ABSTRACT
Background: The tolerability of mRNA COVID-19 vaccines among people living with HIV (PLWH) has been understudied in vaccine trials. CoVPN 3008 (Ubuntu) is the largest multicenter Phase 3 efficacy trial of mRNA vaccines in sub-Saharan Africa. Method(s): We enrolled adults age >=18 years living with HIV or another comorbidity associated with severe COVID-19. Previously vaccinated individuals were excluded. Baseline testing included HIV, CD4 count and HIV viral load (VL) (if HIV+), anti-SARS-CoV-2 antibodies, and nasal swab SARS-CoV-2 nucleic acid amplification test (NAAT). All participants receive vaccinations at months 0 and 6, and SARS-CoV-2 seronegative individuals also receive vaccination at month 1. This analysis includes mRNA-1273 vaccinations at months 0 and 1. Reactogenicity (solicited adverse events [AEs]) was assessed among a representative subset of participants (Safety Subset, SS) for 7 days post-vaccination. Baseline characteristics associated with moderate/severe reactogenicity events were assessed by univariate and multivariate logistic regression. Result(s): 14002 participants were enrolled in the trial (1510 into the SS) at 46 sites from 2 Dec 2021 to 9 Sep 2022. At baseline in the SS, 71% (1065) were female, median age 38 years (IQR 32-46), and median BMI 25.0 (IQR 20.7-30.2). 73% (1108) were SARS-CoV-2 seropositive, and 8.7% (131) had a positive nasal NAAT swab. 16% (197) had a history of tuberculosis. 84% (1267) were PLWH, with median CD4 count of 614 cells/muL (IQR 414-861);7.8% had CD4 count < 200. 21% (238) had detectable HIV VL (>=50 copies/mL), with median VL 1660 (IQR 182-23932). 14% (172/1262) and 12% (64/542) of PLWH reported moderate/severe reactogenicity after the 1st and 2nd vaccination (Figure), with no hospitalizations. Female PLWH and CD4 count >500 had 35% (p=0.03) and 44% (p=0.04) increased odds of moderate/severe reactogenicity, respectively. Other baseline characteristics were not associated with the odds of reporting moderate/severe reactogenicity among PLWH after 1st vaccination. Similar trends were seen after the 2nd vaccination, but none reached statistical significance. In multivariate models, female sex remained associated with increased odds of moderate/severe reactogenicity after the 2nd vaccination. Conclusion(s): Similar to observations in HIV-negative populations, mRNA-1273 was well tolerated by PLWH with more reactogenicity in females. Impaired inflammatory responses among participants with CD4 counts < 500 cell/muL may explain less moderate/severe reactions.
ABSTRACT
Background: Given the paucity of data on safety and effectiveness of mRNA COVID-19 booster vaccinations in lower income settings with high HIV prevalence, we evaluated a heterologous mRNA-1273 (Moderna) boost after priming with 1 or 2 doses of Ad26.COV2.S (Janssen, Johnson & Johnson) vaccine among health care workers (HCWs) in South Africa. Method(s): SHERPA is an open-label, phase 3 mRNA-1273 booster study, nested in the Sisonke Phase 3b implementation trial, that vaccinated ~500000 HCWs with 1 or 2 doses of Ad26.COV2.S from Feb and Dec 2021. Sisonke participants were offered mRNA-1273 boosters between 23 May and 12 Nov 2022 (median 17 and 8 months after 1 and 2 Ad26.COV2.S, respectively), with data cut-off on 12 Dec 2022. Reactogenicity and adverse events (AEs) were self-reported via an online data entry link shared by SMS with participants 1, 7 and 28 days after boosting. Using national databases analyses are underway to compare effectiveness against COVID-19 infections and severe disease with Sisonke participants who did not receive the booster. Result(s): 12188 HCWs (79.5% female, 28.6% with self-reported previous COVID-19 diagnosis) received a mRNA-1273 booster, of whom 44.6% and 55.4% had received 1 and 2 prior Ad26.COV2.S vaccines in Sisonke, respectively. 3056 (25.2%) reported being HIV positive, more among those receiving only 1 previous Ad26.COV2.S (26.8% vs 23.9%), and 1.4% reported not being on antiretroviral therapy. 17.0% of participants reported hypertension and 6.4% diabetes mellitus. 262 participants (2.1% of women, 2.5% of men) reported 234 reactogenicity events and 95 AEs post-vaccination, with more reported by those with prior COVID-19 infection (3.5% vs 1.6%), HIV negative status (2.5% vs 1.2%) and those who received 2 prior doses of Ad26.COV2.S (2.4% vs 1.8%) (Table). Among 159 (1.3%) reporting injection site reactions the commonest were pain (59.7%), swelling (42.1%) and induration (20.1%). Of 177 (1.5%) systemic reactogenicity events (all grade 1 or 2 severity), the commonest were myalgia (69.5%), headache (67.8%) and fever (37.9%). 14 participants had AEs of special interest or serious AEs, of which 4 (all AESIs of ageusia or anosmia) were deemed related to the booster. 13 COVID-19 infections occurred a median of 125 days post booster vaccination (IQR 90-154) after 3477 person-years of follow up. Conclusion(s): A mRNA-1273 booster administered after 1 or 2 doses of Ad26. COV2.S was well tolerated regardless of HIV status, other chronic conditions or prior COVID-19 infection.
ABSTRACT
Background: The Sisonke Phase IIIB open-label implementation study vaccinated health care workers (HCWs) with the single dose Ad26.COV2.S vaccine during two phases of the South African Covid-19 epidemic, dominated first by the Beta followed by the Delta variant of concern. Methods: HCWs were vaccinated over 3 months (17 February-17 May 2021). Safety was monitored by self-reporting, facility reporting and linkage to national databases. Vaccine effectiveness (VE) against Covid-19 related hospitalisation, hospitalisation requiring critical or intensive care and death, ascertained 28 days or more post vaccination was assessed up until 17 July 2021. Nested sub-cohorts (A and B) from two national medical schemes were evaluated to assess VE using a matched retrospective cohort design. Results: Over the 3-month period, 477234 HCWs were vaccinated in 122 vaccination sites across South Africa. VE derived from the sub-cohorts comprising 215 813 HCWs was 83% (95% CI 75-89) to prevent Covid-19 deaths, 75% (95% CI 69-82) to prevent hospital admissions requiring critical or intensive care and 67% (95% CI 62-71) to prevent Covid-19 related hospitalisations. The VE was maintained in older HCWs and those with comorbidities including HIV infection. VE remained consistent throughout the Beta and Delta dominant phases of the study. 10279 adverse events were reported and 139 (1.4%) were serious, including two cases of thrombosis with thrombocytopenia syndrome and four cases of Guillain-Barré syndrome who recovered. Conclusion: The single dose Ad26.COV2.S was safe and effective against severe Covid-19 disease and death post-vaccination, and against both Beta and Delta variants providing real-world evidence for its use globally.
ABSTRACT
Background: Post-Acute Sequelae of SARS-CoV-2 (PASC) is characterized by persistent symptoms negatively impacting quality of life several weeks after SARS-CoV-2 diagnosis. Proposed risk factors include older age, female sex, comorbidities, and severe COVID-19, including hospitalization and oxygen requirement. Yet, associations of these factors with prolonged symptoms remain poorly understood globally. Methods: The global, observational cohort study HVTN 405/HPTN 1901 characterizes the clinical and immunologic course in the first year after SARS-CoV-2 infection among adults. The cohort was categorized by infection severity (asymptomatic;symptomatic with no oxygen requirement [NOR];non-invasive oxygen requirement [NIOR];or invasive oxygen requirement [IOR]). A regression model was applied to estimate geometric mean ratios (GMR) for duration and odds ratios (OR) for persistence of symptoms. Results: 759 participants from Peru (25.2%), USA (26.0%), Republic of South Africa (RSA, 37.7%), and non-RSA Sub-Saharan Africa (11.2%) were enrolled a median of 51 (IQR 35-66) days post-diagnosis, from May 2020 to Mar 2021. 53.8% were female, 69.8% were <55yo (median 44yo, IQR 33-58) and identified as non-Hispanic Black (42.7%), Hispanic (27.9%) or non-Hispanic White (15.8%). Comorbidities included obesity (42.8%), hypertension (24%), diabetes (14%), HIV infection (11.6%) and lung disease (7.5%). 76.2% were symptomatic (NOR 47.4%;NIOR 22.9%;and IOR 5.8%). Among symptomatic participants, median acute COVID-19 duration was 20 days (IQR 11-35);43.3% had ≥1 persistent symptom after COVID-19 resolution (39.8% NOR;49.1 % NIOR+IOR;p=0.037);16.8% reported ≥1 symptom >42 days (14.0% NOR;21.6% NIOR+IOR;p=0.025). Symptom duration was not associated with age or sex assigned at birth but was associated with disease severity (GMR 2.09;95%CI 1.5-2.91, p<0.001 for NIOR vs NOR;not significant for IOR vs NIOR), lung disease (GMR 2.43;95%CI 1.42-4.16, p=0.001), and global region (p<0.05, see Figure 1). Prolonged viral shedding was associated with persistent diarrhea (OR 6.59;95%CI 1.65-26.86;p=0.008). Conclusion: A recovery course consistent with PASC was significantly associated with infection severity, lung disease, and region. Regional differences in symptom profiles and duration may be influenced by viral diversity, genetic, or cultural factors and likely reflect disparities in healthcare access and interventions. Better understanding PASC associations may improve clinical assessment and management globally.