Distinct receptor binding domain IgG thresholds predict protective host immunity across SARS-CoV-2 variants and time.

SARS-CoV-2 neutralising antibodies provide protection against COVID-19. Evidence from early vaccine trials suggested binding antibody thresholds could serve as surrogate markers of neutralising capacity, but whether these thresholds predict sufficient neutralising capacity against variants of concern (VOCs), and whether this is impacted by vaccine or infection history remains unclear. Here we analyse individuals recovered from, vaccinated or with hybrid immunity against SARS-CoV-2. An NT50 ≥ 100 IU confers protection in vaccine trials, however, as VOC induce a reduction in NT50, we use NT50 ≥ 1000 IU as a cut off for WT NT50 that would retain neutralisation against VOC. In unvaccinated convalescent participants, a receptor binding domain (RBD) IgG of 456 BAU/mL predicts an NT50 against WT of 1000 IU with an accuracy of 80% (95%CI 73-86%). This threshold maintains accuracy in determining loss of protective immunity against VOC in two vaccinated cohorts. It predicts an NT50 < 100 IU against Beta with an accuracy of 80% (95%CI 67-89%) in 2 vaccine dose recipients. In booster vaccine recipients with a history of COVID-19 (hybrid immunity), accuracy is 87% (95%CI 77-94%) in determining an NT50 of <100 IU against BA.5. This analysis provides a discrete threshold that could be used in future clinical studies.

Therapeutic approaches to combating lipoatrophy: do they work?

Therapeutic strategies for combating HIV-associated lipodystrophy, and lipoatrophy in particular, have been a major focus of HIV clinical research. The initial impetus focused on protease inhibitor withdrawal strategies, which resulted in improved lipid profiles and insulin resistance but no change in subcutaneous or visceral adipose tissue. Nucleoside reverse transcriptase inhibitor withdrawal strategies, specifically withdrawal of thymidine analogues, have achieved greater success in the reversal of lipoatrophy. In particular, the MITOX extension study demonstrated a 35% improvement in limb fat over a 2 year period after a switch from a thymidine analogue to abacavir. However, recovery from lipoatrophy is a slow process, and limited access to and potential toxicities introduced by alternative therapies can limit switch strategies. The use of thiazolidinediones as agents to reverse lipoatrophy has, unfortunately, been shown to be ineffective, as have alternative therapeutic approaches with agents such as metformin, lipid-lowering agents and growth hormones. Although prevention of lipodystrophy may be the only definitive approach to combat this syndrome, the role of intermittent highly active antiretroviral therapy as a means of reducing the incidence, or slowing the development, of lipodystrophy is currently under evaluation.