Hospitalized patients with severe COVID-19 during the Omicron wave in Israel - benefits of a fourth vaccine dose (preprint)

Importance: Waning immunity against COVID-19 in parallel with an increased incidence during the Omicron outbreak led the Israeli Ministry of Health to recommend a second booster dose of BNT162b2 (Pfizer) to high-risk individuals. Israel was the first country to recommend this, allowing evaluation of the added protection of a fourth vaccine dose to hospitalized patients with severe diseases. Objective: To assess the effect of a fourth dose for hospitalized patients with severe/critical breakthrough COVID-19. Design: A cohort study of hospitalized adults from 01/15/2022-01/31/2022. Settings: A multi center study of 14 medical centers in Israel. Participants: Hospitalized adult patients with PCR-confirmed severe/critical COVID-19. Excluded were patients lacking data on vaccination status. Exposure: Cases were divided according to the total number of vaccine doses received up to 7 days before diagnosis. Unvaccinated adults and single-dose recipients were grouped into an unvaccinated group. Main Outcome: A composite of mechanical ventilation or in-hospital death was defined as poor outcome. Outcomes were compared between 3- and 4-dose vaccinees. Results: Included were 1,049 patients with severe/critical COVID-19, median age 80 (IQR 69-87), 51% males. Among them, 360 unvaccinated, 34, 172, 386 and 88 were after 1, 2, 3 or 4 doses, respectively. Patients after 3 doses were older, had more males and immunosuppression, but with similar outcomes, 49% vs. 51% compared to unvaccinated patients (p=0.72). Patients after 4 doses were similarly older and immunosuppressed, but had improved outcomes compared to unvaccinated patients, 34% vs. 51% (p<0.01). We proceeded to examine independent predictors for poor outcome in fully-vaccinated patients with either 3 doses given a median of 161 (IQR 147-168) days earlier, or 4 doses given a median of 14 (IQR 10-18) days before diagnoses. Receipt of the fourth dose conferred significant protection: OR 0.51 (95%CI 0.30.87). Conclusion and Relevance: Within a population of hospitalized patients with severe/critical breakthrough COVID-19, a recent fourth dose was associated with significant protection against mechanical ventilation or death, compared to fully-vaccinated single boosted individuals.

Immunogenicity and Safety of the BNT162b2 mRNA COVID-19 Vaccine in People Living with HIV-1 (preprint)

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.

Decreased Infectivity Following BNT162b2 Vaccination (preprint)

Background: BNT162b2 was shown to be 92% effective in preventing COVID-19. Prioritizing vaccine rollout, and achievement of herd immunity depend on SARS-CoV-2 transmission reduction. The vaccine’s effect on infectivity is thus a critical priority.Methods: In a cohort of all 9650 HCW of a large single tertiary medical center, we calculated the prevalence of positive SAR-CoV-2 qRT-PCR cases with an asymptomatic presentation, tested following known or presumed exposure and the infectious subset (N-gene-Ct-value<30) of these and the prevalence of never-symptomatic infections. Additionally, infection incidence rates were calculated for symptomatic cases and infectious (Ct<30) cases. Vaccine effectiveness within three months of vaccine rollout was measured as one minus the relative risk or rate ratio, respectively. To further assess infectiousness, we compared the mean Ct-value and the proportion of infections with a positive SARS-CoV-2 antigen test of vaccinated vs. unvaccinated. The correlation between IgG levels within the week before detection and Ct level was assessed.Findings: Reduced prevalence among fully vaccinated HCW was observed for (i) infections detected due to exposure, with asymptomatic presentation (VE(i)=65.1%, 95%CI 45-79%), (ii) the presumed infectious (Ct<30) subset of these (VE(ii)=69.6%, 95%CI 43-84%) (iii) never-symptomatic infections (VE(iii)=72.3%, 95%CI 48-86%), and (iv) the presumed infectious (Ct<30) subset (VE(iv)=83.0%, 95%CI 51-94%).Incidence of (v) symptomatic and (vi) symptomatic-infectious cases was significantly lower among fully vaccinated vs. unvaccinated individuals (VE(v)= 89.7%, 95%CI 84-94%, VE(vi)=88.1%, 95%CI 80-95%).The mean Ct-value was significantly higher in vaccinated vs. unvaccinated (27.3±1.2 vs. 22.2±1.0, p<0.001) and the proportion of positive SARS-CoV-2 antigen tests was also significantly lower among vaccinated vs. unvaccinated PCR-positive HCW (80% vs. 31%, p<0.001). Lower infectivity was correlated with higher IgG concentrations (R=0.36, p=0.01).Interpretation: These results suggest that BNT162b2 is moderately to highly effective in reducing infectivity, via preventing infection and through reducing viral shedding. Funding: Sheba Medical Center, IsraelDeclaration of Interest: All authors declare they have no competing interestsEthical Approval: The Sheba Ethical committee, reviewed the protocol and approved thestudy.

Automated processing of thermal imaging to detect COVID-19 (preprint)

Rapid and sensitive screening tools for SARS-CoV-2 infection are essential to limit the spread of COVID-19 and to properly allocate national resources. Here, we developed a new point-of-care, non-contact thermal imaging tool to detect COVID-19, based on image-processing algorithms and machine learning analysis. We captured thermal images of the back of individuals with and without COVID-19 using a portable thermal camera that connects directly to smartphones. Our novel image processing algorithms automatically extracted multiple texture and shape features of the thermal images and achieved an area under the curve (AUC) of 0.85 in detecting COVID-19 with up to 92% sensitivity. Thermal imaging scores were inversely correlated with clinical variables associated with COVID-19 disease progression. We show, for the first time, that a hand-held thermal imaging device can be used to detect COVID-19. Non-invasive thermal imaging could be used to screen for COVID-19 in out-of-hospital settings, especially in low-income regions with limited imaging resources. HIGHLIGHTSO_LIAutomated processing of thermal images of the back can be used to detect COVID-19 with up to 92% sensitivity. C_LIO_LIThe extracted texture features of the thermal image are associated with COVID-19 disease progression and lung injury. C_LIO_LIA portable thermal camera that connects directly to smartphones can be used to detect COVID-19. C_LIO_LINon-invasive thermal imaging could be used to screen for COVID-19 in out-of-hospital settings and regions with limited imaging resources. C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=68 SRC="FIGDIR/small/20248691v2_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@1afd708org.highwire.dtl.DTLVardef@14e5a5eorg.highwire.dtl.DTLVardef@10ede4corg.highwire.dtl.DTLVardef@1248470_HPS_FORMAT_FIGEXP M_FIG C_FIG