Lena Radler

SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. Here, we systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in unexposed individuals, exposed family members, and individuals with acute or convalescent COVID-19. Acute-phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent-phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits broadly directed and functionally replete memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19.

immunotypes associated with poor clinical outcome. MAIT cell levels normalized in the convalescent phase, consistent with dynamic recruitment to the tissues and later release back into the circulation when disease is resolved. These findings indicate that MAIT cells are engaged in the immune response against SARS-CoV-2 and suggest their possible involvement in COVID-19 immunopathogenesis.

Dendritic cells (DCs) and monocytes are crucial mediators of innate and adaptive immune responses during viral infection, but misdirected responses by these cells may contribute to immunopathology. Here, we performed high-dimensional flow cytometry-analysis focusing on mononuclear phagocyte (MNP) lineages in SARS-CoV-2-infected patients with moderate and severe COVID-19. We provide a deep and comprehensive map of the MNP landscape in COVID-19. A redistribution of monocyte subsets toward intermediate monocytes and a general decrease in circulating DCs was observed in response to infection. Severe disease coincided with the appearance of monocytic myeloid-derived suppressor cell-like cells and a higher frequency of pre-DC2. Furthermore, phenotypic alterations in MNPs, and their late precursors, were cell-lineage-specific and associated either with the general response against SARS-CoV-2 or COVID-19 severity. This included an interferon-imprint in DC1s observed in all patients and a decreased expression of the coinhibitory molecule CD200R in pre-DCs, DC2s, and DC3 subsets of severely sick patients. Finally, unsupervised analysis revealed that the MNP profile, alone, pointed to a cluster of COVID-19 nonsurvivors. This study provides a reference for the MNP response to SARS-CoV-2 infection and unravels mononuclear phagocyte dysregulations associated with severe COVID-19.

BACKGROUND: Lack of reactivity to the tuberculin skin test (TST) is widely observed in individuals with advanced human immunodeficiency virus type 1 (HIV-1) infection. METHODS: Biopsy specimens from the TST reaction site and from skin not infiltrated with purified protein derivative were obtained from 15 HIV-1-infected and 23 uninfected persons who did not have active tuberculosis and who were from a community in which the incidence of tuberculosis was very high. Histologic sections (size, 8 mum) were immunohistochemically stained for CD4, CD8, CD28, CD45RA, CD45RO, CD62L, CD1a, human leukocyte antigen (HLA)-DR, granulysin, interferon-gamma, and FoxP3 and were analyzed by single-cell in situ digital imaging. Peripheral blood mononuclear cells were analyzed using a fluorescence-activated cell sorter. RESULTS: Biopsy specimens obtained from TST-reactive skin of HIV-1-infected persons demonstrated fewer CD4(+) T cells at the TST site (P = .36) but more HLA-DR(+) T cells (P = .037) than did such biopsy specimens obtained from HIV-1-uninfected persons. Among HIV-1-infected persons, the total number of cells (P = .008) and numbers of CD45RO(+) memory T cells (P = .003) were significantly higher in TST-reactive persons than in TST-unreactive persons. For HIV-1-infected persons, TST induration was inversely correlated with the numbers of FoxP3(+) T cells in the blood (P = .026) but was unrelated to the number of circulating CD4(+) T cells. CONCLUSIONS: For HIV-1 infected persons, the TST depends on memory T cells and is more strongly associated with the numbers of circulating FoxP3(+)CD4(+) T cells than with the total number of CD4(+) T cells.

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe disease with increased morbidity and mortality among certain risk groups. The presence of autoantibodies against type I interferons (aIFN-Abs) is one mechanism that contributes to severe coronavirus disease 2019 (COVID-19). METHODS: This study aimed to investigate the presence of aIFN-Abs in relation to the soluble proteome, circulating immune cell numbers, and cellular phenotypes, as well as development of adaptive immunity. RESULTS: aIFN-Abs were more prevalent in critical compared to severe COVID-19 but largely absent in the other viral and bacterial infections studied here. The antibody and T-cell response to SARS-CoV-2 remained largely unaffected by the presence aIFN-Abs. Similarly, the inflammatory response in COVID-19 was comparable in individuals with and without aIFN-Abs. Instead, presence of aIFN-Abs had an impact on cellular immune system composition and skewing of cellular immune pathways. CONCLUSIONS: Our data suggest that aIFN-Abs do not significantly influence development of adaptive immunity but covary with alterations in immune cell numbers.