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SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which adaptive immune responses associate with clearance of long-term SARS-CoV-2 infection in HIV-mediated immunosuppression after suppressive antiretroviral therapy (ART) initiation. We assembled a cohort of SARS-CoV-2 infected people in South Africa (n = 994) including participants with advanced HIV disease characterized by immunosuppression due to T cell depletion. Fifty-four percent of participants with advanced HIV disease had prolonged SARS-CoV-2 infection (>1 month). In the five vaccinated participants with advanced HIV disease tested, SARS-CoV-2 clearance associates with emergence of neutralizing antibodies but not SARS-CoV-2 specific CD8 T cells, while CD4 T cell responses were not determined due to low cell numbers. Further, complete HIV suppression is not required for clearance, although it is necessary for an effective vaccine response. Persistent SARS-CoV-2 infection led to SARS-CoV-2 evolution, including virus with extensive neutralization escape in a Delta variant infected participant. The results provide evidence that neutralizing antibodies are required for SARS-CoV-2 clearance in HIV-mediated immunosuppression recovery, and that suppressive ART is necessary to curtail evolution of co-infecting pathogens to reduce individual health consequences as well as public health risk linked with generation of escape mutants., (© 2024. The Author(s).)

Omicron BA.2.86 subvariant differs from Omicron BA.2 as well as recently circulating variants by over 30 mutations in the spike protein alone. Here we report on the isolation of the live BA.2.86 subvariant from a diagnostic swab collected in South Africa which we tested for escape from neutralizing antibodies and viral replication properties in cell culture. We found that BA.2.86 does not have significantly more escape relative to Omicron XBB.1.5 from neutralizing immunity elicited by either Omicron XBB-family subvariant infection or from residual neutralizing immunity of recently collected sera from the South African population. BA.2.86 does have extensive escape relative to ancestral virus with the D614G substitution (B.1 lineage) when neutralized by sera from pre-Omicron vaccinated individuals and relative to Omicron BA.1 when neutralized by sera from Omicron BA.1 infected individuals. BA.2.86 and XBB.1.5 show similar viral infection dynamics in the VeroE6-TMPRSS2 and H1299-ACE2 cell lines. We also investigate the relationship of BA.2.86 to BA.2 sequences. The closest BA.2 sequences are BA.2 samples from Southern Africa circulating in early 2022. Similarly, many basal BA.2.86 sequences were sampled in Southern Africa. This suggests that BA.2.86 potentially evolved in this region, and that unobserved evolution led to escape from neutralizing antibodies similar in scale to recently circulating strains of SARS-CoV-2., (© 2023. The Author(s).)

Aim: The ability of a hen egg white bovine colostrum supplement to prevent severe COVID-19 was tested in a double-blind randomized control study., Methods: Adults with mild/moderate COVID-19, risk factors for severe disease, and within 5 days of symptom onset were assigned to the intervention (n = 77) or placebo (n = 79) arms. Symptoms were documented until day 42 post-enrollment and viral clearance was assessed at 11-13 days post-symptom onset., Results: One participant developed severe COVID-19. The severe-type symptom score was lower in the active arm at 11-13 days post-symptom onset (p = 0.049). Chest pain, fever/chills, joint pain/malaise, and sore throat were significantly less frequent in the active arm. No differences in viral clearance were observed., Conclusion: The intervention reduced symptoms of mild/moderate COVID-19., Clinical Trial Registration: DOH-27-062021-9191 (South African National Clinical Trials Register)., Competing Interests: The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed., (© 2023 The Authors.)

The extent to which Omicron infection 1-9 , with or without previous vaccination, elicits protection against the previously dominant Delta (B.1.617.2) variant is unclear. Here we measured the neutralization capacity against variants of severe acute respiratory syndrome coronavirus 2 in 39 individuals in South Africa infected with the Omicron sublineage BA.1 starting at a median of 6 (interquartile range 3-9) days post symptom onset and continuing until last follow-up sample available, a median of 23 (interquartile range 19-27) days post symptoms to allow BA.1-elicited neutralizing immunity time to develop. Fifteen participants were vaccinated with Pfizer's BNT162b2 or Johnson & Johnson's Ad26.CoV2.S and had BA.1 breakthrough infections, and 24 were unvaccinated. BA.1 neutralization increased from a geometric mean 50% focus reduction neutralization test titre of 42 at enrolment to 575 at the last follow-up time point (13.6-fold) in vaccinated participants and from 46 to 272 (6.0-fold) in unvaccinated participants. Delta virus neutralization also increased, from 192 to 1,091 (5.7-fold) in vaccinated participants and from 28 to 91 (3.0-fold) in unvaccinated participants. At the last time point, unvaccinated individuals infected with BA.1 had low absolute levels of neutralization for the non-BA.1 viruses and 2.2-fold lower BA.1 neutralization, 12.0-fold lower Delta neutralization, 9.6-fold lower Beta variant neutralization, 17.9-fold lower ancestral virus neutralization and 4.8-fold lower Omicron sublineage BA.2 neutralization relative to vaccinated individuals infected with BA.1. These results indicate that hybrid immunity formed by vaccination and Omicron BA.1 infection should be protective against Delta and other variants. By contrast, infection with Omicron BA.1 alone offers limited cross-protection despite moderate enhancement., (© 2022. The Author(s).)

Background: Anaemia is common in patients with retroviral disease. New or worsening anaemia after initiation of antiretroviral (ARV) treatment has a broad differential diagnosis., Objectives: We describe six patients who developed transfusion-dependent anaemia on first-line therapy (tenofovir, emtricitabine and efavirenz) and, by exclusion, implicated emtricitabine in the aetiology of the anaemia., Method: We conducted a retrospective chart review of patients seen at the Infectious Diseases specialist clinic at King Edward VIII Hospital in KwaZulu-Natal between 2014 and 2016. We focused on patients with isolated, refractory and transfusion-dependent anaemia occurring after initiation of ARVs, in whom bone marrow biopsies were consistent with pure red cell aplasia (PRCA) without an identifiable secondary cause., Results: All the patients were female, with a median (range) age and baseline CD4 cell count of 42.5 (23-61) years and 237 (83-329) cells/mm 3 , respectively. Before presenting with symptomatic anaemia, the duration on emtricitabine was 4.5 (2-8) months. At presentation, all patients had an HIV viral load of < 1000 copies/mL and a CD4 cell count of 314 (213-389) cells/mm 3 . The median time to recovery following the discontinuation of emtricitabine was 2 (1-4) months. After a median of 12 months, all patients were successfully rechallenged with emtricitabine and remained well for a follow-up period of 24 (7-36) months., Conclusion: This study provides strong circumstantial evidence that emtricitabine plays an important role in the pathogenesis of reversible PRCA. The mechanisms through which emtricitabine induces PRCA remain unclear and require further study., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2021. The Authors.)