SARS-CoV-2 viral load is associated with increased disease severity and mortality

Fajnzylber, Jesse; Regan, James; Coxen, Kendyll; Corry, Heather; Wong, Colline; Rosenthal, Alexandra; Worrall, Daniel; Giguel, Françoise; Piechocka-Trocha, Alicja; Atyeo, Caroline; Fischinger, Stephanie; Chan, Andrew T.; 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 R.; Tsibris, Athe; Armstrong, Katrina; Kuritzkes, Daniel R.; Alter, Galit; Walker, Bruce D.; Yu, Xu G.; Li, Jonathan Z.; Abayneh, Betelihem A.; Allen, Patrick; Antille, Diane; Balazs, Alejandro; Bals, Julia; Barbash, Max; Bartsch, Yannic C.; Boucau, Julie; Boyce, Siobhan; Braley, Joan; Branch, Kelley R.; Broderick, Katherine; Carney, Julia; Chevalier, Josh; Choudhary, Manish; Chowdhury, Navin; Cordwell, Trevor; Daley, George Q.; Davidson, Susan; Desjardins, Michaël; Donahue, Lauren; Drew, David A.; Einkauf, Kevin; Elizabeth, Sampson; Elliman, Ashley; Etemad, Behzad; Fallon, Jon; Fedirko, Liz; Finn, Kelsey; Flannery, Jeanne; Forde, Pamela; García-Broncano, Pilar; Gettings, Elise; Golan, David; Goodman, Kirsten; Griffin, Amanda; Grimmel, Sheila; Grinke, Kathleen; Hartana, Ciputra Adijaya; Healy, Meg; Heller, Howard M.; Henault, Deborah; Holland, Grace; Jiang, Chenyang; Jordan, Hannah; Kapłonek, Paulina; Karlson, Elizabeth W.; Karpell, Marshall; Kayitesi, Chantal; Lam, Evan C.; LaValle, Vlasta; Lefteri, Kristina; Lian, Xiaodong; Lichterfeld, Mathias; Lingwood, Daniel; Liu, Huan; Liu, Jinqing; Lopez, K. A. J.; Lu, Yuting; Luthern, Sarah; Ly, Ngoc L.; MacGowan, Maureen; Magispoc, Karen; Marchewka, Jordan; Martino, Brittani; McNamara, Roseann; Michell, Ashlin; Millstrom, Ilan; Miranda, Noah; Nambu, Christian; Nelson, Susan C.; Noone, Marjorie; Novack, Lewis A.; O’Callaghan, Claire; Ommerborn, Christine; Osborn, Matthew; Pacheco, Lois Chris; Phan, Nicole; Pillai, Shiv; Porto, Falisha A.; Rassadkina, Yelizaveta; Reissis, Alexandra; Ruzicka, Francis F.; Seiger, Kyra; Selleck, Kathleen; Sessa, Libera; Sharpe, Arlene; Sharr, Christianne; Shin, Sally; Singh, Nishant K.; Slaughenhaupt, Sue; Sheppard, Kimberly Smith; Sun, Weiwei; Sun, Xiaoming; Suschana, Elizabeth; Talabi, Opeyemi; Ticheli, Hannah; Weiss, Scott T.; Wilson, Vivine; Zhu, Alex

doi:10.1038/s41467-020-19057-5

Cited by 771 publications

(673 citation statements)

References 37 publications

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“…However, we found no correlations of TS viral load with death in our study. Such finding was consistent with Fajnzylber et al’s report, in which they recruited severe COVID-19 patients [ 25 ]. The disparities might be related to the disease severity of recruited patients, sampling time and sample number.…”

Section: Discussionsupporting

confidence: 92%

High anal swab viral load predisposes adverse clinical outcomes in severe COVID-19 patients

Ren

Zhang

et al. 2020

Emerging Microbes & Infections

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The pandemic coronavirus disease 2019 (COVID-19) is characterized by systemic infection and multiorgan dysfunction. The association between the kinetics of viral load and clinical outcome in severe COVID-19 patients has not been well established. A retrospective study was performed on clinical specimens from 188 hospitalized severe COVID-19 patients involved in the LOTUS China trial. A total of 578 paired throat swab (TS) and anal swab (AS) samples were collected. Viral load was measured by using quantitative real-time PCR. Viral RNA was detected in 193 (33.4%) TS and 121 (20.9%) AS samples. A higher viral RNA load was found in TS than in AS, with means of 1.0×10 6 and 2.3×10 5 copies/ml, respectively. The median number of days from symptom onset to positive virus detection in AS samples was significantly lower in non-survivors than in survivors (14 days vs 19 days, P=0.007).

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Section: Discussionsupporting

confidence: 92%

High anal swab viral load predisposes adverse clinical outcomes in severe COVID-19 patients

Ren

Zhang

et al. 2020

Emerging Microbes & Infections

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“…One of the potential determinants of the severity of SARS-CoV2 infection is the degree of activation and multiplication of this new emergent virus in human cells [ 8 , 9 ]. The spike protein of SARS-CoV-2 is used by the virus to engage and bind its target cell receptor, the angiotensin converting enzyme 2 (ACE2) [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Sputum ACE2, TMPRSS2 and FURIN gene expression in severe neutrophilic asthma

et al. 2021

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Background Patients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells. Methods We examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels. Results ACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes. Conclusion Levels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma.

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“…Several studies have suggested that cytokine storms and acute respiratory distress syndrome are associated with high levels of proinflammatory cytokines, including very high levels of IL-6, that correlate with the severity of disease [ 42 , 43 ], especially in patients with a high plasma viral load [ 44 ]. Furthermore, COVID-19 patients have a larger number of activated monocytes that infiltrate the lungs and lead to damage [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Nucleocapsid and Spike Proteins of the Coronavirus SARS-CoV-2 Induce IL6 in Monocytes and Macrophages—Potential Implications for Cytokine Storm Syndrome

et al. 2021

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The pandemic of the new coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has led to the deaths of more than 1.5 million people worldwide. SARS-CoV-2 causes COVID-19, which exhibits wide variation in the course of disease in different people, ranging from asymptomatic and mild courses to very severe courses that can result in respiratory failure and death. Despite the rapid progression of knowledge, we still do not know how individual cells of the immune system interact with the virus or its components, or how immune homeostasis becomes disrupted, leading to the rapid deterioration of a patient’s condition. In the present work, we show that SARS-CoV-2 proteins induce the expression and secretion of IL-6 by human monocytes and macrophages, the first line cells of antiviral immune responses. IL-6 may play a negative role in the course of COVID-19 by inhibiting Th1-dependent immunity and stimulating Th17 lymphocytes, thus leading to an increased probability of a cytokine storm.

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SARS-CoV-2 viral load is associated with increased disease severity and mortality

Cited by 771 publications

References 37 publications

High anal swab viral load predisposes adverse clinical outcomes in severe COVID-19 patients

High anal swab viral load predisposes adverse clinical outcomes in severe COVID-19 patients

Sputum ACE2, TMPRSS2 and FURIN gene expression in severe neutrophilic asthma

Nucleocapsid and Spike Proteins of the Coronavirus SARS-CoV-2 Induce IL6 in Monocytes and Macrophages—Potential Implications for Cytokine Storm Syndrome

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