RESUMEN
OBJECTIVE: Obesity and type 2 diabetes (DM) are risk factors for severe coronavirus disease 2019 (COVID-19) outcomes, which disproportionately affect South Asian populations. This study aims to investigate the humoral and cellular immune responses to SARS-CoV-2 in adult COVID-19 survivors with overweight/obesity (Ov/Ob, BMI ≥â 23 kg/m2) and DM in Bangladesh. METHODS: In this cross-sectional study, SARS-CoV-2-specific antibody and T-cell responses were investigated in 63 healthy and 75 PCR-confirmed COVID-19 recovered individuals in Bangladesh, during the pre-vaccination first wave of the COVID-19 pandemic in 2020. RESULTS: In COVID-19 survivors, SARS-CoV-2 infection induced robust antibody and T-cell responses, which correlated with disease severity. After adjusting for age, sex, DM status, disease severity, and time since onset of symptoms, Ov/Ob was associated with decreased neutralizing antibody titers, and increased SARS-CoV-2 spike-specific IFN-γ response along with increased proliferation and IL-2 production by CD8â +â T cells. In contrast, DM was not associated with SARS-CoV-2-specific antibody and T-cell responses after adjustment for obesity and other confounders. CONCLUSION: Ov/Ob is associated with lower neutralizing antibody levels and higher T-cell responses to SARS-CoV-2 post-COVID-19 recovery, while antibody or T-cell responses remain unaltered in DM.
Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Diabetes Mellitus Tipo 2 , Obesidad , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/complicaciones , Obesidad/inmunología , Obesidad/complicaciones , Masculino , Femenino , SARS-CoV-2/inmunología , Adulto , Estudios Transversales , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Linfocitos T CD8-positivos/inmunología , Linfocitos T/inmunología , Bangladesh , Inmunidad CelularRESUMEN
Interactions with commensal microbes shape host immunity on multiple levels and play a pivotal role in human health and disease. Tissue-dwelling, antigen-specific T cells are poised to respond to local insults, making their phenotype important in the relationship between host and microbes. Here we show that MHC-II restricted, commensal-reactive T cells in the colon of both humans and mice acquire transcriptional and functional characteristics associated with innate-like T cells. This cell population is abundant and conserved in the human and murine colon and endowed with polyfunctional effector properties spanning classic Th1- and Th17-cytokines, cytotoxic molecules, and regulators of epithelial homeostasis. T cells with this phenotype are increased in ulcerative colitis patients, and their presence aggravates pathology in dextran sodium sulphate-treated mice, pointing towards a pathogenic role in colitis. Our findings add to the expanding spectrum of innate-like immune cells positioned at the frontline of intestinal immune surveillance, capable of acting as sentinels of microbes and the local cytokine milieu.
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Escarabajos , Colitis , Humanos , Ratones , Animales , Recuento de Linfocitos , Vigilancia Inmunológica , Colitis/inducido químicamente , CitocinasRESUMEN
The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients.
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Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Inmunidad Humoral/efectos de los fármacos , SARS-CoV-2/efectos de los fármacos , Adenosina Monofosfato/uso terapéutico , Adulto , Alanina/uso terapéutico , Antivirales/uso terapéutico , COVID-19/virología , Fiebre/prevención & control , Humanos , Inmunidad Humoral/inmunología , Recuento de Linfocitos , Masculino , SARS-CoV-2/inmunología , SARS-CoV-2/fisiología , Resultado del TratamientoRESUMEN
MAIT cells are an unconventional T cell population that can be activated through both TCR-dependent and TCR-independent mechanisms. Here, we examined the impact of combinations of TCR-dependent and TCR-independent signals in human CD8+ MAIT cells. TCR-independent activation of these MAIT cells from blood and gut was maximized by extending the panel of cytokines to include TNF-superfamily member TL1A. RNA-seq experiments revealed that TCR-dependent and TCR-independent signals drive MAIT cells to exert overlapping and specific effector functions, affecting both host defense and tissue homeostasis. Although TCR triggering alone is insufficient to drive sustained activation, TCR-triggered MAIT cells showed specific enrichment of tissue-repair functions at the gene and protein levels and in in vitro assays. Altogether, these data indicate the blend of TCR-dependent and TCR-independent signaling to CD8+ MAIT cells may play a role in controlling the balance between healthy and pathological processes of tissue inflammation and repair.