ABSTRACT
While humoral immune responses to infection or vaccination with ancestral SARS-CoV-2 have been well-characterized, responses elicited by infection with variants are less understood. Here we characterized the repertoire, epitope specificity, and cross-reactivity of antibodies elicited by Beta and Gamma variant infection compared to ancestral virus. We developed a high-throughput approach to obtain single-cell immunoglobulin sequences and isolate monoclonal antibodies for functional assessment. Spike-, RBD- and NTD-specific antibodies elicited by Beta- or Gamma-infection exhibited a remarkably similar hierarchy of epitope immunodominance for RBD and convergent V gene usage when compared to ancestral virus infection. Additionally, similar public B cell clones were elicited regardless of infecting variant. These convergent responses may account for the broad cross-reactivity and continued efficacy of vaccines based on a single ancestral variant.
Subject(s)
Tumor Virus InfectionsABSTRACT
BACKGROUND Following 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. METHODS Primary 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. RESULTS Of 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. CONCLUSIONS The 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.
Subject(s)
COVID-19 , Breakthrough Pain , Severe Acute Respiratory SyndromeABSTRACT
Background The 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. Methods Covid-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. Results Among 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. Conclusions MW 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.
Subject(s)
COVID-19ABSTRACT
Background: Ivermectin, an antiparasitic agent, also has antiviral properties. Our aim was to assess whether ivermectin can shorten the viral shedding in patients at an early stage of COVID19 infection. Methods: The double blinded trial compared patients receiving ivermectin 0.2 mg/kg for 3 days vs. placebo in non-hospitalized COVID19 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. Results: Eighty nine patients were eligible (47 in ivermectin and 42 in placebo arm). Their median age was 35 years. Females accounted for 21.6%, and 16.8% 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 2.62; 95% CI: 1.09 to 6.31). 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: 1.06 to 6.45). Cultures at days 2 to 6 were positive in 3/23 (13.0%) of ivermectin samples vs. 14/29 (48.2%) in the placebo group (p=0.008). Conclusions: There were significantly lower viral loads and viable cultures in the ivermectin group, which could lead to shortening isolation time in these patients.
Subject(s)
COVID-19ABSTRACT
Background: The immunogenicity and safety of the Pfizer-BioNTech BNT162b2 mRNA vaccine in people living with HIV-1 (PLWH) are unknown. We thus aimed to assess the immunogenicity and safety of this vaccine in PLWH.Methods: In this prospective open study, we enrolled 143 PLWH, aged ³18 years, who attended our clinic. Patients who had recovered from COVID-19 were excluded. SARS-CoV-2 receptor binding domain (RBD) IgG and neutralizing antibodies were measured and compared to those in a cohort of vaccinated health care workers (HCWs). Adverse events, viral load and CD4 cell counts were monitored.Findings: At a median of 15 (IQR 14-19) days following the first dose of the BNT162b2 vaccine and 18 (IQR 14-21) days after the second dose, anti-RBD IgG was positive in 66/128 (51%) and 139/141 (98%) PLWH, respectively. Among the HCWs, 235/399 (59%) and 269/272 (99%) developed anti-RBD IgG at a median of 14 (IQR 14-14) and 26 (IQR 24-27) days after first and second doses, respectively. Following the second dose, immune sera neutralized SARS-CoV-2 pseudo-virus (psSARS-2) in 97% and 98% of PLWH and HCW, respectively. Vaccination was associated with adverse events in 60% of PLWH, mainly pain at the injection site, fatigue, and headache. AIDS-related adverse events were not reported. HIV viral load increased in 3/143 (2%) patients from < 40 copies/mL to ≤ 100 copies/mL. CD4+ T cell count decreased from a geometric mean of 700 (95% CI 648–757) cells/mm3 to 633.8 (95% CI 588–683) cells/mm 3 (P<0.01). Interpretation: This study on BNT162b2 vaccination in PLWH revealed a high antibody response without detrimental effect on viral load. A small decline in CD4 cell count was noted, but it was not accompanied by clinical deterioration. This study thus provides support for the immunization of PLWH against COVID-19 with the BNT162b2 mRNA Covid-19 vaccine.Funding Statement: None.Declaration of Interests: None.Ethics Approval Statement: Written informed consent was obtained from all participants and the study protocol and informed consent were approved by the Institutional review board of Sheba Medical Center.