Immunology

Interesting study by Belgian researchers reveals risk factors associated with fatal COVID-19 cases among outbreaks elderly patients in nursing homes. Among…

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been associated with substantial global morbidity and mortality. Despite a tropism that is largely confined to the airways, COVID-19 is associated with multiorgan dysfunction and long-term cognitive pathologies. A major driver of this biology stems from the combined effects of virus-mediated interference with the host antiviral defences in infected cells and the sensing of pathogen-associated material by bystander cells. Such a dynamic results in delayed induction of type I and III interferons (IFN-I and IFN-III) at the site of infection, but systemic IFN-I and IFN-III priming in distal organs and barrier epithelial surfaces, respectively. In this Review, we examine the relationship between SARS-CoV-2 biology and the cellular response to infection, detailing how antagonism and dysregulation of host innate immune defences contribute to disease severity of COVID-19. In this Review, Minkoff and tenOever examine the relationship between SARS-CoV-2 biology and innate immunity, and they explore how antagonism and dysregulation of host innate immune defences contribute to COVID-19 disease severity.

Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are debilitating, clinically heterogeneous and of unknown molecular etiology. A transcriptome-wide investigation was performed in 165 acutely infected hospitalized individuals who were followed clinically into the post-acute period. Distinct gene expression signatures of post-acute sequelae were already present in whole blood during acute infection, with innate and adaptive immune cells implicated in different symptoms. Two clusters of sequelae exhibited divergent plasma-cell-associated gene expression patterns. In one cluster, sequelae associated with higher expression of immunoglobulin-related genes in an anti-spike antibody titer-dependent manner. In the other, sequelae associated independently of these titers with lower expression of immunoglobulin-related genes, indicating lower non-specific antibody production in individuals with these sequelae. This relationship between lower total immunoglobulins and sequelae was validated in an external cohort. Altogether, multiple etiologies of post-acute sequelae were already detectable during SARS-CoV-2 infection, directly linking these sequelae with the acute host response to the virus and providing early insights into their development. Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

T cells specific for SARS-CoV-2 are thought to protect against infection and development of COVID-19, but direct evidence for this is lacking. Here, we associated whole-blood-based measurement of SARS-CoV-2-specific interferon-γ-positive T cell responses with positive COVID-19 diagnostic (PCR and/or lateral flow) test results up to 6 months post-blood sampling. Amongst 148 participants donating venous blood samples, SARS-CoV-2-specific T cell response magnitude is significantly greater in those who remain protected versus those who become infected (P < 0.0001); relatively low magnitude T cell response results in a 43.2% risk of infection, whereas high magnitude reduces this risk to 5.4%. These findings are recapitulated in a further 299 participants testing a scalable capillary blood-based assay that could facilitate the acquisition of population-scale T cell immunity data (14.9% and 4.4%, respectively). Hence, measurement of SARS-CoV-2-specific T cells can prognosticate infection risk and should be assessed when monitoring individual and population immunity status. The presence of SARS-CoV-2-specific antibodies alone is not an accurate determinant of immunity. In this work, the authors investigate if whole-blood based measurement of SARS-CoV-2 specific T cell responses could prognosticate the risk of possible SARS-CoV-2 infection, and recapitulate their findings in a capillary blood-based assay.

Demographics of longitudinal study participants. Peripheral blood samples (HLA-A: 02*01+) were obtained from 24 convalescent donors and 9 healthy donors prior to the FDA emergency use authorization of the Johnson & Johnson, Moderna, and Pfizer COVID-19 vaccines.

COVID-19-associated coagulopathy (CAC) is a life-threatening complication of SARS-CoV-2 infection. However, the underlying cellular and molecular mechanisms driving this condition are unclear. Evidence supports the concept that CAC involves complex interactions between the innate immune response, the coagulation and fibrinolytic pathways, and the vascular endothelium, resulting in a procoagulant condition. Understanding of the pathogenesis of this condition at the genomic, molecular and cellular levels is needed in order to mitigate thrombosis formation in at-risk patients. In this Perspective, we categorize our current understanding of CAC into three main pathological mechanisms: first, vascular endothelial cell dysfunction; second, a hyper-inflammatory immune response; and last, hypercoagulability. Furthermore, we pose key questions and identify research gaps that need to be addressed to better understand CAC, facilitate improved diagnostics and aid in therapeutic development. Finally, we consider the suitability of different animal models to study CAC. Here, the authors consider our emerging understanding of COVID-19-associated coagulopathy. They focus on the complex interactions between innate immune, coagulation and fibrinolytic pathways that can lead to potentially life-threatening thrombosis following SARS-CoV-2 infection.

In an international cohort of 112 children hospitalized for moderate to critical COVID-19 pneumonia, we identified 12 children with one of four known recessive

No AccessNewsRequest AccessFull TextA Role for the Vascular Endothelium in Post–Acute COVID-19? Laura P.M.H. de Rooij , Lisa M. Becker and Peter Carmeliet Originally published16 May 2022https://doi.org/10.1161/CIRCULATIONAHA.122.059231Circulation. 2022;145:1503–1505FootnotesThe opinions expressed...

There is a lack of understanding as to why some people suffer from long-lasting symptoms after COVID-19 infection. A new study from Karolinska Institutet in Sweden, the Helmholtz Center Munich (HMGU) and the Technical University of Munich (TUM), both in Germany, now demonstrates that a certain type of immune cell called macrophages show altered inflammatory and metabolic expression several months after mild COVID-19. The findings are published in the journal Mucosal Immunology.

Host immunity to infection with SARS-CoV-2 is highly variable, dictating diverse clinical outcomes ranging from asymptomatic to severe disease and death. We previously reported reduced type I interferon in severe COVID-19 patients preceded clinical worsening. Further studies identified genetic mutations in loci of the TLR3- or TLR7-dependent interferon-I pathways, or neutralizing interferon-I autoantibodies as risk factors for development of COVID-19 pneumonia. Here we show in patient cohorts with different severities of COVID-19, that baseline plasma interferon α measures differ according to the immunoassay used, timing of sampling, the interferon α subtype measured, and the presence of autoantibodies. We also show a consistently reduced induction of interferon-I proteins in hospitalized COVID-19 patients upon immune stimulation, that is not associated with detectable neutralizing autoantibodies against interferon α or interferon ω. Intracellular proteomic analysis shows increased monocyte numbers in hospitalized COVID-19 patients but impaired interferon-I response after stimulation. We confirm this by ex vivo whole blood stimulation with interferon-I which induces transcriptomic responses associated with inflammation in hospitalized COVID-19 patients, that is not seen in controls or non-hospitalized moderate cases. These results may explain the dichotomy of the poor clinical response to interferon-I based treatments in late stage COVID-19, despite the importance of interferon-I in early acute infection and may guide alternative therapeutic strategies. The interferon response has been shown to be linked to severity of SARS-CoV-2 infection and is an essential component of the immune response to COVID-19. Here the authors stratify patients according to COVID-19 severity and asses the interferon response showing defective responses in severe infection and highlight the importance of assay variables and confounding factors that impact the detection of interferon.

Two and a half years into the COVID-19 pandemic, we have gained many insights into the human antibody response to the causative SARS-CoV-2 virus. In this Review, we summarize key observations of humoral immune responses in people with COVID-19, discuss key features of infection- and vaccine-induced neutralizing antibodies, and consider vaccine designs for inducing antibodies that are broadly protective against different variants of the SARS-CoV-2 virus. Qi et al. provide an in-depth analysis of antibody responses generated in response to SARS-CoV-2.