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Nat Immunol
. 2023 Sep 4.
doi: 10.1038/s41590-023-01601-2. Online ahead of print. SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC)
Amy D Proal 1 , Michael B VanElzakker 2 3 , Soo Aleman 4 , Katie Bach 2 5 , Brittany P Boribong 6 7 8 , Marcus Buggert 9 , Sara Cherry 10 , Daniel S Chertow 11 12 , Helen E Davies 13 , Christopher L Dupont 14 , Steven G Deeks 15 , William Eimer 8 16 17 18 , E Wesley Ely 19 , Alessio Fasano 6 7 8 , Marcelo Freire 20 , Linda N Geng 21 , Diane E Griffin 22 , Timothy J Henrich 23 , Akiko Iwasaki 24 25 26 , David Izquierdo-Garcia 27 28 , Michela Locci 29 , Saurabh Mehandru 30 31 , Mark M Painter 32 , Michael J Peluso 15 , Etheresia Pretorius 33 34 , David A Price 35 36 , David Putrino 37 , Richard H Scheuermann 38 39 40 , Gene S Tan 14 41 , Rudolph E Tanzi 8 16 17 18 , Henry F VanBrocklin 42 , Lael M Yonker 6 7 8 , E John Wherry 32
Affiliations
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.
. 2023 Sep 4.
doi: 10.1038/s41590-023-01601-2. Online ahead of print. SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC)
Amy D Proal 1 , Michael B VanElzakker 2 3 , Soo Aleman 4 , Katie Bach 2 5 , Brittany P Boribong 6 7 8 , Marcus Buggert 9 , Sara Cherry 10 , Daniel S Chertow 11 12 , Helen E Davies 13 , Christopher L Dupont 14 , Steven G Deeks 15 , William Eimer 8 16 17 18 , E Wesley Ely 19 , Alessio Fasano 6 7 8 , Marcelo Freire 20 , Linda N Geng 21 , Diane E Griffin 22 , Timothy J Henrich 23 , Akiko Iwasaki 24 25 26 , David Izquierdo-Garcia 27 28 , Michela Locci 29 , Saurabh Mehandru 30 31 , Mark M Painter 32 , Michael J Peluso 15 , Etheresia Pretorius 33 34 , David A Price 35 36 , David Putrino 37 , Richard H Scheuermann 38 39 40 , Gene S Tan 14 41 , Rudolph E Tanzi 8 16 17 18 , Henry F VanBrocklin 42 , Lael M Yonker 6 7 8 , E John Wherry 32
Affiliations
- PMID: 37667052
- DOI: 10.1038/s41590-023-01601-2
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.