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Relationship of SARS-CoV-2-specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis coinfection.

ABSTRACT: T cells are involved in control of coronavirus disease 2019 (COVID-19), but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we used flow cytometry to assess the magnitude, function, and phenotype of SARS coronavirus 2-specific (SARS-CoV-2-specific) CD4+ T cells in 95 hospitalized COVID-19 patients, 38 of them being HIV-1 and/or tuberculosis (TB) coinfected, and 38 non-COVID-19 patients. We showed that SARS-CoV-2-specific CD4+ T cell attributes, rather than magnitude, were associated with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity, and enhanced HLA-DR expression. Moreover, HIV-1 and TB coinfection skewed the SARS-CoV-2 T cell response. HIV-1-mediated CD4+ T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2, and a decrease in the polyfunctional capacity of SARS-CoV-2-specific CD4+ T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mycobacterium tuberculosis-specific CD4+ T cells, with possible implications for TB disease progression. These results corroborate the important role of SARS-CoV-2-specific T cells in COVID-19 pathogenesis and support the concept of altered T cell functions in patients with severe disease.

SUBMITTER: Riou C

PROVIDER: S-EPMC8203446 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Although coinfection with influenza in COVID-19 patients has drawn considerable attention, it is still not completely understood whether simultaneously infected with these two viruses influences disease severity. We therefore aimed to estimate the impact of coinfected with SARS-CoV-2 and influenza on the disease outcomes compared with the single infection of SARS-CoV-2. Materials and Methods: We searched the PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure Database (CNKI) to identify relevant articles up to July 9, 2021. Studies that assessed the effect of SARS-CoV-2 and influenza coinfection on disease outcomes or those with sufficient data to calculate risk factors were included. Risk effects were pooled using fixed or random effects model. Results: We ultimately identified 12 studies with 9,498 patients to evaluate the risk effects of SARS-CoV-2 and influenza coinfection on disease severity. Results indicated that coinfection was not significantly associated with mortality (OR = 0.85, 95%CI: 0.51, 1.43; p = 0.55, I 2 = 76.00%). However, mortality was found significantly decreased in the studies from China (OR = 0.51, 95%CI: 0.39, 0.68; I 2 = 26.50%), while significantly increased outside China (OR = 1.56, 95%CI: 1.12, 2.19; I 2 = 1.00%). Moreover, a lower risk for critical outcomes was detected among coinfection patients (OR = 0.64, 95%CI: 0.43, 0.97; p = 0.04, I 2 = 0.00%). Additionally, coinfection patients presented different laboratory indexes compared with the single SARS-CoV-2 infection, including lymphocyte counts and APTT. Conclusion: Our study revealed that coinfection with SARS-CoV-2 and influenza had no effect on overall mortality. However, risk for critical outcomes was lower in coinfection patients and different associations were detected in the studies from different regions and specific laboratory indexes. Further studies on influenza strains and the order of infection were warranted. Systematic testing for influenza coinfection in COVID-19 patients and influenza vaccination should be recommended.

Project description:INTRODUCTION:Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has infected >6 million people worldwide since December 2019. Global reports of HIV/SARS-CoV-2 coinfection are limited. To better understand the impact of the coronavirus disease 2019 (COVID-19) pandemic on persons with HIV and improve their care, we present an outpatient and inpatient clinical experience of HIV/SARS-CoV-2 coinfection from Rhode Island, US. METHODS:We describe outpatient and inpatient preparedness for the COVID-19 pandemic, and present a case series of all known patients with HIV/SARS-CoV-2 coinfection at The Miriam Hospital and Rhode Island Hospital, and The Miriam Hospital Infectious Diseases and Immunology Center, in Providence, Rhode Island, US. RESULTS AND DISCUSSION:The Infectious Diseases and Immunology Center rapidly prepared for outpatient and inpatient care of persons with HIV and SARS-CoV-2. Between 30 March and 20 May 2020, 27 patients with HIV were diagnosed with SARS-CoV-2. Twenty were male, six female and one transgender female; average age was 49 years; 13/27 were Hispanic and 6/27 were African American. All had HIV viral load <200 copies/mL and were on antiretroviral therapy with CD4 count range 87 to 1441 cells/µL. Twenty-six of the 27 had common COVID-19 symptoms for one to twenty-eight days and most had other co-morbidities and/or risk factors. Nine of the 27 were hospitalized for one to thirteen days; of those, three lived in a nursing home, six received remdesivir through a clinical trial or emergency use authorization and tolerated it well; eight recovered and one died. Overall, 17% of known Center people had HIV/SARS-CoV-2 coinfection, whereas the comparable state-wide prevalence was 9%. CONCLUSIONS:We highlight challenges of outpatient and inpatient HIV care in the setting of the COVID-19 pandemic and present the largest detailed case series to date from the United States on HIV/SARS-CoV-2 coinfection, adding to limited global reports. The aggregated clinical findings suggest that the clinical presentation and outcomes of COVID-19 appear consistent with those without HIV. Whether SARS-CoV-2 infection is more frequent among persons with HIV remains to be determined. More data are needed as we develop our understanding of how HIV and antiretroviral therapy are affected by or have an impact on this pandemic.

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Relationship of SARS-CoV-2-specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis coinfection.

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