Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19

Abstract

The coronavirus disease 2019 outbreak is an ongoing global health emergence, but the pathogenesis remains unclear. We revealed blood cell immune response profiles using 5' mRNA, TCR and BCR V(D)J transcriptome analysis with single-cell resolution. Data from 134,620 PBMCs and 83,387 TCR and 12,601 BCR clones was obtained, and 56 blood cell subtypes and 23 new cell marker genes were identified from 16 participants. The number of specific subtypes of immune cells changed significantly when compared patients with controls. Activation of the interferon-MAPK pathway is the major defense mechanism, but MAPK transcription signaling is inhibited in cured patients. TCR and BCR V(D)J recombination is highly diverse in generating different antibodies against SARS-CoV-2. Therefore, the interferon-MAPK pathway and TCR-and BCR-produced antibodies play important roles in the COVID-19 immune response. Immune deficiency or immune overresponse may result in the condition of patients with COVID-19 becoming critical or severe.

Dissecting the common and compartment-specific features of COVID-19 severity in the lung and periphery with single-cell resolution

“…Cell type-specific immunopathological responses in severe COVID-19 have been investigated at both local and systemic levels in recent studies comparing severe patients to healthy controls [21,22,23,24,25,26,32,53,54,55]. We sought to build on this knowledge by determining the cell-type specific biological responses that differentiate mild and severe disease courses in the lung and systemic circulation.…”

“…A number of recent studies have compared severe patients to healthy control subjects in an effort to define immunological hallmarks of disease severity in both the lung and peripheral circulation using scRNA-seq. These studies have identified that severe disease in the lung compartment is associated with lymphopenia, T cell hyperactivation, and inflammatory macrophage polarization, while severe disease in the blood is associated with lymphopenia, suppression of type I and type II interferon activity, and decreased monocyte HLA class II expression [23,24,25,26]. Although these studies describe immunological dysregulation in severe COVID-19 patients requiring intensive care, they do not explore immunological features distinguishing these patients from those who experience a mild to moderate symptomatic disease course that does not become life-threatening.…”

COVID-19 pandemic control: balancing detection policy and lockdown intervention under ICU sustainability

“…A short range one, that can detect, at time if someone is infected, or not (Polymerase chain reaction or PCR tests, that can detect whether an individual is infected and send her/him in quarantine). And a long range one, that can detect if someone is immune or not (a blood test as in Huang et al (2020)). For this purpose, we introduced a so-called +/− propagation model for the epidemic, which explicitly allows to take into account the detection ratios of immune and infected individuals.…”

Comparative Genomic Analysis of Rapidly Evolving SARS-CoV-2 Viruses Reveal Mosaic Pattern of Phylogeographical Distribution

“…We identified mitogen activated protein kinase 1 291 (MAPK1) and AKT proteins as major hubs forming 24 and 21 interactions in the network 292 respectively, highlighting their crucial role in pathogenesis. Recently, Huang et al,293 demonstrated the role of Mitogen activated protein kinase (MAPK) in COVID-19 mediated 294 blood immune responses in infected patients [53] and showed that MAPK activation certainly 295 plays a major defense mechanism. 296 Gene Ontology based functional annotation studies predicted the role of direct interactions of 297 several viral proteins with host proteins.…”