Correlates of protection and viral load trajectories in omicron breakthrough infections in triple vaccinated healthcare workers.

Vaccination offers protection against severe COVID-19 caused by SARS-CoV-2 omicron but is less effective against infection. Characteristics such as serum antibody titer correlation to protection, viral abundance and clearance of omicron infection in vaccinated individuals are scarce. We present a 4-week twice-weekly SARS-CoV-2 qPCR screening in 368 triple vaccinated healthcare workers. Spike-specific IgG levels, neutralization titers and mucosal spike-specific IgA-levels were determined at study start and qPCR-positive participants were sampled repeatedly for two weeks. 81 (cumulative incidence 22%) BA.1, BA.1.1 and BA.2 infections were detected. High serum antibody titers are shown to be protective against infection (p < 0.01), linked to reduced viral load (p < 0.01) and time to viral clearance (p < 0.05). Pre-omicron SARS-CoV-2 infection is independently associated to increased protection against omicron, largely mediated by mucosal spike specific IgA responses (nested models lr test p = 0.02 and 0.008). Only 10% of infected participants remain asymptomatic through the course of their infection. We demonstrate that high levels of vaccine-induced spike-specific WT antibodies are linked to increased protection against infection and to reduced viral load if infected, and suggest that the additional protection offered by pre-omicron SARS-CoV-2 infection largely is mediated by mucosal spike-specific IgA.

EPOS trial: the effect of air filtration through a plasma chamber on the incidence of surgical site infection in orthopaedic surgery: a study protocol of a randomised, double-blind, placebo-controlled trial.

INTRODUCTION: There is controversy regarding the importance of air-transmitted infections for surgical site infections (SSIs) after orthopaedic surgery. Research has been hindered by both the inability in blinding the exposure, and by the need for recruiting large enough cohorts. The aim of this study is to investigate whether using a new form of air purifier using plasma air purification (PAP) in operating rooms (ORs) lowers the SSI rate or not. METHODS AND ANALYSIS: Multicentre, double-blind, cluster-randomised, placebo-controlled trial conducted at seven hospitals in 2017-2022. All patients that undergo orthopaedic surgery for minimum 30 min are included. Intervention group: patients operated in OR with PAP devices turned on. CONTROL GROUP: patients operated in OR with PAP devices turned off. Randomisation: each OR will be randomised in periods of 4 weeks, 6 weeks or 8 weeks to either have the devices on or off. PRIMARY OUTCOME: any SSI postoperatively defined as a composite endpoint of any of the following: use of isoxazolylpenicillin, clindamycin or rifampicin for 2 days or more, International Classification of Diseases codes or Nordic Medico-Statistical Committee codes indicating postoperative infection. In a second step, we will perform a chart review on those patients with positive indicators of SSI to further validate the outcome. Secondary outcomes are described in the Methods section. Power: we assume an SSI rate of 2%, an SSI reduction rate of 25% and we need approximately 45 000 patients to attain a power of 80% at a significance level of 0.05. ETHICS AND DISSEMINATION: The study is approved by the Swedish Ethical Review Authority. The interim analysis results from the study will be presented only to the researchers involved unless the study thereafter is interrupted for whatever reason. Publication in a medical journal will be presented after inclusion of the last patient. TRIAL REGISTRATION NUMBER: NCT02695368.

Duration of SARS-CoV-2 Immune Responses Up to Six Months Following Homologous or Heterologous Primary Immunization with ChAdOx1 nCoV-19 and BNT162b2 mRNA Vaccines.

Heterologous primary immunization against SARS-CoV-2 is part of applied recommendations. However, little is known about duration of immune responses after heterologous vaccine regimens. To evaluate duration of immune responses after primary vaccination with homologous adeno-vectored ChAdOx1 nCoV-19 vaccine (ChAd) or heterologous ChAd/BNT162b2 mRNA vaccine (BNT), anti-spike-IgG and SARS-CoV-2 VOC-neutralizing antibody responses were measured in 354 healthcare workers (HCW) at 2 weeks, 3 months, 5 months and 6 months after the second vaccine dose. T-cell responses were investigated using a whole blood interferon gamma (IFN-γ) release assay 2 weeks and 3 months post second vaccine dose. Two hundred and ten HCW immunized with homologous BNT were enrolled for comparison of antibody responses. In study participants naïve to SARS-CoV-2 prior to vaccination, heterologous ChAd/BNT resulted in 6-fold higher peak anti-spike IgG antibody titers compared to homologous ChAd vaccination. The half-life of antibody titers was 3.1 months (95% CI 2.8-3.6) following homologous ChAd vaccination and 1.9 months (95% CI 1.7-2.1) after heterologous vaccination, reducing the GMT difference between the groups to 3-fold 6 months post vaccination. Peak T-cell responses were stronger in ChAd/BNT vaccinees, but no significant difference was observed 3 months post vaccination. SARS-CoV-2 infection prior to vaccination resulted in substantially higher peak GMTs and IFN-γ levels and enhanced SARS-CoV-2 specific antibody and T cell responses over time. Heterologous primary SARS-CoV-2 immunization with ChAd and BNT elicits a stronger initial immune response compared to homologous vaccination with ChAd. However, although the differences in humoral responses remain over 6 months, the difference in SARS-CoV-2 specific T cell responses are no longer significant three months after vaccination.

Antibody responses after a single dose of ChAdOx1 nCoV-19 vaccine in healthcare workers previously infected with SARS-CoV-2.

BACKGROUND: Recent reports demonstrate robust serological responses to a single dose of messenger RNA (mRNA) vaccines in individuals previously infected with SARS-CoV-2. Data on immune responses following a single-dose adenovirus-vectored vaccine expressing the SARS-CoV-2 spike protein (ChAdOx1 nCoV-19) in individuals with previous SARS-CoV-2 infection are however limited, and current guidelines recommend a two-dose regimen regardless of preexisting immunity. METHODS: We compared RBD-specific IgG and RBD-ACE2 blocking antibodies against SARS-CoV-2 wild type and variants of concern following two doses of the mRNA vaccine BNT162b2 in SARS-CoV-2 naïve healthcare workers (n=65) and a single dose of the adenovector vaccine ChAdOx1 nCoV-19 in 82 healthcare workers more than (n=45) and less than (n=37) 11 months post mild SARS-CoV-2 infection at time of vaccination. FINDINGS: The post-vaccine levels of RBD-specific IgG and neutralizing antibodies against the SARS-CoV-2 wild type and variants of concern including Delta lineage 1.617.2 were similar or higher in participants receiving a single dose of ChAdOx1 nCoV-19 vaccine post SARS-CoV-2 infection (both more than and less than 11 months post infection) compared to SARS-CoV-2 naïve participants who received two doses of BNT162b2 vaccine. INTERPRETATION: Our data support that a single dose ChAdOx1 nCoV-19 vaccine that is administered up to at least 11 months post SARS-CoV-2 infection serves as an effective immune booster. This provides a possible rationale for a single-dose vaccine regimen. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.