Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing

Abstract

COVID-19, caused by SARS-CoV-2, has recently affected over 1,200,000 people and killed more than 60,000. The key immune cell subsets change and their states during the course of COVID-19 remain unclear. We sought to comprehensively characterize the transcriptional changes in peripheral blood mononuclear cells during the recovery stage of COVID-19 by single-cell RNA sequencing technique. It was found that T cells decreased remarkably, whereas monocytes increased in patients in the early recovery stage (ERS) of COVID-19. There was an increased ratio of classical CD14 ++ monocytes with high inflammatory gene expression as well as a greater abundance of CD14 ++ IL1β + monocytes in the ERS. CD4 + T cells and CD8 + T cells decreased significantly and expressed high levels of inflammatory genes in the ERS. Among the B cells, the plasma cells increased remarkably, whereas the naïve B cells decreased. Several novel B cell-receptor (BCR) changes were identified, such as IGHV3-23 and IGHV3-7, and isotypes (IGHV3-15, IGHV3-30, and IGKV3-11) previously used for virus vaccine development were confirmed. The strongest pairing frequencies, IGHV3-23-IGHJ4, indicated a monoclonal state associated with SARS-CoV-2 specificity, which had not been reported yet. Furthermore, integrated analysis predicted that IL-1β and M-CSF may be novel candidate target genes for inflammatory storm and that TNFSF13, IL-18, IL-2, and IL-4 may be beneficial for the recovery of COVID-19 patients.Our study provides the first evidence of an inflammatory immune signature in the ERS, suggesting COVID-19 patients are still vulnerable after hospital discharge. Identification of novel BCR signaling may lead to the development of vaccines and antibodies for the treatment of COVID-19.

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

“…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 .…”

Harnessing Memory NK Cell to Protect Against COVID-19

“…But, NK cells has been prominently reduced in 59% of the cases (higher incidence rate than others) (Wang et al, 2020b). Accumulating evidence had supported the fact that NK cells had reduced in COVID-19 patients as compared with noninfected cases (Chen G. et al, 2020;Wen et al, 2020;Wilk et al, 2020). Of note, a latter study by Feng Wang et al (Wang et al, 2020a) has been reported that CD4+ T cells were increased in patients with COVID-19, whereas the number of NK cells was decreased in the severe stage of infection.…”

Immune responses to SARS-CoV-2 in children of parents with symptomatic COVID-19

“…Investigating immune responses to SARS-CoV-2 across all age groups is key to understanding disease susceptibility, severity determinants, and vaccine candidates. Detailed investigations of immune responses during SARS-CoV-2 infection have been reported in adults [10][11][12] , with exposure to SARS-CoV-2 causing speci c T cell responses without seroconversion 13 . Data on immune responses in children exposed to SARS-CoV-2 are limited.…”