Convergent epitope specificities, V gene usage and public clones elicited by primary exposure to SARS-CoV-2 variants

An important consequence of infection with a SARS-CoV-2 variant is protective humoral immunity against other variants. The basis for such cross-protection at the molecular level is incompletely understood. Here we characterized the repertoire and epitope specificity of antibodies elicited by Beta, Gamma and ancestral variant infection and assessed their cross-reactivity to these and the more recent Delta and Omicron variants. We developed a high-throughput approach to obtain immunoglobulin sequences and produce monoclonal antibodies for functional assessment from single B cells. Infection with any variant elicited similar cross-binding antibody responses exhibiting a remarkably conserved hierarchy of epitope immunodominance. Furthermore, convergent V gene usage and similar public B cell clones were elicited regardless of infecting variant. These convergent responses despite antigenic variation may represent a general immunological principle that accounts for the continued efficacy of vaccines based on a single ancestral variant.

Fourth Dose COVID mRNA Vaccines' Immunogenicity & Efficacy Against Omicron VOC

BACKGROUNDFollowing the emergence of the Omicron variant of concern, we investigated immunogenicity, efficacy and safety of BNT162b2 or mRNA1273 fourth dose in an open-label, clinical intervention trial. METHODSPrimary end-points were safety and immunogenicity and secondary end-points were vaccine efficacy in preventing SARS-CoV-2 infections and COVID-19 symptomatic disease. The two intervention arms were compared to a matched control group. Eligible participants were healthcare-workers (HCW) vaccinated with three BNT162b2 doses, and whose IgG antibody levels were [≤]700 BAU (40-percentile). IgG and neutralizing titers, direct neutralization of live VOCs, and T-cell activation were assessed. All participants were actively screened for SARS-CoV-2 infections on a weekly basis. RESULTSOf 1050 eligible HCW, 154 and 120 were enrolled to receive BNT162b2 and mRNA1273, respectively, and compared to 426 age-matched controls. Recipients of both vaccine types had a [~]9-10-fold increase in IgG and neutralizing titers within 2 weeks of vaccination and an 8-fold increase in live Omicron VOC neutralization, restoring titers to those measured after the third vaccine dose. Breakthrough infections were common, mostly very mild, yet, with high viral loads. Vaccine efficacy against infection was 30% (95%CI:-9% to 55%) and 11% (95%CI:-43% to +43%) for BNT162b2 and mRNA1273, respectively. Local and systemic adverse reactions were reported in 80% and 40%, respectively. CONCLUSIONSThe fourth COVID-19 mRNA dose restores antibody titers to peak post-third dose titers. Low efficacy in preventing mild or asymptomatic Omicron infections and the infectious potential of breakthrough cases raise the urgency of next generation vaccine development. Trial registration numberclicaltrials.gov: NCT05231005, NCT05230953

The role of mouthwash sampling in SARS-CoV-2 diagnosis

BackgroundThe current practice of COVID-19 diagnosis worldwide is the use of oro-nasopharyngeal (ONP) swabs. Our study aim was to explore mouthwash (MW) as an alternative diagnostic method, in light of the disadvantages of ONP swabs. MethodsCovid-19 outpatients molecular-confirmed by ONP-swab were repeatedly examined with ONP-swab and MW with normal-saline (0.9%). Other types of fluids were compared to normal-saline. The Cq values obtained with each method were compared. ResultsAmong 137 pairs of ONP-swabs and MW samples, 84.6% (116/137) of ONP-swabs were positive by at least one of the genes (N, E, R). However MW detected 70.8% (97/137) of samples as positive, which means 83.6% (97/116) out of positive ONP-swabs, missing mainly Cq value>30. In both methods, the N gene was the most sensitive one. Therefore MW samples targeting N-gene, which was positive in 95/137 (69.3%), is comparable to ONP-swabs targeting E and R genes which gave equal results - 95/137 (69.3%) and 90/137 (65.7%) respectively. Comparing saline MW to distilled-water gave equal results, while commercial mouth-rinsing solutions were less sensitive. ConclusionsMW with normal-saline, especially when tested by N gene, can effectively detect COVID-19 patients. Furthermore, this method was not inferior when compared to R and E genes of ONP-swabs, which are common targets in many laboratories around the world.

Safety of measles, rubella and mumps vaccines in adults: a prospective cohort study.

BACKGROUND: In recent years, multiple outbreaks of measles associated with vaccine hesitancy occurred in high-income countries, where measles incidence had previously been low. Most safety data about the measles, mumps and rubella (MMR) vaccine are derived from studies conducted among children, whereas evidence regarding the safety profile of the vaccine in adults is scarce. METHODS: In 2017, during an outbreak of measles in Europe, Israeli travellers to high-risk locations who were incompletely vaccinated, were urged to complete the two MMR vaccination schedule before their travel. In this prospective cohort study, we analysed adverse events (AEs) of MMR and MMRV (measles, mumps, rubella and varicella) vaccines among these travellers. All participants were followed up using structured questionnaires 2-4 weeks after vaccination. RESULTS: Seven hundred and eighty-five adult travellers whose median age was 49.2 years were vaccinated and followed up. Any AEs were reported by 25.2% of all participants; 11.6% reported local AEs, and 18.6% reported systemic AEs, none of which were severe. In general, AEs were much more common among female travellers (19.4% of males vs 30.1% of females (P < 0.001)). Local AEs, overall systemic AEs, headache and arthralgia were much more common among females, whereas rates of general malaise and fever were not statistically different between genders. We did not observe any significant differences in the rates of total, local or systemic AEs between the MMR and MMRV vaccines. Higher rates of systemic AEs were observed among participants who were younger and probably immunized once with MMR compared to older vaccines immunized once to measles only and to those who were never immunized. CONCLUSIONS: The current study demonstrated low rates of systemic AEs and no serious AEs following either MMR or MMRV administration. More AEs were reported among females, and rates of AEs were similar after either MMR or MMRV.

Favorable outcome on viral load and culture viability using Ivermectin in early treatment of non-hospitalized patients with mild COVID-19, A double-blind, randomized placebo-controlled trial.

BackgroundIvermectin, an anti-parasitic agent, also has anti-viral properties. Our aim was to assess whether ivermectin can shorten the viral shedding in patients at an early-stage of COVID-19 infection. MethodsThe double-blinded trial compared patients receiving ivermectin 0{middle dot}2 mg/kg for 3 days vs. placebo in non-hospitalized COVID-19 patients. RT-PCR from a nasopharyngeal swab was obtained at recruitment and then every two days. Primary endpoint was reduction of viral-load on the 6th day (third day after termination of treatment) as reflected by Ct level>30 (non-infectious level). The primary outcome was supported by determination of viral culture viability. ResultsEighty-nine patients were eligible (47 in ivermectin and 42 in placebo arm). Their median age was 35 years. Females accounted for 21{middle dot}6%, and 16{middle dot}8% were asymptomatic at recruitment. Median time from symptom onset was 4 days. There were no statistical differences in these parameters between the two groups. On day 6, 34 out of 47 (72%) patients in the ivermectin arm reached the endpoint, compared to 21/ 42 (50%) in the placebo arm (OR 2{middle dot}62; 95% CI: 1{middle dot}09-6{middle dot}31). In a multivariable logistic-regression model, the odds of a negative test at day 6 was 2.62 time higher in the ivermectin group (95% CI: 1{middle dot}06-6{middle dot}45). Cultures at days 2 to 6 were positive in 3/23 (13{middle dot}0%) of ivermectin samples vs. 14/29 (48{middle dot}2%) in the placebo group (p=0{middle dot}008). ConclusionsThere were significantly lower viral loads and viable cultures in the ivermectin group, which could lead to shortening isolation time in these patients. The study is registered at ClinicalTrials.gov NCT 044297411.