COVID-19 infection induces readily detectable morphological and inflammation-related phenotypic changes in peripheral blood monocytes, the severity of which correlate with patient outcome

Zhang, Dan; Guo, Rui; Lei, Lei; Liu, Hongjuan; Wang, Yawen; Wang, Yili; Dai, Tongxin; Zhang, Tianxiao; Lai, Yan-Jun; Wang, Jingya; Liu, Zhiqiang; He, Aili; O’Dwyer, Michael; Hu, Jinsong

doi:10.1101/2020.03.24.20042655

Cited by 141 publications

(157 citation statements)

References 26 publications

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“…A significant expansion of populations of CD14 + CD16 + monocytes producing IL-6 was also observed in the peripheral blood of patients with COVID-19 in ICUs compared with those patients who did not require ICU hospitalization 27,28 , a finding also supported by scRNA-seq analysis of peripheral blood mononuclear cells 29 and our personal observations (J.C.M. and R. Josien, unpublished observations).…”

Section: Hyperinflammation In Severe Covid-19supporting

confidence: 73%

Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages

2020

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| The COVID-19 pandemic caused by infection with SARS-CoV-2 has led to more than 200,000 deaths worldwide. Several studies have now established that the hyperinflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. Macrophages are a population of innate immune cells that sense and respond to microbial threats by producing inflammatory molecules that eliminate pathogens and promote tissue repair. However, a dysregulated macrophage response can be damaging to the host, as is seen in the macrophage activation syndrome induced by severe infections, including in infections with the related virus SARS-CoV. Here we describe the potentially pathological roles of macrophages during SARS-CoV-2 infection and discuss ongoing and prospective therapeutic strategies to modulate macrophage activation in patients with COVID-19. volume 20 | June 2020 | 361 nature reviews | ImmunOlOgy P r o g r e s s

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Section: Hyperinflammation In Severe Covid-19supporting

confidence: 73%

Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages

2020

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“…IL-6 and IP-10 are consistently upregulated during a cytokine storm and are associated with severe ARDS 9,10,31,32 . While some studies report inflammatory monocytes as the source of IL-6 9,33,34 , our results suggest that immature neutrophils could also be a non-negligible source of IL-6 during COVID-19-induced cytokine storm. Indeed, neutrophils have been found to produce biologically relevant amounts of IL-6 after engagement of TLR8, a toll like receptor recognising single strand RNAs of viral or bacterial origin 35,36 .…”

Section: Discussioncontrasting

confidence: 65%

Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early prognostic marker for severe COVID-19

Carissimo

Kwok

et al. 2020

Preprint

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39SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 40 pandemic. Severe complications are observed only in a small proportion of infected 41 patients but the cellular mechanisms underlying this progression are still unknown. 42Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients 43 revealed a dramatic increase in the number of immature neutrophils. This increase 44 strongly correlated with disease severity and was associated with elevated IL-6 and 45 IP-10 levels, two key players in the cytokine storm. The most pronounced decrease 46 in cell counts was observed for CD8 T-cells and VD2 γδ T-cells, which both exhibited 47 increased differentiation and activation. ROC analysis revealed that the count ratio of 48 immature neutrophils to CD8 or VD2 T-cells predicts pneumonia onset (0.9071) as 49 well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a 50 useful prognostic marker for preventive patient management and improved 51 healthcare resource management. 52

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“…In this context, it is noteworthy that the replication of SARS-CoV in PBMCs was not sustained for long periods [19,32]. Inflammatory monocytes play a significant role in the immunopathology of COVID-19 [15,16] and ICU patients have high levels of circulating CD14+CD16+ inflammatory monocytes, which correlates with unfavorable outcomes [34,35]. Increased expression of CCR2 and other inflammatory markers by monocytes leads to the infiltration of tissues with high expression of the correspondent CCL2 chemokine [15].…”

Section: Discussionmentioning

confidence: 99%

Infection of human lymphomononuclear cells by SARS-CoV-2

Pontelli

Castro

Martins

et al. 2020

Preprint

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Although SARS-CoV-2 severe infection is associated with a hyperinflammatory state, lymphopenia is an immunological hallmark, and correlates with poor prognosis in COVID-19. However, it remains unknown if circulating human lymphocytes and monocytes are susceptible to SARS-CoV-2 infection. In this study, SARS-CoV-2 infection of human peripheral blood mononuclear cells (PBMCs) was investigated both in vitro and in vivo. We found that in vitro infection of whole PBMCs from healthy donors was productive of virus progeny. Results revealed that monocytes, as well as B and T lymphocytes, are susceptible to SARS-CoV-2 active infection and viral replication was indicated by detection of double-stranded RNA. Moreover, flow cytometry and immunofluorescence analysis revealed that SARS-CoV-2 was frequently detected in monocytes and B lymphocytes from COVID-19 patients, and less frequently in CD4+T lymphocytes. The rates of SARS-CoV-2-infected monocytes in PBMCs from COVID-19 patients increased over time from symptom onset. Additionally, SARS-CoV-2-positive monocytes and B and CD4+T lymphocytes were detected by immunohistochemistry in post mortem lung tissue. SARS-CoV-2 infection of blood circulating leukocytes in COVID-19 patients may have important implications for disease pathogenesis, immune dysfunction, and virus spread within the host.

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COVID-19 infection induces readily detectable morphological and inflammation-related phenotypic changes in peripheral blood monocytes, the severity of which correlate with patient outcome

Abstract: Background:Excessive monocyte/macrophage activation with the development of a cytokine storm and

Cited by 141 publications

References 26 publications

Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages

Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages

Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early prognostic marker for severe COVID-19

Infection of human lymphomononuclear cells by SARS-CoV-2

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