SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC).

Amy D Proal ,Mark M Painter ,Gene S Tan ,Henry F Vanbrocklin ,Brittany P Boribong ,William A Eimer ,Kathy Bach ,Marcelo Freire ,Sara Cherry ,Daniel S Chertow ,Alessio Fasano ,E Wesley Ely ,Diane E Griffin ,Marcus Buggert ,Saurabh Mehandru ,Michael J Peluso ,Linda N Geng ,Timothy J Henrich ,Rudolph E Tanzi ,Lael M Yonker ,Etheresia Pretorius ,David Izquierdo-García ,David A Price ,Akiko Iwasaki ,Richard H Scheuermann ,Steven G Deeks ,Michela Locci ,Chris L Dupont ,Michael B Vanelzakker ,Soo Aleman ,David Putrino ,Helen Davies ,E John Wherry

doi:10.1038/s41590-023-01601-2

Abstract

Millions of people are suffering from Long COVID or post-acute sequelae of COVID-19 (PASC). Several biological factors have emerged as potential drivers of PASC pathology. Some individuals with PASC may not fully clear the coronavirus SARS-CoV-2 after acute infection. Instead, replicating virus and/or viral RNA-potentially capable of being translated to produce viral proteins-persist in tissue as a 'reservoir'. This reservoir could modulate host immune responses or release viral proteins into the circulation. Here we review studies that have identified SARS-CoV-2 RNA/protein or immune responses indicative of a SARS-CoV-2 reservoir in PASC samples. Mechanisms by which a SARS-CoV-2 reservoir may contribute to PASC pathology, including coagulation, microbiome and neuroimmune abnormalities, are delineated. We identify research priorities to guide the further study of a SARS-CoV-2 reservoir in PASC, with the goal that clinical trials of antivirals or other therapeutics with potential to clear a SARS-CoV-2 reservoir are accelerated.

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