Reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) by SARS-CoV-2 in non-hospitalised HIV-infected patients.

BACKGROUND: While acute SARS-CoV-2 infection and associated inflammation resulted in substantial morbidity and mortality during the COVID-19 pandemic, particularly in unvaccinated patients, long-term effects of SARS-CoV-2 exposure for reactivation of latent oncogenic herpesviruses, such as KSHV, is unknown. METHODS: We performed a longitudinal observational cross-sectional study on 407 non-hospitalised adult HIV-infected (CD4 count <350 cells/µL) patients attending antiretroviral therapy services in Gugulethu, South Africa, from October 2020 to April 2023. FINDINGS: KSHV seroprevalence was 53.5%; the quarterly SARS-CoV-2 seroprevalence increased from 76.2% (before roll-out of COVID-19 vaccinations) to 94.9%, with 32.2% being self-reportedly vaccinated against COVID-19. Over the course of recruitment, the quarterly percentage of patients with detectable KSHV viral load (VL) in the peripheral blood increased from 3.3% to 69.2%. The presence of KSHV VL was significantly associated with SARS-CoV-2 RBD antibody titers in unvaccinated (median RBD IgG OD 1.24 [IQR 0.82-2.42] in non-reactivated versus 2.83 [IQR 1.08-4.72] in reactivated patients, p = 0.0030) but not in vaccinated patients (median RBD IgG OD 5.13 [IQR 4.11-6.36] in non-reactivated versus 4.53 [IQR 2.90-5.92] in reactivated patients, p = 0.086). Further logistic regression revealed significantly higher odds of KSHV reactivation in unvaccinated, previously SARS-CoV-2 exposed patients (p = 0.015, adjusted OR 1.28 [95% CI: 1.05-1.55]), but not vaccinated patients (p = 0.080, adjusted OR 0.83 [95% CI: 0.67-1.02]). Interestingly, detectable KSHV VL was not associated with increased inflammatory markers such as C-reactive protein and interleukin-6. INTERPRETATION: High, and most likely repeated, exposure to SARS-CoV-2 in unvaccinated individuals may have long-term consequences for reactivation of KSHV infection as shown here in the context of HIV-infected patients with impaired immune functions. Post-pandemic prevention and/or monitoring strategies of potential KSHV-associated pathologies in high-risk patients with immunodeficiencies are therefore highly recommended. FUNDING: This research was funded by the EDCTP2 programme (Training and Mobility Action TMA2018SF-2446).

SARS-CoV-2 Infection Is Associated with Uncontrolled HIV Viral Load in Non-Hospitalized HIV-Infected Patients from Gugulethu, South Africa.

In South Africa, high exposure to SARS-CoV-2 occurs primarily in densely populated, low-income communities, which are additionally burdened by highly prevalent Human Immunodeficiency Virus (HIV). With the aim to assess SARS-CoV-2 seroprevalence and its association with HIV-related clinical parameters in non-hospitalized patients likely to be highly exposed to SARS-CoV-2, this observational cross-sectional study was conducted at the Gugulethu Community Health Centre Antiretroviral clinic between October 2020 and June 2021, after the first COVID-19 wave in South Africa and during the second and beginning of the third wave. A total of 150 adult (median age 39 years [range 20−65 years]) HIV-infected patients (69% female; 31% male) were recruited. 95.3% of the cohort was on antiretroviral therapy (ART), had a median CD4 count of 220 cells/µL (range 17−604 cells/µL) and a median HIV viral load (VL) of 49 copies/mL (range 1−1,050,867 copies/mL). Furthermore, 106 patients (70.7%) were SARS-CoV-2 seropositive, and 0% were vaccinated. When stratified for HIV VL, patients with uncontrolled HIV viremia (HIV VL > 1000 copies/mL) had significantly higher odds of SARS-CoV-2 seropositivity than patients with HIV VL < 1000 copies/mL, after adjusting for age, sex and ART status (p = 0.035, adjusted OR 2.961 [95% CI: 1.078−8.133]). Although the cause−effect relationship could not be determined due to the cross-sectional study design, these results point towards a higher risk of SARS-CoV-2 susceptibility among viremic HIV patients, or impaired HIV viral control due to previous co-infection with SARS-CoV-2.

Kaposi's Sarcoma-Associated Herpesvirus, but Not Epstein-Barr Virus, Co-infection Associates With Coronavirus Disease 2019 Severity and Outcome in South African Patients.

In South Africa, the Coronavirus Disease 2019 (COVID-19) pandemic is occurring against the backdrop of high Human Immunodeficiency Virus (HIV), tuberculosis and non-communicable disease burdens as well as prevalent herpesviruses infections such as Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV). As part of an observational study of adults admitted to Groote Schuur Hospital, Cape Town, South Africa during the period June-August 2020 and assessed for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we measured KSHV serology and KSHV and EBV viral load (VL) in peripheral blood in relation to COVID-19 severity and outcome. A total of 104 patients with PCR-confirmed SARS-CoV-2 infection were included in this study. 61% were men and 39% women with a median age of 53 years (range 21-86). 29.8% (95% CI: 21.7-39.1%) of the cohort was HIV positive and 41.1% (95% CI: 31.6-51.1%) were KSHV seropositive. EBV VL was detectable in 84.4% (95% CI: 76.1-84.4%) of the cohort while KSHV DNA was detected in 20.6% (95% CI: 13.6-29.2%), with dual EBV/KSHV infection in 17.7% (95% CI: 11.1-26.2%). On enrollment, 48 [46.2% (95% CI: 36.8-55.7%)] COVID-19 patients were classified as severe on the WHO ordinal scale reflecting oxygen therapy and supportive care requirements and 30 of these patients [28.8% (95% CI: 20.8-38.0%)] later died. In COVID-19 patients, detectable KSHV VL was associated with death after adjusting for age, sex, HIV status and detectable EBV VL [p = 0.036, adjusted OR = 3.17 (95% CI: 1.08-9.32)]. Furthermore, in HIV negative COVID-19 patients, there was a trend indicating that KSHV VL may be related to COVID-19 disease severity [p = 0.054, unstandardized co-efficient 0.86 (95% CI: -0.015-1.74)] in addition to death [p = 0.008, adjusted OR = 7.34 (95% CI: 1.69-31.49)]. While the design of our study cannot distinguish if disease synergy exists between COVID-19 and KSHV nor if either viral infection is indeed fueling the other, these data point to a potential contribution of KSHV infection to COVID-19 outcome, or SARS-CoV-2 infection to KSHV reactivation, particularly in the South African context of high disease burden, that warrants further investigation.

Greener synthesis of indolizine analogues using water as a base and solvent: study for larvicidal activity against Anopheles arabiensis.

Greener synthesis of a series of novel indolizine analogues have been achieved by the cyclization of aromatic cycloimmonium ylides with electron-deficient alkynes in the presence of water as the base and solvent at 80 °C. Yield of the title compounds was good and reactions performed were eco-friendly. The structures of these newly synthesized compounds have been confirmed by spectroscopic techniques such as FTIR, NMR, LC-MS, and elemental analysis. Characterized title compounds were evaluated for larvicidal activity against Anopheles arabiensis by standard WHO larvicidal assay using Temefos as standard at 4 µg/mL. Title compounds 2e, 2f, and 2g emerged as promising larvicidal agents.