Low pre-existing endemic human coronavirus (HCoV-NL63)-specific T cell frequencies are associated with impaired SARS-CoV-2-specific T cell responses in people living with HIV

Background: Understanding how HIV affects SARS-CoV-2 immunity is crucial for managing COVID-19 in sub-Saharan populations due to frequent coinfections. Our previous research showed that unsuppressed HIV is associated with weaker immune responses to SARS-CoV-2, but the underlying mechanisms are unclear. We investigated how pre-existing T cell immunity against an endemic human coronavirus HCoV-NL63 impacts SARS-CoV-2 T cell responses in people living with HIV (PLWH) compared to uninfected individuals, and how HIV-related T cell dysfunction influences responses to SARS-CoV-2 variants. Methods: We used flow cytometry to measure T cell responses following PBMC stimulation with peptide pools representing beta, delta, wild-type, and HCoV-NL63 spike proteins. Luminex bead assay was used to measure circulating plasma chemokine and cytokine levels. ELISA and MSD V-PLEX COVID-19 Serology and ACE2 Neutralization assays were used to measure humoral responses. Results: Regardless of HIV status, we found a strong positive correlation between responses to HCoV-NL63 and SARS-CoV-2. However, PLWH exhibited weaker CD4+ T cell responses to both HCoV-NL63 and SARS-CoV-2 than HIV-uninfected individuals. PLWH also had higher proportions of functionally exhausted (PD-1high) CD4+ T cells producing fewer proinflammatory cytokines (IFNγ and TNFα) and had elevated plasma IL-2 and IL-12(p70) levels compared to HIV-uninfected individuals. HIV status didn’t significantly affect IgG antibody levels against SARS-CoV-2 antigens or ACE2 binding inhibition activity. Conclusion: Our results indicate that the decrease in SARS-CoV-2 specific T cell responses in PLWH may be attributable to reduced frequencies of pre-existing cross-reactive responses. However, HIV infection minimally affected the quality and magnitude of humoral responses, and this could explain why the risk of severe COVID-19 in PLWH is highly heterogeneous

Developing and validating a screening tool for female genital schistosomiasis in urban Zambia

BackgroundThe World Health Organization estimates that 56 million women and girls live with female genital schistosomiasis (FGS) in sub-Saharan Africa. FGS is often confused with symptoms of other genital abnormalities, and gold standard diagnosis with colposcopy is infeasible in most health facilities. Schistosomiasis haematobium is endemic in Zambia, yet routine screening or diagnostic efforts for FGS remain unavailable. Our study aimed to develop and pilot test a feasible FGS screening algorithm to implement in Zambian government clinics.Methodology/Principal FindingsWe recruited 499 women from a longitudinal cohort of HIV-negative adult women in Lusaka and Ndola, Zambia. We used demographic, risk factor, and symptom data collected from standardized surveys, gynecological exams, and laboratory tests to develop a screening algorithm for FGS among a derivation cohort (n=349). After cross-validation using 5-fold iterative resampling, the algorithm was applied in a holdout sample of the cohort (n=150). The prevalence of FGS (ascertained by expert review) was 23.4% in the study population. The screening algorithm included childhood and travel exposure to rivers and streams; testing positive for visual inspection of the cervix with acetic acid; hematuria; reporting less than the median average age at sexual debut (<17 years); when asked what diseases can be transmitted via freshwater exposure, reporting ‘none’; being born outside of Lusaka or Copperbelt Province; and reporting occupation as ‘Housekeeper’. The screening algorithm had reasonable discrimination in the derivation cohort (area under the curve [AUC]=0.69, 95% confidence interval [CI]: 0.66-0.79, p-value<0.001). Using a score cut off ≥ 2 the risk algorithm in the derivation cohort had 77% sensitivity, 48% specificity, 35% positive predictive value, and 85% negative predictive value.Conclusions/SignificanceGiven the prevalence of FGS and associated morbidities, improved screening for FGS is imperative. We developed a simple screening algorithm to improve the diagnosis and treatment of FGS among adult women in Zambian government clinics

DataSheet_1_Low pre-existing endemic human coronavirus (HCoV-NL63)-specific T cell frequencies are associated with impaired SARS-CoV-2-specific T cell responses in people living with HIV.pdf

BackgroundUnderstanding how HIV affects SARS-CoV-2 immunity is crucial for managing COVID-19 in sub-Saharan populations due to frequent coinfections. Our previous research showed that unsuppressed HIV is associated with weaker immune responses to SARS-CoV-2, but the underlying mechanisms are unclear. We investigated how pre-existing T cell immunity against an endemic human coronavirus HCoV-NL63 impacts SARS-CoV-2 T cell responses in people living with HIV (PLWH) compared to uninfected individuals, and how HIV-related T cell dysfunction influences responses to SARS-CoV-2 variants.MethodsWe used flow cytometry to measure T cell responses following PBMC stimulation with peptide pools representing beta, delta, wild-type, and HCoV-NL63 spike proteins. Luminex bead assay was used to measure circulating plasma chemokine and cytokine levels. ELISA and MSD V-PLEX COVID-19 Serology and ACE2 Neutralization assays were used to measure humoral responses.ResultsRegardless of HIV status, we found a strong positive correlation between responses to HCoV-NL63 and SARS-CoV-2. However, PLWH exhibited weaker CD4+ T cell responses to both HCoV-NL63 and SARS-CoV-2 than HIV-uninfected individuals. PLWH also had higher proportions of functionally exhausted (PD-1high) CD4+ T cells producing fewer proinflammatory cytokines (IFNγ and TNFα) and had elevated plasma IL-2 and IL-12(p70) levels compared to HIV-uninfected individuals. HIV status didn’t significantly affect IgG antibody levels against SARS-CoV-2 antigens or ACE2 binding inhibition activity.ConclusionOur results indicate that the decrease in SARS-CoV-2 specific T cell responses in PLWH may be attributable to reduced frequencies of pre-existing cross-reactive responses. However, HIV infection minimally affected the quality and magnitude of humoral responses, and this could explain why the risk of severe COVID-19 in PLWH is highly heterogeneous.</p