Biological mechanisms underpinning the development of long COVID
Rubeshan Perumal,
Letitia Shunmugam,
Kogieleum Naidoo,
Dave Wilkins,
Alfredo Garzino-Demo,
Christian Brechot,
Anders Vahlne,
Janko Nikolich
Affiliations
Rubeshan Perumal
South African Medical Research Council (SAMRC)-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban 4001, South Africa; Department of Pulmonology and Critical Care, Division of Internal Medicine, School of Clinical Medicine, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban 4001, South Africa; Department of Immunobiology and the University of Arizona Center on Aging, University of Arizona College of Medicine-Tucson, Tucson, AZ 85724, USA; Corresponding author
Letitia Shunmugam
South African Medical Research Council (SAMRC)-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban 4001, South Africa
Kogieleum Naidoo
South African Medical Research Council (SAMRC)-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban 4001, South Africa
Dave Wilkins
The Global Virus Network, Baltimore, MD 21201, USA
Alfredo Garzino-Demo
The Global Virus Network, Baltimore, MD 21201, USA; Department of Molecular Medicine, University of Padova, Padova 1- 35129, Italy
Christian Brechot
The Global Virus Network, Baltimore, MD 21201, USA; Infectious Disease and International Health, University of South Florida, Tampa, FL 33620, USA
Anders Vahlne
The Global Virus Network, Baltimore, MD 21201, USA; Division of Clinical Microbiology, Karolinska Institute, Stockholm 17165, Sweden
Janko Nikolich
The Global Virus Network, Baltimore, MD 21201, USA; The Aegis Consortium for Pandemic-Free Future, University of Arizona Health Sciences, University of Arizona College of Medicine-Tucson, Tucson, AZ 85724, USA
Summary: As COVID-19 evolves from a pandemic to an endemic disease, the already staggering number of people that have been or will be infected with SARS-CoV-2 is only destined to increase, and the majority of humanity will be infected. It is well understood that COVID-19, like many other viral infections, leaves a significant fraction of the infected with prolonged consequences. Continued high number of SARS-CoV-2 infections, viral evolution with escape from post-infection and vaccinal immunity, and reinfections heighten the potential impact of Long COVID. Hence, the impact of COVID-19 on human health will be seen for years to come until more effective vaccines and pharmaceutical treatments become available. To that effect, it is imperative that the mechanisms underlying the clinical manifestations of Long COVID be elucidated. In this article, we provide an in-depth analysis of the evidence on several potential mechanisms of Long COVID and discuss their relevance to its pathogenesis.
