Severe Acute Respiratory Syndrome Coronavirus 2 Viremia Is Associated With Coronavirus Disease 2019 Severity and Predicts Clinical Outcomes

被引：100

作者：

Jacobs, Jana L. ^{[1
]}

Bain, William ^{[2
,3
,4
]}

Naqvi, Asma ^{[1
]}

Staines, Brittany ^{[1
]}

Castanha, Priscila M. S. ^{[5
]}

Yang, Haopu ^{[2
,6
,7
]}

Boltz, Valerie F. ^{[8
]}

Barratt-Boyes, Simon ^{[5
]}

Marques, Ernesto T. A. ^{[5
]}

Mitchell, Stephanie L. ^{[9
]}

Methe, Barbara ^{[2
,6
]}

Olonisakin, Tolani F. ^{[2
]}

Haidar, Ghady ^{[1
]}

Burke, Thomas W. ^{[10
]}

Petzold, Elizabeth ^{[10
]}

Denny, Thomas ^{[11
]}

Woods, Chris W. ^{[10
,11
]}

McVerry, Bryan J. ^{[2
]}

Lee, Janet S. ^{[2
,3
]}

Watkins, Simon C. ^{[12
]}

St Croix, Claudette M. ^{[12
]}

Morris, Alison ^{[2
,6
]}

Kearney, Mary F. ^{[8
]}

Ladinsky, Mark S. ^{[13
]}

Bjorkman, Pamela J. ^{[13
]}

Kitsios, Georgios D. ^{[2
,3
,6
]}

Mellors, John W. ^{[1
]}

机构：

[1] Univ Pittsburgh, Sch Med, Dept Med, Div Infect Dis, Pittsburgh, PA 15261 USA

[2] Univ Pittsburgh, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15261 USA

[3] Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15261 USA

[4] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA

[5] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA

[6] Univ Pittsburgh, Ctr Med & Microbiome, Dept Med, Pittsburgh, PA 15261 USA

[7] Tsinghua Univ, Sch Med, Beijing, Peoples R China

[8] NCI, HIV Dynam & Replicat Program, Ctr Canc Res, Frederick, MD 21701 USA

[9] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA

[10] Duke Univ, Ctr Appl Genom & Precis Med, Durham, NC USA

[11] Duke Univ, Duke Human Vaccine Inst, Durham, NC USA

[12] Univ Pittsburgh, Dept Cell Biol, Pittsburgh, PA 15261 USA

[13] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA

来源：

CLINICAL INFECTIOUS DISEASES | 2022年 / 74卷 / 09期

关键词：

COVID-19; outcome; SARS-CoV-2; RNAemia; viremia; SARS-COV-2; INFECTION; THERAPY;

D O I：

10.1093/cid/ciab686

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA (vRNA) is detected in the bloodstream of some patients with coronavirus disease 2019 (COVID-19), but it is not clear whether this RNAemia reflects viremia (ie, virus particles) and how it relates to host immune responses and outcomes. Methods. SARS-CoV-2 vRNA was quantified in plasma samples from observational cohorts of 51 COVID-19 patients including 9 outpatients, 19 hospitalized (non-intensive care unit [ICU]), and 23 ICU patients. vRNA levels were compared with cross-sectional indices of COVID-19 severity and prospective clinical outcomes. We used multiple imaging methods to visualize virions in plasma. Results. SARS-CoV-2 vRNA was detected in plasma of 100%, 52.6%, and 11.1% of ICU, non-ICU, and outpatients, respectively. Virions were detected in plasma pellets using electron tomography and immunostaining. Plasma vRNA levels were significantly higher in ICU > non-ICU > outpatients (P < .0001); for inpatients, plasma vRNA levels were strongly associated with higher World Health Organization (WHO) score at admission (P = .01), maximum WHO score (P = .002), and discharge disposition (P = .004). A plasma vRNA level >6000 copies/mL was strongly associated with mortality (hazard ratio, 10.7). Levels of vRNA were significantly associated with several inflammatory biomarkers (P < .01) but not with plasma neutralizing antibody titers (P = .8). Conclusions. Visualization of virus particles in plasma indicates that SARS-CoV-2 RNAemia is due, at least in part, to viremia. The levels of SARS-CoV-2 RNAemia correlate strongly with disease severity, patient outcome, and specific inflammatory biomarkers but not with neutralizing antibody titers.

引用

页码：1525 / 1533

页数：9

共 45 条

[1] A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19 [J].

Lundgren J.D. ;

Grund B. ;

Barkauskas C.E. ;

Holland T.L. ;

Gottlieb R.L. ;

Sandkovsky U. ;

Brown S.M. ;

Knowlton K.U. ;

Self W.H. ;

Files D.C. ;

Jain M.K. ;

Benfield T. ;

Bowdish M.E. ;

Leshnower B.G. ;

Baker J.V. ;

Jensen J.-U. ;

Gardner E.M. ;

Ginde A.A. ;

Harris E.S. ;

Johansen I.S. ;

Markowitz N. ;

Matthay M.A. ;

Østergaard L. ;

Chang C.C. ;

Davey V.J. ;

Goodman A. ;

Higgs E.S. ;

Murray D.D. ;

Murray T.A. ;

Paredes R. ;

Parmar M.K.B. ;

Phillips A.N. ;

Reilly C. ;

Sharma S. ;

Dewar R.L. ;

Teitelbaum M. ;

Wentworth D. ;

Cao H. ;

Klekotka P. ;

Babiker A.G. ;

Gelijns A.C. ;

Kan V.L. ;

Polizzotto M.N. ;

Thompson B.T. ;

Lane H.C. ;

Neaton J.D. .

NEW ENGLAND JOURNAL OF MEDICINE, 2021, 384 (10) :905-914

[2]

Andersson Monique I, 2020, Wellcome Open Res, V5, P181, DOI 10.12688/wellcomeopenres.16002.1

[3]

[Anonymous], 2020, BMJ, DOI 10.1136/BMJ.M3939

[4] Distinct Early Serological Signatures Track with SARS-CoV-2 Survival [J].

Atyeo, Caroline ;

Fischinger, Stephanie ;

Zohar, Tomer ;

Slein, Matthew D. ;

Burke, John ;

Loos, Carolin ;

McCulloch, Denise J. ;

Newman, Kira L. ;

Wolf, Caitlin ;

Yu, Jingyou ;

Shuey, Kiel ;

Feldman, Jared ;

Hauser, Blake Marie ;

Caradonna, Tim ;

Schmidt, Aaron G. ;

Suscovich, Todd J. ;

Linde, Caitlyn ;

Cai, Yongfei ;

Barouch, Dan ;

Ryan, Edward T. ;

Charles, Richelle C. ;

Lauffenburger, Douglas ;

Chu, Helen ;

Alter, Galit .

IMMUNITY, 2020, 53 (03) :524-+

[5] COVID-19 versus Non-COVID-19 Acute Respiratory Distress Syndrome Comparison of Demographics, Physiologic Parameters, Inflammatory Biomarkers, and Clinical Outcomes [J].

Bain, William ;

Yang, Haopu ;

Shah, Faraaz Ali ;

Suber, Tomeka ;

Drohan, Callie ;

Al-Yousif, Nameer ;

DeSensi, Rebecca S. ;

Bensen, Nicole ;

Schaefer, Caitlin ;

Rosborough, Brian R. ;

Somasundaram, Ashwin ;

Workman, Creg J. ;

Lampenfeld, Caleb ;

Cillo, Anthony R. ;

Cardello, Carly ;

Shan, Feng ;

Bruno, Tullia C. ;

Vignali, Dario A. A. ;

Ray, Prabir ;

Ray, Anuradha ;

Zhang, Yingze ;

Lee, Janet S. ;

Methe, Barbara ;

McVerry, Bryan J. ;

Morris, Alison ;

Kitsios, Georgios D. .

ANNALS OF THE AMERICAN THORACIC SOCIETY, 2021, 18 (07) :1202-1210

[6] Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19 [J].

Bermejo-Martin, Jesus F. ;

Gonzalez-Rivera, Milagros ;

Almansa, Raquel ;

Micheloud, Dariela ;

Tedim, Ana P. ;

Dominguez-Gil, Marta ;

Resino, Salvador ;

Martin-Fernandez, Marta ;

Ryan Murua, Pablo ;

Perez-Garcia, Felipe ;

Tamayo, Luis ;

Lopez-Izquierdo, Raul ;

Bustamante, Elena ;

Aldecoa, Cesar ;

Manuel Gomez, Jose ;

Rico-Feijoo, Jesus ;

Orduna, Antonio ;

Mendez, Raul ;

Fernandez Natal, Isabel ;

Megias, Gregoria ;

Gonzalez-Estecha, Montserrat ;

Carriedo, Demetrio ;

Doncel, Cristina ;

Jorge, Noelia ;

Ortega, Alicia ;

de la Fuente, Amanda ;

del Campo, Felix ;

Antonio Fernandez-Ratero, Jose ;

Trapiello, Wysali ;

Gonzalez-Jimenez, Paula ;

Ruiz, Guadalupe ;

Kelvin, Alyson A. ;

Ostadgavahi, Ali Toloue ;

Oneizat, Ruth ;

Maria Ruiz, Luz ;

Miguens, Iria ;

Gargallo, Esther ;

Munoz, Ioana ;

Pelegrin, Sara ;

Martin, Silvia ;

Garcia Olivares, Pablo ;

Antonio Cedeno, Jamil ;

Ruiz Albi, Tomas ;

Puertas, Carolina ;

Angel Berezo, Jose ;

Renedo, Gloria ;

Herran, Ruben ;

Bustamante-Munguira, Juan ;

Enriquez, Pedro ;

Cicuendez, Ramon .

CRITICAL CARE, 2020, 24 (01)

[7] Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19 [J].

Bernard, Isabelle ;

Limonta, Daniel ;

Mahal, Lara K. ;

Hobman, Tom C. .

VIRUSES-BASEL, 2021, 13 (01)

[8] Detectable Serum Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load (RNAemia) Is Closely Correlated With Drastically Elevated Interleukin 6 Level in Critically Ill Patients With Coronavirus Disease 2019 [J].

Chen, Xiaohua ;

Zhao, Binghong ;

Qu, Yueming ;

Chen, Yurou ;

Xiong, Jie ;

Feng, Yong ;

Men, Dong ;

Huang, Qianchuan ;

Liu, Ying ;

Yang, Bo ;

Ding, Jinya ;

Li, Feng .

CLINICAL INFECTIOUS DISEASES, 2020, 71 (08) :1937-1942

[9]

Consortium IC, 4C MORT 4C DET CALC

[10] SARS-CoV-2 viral load is associated with increased disease severity and mortality [J].

Fajnzylber, Jesse ;

Regan, James ;

Coxen, Kendyll ;

Corry, Heather ;

Wong, Colline ;

Rosenthal, Alexandra ;

Worrall, Daniel ;

Giguel, Francoise ;

Piechocka-Trocha, Alicja ;

Atyeo, Caroline ;

Fischinger, Stephanie ;

Chan, Andrew ;

Flaherty, Keith T. ;

Hall, Kathryn ;

Dougan, Michael ;

Ryan, Edward T. ;

Gillespie, Elizabeth ;

Chishti, Rida ;

Li, Yijia ;

Jilg, Nikolaus ;

Hanidziar, Dusan ;

Baron, Rebecca M. ;

Baden, Lindsey ;

Tsibris, Athe M. ;

Armstrong, Katrina A. ;

Kuritzkes, Daniel R. ;

Alter, Galit ;

Walker, Bruce D. ;

Yu, Xu ;

Li, Jonathan Z. .

NATURE COMMUNICATIONS, 2020, 11 (01)

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