2020
DOI: 10.1038/s41586-020-2588-y
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Longitudinal analyses reveal immunological misfiring in severe COVID-19

Abstract: Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19) 1 – 4 . However, the longitudinal immunological correlates of disease outcome remain unclear. Here we serially analysed immune responses in 113 patients with moderate or severe COVID-19. Immune profiling revealed an overall increase in innate cell lineages, with a concomitant reduction in T cell number. An early elevation in cytokine levels was associated with… Show more

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Cited by 1,951 publications
(2,536 citation statements)
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References 32 publications
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“…7 Although the role of elastase in SARS-CoV-2 entry has not been elucidated, elevation of neutrophil counts in BAL and serum have been consistently associated with severe COVID-19 cases. [18][19][20] In spite of its name, AAT has a stronger binding affinity to elastase than trypsin, and this is borne out by the clinically significant sequalae associated with AAT deficiency.…”
Section: The Suspected Roles Of Protease Inhibitors As Uncharacterizementioning
confidence: 99%
“…7 Although the role of elastase in SARS-CoV-2 entry has not been elucidated, elevation of neutrophil counts in BAL and serum have been consistently associated with severe COVID-19 cases. [18][19][20] In spite of its name, AAT has a stronger binding affinity to elastase than trypsin, and this is borne out by the clinically significant sequalae associated with AAT deficiency.…”
Section: The Suspected Roles Of Protease Inhibitors As Uncharacterizementioning
confidence: 99%
“…Independently, reports using peripheral blood from large numbers of COVID-19 patients have consistently documented lymphopenia (reduced lymphocyte frequency) paired with increased monocytes and inflammatory cytokines [5][6][7] . Recent data suggest that moderate COVID-19 patients recovery associates with elevated tissue healing programs and lymphocyte growth factors, where severe patients maintain increased monocyte levels in blood and specific cytokines such as IFN-", IFN-!, and TNF, which appear ineffective in lowering viral load while possibly contributing to cytokine release syndrome (CRS) pathology 7 . Together, these studies indicate the importance of uncovering the full extent of cell states present in COVID-19 patients including within affected tissues, in particular for monocytes and macrophages.…”
Section: Introductionmentioning
confidence: 96%
“…An exacerbated pro-inflammatory immune response generated by the host has been proposed to be responsible for the symptoms observed in patients [1–3]. Numerous studies have correlated the nature and extent of the immune response with the severity of the disease [4–6]. While many countries have succeeded in curtailing the first wave of infection, there is growing evidence that a second wave of infection is expected to take place and has even already started in some countries.…”
Section: Introductionmentioning
confidence: 99%