COVID-19 is currently a global pandemic, but human immune responses to the virus remain poorly understood. We analyzed 125 COVID-19 patients, and compared recovered to healthy individuals using high dimensional cytometry. Integrated analysis of ~200 immune and ~50 clinical features revealed activation of T cell and B cell subsets in a proportion of patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses reaching >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable to uninfected subjects. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. These analyses identified three “immunotypes” associated with poor clinical trajectories versus improving health. These immunotypes may have implications for the design of therapeutics and vaccines for COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality worldwide. Community-level immunity, acquired through infection or vaccination, is necessary to control the pandemic as the virus continues to circulate (1). mRNA vaccines encoding a stabilized version of the full-length SARS-CoV-2 Spike protein have been widely administered and clinical trial data demonstrated up to 95% efficacy in preventing symptomatic COVID-19 (2, 3). These mRNA vaccines induce potent humoral immune responses, with neutralizing antibody titers proposed as the major correlate of protection (4-6). Current evidence suggests that circulating antibodies persist for at least 6 months post-vaccination (7), though there is some decay from peak levels achieved after the second dose. This decline from peak antibody levels may be associated with an increase in infections over time compared to the initial months post-vaccination (8, 9). Yet, vaccine-induced immunity remains highly effective at preventing severe disease, hospitalization, and death even at later timepoints when antibody levels may decline (10)(11)(12).Previous research has largely focused on responses early in the course of vaccination, with transcriptional analysis identifying potential links between myeloid cell responses and neutralizing antibodies (13).

Pediatric COVID-19 following SARS-CoV-2 infection is associated with fewer hospitalizations and often milder disease than in adults. A subset of children, however, present with Multisystem Inflammatory Syndrome in Children (MIS-C) that can lead to vascular complications and shock, but rarely death. The immune features of MIS-C compared to pediatric COVID-19 or adult disease remain poorly understood. We analyzed peripheral blood immune responses in hospitalized SARS-CoV-2 infected pediatric patients (pediatric COVID-19) and patients with MIS-C. MIS-C patients had patterns of T cell-biased lymphopenia and T cell activation similar to severely ill adults, and all patients with MIS-C had SARS-CoV-2 spike-specific antibodies at admission. A distinct feature of MIS-C patients was robust activation of vascular patrolling CX3CR1+ CD8+ T cells that correlated with the use of vasoactive medication. Finally, whereas pediatric COVID-19 patients with acute respiratory distress syndrome (ARDS) had sustained immune activation, MIS-C patients displayed clinical improvement over time, concomitant with decreasing immune activation. Thus, non-MIS-C versus MIS-C SARS-CoV-2 associated illnesses are characterized by divergent immune signatures that are temporally distinct from one another and implicate CD8+ T cells in the clinical presentation and trajectory of MIS-C.

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BackgroundPsoriasis is a chronic inflammatory autoimmune skin disorder. Several studies suggested psoriasis to be a complex multifactorial disease, but the exact triggering factor is yet to be determined. Evidences suggest that in addition to genetic factors, epigenetic reprogramming is also involved in psoriasis development. Major histopathological features, like increased proliferation and abnormal differentiation of keratinocytes, and immune cell infiltrations are characteristic marks of psoriatic skin lesions. Following therapy, histopathological features as well as aberrant DNA methylation reversed to normal levels. To understand the role of DNA methylation in regulating these crucial histopathologic features, we investigated the genome-wide DNA methylation profile of psoriasis patients with different histopathological features.ResultsGenome-wide DNA methylation profiling of psoriatic and adjacent normal skin tissues identified several novel differentially methylated regions associated with psoriasis. Differentially methylated CpGs were significantly enriched in several psoriasis susceptibility (PSORS) regions and epigenetically regulated the expression of key pathogenic genes, even with low-CpG promoters. Top differentially methylated genes overlapped with PSORS regions including S100A9, SELENBP1, CARD14, KAZN and PTPN22 showed inverse correlation between methylation and gene expression. We identified differentially methylated genes associated with characteristic histopathological features in psoriasis. Psoriatic skin with Munro’s microabscess, a distinctive feature in psoriasis including parakeratosis and neutrophil accumulation at the stratum corneum, was enriched with differentially methylated genes involved in neutrophil chemotaxis. Rete peg elongation and focal hypergranulosis were also associated with epigenetically regulated genes, supporting the reversible nature of these characteristic features during remission and relapse of the lesions.ConclusionOur study, for the first time, indicated the possible involvement of DNA methylation in regulating the cardinal pathophysiological features in psoriasis. Common genes involved in regulation of these pathologies may be used to develop drugs for better clinical management of psoriasis.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0541-9) contains supplementary material, which is available to authorized users.