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COVID-19 Papers, Posters, and Presentations

Issues from 2024 2024.

Research Support Newsletter (Spring 2024) , Elizabeth D'Angel

Virtual Facilitation Best Practices and Research Priorities: A Scoping Review , Asya Agulnik, Derrecka Boykin, Denalee M O'Malley, Julia Price, Mia Yang, Mark McKone, Geoffrey Curran, and Mona J Ritchie

How Does COVID-19 Vaccination Affect Long-COVID Symptoms? , Ali Akbar Asadi-Pooya, Meshkat Nemati, Mina Shahisavandi, Hamid Nemati, Afrooz Karimi, Anahita Jafari, Sara Nasiri, Seyyed Saeed Mohammadi, Zahra Rahimian, Hossein Bayat, Ali Akbari, Amir Emami, and Owrang Eilami

Submissions from 2023 2023

Evaluating the Performance of Real Estate Exchange-Traded Funds , Davinder K. Malhotra

Interprofessional Perspectives on School-Wide Mental Health Interventions for Enhancing Resilience in Adolescents , Danielle Costanzo, MS, OTR/L

Changing The Playbook For Immigrant Health , Cheryl Bettigole, Patricia C. Henwood, Sage Myers, and Maura Sammon

Post-Acute Sequelae of COVID-19 (PASC) in Pediatrics: Factors That Impact Symptom Severity and Referral to Treatment. , Catherine Soprano, Ryan Ngo, Casey A Konys, Ashley Bazier, and Katherine Salamon

Assessing the Performance and Risk-Adjusted Returns of Financial Mutual Funds , Davinder Malhotra, Timothy Mooney, Raymond Poteau, and Philip Russel

Directing the U.S. COVID-19 Testing and Diagnostics Working Group, Caring for Afghan Refugees and Children at the Southwest Border , Dean L. Winslow, MD, MACP, FRCP(Lon), FIDSA, FPIDS

Serotonin Reduction in Post-acute Sequelae of Viral Infection , Andrea Wong, Ashwarya Devason, Iboro Umana, Timothy Cox, Lenka Dohnalová, Lev Litichevskiy, Jonathan Perla, Patrick Lundgren, Zienab Etwebi, Luke Izzo, Jihee Kim, Monika Tetlak, Hélène Descamps, Simone Park, Stephen Wisser, Aaron McKnight, Ryan Pardy, Junwon Kim, Niklas Blank, Shaan Patel, Katharina Thum, Sydney Mason, Jean-Christophe Beltra, Michaël Michieletto, Shin Foong Ngiow, Brittany Miller, Megan Liou, Bhoomi Madhu, Oxana Dmitrieva-Posocco, Alex Huber, Peter Hewins, Christopher Petucci, Candice Chu, Gwen Baraniecki-Zwil, Leila Giron, Amy Baxter, Allison Greenplate, Charlotte Kearns, Kathleen Montone, Leslie Litzky, Michael Feldman, Jorge Henao-Mejia, Boris Striepen, Holly Ramage, Kellie Jurado, Kathryn Wellen, Una O'Doherty, Mohamed Abdel-Mohsen, Alan L Landay, Ali Keshavarzian, Timothy Henrich, Steven Deeks, Michael Peluso, Nuala Meyer, E. John Wherry, Benjamin Abramoff, Sara Cherry, Christoph Thaiss, and Maayan Levy

Activation of Coagulation and Proinflammatory Pathways in Thrombosis with Thrombocytopenia Syndrome and Following COVID-19 Vaccination , Malika Aid, Kathryn E. Stephenson, Ai-Ris Y. Collier, Joseph P. Nkolola, James V. Michael, Steven E. McKenzie, and Dan H. Barouch

Clinical Characteristics, Racial Inequities, and Outcomes in Patients with Breast Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Cohort Study , Gayathri Nagaraj, Shaveta Vinayak, Ali Raza Khaki, Tianyi Sun, Nicole M. Kuderer, David M. Aboulafia, Jared D. Acoba, Joy Awosika, Ziad Bakouny, Nicole B. Balmaceda, Ting Bao, Babar Bashir, Stephanie Berg, Mehmet A. Bilen, Poorva Bindal, Sibel Blau, Brianne E. Bodin, Hala T. Borno, Cecilia Castellano, Horyun Choi, John Deeken, Aakash Desai, Natasha Edwin, Lawrence E. Feldman, Daniel B. Flora, Christopher R. Friese, Matthew D. Galsky, Cyndi J. Gonzalez, Petros Grivas, Shilpa Gupta, Marcy Haynam, Hannah Heilman, Dawn L. Hershman, Clara Hwang, Chinmay Jani, Sachin R. Jhawar, Monika Joshi, Virginia Kaklamani, Elizabeth J. Klein, Natalie Knox, Vadim S. Koshkin, Amit A. Kulkarni, Daniel H. Kwon, Chris Labaki, Philip E. Lammers, Kate I. Lathrop, Mark A. Lewis, Xuanyi Li, Gilbert de Lima Lopes, Gary H. Lyman, Della F. Makower, Abdul-Hai Mansoor, Merry-Jennifer Markham, Sandeep H. Mashru, Rana R. McKay, Ian Messing, Vasil Mico, Rajani Nadkarni, Swathi Namburi, Ryan H. Nguyen, Taylor Kristian Nonato, Tracey Lynn O'Connor, Orestis A. Panagiotou, Kyu Park, Jaymin M. Patel, Kanishka GopikaBimal Patel, Jeffrey Peppercorn, Hyma Polimera, Matthew Puc, Yuan James Rao, Pedram Razavi, Sonya A. Reid, Jonathan W. Riess, Donna R. Rivera, Mark Robson, Suzanne J. Rose, Atlantis D. Russ, Lidia Schapira, Pankil K. Shah, M Kelly Shanahan, Lauren C. Shapiro, Melissa Smits, Daniel G. Stover, Mitrianna Streckfuss, Lisa Tachiki, Michael A. Thompson, Sara M. Tolaney, Lisa B. Weissmann, Grace Wilson, Michael T. Wotman, Elizabeth M. Wulff-Burchfield, Sanjay Mishra, Benjamin French, Jeremy L. Warner, Maryam B. Lustberg, Melissa K. Accordino, and Dimpy P. Shah

Bilateral Interstitial Keratitis Following COVID-19: A Case Report , Nathalie D. Daher and Zeba A. Syed

Validation of Automated Data Abstraction for SCCM Discovery VIRUS COVID-19 Registry: Practical EHR Export Pathways (VIRUS-PEEP) , Diana J. Valencia Morales, Vikas Bansal, Smith F. Heavner, Janna C. Castro, Mayank Sharma, Aysun Tekin, Marija Bogojevic, Simon Zec, Nikhil Sharma, Rodrigo Cartin-Ceba, Rahul S. Nanchal, Devang K. Sanghavi, Abigail T. La Nou, Syed A. Khan, Katherine A. Belden, Jen-Ting Chen, Roman R. Melamed, Imran A. Sayed, Ronald A. Reilkoff, Vitaly Herasevich, Juan Pablo Domecq Garces, Allan J. Walkey, Karen Boman, Vishakha K. Kumar, and Rahul Kashyap

Global Impact of Proteoglycan Science on Human Diseases , Christopher Xie, Liliana Schaefer, and Renato V. Iozzo

Making Decisions "In the Dark": Learning Through Uncertainty in Clinical Practice During COVID-19 , Urvashi Vaid, Henriette Lundgren, Karen E. Watkins, Deborah Ziring, Grace A. Alcid, Victoria J. Marsick, and Dimitrios Papanagnou

Association Between Number of Vasopressors and Mortality in COVID-19 Patients , Michael Sunnaa, Mina Kerolos, Max Ruge, Ahmad Gill, Jeanne M. Du-Fay-de-Lavallaz, Perry Robin, Joanne Michelle Dumlao Gomez, Kim Williams, Anupama Rao, Annabelle Santos Volgman, Karolina Marinescu, and Tisha Marie Suboc

Honickman Center to Include Employee Wellness Space

Reduced maternal immunity and vertical transfer of immunity against SARS-CoV-2 variants of concern with COVID-19 exposure or initial vaccination in pregnancy. , Rupsa Boelig, Sidhartha Chaudhury, Gregory D Gromowski, Sandra Mayer, Jocelyn King, Zubair H Aghai, and Elke Bergmann-Leitner

Effectiveness of a Messenger RNA Vaccine Booster Dose Against Coronavirus Disease 2019 Among US Healthcare Personnel, October 2021-July 2022 , Ian D. Plumb, Nicholas M. Mohr, Melissa Hagen, Ryan Wiegand, Ghinwa Dumyati, Karisa K. Harland, Anusha Krishnadasan, Jade James Gist, Glen Abedi, Katherine E Fleming-Dutra, Nora Chea, Jane Lee, Devra Barter, Monica Brackney, Scott K. Fridkin, Lucy E. Wilson, Sara A. Lovett, Valerie Ocampo, Erin C. Phipps, Tiffanie M. Marcus, Howard A. Smithline, Peter C. Hou, Lilly C. Lee, Gregory J. Moran, Elizabeth Krebs, Mark T. Steele, Stephen C. Lim, Walter A. Schrading, Brian Chinnock, David G. Beiser, Brett Faine, John P. Haran, Utsav Nandi, Anne K. Chipman, Frank LoVecchio, David A. Talan, and Tamara Pilishvili

Nutrition-Related Experiences of Women With Perinatal Depression During the COVID-19 Pandemic: A Qualitative Study , Dahlia Stott, Cynthia Klobodu, Lisa A. Chiarello, Bobbie Posmontier, Mona Egohail, Pamela A. Geller, June Andrews Horowitz, and Brandy-Joe Milliron

Are Patients With an International Classification of Diseases, 10th Edition Discharge Diagnosis Code for Sepsis Different in Regard to Demographics and Outcome Variables When Comparing Those With Sepsis Only to Those Also Diagnosed With COVID-19 or Those With a COVID-19 Diagnosis Alone? , David F. Gaieski, Jumpei Tsukuda, Parker Maddox, and Michael Li

IGG3 Subclass Antibodies Recognize Antigenically Drifted Influenza Viruses and SARS-CoV-2 Variants Through Efficient Bivalent Binding , Marcus J. Bolton, Jefferson J.S. Santos, Claudia P. Arevalo, Trevor Griesman, Megan Watson, Shuk Hang Li, Paul Bates, Holly Ramage, Patrick C. Wilson, and Scott E. Hensley

Sudden Vision Loss Heralding Covid-19-Associated Aspergillosis. Report of 2 Cases , Tamara R. Vrabec, David R. Anderson, Priyal K. Shaw, and Tatyana Milman

A Novel Virtual-Based Comprehensive Clinical Approach to Headache Care , Thomas Berk, Stephen Silberstein, and Peter McAllister

Systemic Anticancer Therapy and Thromboembolic Outcomes in Hospitalized Patients With Cancer and COVID-19 , Shuchi Gulati, Chih-Yuan Hsu, Surbhi Shah, Pankil K. Shah, Rebecca Zon, Susan Alsamarai, Joy Awosika, Ziad El-Bakouny, Babar Bashir, Alicia Beeghly, Stephanie Berg, Daniel de-la-Rosa-Martinez, Deborah B. Doroshow, Pamela C. Egan, Joshua Fein, Daniel B. Flora, Christopher R. Friese, Ariel Fromowitz, Elizabeth A. Griffiths, Clara Hwang, Chinmay Jani, Monika Joshi, Hina Khan, Elizabeth J. Klein, Natalie Knox Heater, Vadim S. Koshkin, Daniel H. Kwon, Chris Labaki, Tahir Latif, Rana R. McKay, Gayathri Nagaraj, Elizabeth S. Nakasone, Taylor Nonato, Hyma V. Polimera, Matthew Puc, Pedram Razavi, Erika Ruiz-Garcia, Renee Maria Saliby, Aditi Shastri, Sunny R.K. Singh, Vicky Tagalakis, Diana Vilar-Compte, Lisa B. Weissmann, Cy R. Wilkins, Trisha M. Wise-Draper, Michael T. Wotman, James J. Yoon, Sanjay Mishra, Petros Grivas, Yu Shyr, Jeremy L. Warner, Jean M. Connors, Dimpy P. Shah, and Rachel P. Rosovsky

A Provocateur for Improvement , David B. Nash, MD, MBA

Major Cardiovascular Events After COVID-19, Event Rates Post-vaccination, Antiviral or Anti-inflammatory Therapy, and Temporal Trends: Rationale and Methodology of the Corona-VTE-Network Study , Behnood Bikdeli, Candrika D Khairani, Darsiya Krishnathasan, Antoine Bejjani, Andre Armero, Anthony Tristani, Julia Davies, Nicole Porio, Ali A Assi, Victor Nauffal, Umberto Campia, Zaid Almarzooq, Eric Wei, Aditya Achanta, Sirus J Jesudasen, Bruce C Tiu, Geno J. Merli, Orly Leiva, John Fanikos, Aditya Sharma, Alec Vishnevsky, Judith Hsia, Mark R Nehler, James Welker, Marc P Bonaca, Brett J Carroll, Zhou Lan, Samuel Z Goldhaber, and Gregory Piazza

Mechanically Ventilated COVID-19 Patients Admitted to the Intensive Care Unit in the United States With or Without Respiratory Failure Secondary to COVID-19 Pneumonia: A Retrospective Comparison of Characteristics and Outcomes , Jesse Johnson, Kashka F. Mallari, Vincent Pepe, Taylor Treacy, Gregory McDonough, P. Khaing, Christopher McGrath, Brandon George, and Erika J. Yoo

Evaluating Non-pharmacological Approaches to Nursing Home Dementia Care: A Protocol , Natalie E Leland, Victoria Shier, Catherine V. Piersol, Cara Lekovitch, Jenny Martínez, Yuna H Bae-Shaaw, Neeraj Sood, Claire Day, Paul Cass, Dominique Como, Carin Wong, and Felicia Chew

IFIT2 Restricts Murine coronavirus Spread to the Spinal Cord White Matter and Its Associated Myelin Pathology , Madhav Sharma, Debanjana Chakravarty, Afaq Hussain, Ajay Zalavadia, Amy Burrows, Patricia Rayman, Nikhil Sharma, Lawrence C. Kenyon, Cornelia Bergmann, Ganes C. Sen, and Jayasri Das Sarma

Long COVID Clinical Phenotypes up to 6 Months After Infection Identified by Latent Class Analysis of Self-Reported Symptoms , Michael Gottlieb, Erica S. Spatz, Huihui Yu, Lauren E Wisk, Joann G. Elmore, Nicole L. Gentile, Mandy Hill, Ryan M. Huebinger, Ahamed H. Idris, Efrat M. Kean, Katherine Koo, Shu-Xia Li, Samuel McDonald, Juan Carlos C Montoy, Graham Nichol, Kelli N. O'Laughlin, Ian D. Plumb, Kristin L. Rising, Michelle Santangelo, Sharon Saydah, Ralph C. Wang, Arjun Venkatesh, Kari A. Stephens, and Robert A. Weinstein

Multiple Sterile Withdrawals from Iohexol Bottles Does Not Increase Contamination Risk , Caroline Purtill, Manraj Dhesi, Daniel Haber, Nicholas D'Antonio, Noreen J. Hickok, and Jeremy I. Simon

Association Between SARS-CoV-2 Variants and Frequency of Acute Symptoms: Analysis of a Multi-institutional Prospective Cohort Study-December 20, 2020-June 20, 2022. , Ralph C, Wang; Michael Gottlieb; Juan Carlos C. Montoy; Robert M. Rodriguez; Huihui Yu; Erica S. Spatz; Christopher W. Chandler; Joann G. Elmore; Paavali A. Hannikainen; Anna Marie Chang; Mandy Hill; Ryan M. Huebinger; Ahamed H. Idris; Katherine Koo; Shu-Xia Li; Samuel McDonald; Graham Nichol; Kelli N. O'Laughlin; Ian D. Plumb; Michelle Santangelo; Sharon Saydah; Kari A. Stephens; Arjun K. Venkatesh; and Robert A. Weinstein

What Were the Information Voids? A Qualitative Analysis of Questions Asked by Dear Pandemic Readers between August 2020-August 2021 , Rachael Piltch-Loeb, Richard James, Sandra S. Albrecht, Alison M. Buttenheim, Jennifer Beam Dowd, Aparna Kumar, Malia Jones, Lindsey J. Leininger, Amanda Simanek, and Shoshana Aronowitz

SARS-CoV-2 Covid-19 Infection During Pregnancy and Differential DNA Methylation in Human Cord Blood Cells From Term Neonates , Pedro Urday, Suhita Gayen Nee' Betal, Rochelle Sequeira Gomes, Huda B. Al-Kouatly, Kolawole Solarin, Joanna S.Y. Chan, Dongmei Li, Irfan Rahman, Sankar Addya, Rupsa C. Boelig, and Zubair H. Aghai

African American Males Have More Distress During Cancer Treatment Than White Males , Stephanie Kjelstrom, Charis Wynn, and Sharon Larson

Effect of Fibrinolytic Therapy on ST-Elevation Myocardial Infarction Clinical Outcomes during the COVID-19 Pandemic: A Systematic Review and Meta-Analysis , Anwar Khedr, Hussam Al Hennawi, Muhammed Khuzzaim Khan, Mostafa Elbanna, Abbas B. Jama, Ekaterina Proskuriakova, Hisham Mushtaq, Mikael Mir, Sydney Boike, Ibtisam Rauf, Aalaa Eissa, Meritxell Urtecho, Thoyaja Koritala, Nitesh Jain, Lokesh Goyal, Salim Surani, and Syed A Khan

A Rapid Systematic Review of Food Insecurity Interventions and Their Effects on Maternal Health Outcomes During the COVID-19 Pandemic , Nichole Peta

The Impact of COVID-19 on Hospitalization Outcomes of Patients With Acute Myocardial Infarction in the USA , F.E. Markson; E. Akuna; C.Y. Lim; L. Khemani; and A, Amanullah

Perfect Storm? COVID-19, Area Deprivation, and Their Association with Pediatric Trauma , Devon Pace, MD, MPH

Physical and Stressful Psychological Impacts of Prolonged Personal Protective Equipment Use During the COVID-19 Pandemic: A Cross-Sectional Survey Study , Giuseppe Candido, Costanza Tortù, Chiara Seghieri, Riccardo Tartaglia, Chiara Baglioni, Paolo Citti, Ida Marina Raciti, Micaela La Regina, Silvia Simonini, Moira Urbani, Chiara Parretti, and Paul Barach

Implementation of a Virtual Interprofessional ICU Learning Collaborative: Successes, Challenges, and Initial Reactions From the Structured Team- Based Optimal Patient-Centered Care for Virus COVID-19 Collaborators , Simon Zec, Nika Zorko Garbajs, Yue Dong, Ognjen Gajic, Christina Kordik, Lori Harmon, Marija Bogojevic, Romil Singh, Yuqiang Sun, Vikas Bansal, Linh Vu, Kelly Cawcutt, John M. Litell, Sarah Redmond, Elly Fitzpatrick, Kirstin J. Kooda, Michelle Biehl, Neha S. Dangayach, Viren Kaul, June M. Chae, Aaron Leppin, Mathew Siuba, Rahul Kashyap, Allan J. Walkey, and Alexander S. Niven

COVID-19 Severity and Cardiovascular Outcomes in SARS-CoV-2-Infected Patients With Cancer and Cardiovascular Disease , Melissa Y.Y. Moey, Cassandra Hennessy, Benjamin French, Jeremy L. Warner, Matthew D. Tucker, Daniel J. Hausrath, Dimpy P. Shah, Jeanne M. DeCara, Ziad Bakouny, Chris Labaki, Toni K. Choueiri, Susan Dent, Nausheen Akhter, Roohi Ismail-Khan, Lisa Tachiki, David Slosky, Tamar S. Polonsky, Joy A. Awosika, Audrey Crago, Trisha Wise-Draper, Nino Balanchivadze, Clara Hwang, Leslie A. Fecher, Cyndi Gonzalez Gomez, Brandon Hayes-Lattin, Michael J. Glover, Sumit A. Shah, Dharmesh Gopalakrishnan, Elizabeth A. Griffiths, Daniel H. Kwon, Vadim S. Koshkin, Sana Mahmood, Babar Bashir, Taylor Nonato, Pedram Razavi, Rana R. McKay, Gayathri Nagaraj, Eric Oligino, Matthew Puc, Polina Tregubenko, Elizabeth M. Wulff-Burchfield, Zhuoer Xie, Thorvardur R. Halfdanarson, Dimitrios Farmakiotis, Elizabeth J. Klein, Elizabeth V. Robilotti, Gregory J. Riely, Jean-Bernard Durand, Salim S. Hayek, Lavanya Kondapalli, Stephanie Berg, Timothy E. O'Connor, Mehmet A. Bilen, Cecilia Castellano, Melissa K. Accordino, Blau Sibel, Lisa B. Weissmann, Chinmay Jani, Daniel B. Flora, Lawrence Rudski, Miriam Santos Dutra, Bouganim Nathaniel, Erika Ruíz-García, Diana Vilar-Compte, Shilpa Gupta, Alicia Morgans, and Anju Nohria

A Computationally Designed ACE2 Decoy Has Broad Efficacy Against SARS-CoV-2 Omicron Variants and Related Viruses in Vitro and in Vivo , Brandon Havranek, Graeme Walker Lindsey, Yusuke Higuchi, Yumi Itoh, Tatsuya Suzuki, Toru Okamoto, Atsushi Hoshino, Erik Procko, and Shahidul M. Islam

Delayed Presentation of Biopsy-Proven Eosinophilic Myocarditis Following COVID-19 mRNA Vaccine , Chaitra Janga, Tirth Patel, Hussam Al Hennawi, Sarin Atam, Shreeja Shah Shah, Ifrah Naeem, Rahat Memon, and Donald C. Haas

Impact of the COVID-19 Pandemic on the Management of Risk Factors In Patients With Stable Atherosclerotic Vascular Disease , Dean Karalis, Patrick Moeller, Albert Crawford, Maria Janelli, and Scott Hessen

A Systematic Review Identifying Adverse Health Outcomes and Mortality Rates Associated with Telehealth , Fidelia Cascini, Ana Pantovic, Yazan A. Al-Ajlouni, Omar Al Ta'ani, Giovanna Failla, Andriy Melnyk, Paul Barach, and Walter Ricciardi

Increasing COVID-19 Vaccination Coverage for Newcomer Communities: The Importance of Disaggregation by Language , Abigail Steiner, Kristine Knuti Rodrigues, Nadège Mudenge, Janine Young, Rasulo Rasulo, Colleen Payton, Malini DeSilva, Jeremy Michel, Mary Fabio, and Katherine Yun

Does Race, Ethnicity, and Insurance Status Predict Functional Outcomes in Hospitalized COVID-19 Patients? , Malachy Clancy, PhD, OTR/L, BCPR

Post COVID-19 Condition: Understanding Implications for OT Practice , Malachy Clancy, PhD, OTR/L, BCPR

COVID-19 related biliary injury: A review of recent literature , Sujani Yadlapati, Simone A. Jarrett, Daniel Baik, and Adib Chaaya

Blueprint for Ambulatory Covid-19 Population Health Management: A Chronic Disease Approach , Jacqueline Biesiadecki, MS

Medicare Shared Savings Program: Key Factors Triggering Success , Guorong Li, MS, MBA

The Phillies, the Union, the Eagles and Jefferson Health , Charles Yeo, MD, FACS

Outcomes Among Heart Failure Patients Hospitalized for Acute Pulmonary Embolism and COVID-19 Infection: Insight From the National Inpatient Sample , Bruce Adrian Casipit, Sahana Tito, Isaac Ogunmola, Abiodun Idowu, Shivaraj Patil, Kevin Lo, and Behnam Bozorgnia

Telehealth for Adolescents Experiencing Mental Health Challenges: A Rapid Systematic Review , Dana Harmer

An Exploration of Careers in the United States Public Health Services , Shauntel Jones

What Do Members of Black and Latino Communities Have to Say About the COVID-19 Vaccine? A Rapid Systematic Review of Qualitative Studies , Taylor Lightner

Perfect Storm? COVID-19, Area Deprivation, and Their Association with Pediatric Trauma , Devon Pace

Dear Pandemic: A topic modeling analysis of COVID-19 information needs among readers of an online science communication campaign. , Aleksandra M Golos, Sharath Chandra Guntuku, Rachael Piltch-Loeb, Lindsey J Leininger, Amanda M Simanek, Aparna Kumar, Sandra S Albrecht, Jennifer Beam Dowd, Malia Jones, and Alison M Buttenheim

Design and Preclinical Evaluation of a Universal SARS-CoV-2 mRNA Vaccine , Jane Qin, Ju Hyeong Jeon, Jiangsheng Xu, Laura Katherine Langston, Ramesh Marasini, Stephanie Mou, Brian Montoya, Carolina R Melo-Silva, Hyo Jin Jeon, Tianyi Zhu, Luis J. Sigal, Renhuan Xu, and Huabin Zhu

An Unusual Case of Hemophagocytic Lymphohistiocytosis Associated with Mycobacterium Chimaera or Large-Cell Neuroendocrine Carcinoma , Tejaswi Venigalla, Sheila Kalathil, Meena Bansal, Mark Morginstin, Vinicius Jorge, and Patricia Perosio

Gibbon Surgical Review, Volume 6, Issue 1, 2023

Demographic Data Associated With Digital Inequity Reported in Patient-to-Provider Teledermatology Studies in the United States From 2011 to 2021: Scoping Review , John Miller, Patrick Ioffreda, Shannon Nugent, and Elizabeth Jones

Preoperative Teleconsultation Visits are as Efficient as In-person Appointments in Avoiding Unnecessary Cancellation of Elective Surgical Procedures , Janeen Duckworth, MSN, APRN, BC; Jacqueline Dennis, BSN, RN; Catriona Harrop, MD, FACP; Geno J. Merli, MD; Howard Weitz, MD; and Pious D. Patel, MD

Teledermatology in Medical Student, Postgraduate Trainee, and Global Dermatology Education: A Systematic Review , Heli Patel, Rishab Revankar, Aly Valliani, Nikita Revankar, Shivani Yerigeri, Nadine Kaskas, and Benjamin Stoff

Retrospective Analyses of the Outcomes Among Hospitalized Liver Cirrhosis Patients With Heart Failure and COVID-19 Infection: Insight From the National Inpatient Sample , Bruce Adrian Casipit, Hussein Al-Sudani, Ahmer Khan, Emmanuel Akuna, and Aman Amanullah

New Psychoactive Substances Intoxications and Fatalities During the COVID-19 Epidemic , Alfredo Fabrizio Lo Faro, Diletta Berardinelli, Tommaso Cassano, Gregory Dendramis, Eva Montanari, Marche Polytechnic University, Paolo Beretta, Simona Zaami, Francesco Paolo Busardò, and Marilyn Ann Huestis

Broad Efficacy of a Computationally Designed ACE2 Decoy Against SARS-CoV-2 Omicron Variants and Related Viruses In Vitro and In Vivo , Brandon Havranek, Graeme W. Lindsey, Yusuke Higuchi, Yumi Itoh, Tatsuya Suzuki, Toru Okamoto, Atsushi Hoshino, Erik Procko, and Shahidul M. Islam

Presence of Symptoms 6 Weeks After COVID-19 Among Vaccinated and Unvaccinated US Healthcare Personnel: A Prospective Cohort Study , Nicholas M. Mohr, Ian D. Plumb, Kari K. Harland, Tamara Pilishvili, Katherine E. Fleming-Dutra, Anusha Krishnadasan, Karin F. Hoth, Sharon H. Saydah, Zachary Mankoff, John P. Haran, Melissa Briggs-Hagen, Eliezer Santos León, and David A. Talan

Efficacy of COVID-19 Public Health Measures in Philadelphia, New York City, Baltimore, and Chicago , Brian Goldstein and Willie H. Oglesby

Reducing the Risk of Mortality in Chronic Obstructive Pulmonary Disease With Pharmacotherapy: A Narrative Review , Matthew Mintz, Igor Barjaktarevic, Donald A. Mahler, Barry Make, Neil Skolnik, Barbara Yawn, Bree Zeyzus-Johns, and Nicola A. Hanania

Between Two Pandemics: Race, Health, and COVID-19 , Wanjikũ F. M. Njoroge, MD, DFAACAP

Development of a Novel Mathematical Model That Explains SARS-CoV-2 Infection Dynamics in Caco-2 Cells , Vladimir Staroverov, Stepan Nersisyan, Alexei Galatenko, Dmitriy Alekseev, Sofya Lukashevich, Fedor Ployakov, Nikita Anisimov, and Alexander Tonevitsky

Safety of Adenosine for the Treatment of Supraventricular Tachycardia in Hospitalized Patients with COVID-19 Pneumonia , T. Zivan, Ramon L Ruiz, Alexandre Martinez, and Behzad B. Pavri

Suffering in Silence: Healthcare Professionals with Substance Use Disorders , Jacob Buinewicz, MD and Frantz Aubry, MD

Analyses of Orthopaedic Surgery Residency Interviews , Alexander J Adams, Matthew Sherman, and James J. Purtill

How the Rural Risk Environment Underpins Hepatitis C Risk: Qualitative Findings From Rural Southern Illinois, United States , Suzan M Walters, David Frank, Marisa Felsher, Jessica Jaiswal, Scott Fletcher, Alex S Bennett, Samuel R Friedman, Lawrence J Ouellet, Danielle C Ompad, Wiley Jenkins, and Mai T Pho

Patient and Provider Satisfaction and Provider Intent to Use Virtual Video Technology for Medical and Surgical Visits in an Urban Ambulatory Setting During and in Peri-COVID-19 Era , Irene Borgen

Interactions Between Genetics, Protein, and Inflammation in Modeling Synucleinopathies , Matthew Daniel Byrne

Outcomes Among ST-Elevation Myocardial Infarction (STEMI) Patients with Cardiogenic Shock and COVID-19: A Nationwide Analysis , Bruce Adrian Casipit, Zurab Azmaiparashvili, Kevin Bryan Lo, and Aman Amanullah

Respiratory Therapy Staff Retention: A Systems Thinking Approach , Jerin G. Juby

Studies on the Role of Necroptosis Proteins RIPK3 and MLKL in Resistance to Viral Infection and on the Role of CD8 T-Cells Induced by mRNA-LNP Vaccines in Protection from SARS-CoV-2 in Mice , Brian Montoya

Formulation of the Rabies Virus Vaccine Vector Against Emerging Viruses , Catherine Yankowski

Manuscripts from 2022 2022

Health Status and Preventive Health Services Among Reproductive-Aged Women in Treatment for Opioid Use Disorder , Vanessa Short, Dennis J. Hand, Lauren Pyfer, Hanna Steiger, Meghan Gannon, Gregory A. Jaffe, and Diane J. Abatemarco

Efficacy and Safety of Pacritinib vs Placebo for Patients With Severe COVID-19: A Phase 2 Randomized Clinical Trial , John Cafardi, Carole Miller, Howard Terebelo, Chad Tewell, Sadia Benzaquen, David Park, Pamela Egan, Daniel Lebovic, Kristen Pettit, Eric Whitman, Douglas Tremblay, Jonathan Feld, Sarah Buckley, Karisse Roman-Torres, Jennifer Smith, Adam Craig, and John Mascarenhas

COVID-19 Vaccine Equity: Codesigning Public Health Interventions With Community Partners , Eva Varotsis, Lauren Schlegel, B. H. Slovis, Patricia C. Henwood, Sandra E Brooks, Robert S. Pugliese, Bon Ku, and Morgan Hutchinson

Association of Initial SARS-CoV-2 Test Positivity With Patient-Reported Well-being 3 Months After a Symptomatic Illness. , Lauren E Wisk, Michael A Gottlieb, Erica S Spatz, Huihui Yu, Ralph C Wang, B. H. Slovis, Sharon Saydah, Ian D Plumb, Kelli N O'Laughlin, Juan Carlos C Montoy, Samuel A McDonald, Zhenqiu Lin, Jin-Mann S Lin, Katherine Koo, Ahamed H Idris, Ryan M Huebinger, Mandy J Hill, Nicole L Gentile, Anna Marie Chang, Jill Anderson, Bala Hota, Arjun K Venkatesh, Robert A Weinstein, Joann G Elmore, and Graham Nichol

Bioethics in the Era of COVID-19 , Rebecca Brendel, MD, JD

Changes in Prenatal Testing During the COVID-19 Pandemic , Sara C Handley, Rachel Ledyard, Lisbet S Lundsberg, Molly Passarella, Nancy Yang, Moeun Son, Kathryn McKenney, Jay S. Greenspan, Kevin Dysart, Jennifer F Culhane, and Heather H Burris

Conducting a Supportive Oncology Clinical Trial During the COVID-19 Pandemic: Challenges and Strategies , Jie Deng, John N. Lukens, Joy C. Cohn, Erin McMenamin, Barbara Murphy, Bryan A. Spinelli, Niya Murphy, Alicia K. Steinmetz, Megan A. Landriau, and Alexander Lin

Commentary: Examining contextual factors contributing to differentials in COVID-19 mortality in U.S. vs. India. , Preeti Zanwar, Katrine L Wallace, Christopher Soria, and Arokiasamy Perianayagam

Efficacy of Early Inpatient Rehabilitation of Post-COVID-19 Survivors: Single-Center Retrospective Analysis , Ning Cao, Jaclyn Barcikowski, Franklin Womble, Bianca Martinez, Yevgeniya Sergeyenko, Jacob H. Koffer, Michael Kwasniewski, Thomas Watanabe, Rui Xiao, and Alberto Esquenazi

Increased Incidence of Suspected Smoke Inhalation During the Coronavirus Disease 2019 Pandemic: A National Database Study , Theodore E Habarth-Morales, Arturo J. Rios Diaz, Emily Isch, Shreyas Chandragiri, Lucy Qi, Rose Ni, and Edward J. Caterson

Smoking and Other Determinants of COVID Severity Among Cancer Patients , Sameh Gomaa; Lindsay Wilde, MD; Tara Rakiewicz; and Kuang-Yi Wen

Emerging Lessons From the COVID-19 Pandemic About the Decisive Competencies Needed for the Public Health Workforce: A Qualitative Study , Osnat Bashkin, Robert Otok, Lore Leighton, Kasia Czabanowska, Paul Barach, Nadav Davidovitch, Keren Dopelt, Mariusz Duplaga, Leah Okenwa Emegwa, Fiona MacLeod, Yehuda Neumark, Maya Peled Raz, Theodore Tulchinsky, and Zohar Mor

Pre-exposure to mRNA-LNP Inhibits Adaptive Immune Responses and Alters Innate Immune Fitness in an Inheritable Fashion , Zhen Qin, Aurélie Bouteau, Christopher Herbst, and Botond Z. Igyártó

Coronavirus Disease-19 Infection and Angioedema in African Americans: A Case Series , Jose Manuel Martinez Manzano, Otoniel Ysea-Hill, Brenda Chiang, Simone A Jarrett, Kevin Bryan Lo, and Zurab Azmaiparashvili

Highlights from the 67th Annual Meeting of the American Society for Artificial Internal Organs in Chicago, IL , Christopher D. Pritting, Alice L. Sweedo, Vakhtang Tchantchaleishvili, Dongfang Wang, and Joseph B. Zwischenberger

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Features, evaluation, and treatment of coronavirus (covid-19).

Marco Cascella ; Michael Rajnik ; Abdul Aleem ; Scott C. Dulebohn ; Raffaela Di Napoli .

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Last Update: August 18, 2023 .

• Continuing Education Activity

Coronavirus disease 2019 (COVID-19) is a highly contagious infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has had a catastrophic effect on the world, resulting in more than 6 million deaths worldwide. It has emerged as the most consequential global health crisis since the era of the influenza pandemic of 1918. As the virus mutates, treatment guidelines are altered to reflect the most efficacious therapies. This activity is a comprehensive review of the disease presentation, complications, and current guideline-recommended treatment options for managing this disease.

• Screen individuals based on exposure and symptom criteria to identify potential COVID-19 cases.
• Identify the clinical features and radiological findings expected in patients with COVID-19.
• Apply the recommended treatment options for patients with COVID-19.
• Create strategies with the interprofessional team for improving care coordination to care for patients with COVID-19 to help improve clinical outcomes.
• Introduction

Coronavirus disease 2019 (COVID-19) is a highly contagious viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has had a catastrophic effect on the world, resulting in more than 6 million deaths worldwide. After the first cases of this predominantly respiratory viral illness were reported in Wuhan, Hubei Province, China, in late December 2019, SARS-CoV-2 rapidly disseminated worldwide. This compelled the World Health Organization (WHO) to declare it a global pandemic on March 11, 2020. [1]

Even though substantial progress in clinical research has led to a better understanding of SARS-CoV-2, many countries continue to have outbreaks of this viral illness. These outbreaks are primarily attributed to the emergence of mutant variants of the virus. Like other RNA viruses, SARS-CoV-2 adapts with genetic evolution and developing mutations. This results in mutant variants that may have different characteristics than their ancestral strains. Several variants of SARS-CoV-2 have been described during the course of this pandemic, among which only a few are considered variants of concern (VOCs). Based on the epidemiological update by the WHO, 5 SARS-CoV-2 VOCs have been identified since the beginning of the pandemic:

• Alpha (B.1.1.7): First variant of concern, which was described in the United Kingdom (UK) in late December 2020 [2]
• Beta (B.1.351) : First reported in South Africa in December 2020 [2]
• Gamma (P.1) : First reported in Brazil in early January 2021 [2]
• Delta (B.1.617.2):  First reported in India in December 2020 [2]
• Omicron   (B.1.1.529): First reported in South Africa in November 2021 [3]

Despite the unprecedented speed of vaccine development against the prevention of COVID-19 and robust global mass vaccination efforts, the emergence of new SARS-CoV-2 variants threatens to overturn the progress made in limiting the spread of this disease. This review aims to comprehensively describe the etiology, epidemiology, pathophysiology, and clinical features of COVID-19. This review also provides an overview of the different variants of SARS-CoV-2 and the guideline-recommended treatment (as of January 2023) for managing this disease. 

Coronaviruses (CoVs) are positive-sense single-stranded RNA (+ssRNA) viruses with a crown-like appearance under an electron microscope ( coronam  is the Latin term for crown) due to the presence of spike glycoproteins on the envelope. [1] The subfamily  Orthocoronavirinae  of the  Coronaviridae  family (order  Nidovirales ) classifies into 4 genera of CoVs: 

• Alphacoronavirus (alphaCoV)
• Betacoronavirus (betaCoV)
• Deltacoronavirus (deltaCoV)
• Gammacoronavirus (gammaCoV)

BetaCoV genus is further divided into 5 sub-genera or lineages. [4]  Genomic characterization has shown that bats and rodents are the probable gene sources of alphaCoVs and betaCoVs. Avian species seem to be the source of deltaCoVs and gammaCoVs. CoVs have become significant pathogens of emerging respiratory disease outbreaks. Members of this large family of viruses can cause respiratory, enteric, hepatic, and neurological diseases in different animal species, including camels, cattle, cats, and bats.

These viruses can cross species barriers and infect humans as well. Seven human CoVs (HCoVs) capable of infecting humans have been identified. Some HCoVs were identified in the mid-1960s, while others were only detected in the new millennium. In general, estimates suggest that 2% of the population are healthy carriers of CoVs and that these viruses are responsible for about 5% to 10% of acute respiratory infections. [5]  

• Common human CoVs : HCoV-OC43 and HCoV-HKU1 (betaCoVs of the A lineage), HCoV-229E, and HCoV-NL63 (alphaCoVs). These viruses can cause common colds and self-limiting upper respiratory tract infections in immunocompetent individuals. However, in immunocompromised and older patients, lower respiratory tract infections can occur due to these viruses.
• Other human CoVs : SARS-CoV and MERS-CoV (betaCoVs of the B and C lineage, respectively). These viruses are considered more virulent and capable of causing epidemics with respiratory and extra-respiratory manifestations of variable clinical severity. [1]  

SARS-CoV-2 is a novel betaCoV belonging to the same subgenus as the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which have been previously implicated in SARS-CoV and MERS-CoV epidemics with mortality rates up to 10% and 35%, respectively. [6]  It has a round or elliptic and often pleomorphic form and a diameter of approximately 60 to 140 nm. Like other CoVs, it is sensitive to ultraviolet rays and heat. [6]  

The inactivation temperature of SARS-CoV-2 is being researched. A stainless steel surface held at an air temperature of 54.5°C (130 °F) results in the inactivation of 90% of SARS-CoV-2 in approximately 36 minutes. [7]  It resists lower temperatures, even those below 0°C. However, lipid solvents can effectively inactivate these viruses, including ether (75%), ethanol, chlorine-containing disinfectant, peroxyacetic acid, and chloroform (except for chlorhexidine).

Although the origin of SARS-CoV-2 is currently unknown, it is widely postulated to have a zoonotic transmission. [1]  Genomic analyses suggest that SARS-CoV-2 probably evolved from a strain found in bats. The genomic comparison between the human SARS-CoV-2 sequence and known animal coronaviruses revealed high homology (96%) between the SARS-CoV-2 and the betaCoV RaTG13 of bats ( Rhinolophus affinis ). [8]  Similar to SARS and MERS, it has been hypothesized that SARS-CoV-2 advanced from bats to intermediate hosts, such as pangolins and minks, and then to humans. [9] [10]

SARS-CoV-2 Variants

A globally dominant D614G variant was eventually identified and associated with increased transmissibility but without the ability to cause severe illness. [11] Another variant was attributed to transmission from infected farmed mink in Denmark but was not associated with increased transmissibility. [10]  Since then, multiple variants of SARS-CoV-2 have been described, of which a few are considered variants of concern (VOCs) due to their potential to cause enhanced transmissibility or virulence. The United States Centers for Disease Control and Prevention (CDC) and the WHO have independently established a classification system for distinguishing the emerging variants of SARS-CoV-2 into variants of concern(VOCs) and variants of interest(VOIs).

SARS-CoV-2 Variants of Concern (VOCs)

• Alpha (B.1.1.7 lineage)
• In late December 2020, the Alpha variant,   or GRY  (formerly GR/501Y.V1), was reported in the UK based on whole-genome sequencing of samples from patients who tested positive for SARS-CoV-2. [12] [13]
• The variant   was also identified using a commercial assay characterized by the absence of the S gene (S-gene target failure, SGTF) in PCR samples. The B.1.1.7 variant includes 17 mutations in the viral genome. Of these, 8 mutations (Δ69-70 deletion, Δ144 deletion, N501Y, A570D, P681H, T716I, S982A, D1118H) are in the spike (S) protein. N501Y shows an increased affinity of the spike protein to ACE 2 receptors, enhancing the viral attachment and subsequent entry into host cells. [14] [15] [16]
• This alpha variant was reportedly 43% to 82% more transmissible, surpassing preexisting variants of SARS-CoV-2 to emerge as the dominant SARS-CoV-2 variant in the UK. [15]  
• An initial matched case-control study reported no significant difference in the risk of hospitalization or associated mortality with the B.1.1.7 lineage variant compared to other existing variants. However, subsequent studies have reported that people infected with B.1.1.7 lineage variant had increased disease severity compared to those infected with other circulating variants. [17] [13]  
• A large matched cohort study in the UK reported that the mortality hazard ratio of patients infected with the B.1.1.7 lineage variant was 1.64 (95% confidence interval 1.32 to 2.04, P<0.0001) compared to patients with previously circulating strains. [18]
• Another study reported that the B 1.1.7 variant was associated with increased mortality compared to other SARS-CoV-2 variants (HR= 1.61, 95% CI 1.42-1.82). [19]  The risk of death was reportedly greater (adjusted hazard ratio 1.67, 95% CI 1.34-2.09) among individuals with confirmed B.1.1.7 infection compared to individuals with non-B.1.1.7 SARS-CoV-2. [20]
• Beta (B.1.351 lineage)
• The Beta variant, or GH501Y.V2 with multiple spike mutations, resulted in the second wave of COVID-19 infections and was first detected in South Africa in October 2020. [21]
• The B.1.351 variant includes 9 mutations (L18F, D80A, D215G, R246I, K417N, E484K, N501Y, D614G, and A701V) in the spike protein, of which 3 mutations (K417N, E484K, and N501Y) are located in the receptor binding domain (RBD) and increase its binding affinity for the ACE receptors. [22] [14] [23]  
• SARS-CoV-2 501Y.V2 (B.1.351 lineage) was reported in the US at the end of January 2021.
• This variant had an increased risk of transmission and reduced neutralization by monoclonal antibody therapy, convalescent sera, and post-vaccination sera. [24]
• Gamma (P.1 lineage)
• The Gamma variant, or  GR/501Y.V3 , was identified in December 2020 in Brazil and was first detected in the US in January 2021. [25]  
• This B.1.1.28 variant harbors ten mutations in the spike protein (L18F, T20N, P26S, D138Y, R190S, H655Y, T1027I V1176, K417T, E484K, and N501Y). Three mutations (L18F, K417N, E484K) are located in the RBD, similar to the B.1.351 variant. [25]
• The Delta variant was initially identified in December 2020 in India and was responsible for the deadly second wave of COVID-19 infections in April 2021 in India. In the United States, this variant was first detected in March 2021. [2]
• The B.1.617.2 variant harbors ten mutations ( T19R, (G142D*), 156del, 157del, R158G, L452R, T478K, D614G, P681R, D950N) in the spike protein.
• The Omicron variant was first identified in South Africa on 23 November 2021 after an uptick in the number of cases of COVID-19. [26]  
• Omicron was quickly recognized as a VOC due to more than 30 changes to the spike protein of the virus and the sharp rise in the number of cases observed in South Africa. [27]  The reported mutations include T91 in the envelope, P13L, E31del, R32del, S33del, R203K, G204R in the nucleocapsid protein, D3G, Q19E, A63T in the matrix, N211del/L212I, Y145del, Y144del, Y143del, G142D, T95I, V70del, H69del, A67V in the N-terminal domain of the spike, Y505H, N501Y, Q498R, G496S, Q493R, E484A, T478K, S477N, G446S, N440K, K417N, S375F, S373P, S371L, G339D in the receptor-binding domain of the spike, D796Y in the fusion peptide of the spike, L981F, N969K, Q954H in the heptad repeat 1 of the spike as well as multiple other mutations in the non-structural proteins and spike protein. [28]
• Many subvariants of Omicron, such as BA.1, BA.2, BA.3, BA.4, and BA.5, have been identified. [3]

Transmission of SARS-CoV-2

• The primary mode of transmission of SARS-CoV-2 is via exposure to respiratory droplets carrying the infectious virus from close contact or direct transmission from presymptomatic, asymptomatic, or symptomatic individuals harboring the virus. [1]
• Airborne transmission with aerosol-generating procedures has also been implicated in the spread of COVID-19. Data implicating airborne transmission of SARS-CoV-2 in the absence of aerosol-generating procedures is present; however, this mode of transmission has not been universally acknowledged.
• Fomite transmission from contamination of inanimate surfaces with SARS-CoV-2 has been well characterized based on many studies reporting the viability of SARS-CoV-2 on various porous and nonporous surfaces. Under experimental conditions, SARS-CoV-2 was stable on stainless steel and plastic surfaces compared to copper and cardboard surfaces, with the viable virus being detected up to 72 hours after inoculating the surfaces with the virus. [29]  The viable virus was isolated for up to 28 days at 20°C from nonporous surfaces such as glass and stainless steel. Conversely, recovery of SARS-CoV-2 on porous materials was reduced compared with nonporous surfaces. [30]  In hospital settings, the SARS-CoV-2 has been detected on floors, computer mice, trash cans, sickbed handrails, and in the air (up to 4 meters from patients). [31]  The Centers for Disease Control and Prevention (CDC) has stated that individuals can be infected with SARS-CoV-2 via contact with surfaces contaminated by the virus, but the risk is low and is not the main route of transmission of this virus.
• Epidemiologic data from several case studies have reported that patients with SARS-CoV-2 infection have the live virus in feces implying possible fecal-oral transmission. [32]
• A meta-analysis that included 936 neonates from mothers with COVID-19 showed vertical transmission is possible but occurs in a minority of cases. [33]
• Epidemiology

COVID-19 was the third leading cause of death in the United States (USA) in 2020 after heart disease and cancer, with approximately 375,000 deaths. [34]  

Individuals of all ages are at risk of contracting this infection. However, patients aged ≥60 and patients with underlying medical comorbidities (obesity, cardiovascular disease, chronic kidney disease, diabetes, chronic lung disease, smoking, cancer, solid organ or hematopoietic stem cell transplant patients) have an increased risk of developing severe COVID-19 infection.

According to the CDC, age remains the strongest predictor of poor outcomes and severe illness in patients with COVID-19. Data from the National Vital Statistics System (NVSS) at CDC states that patients with COVID-19 aged 50 to 64 years have a 25 times higher risk of death when compared to adults infected with this illness and aged less than 30 years. In patients 65 to 74 years old, this risk increases to 60 times. In patients older than 85, the risk of death increases to 340 times. According to the CDC, these data include all deaths in the United States throughout the pandemic, from February 2020 to July 1, 2022, including deaths among unvaccinated individuals.

The percentage of COVID-19 patients requiring hospitalization was 6 times higher in those with preexisting medical conditions than those without medical conditions (45.4% vs. 7.6%) based on an analysis by Stokes et al. of confirmed cases reported to the CDC from January 22 to May 30, 2020. [35]  The study also reported that the percentage of patients who succumbed to this illness was 12 times higher in those with preexisting medical conditions than those without (19.5% vs 1.6%). [35]  

Data regarding the gender-based differences in COVID-19 suggests that male patients have a higher risk of severe illness and increased mortality due to COVID-19 compared to female patients. [36] [37]  Results from a retrospective cohort study from March 1 to November 21, 2020, evaluating the mortality rate in 209 United States of America (USA) acute care hospitals that included 42604 patients with confirmed SARS-CoV-2 infection, reported a higher mortality rate in male patients (12.5%) compared to female patients (9.6%). [38]

Racial and ethnic minority groups have been reported to have a higher percentage of COVID-19-related hospitalizations than White patients based on a recent CDC analysis of hospitalizations from an extensive administrative database that included approximately 300,000 COVID-19 patients hospitalized from March 2020 to December 2020. This high percentage of COVID-19-related hospitalizations among racial and ethnic groups was driven by a higher risk of exposure to SARS-CoV-2 and an increased risk of developing severe COVID-19 disease. [39]   A meta-analysis of 50 studies from USA and UK researchers noted that people of Black, Hispanic, and Asian ethnic minority groups are at increased risk of contracting and dying from COVID-19 infection. [40]  

COVID-19-related death rates were the highest among Hispanic persons. [34]  Another analysis by the CDC evaluating the risk of COVID-19 among sexual minority adults reported that underlying medical comorbidities which increase the risk of developing severe COVID-19 were more prevalent in sexual minority individuals than heterosexual individuals within the general population and within specific racial/ethnic groups. [41]

• Pathophysiology

Structurally and phylogenetically, SARS-CoV-2 is similar to SARS-CoV and MERS-CoV and is composed of 4 main structural proteins: spike (S), envelope (E) glycoprotein, nucleocapsid (N), and membrane (M) protein. It also contains 16 nonstructural proteins and 5-8 accessory proteins. [42]  

The surface spike (S) glycoprotein, which resembles a crown, is located on the outer surface of the virion. It undergoes cleavage into an amino (N)-terminal S1 subunit, which facilitates the incorporation of the virus into the host cell. The carboxyl (C)-terminal S2 subunit contains a fusion peptide, a transmembrane domain, and a cytoplasmic domain responsible for virus-cell membrane fusion. [43] [44]  The S1 subunit is further divided into a receptor-binding domain (RBD) and an N-terminal domain (NTD), which facilitates viral entry into the host cell and serves as a potential target for neutralization in response to antisera or vaccines . [45]  

The RBD is a fundamental peptide in the pathogenesis of infection as it represents a binding site for the human angiotensin-converting enzyme 2 (ACE2) receptors. Inhibition of the renin-angiotensin-aldosterone system (RAAS) does not increase the risk of hospitalization for COVID-19 and severe disease. [46]

SARS-CoV-2 gains entry into the host cells by binding the SARS-CoV-2 spike or S protein (S1) to the ACE2 receptors in the respiratory epithelium. ACE2 receptors are also expressed by other organs such as the upper esophagus, enterocytes from the ileum, myocardial cells, proximal tubular cells of the kidney, and urothelial cells of the bladder. [47]  The viral attachment process is followed by priming the spike protein S2 subunit by the host transmembrane serine protease 2 (TMPRSS2) that facilitates cell entry and subsequent viral replication. [48]

In the early phase of the infection, viral replication results in direct virus-mediated tissue damage. In the late phase, the infected host cells trigger an immune response by recruiting T lymphocytes, monocytes, and neutrophils. Cytokines such as tumor necrosis factor-α (TNF α), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 (IL-1), interleukin-6 (IL-6), ), IL-1β, IL-8, IL-12 and interferon (IFN)-γ are released. In severe COVID-19 illness, a 'cytokine storm' is seen. This is due to the over-activation of the immune system and high levels of cytokines in circulation. This results in a local and systemic inflammatory response. [49] [50]  

Effect of SARS-CoV-2 on the Respiratory System

Increased vascular permeability and subsequent development of pulmonary edema in patients with severe COVID-19 are explained by multiple mechanisms. [51] [52] [53]  These mechanisms include:

• Endotheliitis as a result of direct viral injury and perivascular inflammation leading to microvascular and microthrombi deposition
• Dysregulation of RAAS due to increased binding of the virus to the ACE2 receptors
• Activation of the kallikrein-bradykinin pathway, the activation of which enhances vascular permeability
• Enhanced epithelial cell contraction causes swelling of cells and disturbance of intercellular junctions
• The binding of SARS-CoV-2 to the Toll-Like Receptor (TLR) induces the release of pro-IL-1β, which mediates lung inflammation until fibrosis . [54]

Effect of SARS-CoV-2 on Extrapulmonary Organ Systems

Although the respiratory system is the principal target for SARS-CoV-2, other major organ systems such as the gastrointestinal tract (GI), hepatobiliary, cardiovascular, renal, and central nervous systems may also be affected. SARS-CoV-2–induced organ dysfunction is likely due to a combination of mechanisms, such as direct viral toxicity, ischemic injury caused by vasculitis, thrombosis, immune dysregulation, and renin-angiotensin-aldosterone system (RAAS) dysregulation. [55]

Cardiac involvement in COVID-19 is common and likely multifactorial. ACE2 receptors exhibited by myocardial cells may cause direct cytotoxicity to the myocardium leading to myocarditis. Proinflammatory cytokines such as IL-6 can also lead to vascular inflammation, myocarditis, and cardiac arrhythmias. [56]

Acute coronary syndrome (ACS) is a well-recognized cardiac manifestation of COVID-19. It is likely due to multiple factors, including proinflammatory cytokines, worsening of preexisting severe coronary artery disease, coronary plaque destabilization, microthrombogenesis, and reduced coronary blood flow. [57]  

SARS-CoV-2 has a significant effect on the hematological and hemostatic systems as well. The mechanism of leukopenia, one of the most common laboratory abnormalities encountered in COVID-19, is unknown. Several hypotheses have been postulated that include ACE 2 mediated lymphocyte destruction by direct invasion by the virus, lymphocyte apoptosis due to proinflammatory cytokines, and possible invasion of the virus in the lymphatic organs. [58]  

Thrombocytopenia is common in COVID-19 and is likely due to multiple factors, including virus-mediated suppression of platelets, autoantibodies formation, and coagulation cascade activation, resulting in platelet consumption. [59]  

Thrombocytopenia and neutrophilia are considered a hallmark of severe illness. [55] Although it is well known that COVID-19 is associated with a state of hypercoagulability, the exact mechanisms that lead to the activation of the coagulation system are unknown and likely attributed to the cytokine-induced inflammatory response. The pathogenesis of this associated hypercoagulability is multifactorial. The hypercoagulability is probably induced by direct viral-mediated damage or cytokine-induced injury of the vascular endothelium leading to the activation of platelets, monocytes, and macrophages, with increased expression of von Willebrand factor and Factor VIII that results in the generation of thrombin and formation of a fibrin clot. [59] [60]  

Other mechanisms that have been proposed include possible mononuclear phagocyte-induced prothrombotic sequelae, derangements in the renin-angiotensin system (RAS) pathways, and complement-mediated microangiopathy. [59]

• History and Physical

Clinical Manifestations of COVID-19

• The median incubation period for SARS-CoV-2 is estimated to be 5.1 days, and most patients will develop symptoms within 11.5 days of infection. [61]
• The clinical spectrum of COVID-19 varies from asymptomatic or paucisymptomatic forms to clinical illness characterized by acute respiratory failure requiring mechanical ventilation, septic shock, and multiple organ failure. 
• It is estimated that 17.9% to 33.3% of infected patients will remain asymptomatic. [62] [63]
• Most symptomatic patients present with fever, cough, and shortness of breath. Less common symptoms include sore throat, anosmia, dysgeusia, anorexia, nausea, malaise, myalgias, and diarrhea. Stokes et al. reported that among 373,883 confirmed symptomatic COVID-19 cases in the USA, 70% experienced fever, cough, and shortness of breath, 36% reported myalgia, and 34% reported headache. [35]
• A large meta-analysis evaluating clinicopathological characteristics of 8697 patients with COVID-19 in China reported laboratory abnormalities that included lymphopenia (47.6%), elevated C-reactive protein levels (65.9%), elevated cardiac enzymes (49.4%), and abnormal liver function tests (26.4%). Other laboratory abnormalities included leukopenia (23.5%), elevated D-dimer (20.4%), elevated erythrocyte sedimentation rate (20.4%), leukocytosis (9.9%), elevated procalcitonin (16.7%), and abnormal renal function (10.9%). [64]
• A meta-analysis of 212 published studies with 281,461 individuals from 11 countries/regions reported that severe disease course was noted in about 23% of the patients, with a mortality rate of about 6% in patients infected with COVID-19. [65]
• An elevated neutrophil-to-lymphocyte ratio (NLR), an elevated derived NLR ratio (d-NLR), and an elevated platelet-to-lymphocyte ratio indicate a cytokine-induced inflammatory storm. [66]

Based on the severity of the presenting illness, which includes clinical symptoms, laboratory and radiographic abnormalities, hemodynamics, and organ function, the National Institutes of Health (NIH) issued guidelines that classify COVID-19 into 5 distinct types.[ NIH COVID-19 Treatment Guidelines ]

• Asymptomatic or Presymptomatic Infection : Individuals with positive SARS-CoV-2 test without any clinical symptoms consistent with COVID-19.
• Mild illness : Individuals who have symptoms of COVID-19, such as fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, anosmia, or dysgeusia but without shortness of breath or abnormal chest imaging.
• Moderate illness : Individuals with clinical symptoms or radiologic evidence of lower respiratory tract disease and oxygen saturation (SpO 2 ) ≥94% on room air.
• Severe illness : Individuals who have SpO 2 less than 94% on room air, a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO 2 /FiO 2 ) of less than 300, marked tachypnea with a respiratory frequency of greater than 30 breaths/min, or lung infiltrates that are greater than 50% of total lung volume.
• Critical illness : Individuals with acute respiratory failure, septic shock, or multiple organ dysfunction. Patients with severe COVID-19 illness may become critically ill with the development of acute respiratory distress syndrome (ARDS). This tends to occur approximately one week after the onset of symptoms.

ARDS is characterized by a severe new-onset respiratory failure or worsening of an already identified respiratory picture. The diagnosis requires bilateral opacities (lung infiltrates >50%), not fully explained by effusions or atelectasis. The Berlin definition classifies ARDS into 3 types based on the degree of hypoxia, with the reference parameter being PaO 2 /FiO 2 or P/F ratio: [67]

• Mild ARDS : 200 mm Hg <PaO 2 /FiO 2 ≤300 mm Hg in patients not receiving mechanical ventilation or in those managed through noninvasive ventilation (NIV) by using positive end-expiratory pressure (PEEP) or a continuous positive airway pressure (CPAP) ≥5 cm H2O.
• Moderate ARDS : 100 mm Hg <PaO 2 /FiO 2 ≤200 mm Hg
• Severe ARDS : PaO 2 /FiO 2 ≤100 mm Hg

When PaO 2 is unavailable, a ratio of SpO 2 /FiO 2 ≤315 suggests ARDS. A multicenter prospective observational study that analyzed 28-day mortality in mechanically ventilated patients with ARDS concluded that COVID-19 patients with ARDS had features similar to other ARDS cohorts, and the risk of 28-day mortality increased with ARDS severity. [68]

Extrapulmonary Manifestations 

• Acute kidney injury (AKI) is the most frequently encountered extrapulmonary manifestation of COVID-19 and is associated with an increased mortality risk. [69] A large multicenter cohort study of hospitalized patients with COVID-19 that involved 5,449 patients admitted with COVID-19 reported that 1993 (36.6%) patients developed AKI during their hospitalization, of which 14.3% of patients required renal replacement therapy (RRT). [70]  
• Myocardial injury manifesting as myocardial ischemia/infarction (MI) and myocarditis are well-recognized cardiac manifestations in patients with COVID-19. Single-center retrospective study analysis of 187 patients with confirmed COVID-19 reported that 27.8% of patients exhibited myocardial injury indicated by elevated troponin levels. The study also noted that patients with elevated troponin levels had more frequent malignant arrhythmias and a higher mechanical ventilation frequency than patients with normal troponin levels. [71]  A meta-analysis of 198 published studies involving 159698 COVID-19 patients reported that acute myocardial injury and a high burden of pre-existing cardiovascular disease were significantly associated with higher mortality and ICU admission. [72]
• Lymphopenia is a common laboratory abnormality in most patients with COVID-19. Other laboratory abnormalities include thrombocytopenia, leukopenia, elevated ESR levels, C-reactive protein (CRP), lactate dehydrogenase (LDH), and leukocytosis.
• COVID-19 is also associated with a hypercoagulable state, evidenced by the high prevalence of venous thromboembolic events. COVID-19 is associated with markedly elevated D-dimer and fibrinogen levels and prolonged prothrombin time (PT) and partial thromboplastin time (aPTT). [71] [55]  
• GI symptoms (such as diarrhea, nausea, vomiting), anorexia, and abdominal pain are common. A meta-analysis reported that the weighted pool prevalence of diarrhea was 12.4% (95% CI, 8.2% to 17.1%), nausea or vomiting was 9% (95% CI, 5.5% to 12.9%), loss of appetite was 22.3% (95% CI, 11.2% to 34.6%) and abdominal pain was 6.2% (95% CI, 2.6% to 10.3%). The study also reported that the mortality rate among patients with GI symptoms was similar to the overall mortality rate. [73] Cases of acute mesenteric ischemia and portal vein thrombosis have also been described. [74]
• An acute increase in aspartate transaminase (AST) and alanine transaminase (ALT) is noted in 14% to 53% of patients with COVID-19 infection. [75]
• Guillain-Barré syndrome (GBS) cases from Northern Italy have also been reported. [76] [77]
• Acral lesions resembling pseudo chilblains (40.4%) are the most common cutaneous manifestation noted in patients with COVID-19. [78]
• Other cutaneous manifestations include erythematous maculopapular rash (21.3%), vesicular rashes (13%), urticarial rashes (10.9%), vascular rashes (4%) resembling livedo or purpura, and erythema multiforme-like eruptions (3.7%). [78]

Diagnostic Testing in COVID-19

A nasopharyngeal swab for SARS-CoV-2 nucleic acid using a real-time PCR assay is the standard diagnostic test.[ NIH COVID-19 Treatment Guidelines ] Commercial PCR assays have been authorized by the USA Food and Drug Administration (FDA) for the qualitative detection of SARS-CoV-2 virus using specimens obtained from nasopharyngeal swabs as well as other sites such as oropharyngeal, anterior/mid-turbinate nasal swabs, nasopharyngeal aspirates, bronchoalveolar lavage (BAL) and saliva. 

The sensitivity of PCR testing depends on multiple factors, including the specimen's adequacy, time from exposure, and specimen source. [79]  However, the specificity of most commercial FDA-authorized SARS-CoV-2 PCR assays is nearly 100%, provided there is no cross-contamination during specimen processing. SARS-CoV-2 antigen tests are less sensitive but have a faster turnaround time than molecular PCR testing. [80]  

Despite the numerous antibody tests designed to date, serologic testing has limitations in specificity and sensitivity, and results from different tests vary. According to the NIH guidelines, diagnosing acute SARS-CoV-2 infection based on serologic testing is not recommended. They also stated that there is insufficient evidence to recommend for or against using serologic testing to assess immunity, even if it is used to guide clinical decisions about COVID-19 vaccines/monoclonal antibodies.[ NIH COVID-19 Treatment Guidelines ]

Other Laboratory Assessment

• Complete blood count (CBC), a comprehensive metabolic panel (CMP) that includes renal and liver function testing, and a coagulation panel should be performed in all hospitalized patients.
• Additional tests, such as ESR, C-reactive protein (CRP), ferritin, lactate dehydrogenase, and procalcitonin, can be considered in hospitalized patients. However, their prognostic significance in COVID-19 is not clear.
• A D-dimer level is required as it guides the use of therapeutic versus prophylactic doses of anticoagulation.

Imaging ModalitiesThis s viral illness commonly manifests as pneumonia, so radiological imaging such as chest x-rays, lung ultrasounds, and chest computed tomography (CT) are often obtained. However, there are no guidelines regarding the timing and choice of pulmonary imaging in patients with COVID-19.

When obtained, the chest X-ray usually shows bilateral multifocal alveolar opacities. Pleural effusions can also be demonstrated. The most common CT chest findings in COVID-19 are multifocal bilateral ground glass opacities with consolidation changes, usually in a patchy peripheral distribution. [81]

Radiologic imaging is not a sensitive method for detecting this disease. A retrospective study of 64 patients with documented COVID-19 reported that 20% had no abnormalities on chest radiographs during the illness. [82]  A chest CT is more sensitive than a radiograph but is not specific. No finding on radiographic imaging can completely rule in or rule out COVID-19 illness. Therefore the American College of Radiology (ACR) advises against the routine use of chest CT for screening or diagnosis of COVID-19.[ ACR Position Statement for Diagnosis of COVID-19 ]

• Treatment / Management

According to the National Institutes of Health (NIH), the 2 main processes driving the pathogenesis of COVID-19 include replication of the virus in the early phase of the illness and dysregulated immune/inflammatory response to SARS-CoV-2 that leads to systemic tissue damage in the later phase of the disease.[ NIH COVID-19 Treatment Guidelines ] The guidelines, therefore, advise antiviral medications to halt viral replication in the early phase of the illness and immunomodulators in the later phase.

Remdesivir is the only antiviral drug approved by the USA Food and Drug Administration (FDA) to treat COVID-19. Ritonavir-boosted nirmatrelvir, molnupiravir, and high-titer COVID-19 convalescent plasma have Emergency Use Authorizations (EUAs) for treating COVID-19. Tixagevimab 300 mg plus cilgavimab 300 mg monoclonal antibodies have received EUAs that allow them to be used as SARS-CoV-2 preexposure prophylaxis (PrEP) in certain patients.

Many other monoclonal antibodies had EUAs; however, as Omicron subvariants emerged, their EUAs were revoked as they were no longer effective. 

The most recent NIH treatment guidelines for the management of COVID-19 illness (accessed on January 3rd, 2023) are outlined below:[ NIH COVID-19 Treatment Guidelines ]

Nonhospitalized Adults With Mild-to-Moderate COVID-19 Illness Who Do Not Require Supplemental Oxygen

• The NIH recommends against using dexamethasone or any other systemic corticosteroids in patients who are not hypoxic. [83]   
• Ritonavir-boosted nirmatrelvir is a combination of oral protease inhibitors. It has been shown to reduce hospitalization and death when given to high-risk, unvaccinated, nonhospitalized patients. It must be given within 5 days of symptoms onset. [84]
• It is a strong cytochrome P450 inhibitor with many drug-drug interactions that must be carefully assessed.
• Some interactions can be managed by temporarily holding the medication, some may be managed with dose adjustment, but some may warrant the use of alternate COVID-19 therapy. 
• Ritonavir-boosted nirmatrelvir is not recommended in patients with an estimated glomerular filtration rate (eGFR) of less than 30 mL/min.
• The recommended dose is nirmatrelvir 300 mg with ritonavir 100 mg orally twice daily for 5 days.
• This is a nucleotide analog that inhibits the SARS-CoV-2 RNA polymerase  
• The recommended duration of therapy in this setting is 3 days.
• The recommended dose is 200 mg IV on day 1, followed by 100 mg IV for 2 more days.
• It is a mutagenic ribonucleoside antiviral agent.
• Fetal toxicity has been reported in animal studies with this agent. Due to the risk of genotoxicity with this agent, it is not recommended in pregnant patients. 
• This agent should only be used if both therapies are unavailable or cannot be given.
• The NIH guidelines recommend against using anti-SARS-CoV-2 monoclonal antibodies (mAbs) for treating COVID-19 in this cohort because the Omicron subvariants are not susceptible to these agents.  
• Adequate and close medical follow-up is recommended; however, the frequency and duration of follow-up depend on individual risk factors and the severity of their symptoms. 
• Risk factors for progression to severe disease include advanced age and underlying medical conditions. The CDC maintains an updated list of medical conditions associated with a high risk of progression. 
•  Asthma
• Cerebrovascular disease
• Chronic kidney disease
• Bronchiectasis
• COPD (Chronic obstructive pulmonary disease)
• Interstitial lung disease
• Pulmonary embolism
• Pulmonary hypertension
• Nonalcoholic fatty liver disease
• Alcoholic liver disease
• Autoimmune hepatitis
• Cystic fibrosis
• Diabetes, type 1 and 2
• Heart conditions (such as heart failure, coronary artery disease, or cardiomyopathies)
• HIV (Human immunodeficiency virus)
• Mental health conditions such as mood disorders and Schizophrenia spectrum disorders
• Obesity (defined as body mass index (BMI) of greater than 30 kg/m 2 or greater than 95th percentile in children)
• Pregnancy and recent pregnancy
• Smoking, current and former
• Solid organ or blood stem cell transplantation
• Tuberculosis
• Use of corticosteroids or other immunosuppressive medications ( CDC: Underlying Medical Conditions Associated with Higher Risk )

Therapeutic Management of Hospitalized Adults With COVID-19   Who Do Not Require Oxygen

• If patients are hospitalized for reasons other than COVID-19 illness and are not on oxygen, their management is similar to nonhospitalized patients. 
• If they are hospitalized for COVID-19 illness but do not require oxygen, the NIH advises against the use of dexamethasone or any other systemic corticosteroid.
• A prophylactic dose of anticoagulation should be given if there is no contraindication. 
• If they are hospitalized for COVID-19 illness, do not require oxygen, but are at high risk of progression to severe disease, they should be treated with remdesivir.
• The benefit of remdesivir is greatest when given early, ideally within ten days of symptom onset.
• Remdesivir should be given for 5 days or until hospital discharge. 

Therapeutic Management of Hospitalized Adults With COVID-19 Who Require Conventional Oxygen

• Conventional oxygen is defined as oxygen that is NOT high-flow nasal cannula, noninvasive mechanical ventilation, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)
• For most patients in this cohort, the recommended treatment is dexamethasone plus remdesivir.
• Dexamethasone dose is 6 mg IV or oral (PO) once daily for up to 10 days or until hospital discharge (dexamethasone should not be continued at discharge). [83]  
• If the patient is on minimal oxygen, remdesivir monotherapy (without dexamethasone) should be used. 
• If remdesivir cannot be obtained or given, dexamethasone monotherapy is recommended.
• If dexamethasone is unavailable, corticosteroids such as prednisone, methylprednisolone, or hydrocortisone may be used.
• If the patient is already receiving dexamethasone but has rapidly increasing oxygen needs and/or signs of systemic inflammation, oral baricitinib or intravenous (IV) tocilizumab should be added to the treatment regimen as these agents have been shown to improve outcomes in rapidly decompensating patients. [85]
• Alternate immunomodulatory agents for this cohort include oral tofacitinib and IV sarilumab. These agents should only be used if baricitinib and tocilizumab are not available. 
• If the D-dimer level is above normal in this cohort of patients, they recommend therapeutic anticoagulation if the patient is not pregnant and has no increased risk of bleeding. Contraindications for therapeutic anticoagulation in these patients include a platelet count of less than 50 x10^9 /L, hemoglobin less than 8 g/dL, use of dual antiplatelet therapy, any significant bleeding within the past 30 days, a history of a bleeding disorder or an inherited or active acquired bleeding disorder. 
• For pregnant patients, a prophylactic dose of anticoagulation is recommended.

Therapeutic Management of Hospitalized Adults With COVID-19 who Require High-flow Nasal Cannula (HFNC) or Noninvasive Mechanical Ventilation (NIV)

• A meta-analysis study evaluating the effectiveness of HFNC compared to conventional oxygen therapy and NIV before mechanical ventilation reported that HFNC, when used before mechanical ventilation, could improve the prognosis of patients compared to conventional oxygen therapy and NIV. [86]  HFNC or NIV is associated with decreased dispersion of exhaled air, especially when used with good interface fitting, thus creating a low risk of nosocomial transmission of the infection. [87]  However, these treatment modalities are associated with a greater risk of aerosolization and should be used in negative-pressure rooms. [88]
• According to the NIH, dexamethasone plus oral baricitinib or dexamethasone plus IV tocilizumab are the preferred treatment regimens in these patients.
• Alternate immunomodulatory agents for this cohort include oral tofacitinib and IV sarilumab.
• Dexamethasone monotherapy is recommended if baricitinib, tocilizumab, or sarilumab cannot be obtained/given.
• Clinicians may consider adding remdesivir to corticosteroid and immunomodulator combination regimens in immunocompromised patients who require HFNC or NIV ventilation; however, using remdesivir without immunomodulators is not recommended.
• A prophylactic dose of anticoagulation is recommended in these patients. 
• If patients were started on a therapeutic dose of heparin while on conventional oxygen therapy, they should be switched to prophylactic dosing at this time unless they have another indication for full anticoagulation.

Therapeutic Management of Hospitalized Adults With COVID-19 who Require Mechanical Ventilation (MV)

• The management of this cohort is the same as those requiring HFNC or NIV, except that remdesivir is not recommended. 
• Remdesivir is most effective earlier in the course of the disease and in patients not on mechanical ventilation or ECMO.
• According to the NIH, one study showed a slight trend toward an increase in mortality in patients who received remdesivir while on mechanical ventilation or ECMO. [89]
• With this data in mind, the NIH recommends against using remdesivir in patients receiving MV or ECMO; however, if the patient was started on remdesivir and progressed to requiring mechanical ventilation or ECMO, they recommended continuing remdesivir to complete the treatment course. 

High-Titer COVID-19 Convalescent Plasma (CCP)

• The United States Food and Drug Administration (FDA) approved convalescent plasma therapy under a EUA for patients with severe life-threatening COVID-19. [90] [91]   Data from multiple studies evaluating the use of convalescent plasma in life-threatening COVID-19 has generated mixed results. Data from 3 small randomized control trials showed no significant differences in clinical improvement or overall mortality in patients treated with convalescent plasma versus standard therapy. [92] [93] [94]  
• According to the NIH, high-titer CCP is not recommended in immunocompetent individuals.
• However, the NIH states that some experts consider it appropriate for use in immunocompromised individuals. Therefore, the current NIH guidelines state that there is insufficient evidence for or against the use of high-titer CCP for treating COVID-19 in hospitalized or nonhospitalized patients who are immunocompromised.

Medications/Treatments That Should NOT Be Used for the Treatment of COVID-19 According to the Latest NIH Guidelines [ NIH COVID-19 Treatment Guidelines ]

• Chloroquine or hydroxychloroquine with or without azithromycin
• Lopinavir/ritonavir
• Azithromycin
• Doxycycline
• Fluvoxamine
• Inhaled corticosteroids
• Excess supplementation of vitamin C, vitamin D, and zinc
• Interferons alfa, beta, or lambda
• Nitazoxanide
• Bamlanivimab plus etesevimab
• Bebtelovimab
• Casirivimab plus imdevimab

Preexposure Prophylaxis for SARS-CoV-2 Infection

• According to the NIH guidelines, tixagevimab plus cilgavimab is authorized by the FDA for preexposure prophylaxis of SARS-CoV-2 in people who are not expected to mount an adequate immune response to COVID-19 vaccination; however, the prevalence of Omicron subvariants that are resistant to tixagevimab plus cilgavimab is noted to be increasing rapidly. 
• In the absence of alternative options, the NIH still recommends tixagevimab 300 mg plus cilgavimab 300 mg at this time.
• Tixagevimab and cilgavimab are potent anti-spike neutralizing monoclonal antibodies obtained from antibodies isolated from B cells of patients infected with SARS-CoV-2 that have demonstrated neutralizing activity against SARS-CoV-2 virus by binding to nonoverlapping epitopes of the viral spike-protein RBD. [95] [96] [97]  
• The EUA authorizes its use in adult and pediatric patients with no current evidence of SARS-CoV-2 infection and no recent exposure to SARS-CoV-2-positive individuals. They must be moderately or severely immunocompromised or be on immunosuppressive medications.
• Differential Diagnosis

The symptoms of the early stages of the disease are nonspecific. Differential diagnosis should include the possibility of a wide range of infectious and noninfectious respiratory disorders.

• Community-acquired bacterial pneumonia
• Viral pneumonia 
• Influenza infection
• Aspiration pneumonia
• Pneumocystis jirovecii pneumonia
• Middle East respiratory syndrome (MERS)
• Avian influenza A (H7N9) viral infection
• Avian influenza A (H5N1) viral infection
• Pulmonary tuberculosis

The prognosis of COVID-19 depends on various factors, including the patient's age, the severity of illness at presentation, preexisting conditions, how quickly treatment can be implemented, and response to treatment. The WHO currently estimates the global case fatality rate for COVID-19 is 2.2%. Results from a European multicenter prospective cohort study that included 4000 critically ill patients with COVID-19 reported a 90-day mortality of 31%, with higher mortality noted in geriatric patients and patients with diabetes, obesity, and severe ARDS. [98]

• Complications

COVID-19 is a systemic viral illness based on its involvement in multiple major organ systems.

• Patients with advanced age and comorbid conditions such as obesity, diabetes mellitus, chronic lung disease, cardiovascular disease, chronic kidney disease, chronic liver disease, and neoplastic conditions are at risk of developing severe COVID-19 and its associated complications. The most common complication of severe COVID-19 illness is progressive or sudden clinical deterioration leading to acute respiratory failure and ARDS or multiorgan failure leading to death.
• Patients with COVID-19 illness are also at increased risk of developing prothrombotic complications such as pulmonary embolisms, myocardial infarctions, ischemic strokes, and arterial thrombosis. [55]
• Cardiovascular system involvement results in malignant arrhythmias, cardiomyopathy, and cardiogenic shock.
• GI complications such as bowel ischemia, transaminitis, gastrointestinal bleeding, pancreatitis, Ogilvie syndrome, mesenteric ischemia, and severe ileus are often noted in critically ill patients with COVID-19. [99]
• Acute renal failure is the most common extrapulmonary manifestation of COVID-19 and is associated with an increased mortality risk. [69]
• A meta-analysis study of 14 studies evaluating the prevalence of disseminated intravascular coagulation (DIC) in hospitalized patients with COVID-19 reported that DIC was observed in 3% (95%: 1%-5%, P <0.001) of the included patients. Additionally, DIC was noted to be associated with severe illness and was a poor prognostic indicator. [100]
• More recent data have emerged regarding prolonged symptoms in patients who have recovered from COVID-19 infection, termed "post-acute COVID-19 syndrome." A large cohort study of 1773 patients performed 6 months after hospitalization with COVID-19 revealed that most exhibited at least one persistent symptom: fatigue, muscle weakness, sleep difficulties, or anxiety. Patients with severe illness also had an increased risk of chronic lung issues. [101]
• A retrospective cohort study that included 236,379 patients reported substantial neurological (intracranial hemorrhage, ischemic stroke) and psychiatric morbidity (anxiety disorder, psychotic disorder) 6 months after being diagnosed with COVID-19. [102]
• Secondary invasive fungal infections such as COVID-19-associated pulmonary aspergillosis and rhino-cerebro-orbital mucormycosis have increasingly been reported as complications in patients recovering from COVID-19. Risk factors for developing secondary fungal infection include comorbid conditions such as uncontrolled diabetes, associated lymphopenia, and excessive use of corticosteroids.
• Deterrence and Patient Education

The NIH COVID-19 Treatment Guidelines recommend COVID-19 vaccination as soon as possible for all eligible individuals. The CDC’s Advisory Committee on Immunization Practices (AI) determines eligibility eligibility. Four vaccines are authorized or approved in the United States to prevent COVID-19. According to the NIH guidelines, the preferred vaccines include:[ NIH COVID-19 Treatment Guidelines ]

• mRNA vaccine BNT162b2 (Pfizer-BioNTech)
• mRNA-1273 (Moderna)
• Recombinant spike protein with matrix-M1 adjuvant vaccine NVX-CoV2373 (Novavax)

The adenovirus vector vaccine Ad26.COV2.S (Johnson & Johnson/Janssen) is less preferred due to its risk of serious adverse events.[ NIH COVID-19 Treatment Guidelines ]

A primary series of COVID-19 vaccination is recommended for everyone older than 6 months in the United States. Bivalent mRNA vaccines that protect against the original SARS-CoV-2 virus strain and Omicron subvariants are recommended at least 2 months after receiving the primary vaccine series or a booster dose.[ NIH COVID-19 Treatment Guidelines ] 

• Enhancing Healthcare Team Outcomes

SARS-CoV-2 and its variants continue to cause significant morbidity and mortality worldwide. Prevention and management of this highly transmissible respiratory viral illness require a holistic and interprofessional approach that includes physicians' expertise across specialties, nurses, pharmacists, public health experts, and government authorities. There should be open communication among the clinical providers, pharmacists, and nursing staff while managing patients with COVID-19. Each team member should strive to keep abreast of the latest recommendations and guidelines and be free to speak up if they notice anything that does not comply with the latest tenets for managing COVID patients; there is no place for a hierarchy in communication that prohibits any team member from voicing their concerns. This open interprofessional approach will yield the best outcomes. 

Clinical providers managing COVID-19 patients on the frontlines should keep themselves periodically updated with the latest clinical guidelines about diagnostic and therapeutic options available in managing COVID-19, especially considering the emergence of new SARS-CoV-2 variants, which could significantly impact morbidity and mortality. Continued viral surveillance of new variants is crucial at regular intervals with viral genomic sequencing, given the possibility that more highly transmissible, more virulent, and treatment-resistant variants could emerge that can have a more catastrophic effect on global health in addition to the current scenario. A multi-pronged approach involving interprofessional team members can improve patient care and outcomes for this potentially devastating disease and help the world end this pandemic.

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Disclosure: Marco Cascella declares no relevant financial relationships with ineligible companies.

Disclosure: Michael Rajnik declares no relevant financial relationships with ineligible companies.

Disclosure: Abdul Aleem declares no relevant financial relationships with ineligible companies.

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Disclosure: Raffaela Di Napoli declares no relevant financial relationships with ineligible companies.

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• Cite this Page Cascella M, Rajnik M, Aleem A, et al. Features, Evaluation, and Treatment of Coronavirus (COVID-19) [Updated 2023 Aug 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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Mystery in Japan as dangerous streptococcal infections soar to record levels

Health officials racing to identify cause of rise in streptococcal toxic shock syndrome, which has a 30% fatality rate

Experts warn that a rare but dangerous bacterial infection is spreading at a record rate in Japan , with officials struggling to identify the cause.

The number of cases in 2024 is expected to exceed last year’s record numbers, while concern is growing that the harshest and potentially deadly form of group A streptococcal disease – streptococcal toxic shock syndrome (STSS) – will continue to spread, after the presence of highly virulent and infectious strains were confirmed in Japan.

The National Institute of Infectious Diseases (NIID) said: “There are still many unknown factors regarding the mechanisms behind fulminant (severe and sudden) forms of streptococcus, and we are not at the stage where we can explain them.”

Provisional figures released by the NIID recorded 941 cases of STSS were reported last year. In the first two months of 2024, 378 cases have already been recorded, with infections identified in all but two of Japan’s 47 prefectures.

While older people are considered at greater risk, the group A strain is leading to more deaths among patients under 50, according to NIID. Of the 65 people under 50 who were diagnosed with STSS between July and December in 2023, about a third, or 21, died, the Asahi Shimbun newspaper reported.

Most cases of STSS are caused by a bacterium called streptococcus pyogenes. More commonly known as strep A – it can cause sore throats, mainly in children, and lots of people have it without knowing it and do not become ill.

But the highly contagious bacteria that cause the infection can, in some cases, cause serious illnesses, health complications and death, particularly in adults over 30. About 30% of STSS cases are fatal.

Older people can experience cold-like symptoms but in rare cases, the symptoms can worsen to include strep throat, tonsillitis, pneumonia and meningitis. In the most serious cases it can lead to organ failure and necrosis.

Some experts believe the rapid rise in cases last year were connected to the lifting of restrictions imposed during the coronavirus pandemic.

In May 2023, the government downgraded Covid-19’s status from class two – which includes tuberculosis and Sars – to class five, placing it on a legal par with seasonal flu. The change meant local authorities were no longer able to order infected people to stay away from work or to recommend hospitalisation.

The move also prompted people to lower their guard, in a country where widespread mask wearing, hand sanitising and avoiding the “three Cs” were credited with keeping Covid-19 deaths comparatively low. About 73,000 Covid-19 deaths were recorded compared with more than 220,000 in Britain, which has a population just over half that of Japan.

Ken Kikuchi, a professor of infectious diseases at Tokyo Women’s Medical University, says he is “very concerned” about the dramatic rise this year in the number of patients with severe invasive streptococcal infections.

He believes the reclassification of Covid-19 was the most important factor behind the increase in streptococcus pyogenes infections. This, he added, had led more people to abandon basic measures to prevent infections, such as regular hand disinfection.

“In my opinion, over 50% Japanese people have been infected by Sars-CoV-2 [the virus that causes Covid-19],” Kikuchi tells the Guardian. “People’s immunological status after recovering from Covid-19 might alter their susceptibility to some microorganisms. We need to clarify the infection cycle of severe invasive streptococcal pyogenes diseases and get them under control immediately.”

Streptococcal infections, like those of Covid-19, are spread through droplets and physical contact. The bacterium can also infect patients through wounds on the hands and feet.

Strep A infections are treated with antibiotics, but patients with the more severe invasive group A streptococcal disease are likely to need a combination of antibiotics and other drugs, along with intensive medical attention.

Japan’s health ministry recommends that people take the same basic hygiene precautions against strep A that became a part of everyday life during the coronavirus pandemic.

“We want people to take preventive steps such as keeping your fingers and hands clean, and exercising cough etiquette,” the health minister, Keizo Takemi, told reporters earlier this year, according to the Japan Times.

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