Dataset Information

Increased Complement Receptor-3 levels in monocytes and granulocytes distinguish COVID-19 patients with pneumonia from those with mild symptoms.

ABSTRACT:

Background

The reasons why some patients with COVID-19 develop pneumonia and others do not are unclear. To better understand this, we used multiparameter flow cytometry to profile circulating leukocytes from non-immunocompromised adult patients with PCR-proven COVID-19 and specifically compared those with mild symptoms with those who had developed pneumonia.

Methods

Using clinically validated antibody panels we studied leukocytes from 29 patients with PCR-proven COVID-19. Ten were hypoxic requiring ventilatory support, eleven were febrile but otherwise well, and eight were convalescing having previously required ventilatory support. Additionally, we analysed patients who did not have COVID-19 but received ventilatory support for other reasons. We examined routine Full Blood Count (FBC) specimens that were surplus to routine diagnostic requirements; normal ranges were established in a historic group of healthy volunteers.

Findings

We observed striking and unexpected differences in cells of the innate immune system. Levels of CD11b and CD18, which together comprise Complement Receptor 3 (CR3), were increased in granulocytes and monocytes from hypoxic COVID-19 patients, but not in those with COVID-19 who remained well, or in those without COVID-19 but ventilated for other reasons. Granulocyte and monocyte numbers were unchanged, however Natural Killer (NK) cell numbers were two-fold higher than normal in COVID-19 patients who remained well.

Interpretation

CR3 is central to leukocyte activation and subsequent cytokine release in response to infection. It is also a fibrinogen receptor, and its over-expression in granulocytes and monocytes of patients with respiratory failure tables it as a candidate effector of both the thrombotic and inflammatory features of COVID-19 pneumonia, and both a biomarker of impending respiratory failure and potential therapeutic target. NK cells are innate immune cells that retain immunological memory. Rapid expansion of memory NK cells targeting common antigens shared with other Coronaviruses may explain why most patients with COVID-19 do not develop respiratory complications. Understanding the innate immune response to SARS-CoV-may uncover why most infected individuals experience mild symptoms, and inform a preventive approach to COVID-19 pneumonia in the future.

SUBMITTER: Gupta R

PROVIDER: S-EPMC7836814 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Increased Complement Receptor-3 levels in monocytes and granulocytes distinguish COVID-19 patients with pneumonia from those with mild symptoms.

Gupta Rajeev R Gant Vanya Alasdair VA Williams Bryan B Enver Tariq T

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 20200806

<h4>Background</h4>The reasons why some patients with COVID-19 develop pneumonia and others do not are unclear. To better understand this, we used multiparameter flow cytometry to profile circulating leukocytes from non-immunocompromised adult patients with PCR-proven COVID-19 and specifically compared those with mild symptoms with those who had developed pneumonia.<h4>Methods</h4>Using clinically validated antibody panels we studied leukocytes from 29 patients with PCR-proven COVID-19. Ten were ...[more]

PMID: 32771640

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Project description:BackgroundEmerging evidence argues that monocytes, circulating innate immune cells, are principal players in COVID-19 pneumonia. The study aimed to investigate the role of soluble (s)CD163 and sCD14 plasmatic levels in predicting disease severity and characterize peripheral blood monocytes and dendritic cells (DCs), in patients with COVID-19 pneumonia (COVID-19 subjects).MethodsOn admission, in COVID-19 subjects sCD163 and sCD14 plasmatic levels, and peripheral blood monocyte and DC subsets were compared to healthy donors (HDs). According to clinical outcome, COVID-19 subjects were divided into ARDS and non-ARDS groups.ResultsCompared to HDs, COVID-19 subjects showed higher sCD163 (p<0.0001) and sCD14 (p<0.0001) plasmatic levels. We observed higher sCD163 plasmatic levels in the ARDS group compared to the non-ARDS one (p=0.002). The cut-off for sCD163 plasmatic level greater than 2032 ng/ml was predictive of disease severity (AUC: 0.6786, p=0.0022; sensitivity 56.7% [CI: 44.1-68.4] specificity 73.8% [CI: 58.9-84.7]). Positive correlation between plasmatic levels of sCD163, LDH and IL-6 and between plasmatic levels of sCD14, D-dimer and ferritin were found. Compared to HDs, COVID-19 subjects showed lower percentages of non-classical (p=0.0012) and intermediate monocytes (p=0.0447), slanDCs (p<0.0001), myeloid DCs (mDCs, p<0.0001), and plasmacytoid DCs (pDCs, p=0.0014). Compared to the non-ARDS group, the ARDS group showed lower percentages of non-classical monocytes (p=0.0006), mDCs (p=0.0346), and pDCs (p=0.0492).ConclusionsThe increase in sCD163 and sCD14 plasmatic levels, observed on hospital admission in COVID-19 subjects, especially in those who developed ARDS, and the correlations of these monocyte/macrophage activation markers with typical inflammatory markers of COVID-19 pneumonia, underline their potential use to assess the risk of progression of the disease. In an early stage of the disease, the assessment of sCD163 plasmatic levels could have clinical utility in predicting the severity of COVID-19 pneumonia.

Dataset Information

Increased Complement Receptor-3 levels in monocytes and granulocytes distinguish COVID-19 patients with pneumonia from those with mild symptoms.

Background

Methods

Findings

Interpretation

Publications

Increased Complement Receptor-3 levels in monocytes and granulocytes distinguish COVID-19 patients with pneumonia from those with mild symptoms.

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