ABSTRACT
Background: Emerging data indicate that people with HIV (PWH) are at risk of more severe outcomes from COVID-19. We described the clinical course and laboratory parameters pre-and post-COVID-19 in an early-treated HIV cohort in Thailand. Method(s): RV254 cohort participants were enrolled during Fiebig I-V acute HIV and initiated antiretroviral therapy (ART) within days. They underwent regular blood tests (CD4+ & CD8+ T-cell counts, HIV RNA), neuropsychiatric (NP) assessment (Color Trails 1 & 2, non-dominant hand Grooved Pegboard, Trails Making A), and mood questionnaires (Patient Health Questionnaire-9, Distress Thermometer) post-enrollment longitudinally. Their assessment outcomes pre-and post-COVID-19 were compared using Generalized Estimating Equations (GEE) with a normal distribution and identity link (CD4+, CD8+ T-cell counts, NP parameters) or binomial distribution with log link (HIV RNA), and autoregressive correlation structure. Result(s): Between 4/2021 and 9/2022, 295 participants on ART (98% male, median age 32 [IQR 28-37] were diagnosed with COVID-19. Of these, 16(5%), 38(13%) and 241(82%) were infected with alpha, delta and o variants, determined by the predominant strain circulating in Thailand at the time of infection;238(81%) received >=2 doses of COVID-19 vaccines prior to diagnosis;121(41%) received favipiravir. While 106 (36%) were managed in hospital or 'hospitel', including one intensive care unit admission, only 4(1.4%) received supplemental oxygen and none required mechanical ventilation (mean length of stay: 12 days). The participants were followed a median of 8 [IQR 5-15] weeks post-COVID. Comparing the outcomes pre-and post-COVID, plasma HIV suppression rate remained stable (98% vs. 96%, p=0.212). CD4+ (782 [IQR 708-856] vs. 823 [IQR 748-899], p=0.018) and CD8+ (622 [IQR 563-681] vs. 667 [IQR 605-728], p=0.023) T-cell counts were higher at follow-up after adjusting for age, sex, and duration between COVID-19 diagnosis and follow-up. The increasing trends of CD4+ and CD8+ T-cell were sustained on subsequent visits. Mood scores and NP performance (n=217) were stable at follow-up. Conclusion(s): In this cohort of young PWH on stable ART, we did not observe major clinical adverse events after COVID-19. Increases of CD4+ and CD8+ T-cell counts were observed while mood and NP parameters remained stable. More extensive NP assessment with incorporation of multimodal imaging outcomes and longer follow-up are needed to determine the long-term sequelae of COVID-19 in PWH.
ABSTRACT
Background: COVID-19 clinical manifestations range from asymptomatic to severe disease. Prior immune responses to human coronaviruses may affect individual responses to SARS-CoV-2. We surveyed coronavirus responses pre-pandemic in individuals from Kenya, Nigeria, Tanzania, Uganda and Thailand;81% were people living with HIV. Methods: Specimens were screened for SARS-CoV-2 Spike S2 subunit IgG responses. Selected samples were tested using a bead-based immunoassay that profiled the specificity, isotype and subclass of antibody responses to coronavirus, flavivirus and HIV antigens. Wilcoxon rank sum tests were performed to compare responses across antigens and participant group. Results: We screened 1,875 samples (one per individual) collected between 2013 and October 2019: 1,630 samples were from Africa (87%) and 245 from Thailand. 6.99% of participants (n=131, 116 from Africa (89%) and 15 from Thailand) showed responses above the naïve signal threshold and were further tested. Using a signal to noise ratio of >10 as a cut-off value, 44, 27 and 42 samples showed IgG responses to the Spike protein of SARS-CoV-2, SARS-CoV-1 and MERS-CoV respectively, while 7, 9 and 4 samples showed responses to Nucleocapsid for these same antigens. Some individuals had higher responses than those seen in SARS-CoV-2 convalescent individuals. We found a strikingly different pattern of reactivity in Africa compared to Thailand (Figure 1). Antibody responses were significantly higher in the African participants compared to Thai participants across antigens corresponding to SARS-CoV-2 (p<0.001), SARS-CoV-1 (p<0.001) and MERS-CoV (p<0.01). Similar patterns were seen for IgG subclasses, IgA and IgM. The difference was less pronounced for the four endemic coronaviruses, nonetheless anti-Spike responses were significantly higher in African participants for HKU1 and OC43 (p≤0.018). In addition, mapping responses to 21 flavivirus antigens showed the highest reactivity in Thailand and in Nigeria. Conclusion: Our serosurvey of pre-pandemic samples showed that there were significantly higher antibody responses against coronaviruses, including SARS-CoV-2, in Africa than in Thailand. Profiling flavivirus responses showed that the difference between the two regions was not due to a higher background reactivity across African samples. Further analysis is needed to explain pre-pandemic SARS-CoV-2-like antibody responses among African participants and explore implications for geographic diversity in disease severity.