SARS-CoV-2 infection and persistence throughout the human body and brain

Chertow, Daniel S.; Stein, Sydney; Ramelli, Sabrina; Grazioli, Alison; Chung, Joon‐Yong; Singh, Manmeet; Yinda, Claude Kwe; Winkler, Clayton W.; Dickey, James P.; Ylaya, Kris; Ko, Sung Hee; Platt, Andrew; Burbelo, Peter D.; Quezado, Martha; Pittaluga, Stefania; Purcell, Madeleine; Munster, Vincent J.; Belinky, Frida; Ramos‐Benitez, Marcos J.; Boritz, Eli; Herr, Daniel; Rabin, Joseph; Saharia, Kapil; Madathil, Ronson J.; Tabatabai, Ali; Soherwardi, Shahabuddin; McCurdy, M.B.; Peterson, Karin E.; Cohen, Jeffrey I.; Wit, Emmie de; Vannella, Kevin M.; Hewitt, Stephen M.; Kleiner, David E.

doi:10.21203/rs.3.rs-1139035/v1

Cited by 113 publications

(125 citation statements)

References 18 publications

(26 reference statements)

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“…Nevertheless, some studies have observed infiltration of immune cells into the BAL fluid, post-mortem lung tissue acquired from fatal COVID-19 cases, or from individuals undergoing medically necessary procedures 12,14,25,26 . Notably, on autopsy several reports have observed a surprising lack of immune cells infiltrating into extrapulmonary tissues despite the prescience of high levels of virus [27][28][29][30][31] . These data highlight the importance of understanding the early host response in pulmonary and extrapulmonary tissues in the first few days after SARS-CoV-2 infection.…”

Section: Introductionmentioning

confidence: 99%

Mild SARS-CoV-2 infection in rhesus macaques is associated with viral control prior to antigen-specific T cell responses in tissues

Nelson

Namasivayam

Foreman

et al. 2022

Preprint

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SARS-CoV-2 primarily replicates in mucosal sites, and more information is needed about immune responses in infected tissues. We used rhesus macaques to model protective primary immune responses in tissues during mild COVID-19. Viral RNA levels were highest on days 1-2 post-infection and fell precipitously thereafter. 18F-fluorodeoxyglucose (FDG)-avid lung abnormalities and interferon (IFN)-activated myeloid cells in the bronchoalveolar lavage (BAL) were found on days ~3-4. Virus-specific effector CD8 and CD4 T cells were detectable in the BAL and lung tissue on days ~7-10, after viral RNA, lung inflammation, and IFN-activated myeloid cells had declined. Notably, SARS-CoV-2-specific T cells were not detectable in the nasal turbinates, salivary glands, and tonsils on day 10 post-infection. Thus, SARS-CoV-2 replication wanes in the lungs prior to T cell responses, and in the nasal and oral mucosa despite the apparent lack of Ag-specific T cells, suggesting that innate immunity efficiently restricts viral replication during mild COVID-19.

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Section: Introductionmentioning

confidence: 99%

Mild SARS-CoV-2 infection in rhesus macaques is associated with viral control prior to antigen-specific T cell responses in tissues

Nelson

Namasivayam

Foreman

et al. 2022

Preprint

Self Cite

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“…Evidence for systemic SARS-CoV-2 infection was provided from the complete autopsies of 44 patients with COVID-19 and demonstrated SARS-CoV-2 distribution, replication, and cell-type specificity throughout the human body. The virus was widely distributed even in deceased patients with asymptomatic to mild COVID-19 30 . In fact, viral replication was detected in multiple extrapulmonary tissues and systemic infection persisted for more than several months.…”

Section: Discussionmentioning

confidence: 98%

Immune Response To SARS-Cov-2 In Severe And Long COVID-19

Sumi

Harada

2022

Preprint

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COVID-19 is mild to moderate in otherwise healthy individuals but may nonetheless cause life-threatening disease and/or a wide range of persistent symptoms. The general determinant of disease severity is age mainly because the immune response declines in aging patients. Here, we developed a mathematical model of the immune response to SARS-CoV-2 and revealed that typical age-related risk factors such as only a several 10 % decrease in innate immune cell activity and inhibition of type-I interferon signaling by autoantibodies drastically increased the viral load. It was reported that the numbers of certain dendritic cell subsets remained less than half those in healthy donors even seven months after infection. Hence, the inflammatory response was ongoing. Our model predicted the persistent DC reduction and showed that certain patients with severe and even mild symptoms could not effectively eliminate the virus and could potentially develop long COVID.

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“…24,27 Furthermore, CNS infection can persist, lasting up to 230 days. 24 Overall, neuroinvasion of SARS-CoV-2 raises the concern for acute or chronic neurodegeneration via damaging neuroinflammation in children with MtD. 28…”

Section: Discussionmentioning

confidence: 99%

Undiagnosed COVID-19 in households with a child with mitochondrial disease

Gordon-Lipkin

Marcum

Kruk

et al. 2022

Preprint

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Background: The impact of the COVID-19 pandemic on medically fragile populations, who are at higher risk of severe illness and sequelae, has not been well characterized. Viral infection is a major cause of morbidity in children with mitochondrial disease (MtD), and the COVID-19 pandemic represents an opportunity to study this vulnerable population. Methods: A convenience sampling cross-sectional serology study was conducted (October 2020 to June 2021) in households (N = 20) containing a child with MtD. Samples (N = 83) were collected in the home using a microsampling apparatus and shipped to investigators. Antibodies against SARS-CoV-2 nucleocapsid (IgG), spike protein (IgG, IgM, IgA), and receptor binding domain (IgG, IgM, IgA) were determined by enzyme linked immunosorbent assay. Results: While only 4.8% of participants were clinically diagnosed for SARS-CoV-2 infection, 75.9% of study participants were seropositive for SARS-CoV-2 antibodies. Most samples were IgM positive for spike or RBD (70%), indicating that infection was recent. This translated to all 20 families showing evidence of infection in at least one household member. For the children with MtD (N = 22), 91% had antibodies against SARS-CoV-2 and had not experienced any adverse outcomes at the time of assessment. For children with recent infections (IgM+ only) serologic data suggest household members as a possible source. Conclusions: COVID-19 was highly prevalent and undiagnosed in households with a child with MtD through the 2020-2021 winter wave of the pandemic. Children with MtD tolerated SARS-CoV-2 infection well, potentially due to household adherence to CDC recommendations for risk mitigation. Funding: This study was funded by the Intramural Research Program of the National Institutes of Health (HG200381-03). Clinical trial number: NCT04419870

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SARS-CoV-2 infection and persistence throughout the human body and brain

Cited by 113 publications

References 18 publications

Mild SARS-CoV-2 infection in rhesus macaques is associated with viral control prior to antigen-specific T cell responses in tissues

Mild SARS-CoV-2 infection in rhesus macaques is associated with viral control prior to antigen-specific T cell responses in tissues

Immune Response To SARS-Cov-2 In Severe And Long COVID-19

Undiagnosed COVID-19 in households with a child with mitochondrial disease

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