The effect of Omicron breakthrough infection and extended BNT162b2 booster dosing on neutralization breadth against SARS-CoV-2 variants of concern (preprint)

COVID-19 vaccines are playing a vital role in controlling the COVID-19 pandemic. As SARS-CoV-2 variants encoding mutations in the surface glycoprotein, Spike, continue to emerge, there is increased need to identify immunogens and vaccination regimens that provide the broadest and most durable immune responses. We compared the magnitude and breadth of the neutralizing antibody response, as well as levels of Spike-reactive memory B cells, in individuals receiving a second dose of BNT126b2 at a short (3-4 week) or extended interval (8-12 weeks) and following a third vaccination approximately 6-8 months later. We show that whilst an extended interval between the first two vaccinations can greatly increase the breadth of the immune response and generate a higher proportion of Spike reactive memory B cells, a third vaccination leads to similar levels between the two groups. Furthermore, we show that the third vaccine dose enhances neutralization activity against omicron lineage members BA.1, BA.2 and BA.4/BA.5 and this is further increased following breakthrough infection during the UK omicron wave. These findings are relevant for vaccination strategies in populations where COVID-19 vaccine coverage remains low.

Increasing Rates of Intensive Care Unit Bloodstream Infections During the Second COVID-19 Pandemic Wave, Particularly Primary Endogenous Enterococcus faecium, with High Crude Mortality and Associated with Introduction of Immunomodulatory Therapy (preprint)

Background: Reports indicate that COVID-19 patients have more bloodstream infections (BSI) on the intensive care unit (ICU) potentially due to lapses in infection control practice or other factors.Methods: Retrospective single-site study of ICU-BSIs in mechanically ventilated (MV) COVID-19 patients during the first pandemic year. Clinical, demographic and laboratory data including targeted pathogen genome sequencing was analysed during first (March 13th - May 31st 2020) and second (October 1st 2020 - March 15th 2021) pandemic waves.Findings: There were 305 MV-ICU patients in wave one and 440 in wave two with peak occupancy of 113 and 155 patients, respectively. The BSI rate was higher during both waves than pre-pandemic, but more in wave-two than wave-one, particularly during the first 28 days on ICU (14.1 vs. 9.4/1000 bed days; p=0.03) and with E. faecium (3.57 vs. 0.47/1000 bed days; p=0.0067). 22/28 (77%) of E. faecium BSIs had no microbiologically definable focus and the high wave-two rate could not be explained by transmission. Wave-two BSI-patients received more corticosteroids and tocilizumab and had higher crude hospital mortality compared with non-BSI patients (41% vs. 21% p<0.0001), a phenomenon not seen in wave one (32% vs. 27% p=0.551). Interpretation: MV-COVID-19 patients had a greater BSI-burden in wave two associated with the emergence of primary endogenous E. faecium. Identifying mechanisms and causal links between admission COVID-19 disease severity, immunomodulation, BSI and death could help identify new approaches to improving outcomes for COVID-19 patients.