dominant new COVID-19 strain. 

According to the Centers for Disease Control and Prevention's every-other-week variant estimates , KP.2 and another strain with the same FLiRT mutations, called KP.1.1, together make up a projected 35.3% of infections this week. This is up from 7.1% a month ago.

"That means that while KP.2 is proportionally the most predominant variant, it is not causing an increase in infections as transmission of SARS-CoV-2 is low," a CDC spokesperson told CBS News in a statement.

The strain also does not have large amounts of worrying changes, unlike some previously highly-mutated variants that have raised alarm in years past. 

However, the swift change in circulating variants has resulted in the Food and Drug Administration this week delaying a key step in its process for picking out the strain to target with this fall's COVID-19 vaccines, citing the need for more "up-to-date" data.

While federal requirements for hospitals to report COVID-19 data to authorities lapsed this month, the CDC says it still has reliable figures from sources like wastewater testing and emergency rooms to continue tracking activity from the virus. 

Here's the latest of what we know about COVID-19 variants in the U.S.

What is the current new variant of COVID-19?

According to the latest projections published by the CDC, around 28.2% of COVID-19 cases nationwide are now being caused by a sublineage of the virus called the KP.2 variant. 

The next largest variant on the rise is another JN.1 descendant called JN.1.16. That strain has not grown as quickly, only inching up to an estimated 10% of cases this week.

That projection is based on genetic sequences of the virus reported by mostly public health labs, which have dropped significantly in recent weeks alongside the slowdown in cases overall. Other CDC data from wastewater and traveler testing still does not separate out KP.2 from its JN.1 parent.

KP.2 is a closely related descendant of the JN.1 variant from this past winter, which turned out not to be significantly more severe than the variants that were dominant before it, despite its large number of mutations.

"So it's one that we are watching. It's one that we are monitoring. And again, reiterate the need for continued surveillance of SARS-CoV-2 in people around the world, so that we can monitor this evolution," the World Health Organization's Maria Van Kerkhove told reporters Wednesday.

Why are these COVID-19 variants called FLiRT?

The nickname FLiRT comes from two distinctive mutations seen in several descendants of the JN.1 variant that have sprung up around the world after its sweep over the winter. Some of the largest strains with FLiRT mutations in the U.S. right now are KP.2 and KP.1.1.

"It is essentially just making a word out of the specific amino acid changes in the spike protein F456L + R346T, or phenylalanine (F) to leucine (L) at position 456 and arginine [R] to threonine [T] at position 346," Canadian biologist Ryan Gregory, a professor at the University of Guelph, told CBS News in an email. 

Gregory coined this nickname in March , and it gained traction among the variant trackers who have spotted and nicknamed many distinctive changes to the virus during the pandemic. Though unofficial, these nicknames have become commonly used names for a number of variants.

FLiRT won out over another nickname — "tiLT" variants — which had been coined by Australian consultant Mike Honey. FLiRT refers to a collection of faster-growing JN.1 offshoots the trackers are keeping an eye on, KP.2 among them.

"Basically, pretty much everything right now is a descendant of BA.2.86.1.1 (JN.1) and things are evolving rapidly, so it makes more sense to focus on mutations of interest rather than individual variants for the time being," wrote Gregory.

Do FLiRT variants lead to different COVID-19 symptoms?

Unlike some previous highly mutated variants that had raised concerns over potential changes to symptoms in recent years, the JN.1 variant many Americans already likely caught over the winter is closely related to the KP.2 strain now on the rise. 

"Based on current data there are no indicators that KP.2 would cause more severe illness than other strains," a CDC spokesperson told CBS News. 

KP.2's two distinctive so-called FLiRT mutations have also been seen before, in XBB.1.5 variants that were circulating throughout 2023, the spokesperson said. 

A draft study from scientists in Japan, released as a preprint that has yet to be peer-reviewed, found that the variant did appear to dodge antibodies better than the JN.1 variant. This "increased immune resistance" likely explains its rise, the scientists said.

In general, health authorities and experts have downplayed claims that variants were causing different symptoms. Changes to a person's immunity from vaccines and prior infections often play a role in different symptoms, rather than specific mutations.

"Mutations happen frequently, but only sometimes change the characteristics of the virus," the CDC says .

Will vaccines work against FLiRT variants?

The CDC has not made any changes to its current vaccine recommendations, which were last updated in April. But the emergence of these new JN.1 variant descendants like KP.2 might affect what vaccine the FDA picks out for this coming fall and winter.

Most Americans remain eligible to get at least one dose of this past season's updated COVID-19 vaccine, which CDC data so far suggests was up to 51% effective against emergency room or urgent care visits during a time when JN.1 was on the rise.

"CDC will continue to monitor community transmission of the virus and how vaccines perform against this strain," the agency said of KP.2.

Last month, the World Health Organization's experts recommended that vaccine manufacturers produce shots targeted at the JN.1 variant for next season. A panel of the FDA's own vaccine experts were scheduled to weigh that approach for the American vaccine market next week. 

However, the agency recently announced it had decided to delay the meeting until June in hopes of buying more time to ensure it picks out a vaccine target that is "most appropriate to be used for the strain(s) anticipated to be circulating" in the fall.

"The FDA, along with its public health partners, carefully monitors trends in the circulating strains of SARS-CoV-2. As has happened since the emergence of COVID-19, we have recently observed shifts in the dominant circulating strains of SARS-CoV-2," an FDA spokesperson told CBS News in a statement.

Pfizer has generated data from research of its vaccines against KP.2, but a company spokesperson said they were currently unable to share the results. A Moderna spokesperson did not respond to a request for comment.

A Novavax spokesperson said they had data showing their vaccine candidate for the fall aimed at JN.1 has "good cross-reactivity" for KP.2. While Novavax's vaccine takes longer to make than the mRNA shots from Pfizer and Moderna, the spokesperson said FDA's delay to the meeting "will not affect" their ability to deliver a shot this fall.

"We have manufactured JN.1 consistent with the recommendations and are on track to deliver an updated vaccine this fall," the Novavax spokesperson said.

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Alexander Tin is a digital reporter for CBS News based in the Washington, D.C. bureau. He covers the Biden administration's public health agencies, including the federal response to infectious disease outbreaks like COVID-19.

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COVID-19 and pets: Can dogs and cats get COVID-19?

Can my pet get the virus that causes covid-19.

The virus that causes COVID-19, also called coronavirus disease 2019, mostly spreads from person to person. But it can spread between people and animals.

COVID-19 is caused by a type of coronavirus. Coronaviruses are a large family of viruses. Some coronaviruses make people sick. Others make animals, such as bats, sick. Also, some coronaviruses infect only animals.

Can pets such as dogs and cats get COVID-19?

Pets have been infected with the virus that causes COVID-19, including cats, dogs, hamsters and ferrets. Most of these animals got infected after close contact with people who had the COVID-19 virus.

Can pets spread the virus that causes COVID-19?

The risk of animals spreading the COVID-19 virus to people is thought to be low. There is no proof that viruses can spread to people or other animals from a pet's skin, fur or hair.

But animals can carry other germs that can make people sick. Young children, people with weakened immune systems and people age 65 and older are at higher than typical risk. For these groups it's even more important to wash hands after touching an animal.

What do I do if I have COVID-19 and have a pet?

If you have COVID-19 and have a pet:

• Until your symptoms are getting better and you don't have a fever, stay away from everyone, including your pet, except to provide basic care. If you can, have someone else care for your pet.
• Don't pet, snuggle, or share food or your bed with your pet. Don't let your pet kiss or lick you.
• If you care for your pet or are around animals while you're sick, wear a face mask. Wash your hands before and after handling animals and their food, waste and supplies. Also, be sure to clean up after your pet.

If you have COVID-19 and your pet becomes sick, don't take your pet to the veterinarian yourself. Instead, contact the veterinarian. You might be able to have a virtual visit or make another plan for treating your pet. Only pets that have symptoms after being around someone with COVID-19 need to be tested.

What do I do if my pet has COVID-19?

If your pet tests positive for infection with the COVID-19 virus, follow the same plan you would if a family member became infected. Keep your pet at home. Also, follow these tips:

• Wear gloves when you touch your pet or its food, dishes, waste or bedding.
• Wash your hands after touching anything your pet touches.

Don't put a face mask on your pet. Don't wipe your pet with disinfectants or other chemicals. If your pet gets new symptoms or seems to be getting worse, call a veterinarian.

If your pet gets sick, try not to worry. Of the small number of dogs and cats that have been infected by the COVID-19 virus, some had no symptoms. Most of the pets that got ill had mild symptoms. They could be cared for at home. Pets have rarely become seriously ill with COVID-19.

If you have questions or worries about your pet's health and COVID-19, contact your veterinarian.

Daniel C. DeSimone, M.D.

• COVID-19 vaccine: Should I reschedule my mammogram?
• COVID-19 and vitamin D
• Animals and COVID-19. Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/animals.html. Accessed March 6, 2024.
• What you should know about COVID-19 and pets. Centers for Disease Control and Prevention. https://www.cdc.gov/healthypets/covid-19/pets.html. Accessed March 6, 2024.
• SARS-CoV-2 in animals. American Veterinary Medical Association. https://www.avma.org/resources-tools/one-health/covid-19/sars-cov-2-animals-including-pets. Accessed March 6, 2024.
• Passarella Telxeira AI, et al. The role of pets in SARS-CoV-2 transmission: An exploratory analysis. Infection. 2023; doi:10.1007/s15010-022-01860-5.
• How to stay healthy around pets and other animals. Centers for Disease Control and Prevention. https://www.cdc.gov/healthypets/keeping-pets-and-people-healthy/how.html. Accessed March 6, 2024.

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New COVID-19 FLiRT variants are now the dominant variant. Could there be a summer surge?

The Centers for Disease Control and Prevention has detected a new set of COVID-19 variants nicknamed FLiRT in wastewater surveillance, according to data from the agency.

From April 28 through May 11, the variant, labeled KP.2 , makes up about 28% of the cases in the United States, according to the CDC. That makes it the new dominant variant in the country, overtaking JN.1. The  JN.1 variant , which spread globally over the winter, made up about 16% of COVID-19 cases in the U.S. in the same two-week span.

KP.1.1, another FLiRT variant that is circulating, made up about 7% of COVID-19 cases in that two-week span, according to CDC data.

"The CDC is tracking SARS-CoV-2 variants KP.2 and KP.1.1, sometimes referred to as 'FLiRT,' and working to better understand their potential impact on public health," the agency said in an emailed statement to USA TODAY last week.

"Currently, KP.2 is the dominant variant in the United States, but laboratory testing data indicate low levels of SARS-CoV-2 transmission overall at this time. That means that while KP.2 is proportionally the most predominant variant, it is not causing an increase in infections as transmission of SARS-CoV-2 is low," the CDC said in the statement.

According to the CDC, only  22.6% of adults reported having received an updated 2023-24 COVID-19 vaccine  since September 2023. Data also shows that vaccination coverage increased by age and was highest among adults 75 and older.

FLiRT variant: There's a new COVID-19 variant called FLiRT: Here's what you need to know about it

What are the 'FLiRT' variants?

FLiRT is the term being used to describe a whole family of different variants, including KP.2, JN.1.7 and any other variants starting with KP or JN that appear to have picked up the same set of mutations, according to Andy Pekosz, PhD, a professor in molecular microbiology and immunology at the Bloomberg School of Public Health at Johns Hopkins University, in an article posted by the university.

"They are all descendants of the JN.1 variant that has been dominant in the U.S. for the past several months," Pekosz said in the article. "Viruses like SARS-CoV-2 mutate frequently, and when they mutate to evade recognition by antibodies, this often weakens their ability to bind to the cells they want to infect. We then see mutations appear that improve that binding ability."

Will there be a summer surge in COVID cases due to 'FLiRT' variants?

Pekosz said a summer surge is certainly possible, and that the FLiRT variants would be high on his list of viruses that could cause another wave of infections in the U.S.

"That said, our definition of a wave has changed; while we still see case rates rise and fall throughout the year, we see much lower numbers of cases of hospitalizations or deaths than we saw in the first couple years of the pandemic," Pekosz said in the article.

Pekosz also noted that while the waves are becoming smaller, they are still impacting our susceptible populations: the elderly, people who are immunocompromised, and those with other secondary medical conditions.

Symptoms of COVID 'FLiRT' variant

According to the CDC, there are "no current indicators" that KP.2 would cause more severe illness than other strains. The agency said it would continue to monitor community transmission of the virus and how vaccines perform against this strain.

The "FLiRT" variant reportedly has similar symptoms to those from JN.1 which include:

• Fever or chills
• Sore throat
• Congestion or runny nose
• Muscle aches
• Difficulty breathing
• New loss of taste or smell
• "Brain fog" (feeling less wakeful and aware)
• Gastrointestinal symptoms (upset stomach, mild diarrhea, vomiting)

The CDC notes that the list does not include all possible symptoms and that symptoms may change with new variants and can vary by person.

In general, the agency says,  people with COVID-19 have a wide range of symptoms , ranging from mild to severe illness. Symptoms may appear two to 14 days after exposure.

Latest COVID guidance from the CDC

In March 2024, the  CDC updated its COVID-19 guidance  so people who test positive for the virus will no longer be directed to isolate at home for five days.

Health officials announced a new policy focusing on actions people can take to reduce spreading a variety of common respiratory viruses, such as influenza, respiratory syncytial virus (RSV) and COVID-19. Those actions include staying home when sick, staying up to date with vaccines, practicing good hygiene and improving indoor air quality.

The change marked the first time the agency has revised its coronavirus guidelines since 2021. It is intended for people and employers, not for hospitals or nursing homes that have separate guidance, the CDC said.

CDC officials called the change a streamlined approach that’s easier for people to understand and more in line with circulating respiratory viruses that spread the same way and have similar symptoms. 

Contributing: Eduardo Cuevas, Adrianna Rodriguez, Ken Alltucker, Mary Walrath-Holdridge and Mike Snider

Gabe Hauari is a national trending news reporter at USA TODAY. You can follow him on X  @GabeHauari  or email him at [email protected].

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A Review of Coronavirus Disease-2019 (COVID-19)

Tanu singhal.

Department of Pediatrics and Infectious Disease, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, India

There is a new public health crises threatening the world with the emergence and spread of 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus originated in bats and was transmitted to humans through yet unknown intermediary animals in Wuhan, Hubei province, China in December 2019. There have been around 96,000 reported cases of coronavirus disease 2019 (COVID-2019) and 3300 reported deaths to date (05/03/2020). The disease is transmitted by inhalation or contact with infected droplets and the incubation period ranges from 2 to 14 d. The symptoms are usually fever, cough, sore throat, breathlessness, fatigue, malaise among others. The disease is mild in most people; in some (usually the elderly and those with comorbidities), it may progress to pneumonia, acute respiratory distress syndrome (ARDS) and multi organ dysfunction. Many people are asymptomatic. The case fatality rate is estimated to range from 2 to 3%. Diagnosis is by demonstration of the virus in respiratory secretions by special molecular tests. Common laboratory findings include normal/ low white cell counts with elevated C-reactive protein (CRP). The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is essentially supportive; role of antiviral agents is yet to be established. Prevention entails home isolation of suspected cases and those with mild illnesses and strict infection control measures at hospitals that include contact and droplet precautions. The virus spreads faster than its two ancestors the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. The global impact of this new epidemic is yet uncertain.

Introduction

The 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) as it is now called, is rapidly spreading from its origin in Wuhan City of Hubei Province of China to the rest of the world [ 1 ]. Till 05/03/2020 around 96,000 cases of coronavirus disease 2019 (COVID-19) and 3300 deaths have been reported [ 2 ]. India has reported 29 cases till date. Fortunately so far, children have been infrequently affected with no deaths. But the future course of this virus is unknown. This article gives a bird’s eye view about this new virus. Since knowledge about this virus is rapidly evolving, readers are urged to update themselves regularly.

Coronaviruses are enveloped positive sense RNA viruses ranging from 60 nm to 140 nm in diameter with spike like projections on its surface giving it a crown like appearance under the electron microscope; hence the name coronavirus [ 3 ]. Four corona viruses namely HKU1, NL63, 229E and OC43 have been in circulation in humans, and generally cause mild respiratory disease.

There have been two events in the past two decades wherein crossover of animal betacorona viruses to humans has resulted in severe disease. The first such instance was in 2002–2003 when a new coronavirus of the β genera and with origin in bats crossed over to humans via the intermediary host of palm civet cats in the Guangdong province of China. This virus, designated as severe acute respiratory syndrome coronavirus affected 8422 people mostly in China and Hong Kong and caused 916 deaths (mortality rate 11%) before being contained [ 4 ]. Almost a decade later in 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV), also of bat origin, emerged in Saudi Arabia with dromedary camels as the intermediate host and affected 2494 people and caused 858 deaths (fatality rate 34%) [ 5 ].

Origin and Spread of COVID-19 [ 1 , 2 , 6 ]

In December 2019, adults in Wuhan, capital city of Hubei province and a major transportation hub of China started presenting to local hospitals with severe pneumonia of unknown cause. Many of the initial cases had a common exposure to the Huanan wholesale seafood market that also traded live animals. The surveillance system (put into place after the SARS outbreak) was activated and respiratory samples of patients were sent to reference labs for etiologic investigations. On December 31st 2019, China notified the outbreak to the World Health Organization and on 1st January the Huanan sea food market was closed. On 7th January the virus was identified as a coronavirus that had >95% homology with the bat coronavirus and > 70% similarity with the SARS- CoV. Environmental samples from the Huanan sea food market also tested positive, signifying that the virus originated from there [ 7 ]. The number of cases started increasing exponentially, some of which did not have exposure to the live animal market, suggestive of the fact that human-to-human transmission was occurring [ 8 ]. The first fatal case was reported on 11th Jan 2020. The massive migration of Chinese during the Chinese New Year fuelled the epidemic. Cases in other provinces of China, other countries (Thailand, Japan and South Korea in quick succession) were reported in people who were returning from Wuhan. Transmission to healthcare workers caring for patients was described on 20th Jan, 2020. By 23rd January, the 11 million population of Wuhan was placed under lock down with restrictions of entry and exit from the region. Soon this lock down was extended to other cities of Hubei province. Cases of COVID-19 in countries outside China were reported in those with no history of travel to China suggesting that local human-to-human transmission was occurring in these countries [ 9 ]. Airports in different countries including India put in screening mechanisms to detect symptomatic people returning from China and placed them in isolation and testing them for COVID-19. Soon it was apparent that the infection could be transmitted from asymptomatic people and also before onset of symptoms. Therefore, countries including India who evacuated their citizens from Wuhan through special flights or had travellers returning from China, placed all people symptomatic or otherwise in isolation for 14 d and tested them for the virus.

Cases continued to increase exponentially and modelling studies reported an epidemic doubling time of 1.8 d [ 10 ]. In fact on the 12th of February, China changed its definition of confirmed cases to include patients with negative/ pending molecular tests but with clinical, radiologic and epidemiologic features of COVID-19 leading to an increase in cases by 15,000 in a single day [ 6 ]. As of 05/03/2020 96,000 cases worldwide (80,000 in China) and 87 other countries and 1 international conveyance (696, in the cruise ship Diamond Princess parked off the coast of Japan) have been reported [ 2 ]. It is important to note that while the number of new cases has reduced in China lately, they have increased exponentially in other countries including South Korea, Italy and Iran. Of those infected, 20% are in critical condition, 25% have recovered, and 3310 (3013 in China and 297 in other countries) have died [ 2 ]. India, which had reported only 3 cases till 2/3/2020, has also seen a sudden spurt in cases. By 5/3/2020, 29 cases had been reported; mostly in Delhi, Jaipur and Agra in Italian tourists and their contacts. One case was reported in an Indian who traveled back from Vienna and exposed a large number of school children in a birthday party at a city hotel. Many of the contacts of these cases have been quarantined.

These numbers are possibly an underestimate of the infected and dead due to limitations of surveillance and testing. Though the SARS-CoV-2 originated from bats, the intermediary animal through which it crossed over to humans is uncertain. Pangolins and snakes are the current suspects.

Epidemiology and Pathogenesis [ 10 , 11 ]

All ages are susceptible. Infection is transmitted through large droplets generated during coughing and sneezing by symptomatic patients but can also occur from asymptomatic people and before onset of symptoms [ 9 ]. Studies have shown higher viral loads in the nasal cavity as compared to the throat with no difference in viral burden between symptomatic and asymptomatic people [ 12 ]. Patients can be infectious for as long as the symptoms last and even on clinical recovery. Some people may act as super spreaders; a UK citizen who attended a conference in Singapore infected 11 other people while staying in a resort in the French Alps and upon return to the UK [ 6 ]. These infected droplets can spread 1–2 m and deposit on surfaces. The virus can remain viable on surfaces for days in favourable atmospheric conditions but are destroyed in less than a minute by common disinfectants like sodium hypochlorite, hydrogen peroxide etc. [ 13 ]. Infection is acquired either by inhalation of these droplets or touching surfaces contaminated by them and then touching the nose, mouth and eyes. The virus is also present in the stool and contamination of the water supply and subsequent transmission via aerosolization/feco oral route is also hypothesized [ 6 ]. As per current information, transplacental transmission from pregnant women to their fetus has not been described [ 14 ]. However, neonatal disease due to post natal transmission is described [ 14 ]. The incubation period varies from 2 to 14 d [median 5 d]. Studies have identified angiotensin receptor 2 (ACE 2 ) as the receptor through which the virus enters the respiratory mucosa [ 11 ].

The basic case reproduction rate (BCR) is estimated to range from 2 to 6.47 in various modelling studies [ 11 ]. In comparison, the BCR of SARS was 2 and 1.3 for pandemic flu H1N1 2009 [ 2 ].

Clinical Features [ 8 , 15 – 18 ]

The clinical features of COVID-19 are varied, ranging from asymptomatic state to acute respiratory distress syndrome and multi organ dysfunction. The common clinical features include fever (not in all), cough, sore throat, headache, fatigue, headache, myalgia and breathlessness. Conjunctivitis has also been described. Thus, they are indistinguishable from other respiratory infections. In a subset of patients, by the end of the first week the disease can progress to pneumonia, respiratory failure and death. This progression is associated with extreme rise in inflammatory cytokines including IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1A, and TNFα [ 15 ]. The median time from onset of symptoms to dyspnea was 5 d, hospitalization 7 d and acute respiratory distress syndrome (ARDS) 8 d. The need for intensive care admission was in 25–30% of affected patients in published series. Complications witnessed included acute lung injury, ARDS, shock and acute kidney injury. Recovery started in the 2nd or 3rd wk. The median duration of hospital stay in those who recovered was 10 d. Adverse outcomes and death are more common in the elderly and those with underlying co-morbidities (50–75% of fatal cases). Fatality rate in hospitalized adult patients ranged from 4 to 11%. The overall case fatality rate is estimated to range between 2 and 3% [ 2 ].

Interestingly, disease in patients outside Hubei province has been reported to be milder than those from Wuhan [ 17 ]. Similarly, the severity and case fatality rate in patients outside China has been reported to be milder [ 6 ]. This may either be due to selection bias wherein the cases reporting from Wuhan included only the severe cases or due to predisposition of the Asian population to the virus due to higher expression of ACE 2 receptors on the respiratory mucosa [ 11 ].

Disease in neonates, infants and children has been also reported to be significantly milder than their adult counterparts. In a series of 34 children admitted to a hospital in Shenzhen, China between January 19th and February 7th, there were 14 males and 20 females. The median age was 8 y 11 mo and in 28 children the infection was linked to a family member and 26 children had history of travel/residence to Hubei province in China. All the patients were either asymptomatic (9%) or had mild disease. No severe or critical cases were seen. The most common symptoms were fever (50%) and cough (38%). All patients recovered with symptomatic therapy and there were no deaths. One case of severe pneumonia and multiorgan dysfunction in a child has also been reported [ 19 ]. Similarly the neonatal cases that have been reported have been mild [ 20 ].

Diagnosis [ 21 ]

A suspect case is defined as one with fever, sore throat and cough who has history of travel to China or other areas of persistent local transmission or contact with patients with similar travel history or those with confirmed COVID-19 infection. However cases may be asymptomatic or even without fever. A confirmed case is a suspect case with a positive molecular test.

Specific diagnosis is by specific molecular tests on respiratory samples (throat swab/ nasopharyngeal swab/ sputum/ endotracheal aspirates and bronchoalveolar lavage). Virus may also be detected in the stool and in severe cases, the blood. It must be remembered that the multiplex PCR panels currently available do not include the COVID-19. Commercial tests are also not available at present. In a suspect case in India, the appropriate sample has to be sent to designated reference labs in India or the National Institute of Virology in Pune. As the epidemic progresses, commercial tests will become available.

Other laboratory investigations are usually non specific. The white cell count is usually normal or low. There may be lymphopenia; a lymphocyte count <1000 has been associated with severe disease. The platelet count is usually normal or mildly low. The CRP and ESR are generally elevated but procalcitonin levels are usually normal. A high procalcitonin level may indicate a bacterial co-infection. The ALT/AST, prothrombin time, creatinine, D-dimer, CPK and LDH may be elevated and high levels are associated with severe disease.

The chest X-ray (CXR) usually shows bilateral infiltrates but may be normal in early disease. The CT is more sensitive and specific. CT imaging generally shows infiltrates, ground glass opacities and sub segmental consolidation. It is also abnormal in asymptomatic patients/ patients with no clinical evidence of lower respiratory tract involvement. In fact, abnormal CT scans have been used to diagnose COVID-19 in suspect cases with negative molecular diagnosis; many of these patients had positive molecular tests on repeat testing [ 22 ].

Differential Diagnosis [ 21 ]

The differential diagnosis includes all types of respiratory viral infections [influenza, parainfluenza, respiratory syncytial virus (RSV), adenovirus, human metapneumovirus, non COVID-19 coronavirus], atypical organisms (mycoplasma, chlamydia) and bacterial infections. It is not possible to differentiate COVID-19 from these infections clinically or through routine lab tests. Therefore travel history becomes important. However, as the epidemic spreads, the travel history will become irrelevant.

Treatment [ 21 , 23 ]

Treatment is essentially supportive and symptomatic.

The first step is to ensure adequate isolation (discussed later) to prevent transmission to other contacts, patients and healthcare workers. Mild illness should be managed at home with counseling about danger signs. The usual principles are maintaining hydration and nutrition and controlling fever and cough. Routine use of antibiotics and antivirals such as oseltamivir should be avoided in confirmed cases. In hypoxic patients, provision of oxygen through nasal prongs, face mask, high flow nasal cannula (HFNC) or non-invasive ventilation is indicated. Mechanical ventilation and even extra corporeal membrane oxygen support may be needed. Renal replacement therapy may be needed in some. Antibiotics and antifungals are required if co-infections are suspected or proven. The role of corticosteroids is unproven; while current international consensus and WHO advocate against their use, Chinese guidelines do recommend short term therapy with low-to-moderate dose corticosteroids in COVID-19 ARDS [ 24 , 25 ]. Detailed guidelines for critical care management for COVID-19 have been published by the WHO [ 26 ]. There is, as of now, no approved treatment for COVID-19. Antiviral drugs such as ribavirin, lopinavir-ritonavir have been used based on the experience with SARS and MERS. In a historical control study in patients with SARS, patients treated with lopinavir-ritonavir with ribavirin had better outcomes as compared to those given ribavirin alone [ 15 ].

In the case series of 99 hospitalized patients with COVID-19 infection from Wuhan, oxygen was given to 76%, non-invasive ventilation in 13%, mechanical ventilation in 4%, extracorporeal membrane oxygenation (ECMO) in 3%, continuous renal replacement therapy (CRRT) in 9%, antibiotics in 71%, antifungals in 15%, glucocorticoids in 19% and intravenous immunoglobulin therapy in 27% [ 15 ]. Antiviral therapy consisting of oseltamivir, ganciclovir and lopinavir-ritonavir was given to 75% of the patients. The duration of non-invasive ventilation was 4–22 d [median 9 d] and mechanical ventilation for 3–20 d [median 17 d]. In the case series of children discussed earlier, all children recovered with basic treatment and did not need intensive care [ 17 ].

There is anecdotal experience with use of remdeswir, a broad spectrum anti RNA drug developed for Ebola in management of COVID-19 [ 27 ]. More evidence is needed before these drugs are recommended. Other drugs proposed for therapy are arbidol (an antiviral drug available in Russia and China), intravenous immunoglobulin, interferons, chloroquine and plasma of patients recovered from COVID-19 [ 21 , 28 , 29 ]. Additionally, recommendations about using traditional Chinese herbs find place in the Chinese guidelines [ 21 ].

Prevention [ 21 , 30 ]

Since at this time there are no approved treatments for this infection, prevention is crucial. Several properties of this virus make prevention difficult namely, non-specific features of the disease, the infectivity even before onset of symptoms in the incubation period, transmission from asymptomatic people, long incubation period, tropism for mucosal surfaces such as the conjunctiva, prolonged duration of the illness and transmission even after clinical recovery.

Isolation of confirmed or suspected cases with mild illness at home is recommended. The ventilation at home should be good with sunlight to allow for destruction of virus. Patients should be asked to wear a simple surgical mask and practice cough hygiene. Caregivers should be asked to wear a surgical mask when in the same room as patient and use hand hygiene every 15–20 min.

The greatest risk in COVID-19 is transmission to healthcare workers. In the SARS outbreak of 2002, 21% of those affected were healthcare workers [ 31 ]. Till date, almost 1500 healthcare workers in China have been infected with 6 deaths. The doctor who first warned about the virus has died too. It is important to protect healthcare workers to ensure continuity of care and to prevent transmission of infection to other patients. While COVID-19 transmits as a droplet pathogen and is placed in Category B of infectious agents (highly pathogenic H5N1 and SARS), by the China National Health Commission, infection control measures recommended are those for category A agents (cholera, plague). Patients should be placed in separate rooms or cohorted together. Negative pressure rooms are not generally needed. The rooms and surfaces and equipment should undergo regular decontamination preferably with sodium hypochlorite. Healthcare workers should be provided with fit tested N95 respirators and protective suits and goggles. Airborne transmission precautions should be taken during aerosol generating procedures such as intubation, suction and tracheostomies. All contacts including healthcare workers should be monitored for development of symptoms of COVID-19. Patients can be discharged from isolation once they are afebrile for atleast 3 d and have two consecutive negative molecular tests at 1 d sampling interval. This recommendation is different from pandemic flu where patients were asked to resume work/school once afebrile for 24 h or by day 7 of illness. Negative molecular tests were not a prerequisite for discharge.

At the community level, people should be asked to avoid crowded areas and postpone non-essential travel to places with ongoing transmission. They should be asked to practice cough hygiene by coughing in sleeve/ tissue rather than hands and practice hand hygiene frequently every 15–20 min. Patients with respiratory symptoms should be asked to use surgical masks. The use of mask by healthy people in public places has not shown to protect against respiratory viral infections and is currently not recommended by WHO. However, in China, the public has been asked to wear masks in public and especially in crowded places and large scale gatherings are prohibited (entertainment parks etc). China is also considering introducing legislation to prohibit selling and trading of wild animals [ 32 ].

The international response has been dramatic. Initially, there were massive travel restrictions to China and people returning from China/ evacuated from China are being evaluated for clinical symptoms, isolated and tested for COVID-19 for 2 wks even if asymptomatic. However, now with rapid world wide spread of the virus these travel restrictions have extended to other countries. Whether these efforts will lead to slowing of viral spread is not known.

A candidate vaccine is under development.

Practice Points from an Indian Perspective

At the time of writing this article, the risk of coronavirus in India is extremely low. But that may change in the next few weeks. Hence the following is recommended:

• Healthcare providers should take travel history of all patients with respiratory symptoms, and any international travel in the past 2 wks as well as contact with sick people who have travelled internationally.
• They should set up a system of triage of patients with respiratory illness in the outpatient department and give them a simple surgical mask to wear. They should use surgical masks themselves while examining such patients and practice hand hygiene frequently.
• Suspected cases should be referred to government designated centres for isolation and testing (in Mumbai, at this time, it is Kasturba hospital). Commercial kits for testing are not yet available in India.
• Patients admitted with severe pneumonia and acute respiratory distress syndrome should be evaluated for travel history and placed under contact and droplet isolation. Regular decontamination of surfaces should be done. They should be tested for etiology using multiplex PCR panels if logistics permit and if no pathogen is identified, refer the samples for testing for SARS-CoV-2.
• All clinicians should keep themselves updated about recent developments including global spread of the disease.
• Non-essential international travel should be avoided at this time.
• People should stop spreading myths and false information about the disease and try to allay panic and anxiety of the public.

Conclusions

This new virus outbreak has challenged the economic, medical and public health infrastructure of China and to some extent, of other countries especially, its neighbours. Time alone will tell how the virus will impact our lives here in India. More so, future outbreaks of viruses and pathogens of zoonotic origin are likely to continue. Therefore, apart from curbing this outbreak, efforts should be made to devise comprehensive measures to prevent future outbreaks of zoonotic origin.

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• NEWS EXPLAINER
• 16 February 2021

COVID vaccines and safety: what the research says

• Ariana Remmel

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As people around the world receive COVID-19 vaccines, reports of temporary side effects such as headaches and fevers are rolling in. Much of this was expected — clinical-trial data for the vaccines authorized so far suggested as much. But now that millions of people are vaccinated, compared with the thousands enrolled in early studies, reports of some rare, allergic reactions are surfacing, and questions are arising about whether any deaths are linked to the shots.

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Nature 590 , 538-540 (2021)

doi: https://doi.org/10.1038/d41586-021-00290-x

With reporting from Smriti Mallapaty and Amy Maxmen.

Logunov, D. Y. et al. Lancet https://doi.org/10.1016/S0140-6736(21)00234-8 (2021).

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McNeil, M. M. et al. J. Allergy Clin. Immunol . 2 , T37–T52 (2016).

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Yang, Q. et al. Anal. Chem . 88 , 11804–11812 (2016).

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