Abstract
Increasing numbers of SARS-CoV-2-positive (SARS-CoV-2pos) subjects are detected at silent SARS-CoV-2 infection stage (SSIS). Yet, SSIS represents a poorly examined time-window wherein unknown immunity patterns may contribute to the fate determination towards persistently asymptomatic or overt disease. Here, we retrieved blood samples from 19 asymptomatic and 12 presymptomatic SARS-CoV-2pos subjects, 47 age/gender-matched patients with mild or moderate COVID-19 and 27 normal subjects, and interrogated them with combined assays of 44-plex CyTOF, RNA-seq and Olink. Notably, both asymptomatic and presymptomatic subjects exhibited numerous readily detectable immunological alterations, while certain parameters including more severely decreased frequencies of CD107alow classical monocytes, intermediate monocytes, non-classical monocytes and CD62Lhi CD8+ Tnaïve cells, reduced plasma STC1 level but an increased frequency of CD4+ NKT cells combined to distinguish the latter. Intercorrelation analyses revealed a particular presymptomatic immunotype mainly manifesting as monocytic overactivation and differentiation blockage, a likely lymphocyte exhaustion and immunosuppression, yielding mechanistic insights into SSIS fate determination, which could potentially improve SARS-CoV-2 management.
Highlights
The pandemic coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become an unprecedented world-wide emergency lasting for over one year, with 185,291,530 global cases including 4,010,834 deaths having been confirmed until 9 July 20211,2
Clinical and general immunological features of SARS-CoV-2pos subjects at the SARS-CoV-2 infection stage (SSIS) We enrolled 31 SARS-CoV-2pos young adults at their SSIS (19 turned out to be persistently asymptomatic subjects as judged by follow-up for > 21 days, and 12 were at presymptomatic stage that later developed into moderate COVID-19), 47 COVID-19 patients at acute phase (23 mild and 24 moderate cases) and 27 healthy donors, and employed combined assays of mass cytometry (CyTOF), RNA sequencing (RNA-seq) and Olink to systemically profile the alterations occurring to their peripheral blood mononuclear cells (PBMCs) and plasma proteins sampled before treatment (Fig. 1a, b and Supplementary information, Table S1)
Consistent with the previous findings,[11] a reduction in white blood cell (WBC) counts mostly attributed to the lymphopenia was seen in the mild and moderate cases but not in the two SSIS groups, with a significantly increased neutrophils to lymphocytes ratio (NLR) only detected in the moderate cases compared to the healthy persons (Fig. 1c)
Summary
The pandemic coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become an unprecedented world-wide emergency lasting for over one year, with 185,291,530 global cases including 4,010,834 deaths having been confirmed until 9 July 20211,2 (https://covid19.who.int). Longitudinal studies showed that approximately three quarters of them virtually were the real asymptomatic cases who, until their SARSCoV-2 test turning to negative, manifested neither COVID-19related symptoms nor CT-confirmed pneumonia with or without receiving nonspecific medication,[3] leaving the rest being presymptomatic cases that would progress into the acute phase. 75.9% of the total SARS-CoV-2 transmission,[4] with the presymptomatic subjects being more infectious.[5] viral detection assay alone is unable to distinguish the presymptomatic cases from the asymptomatic subjects.[3]
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