Antibody-Mediated Immunogenicity Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Following Priming, Boosting, and Hybrid Immunity: Insights From 11 Months of Follow-up of a Healthcare Worker Cohort in Israel, December 2020-October 2021.

BACKGROUND: We determined circulating anti-S severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibody titers in a vaccinated healthcare workers (HCWs) cohort from Northern Israel in the 11 months following primary vaccination according to age, ethnicity, and previous infection status. METHODS: All consenting HCWs were invited to have their IgG levels measured before vaccination and at 6 subsequent timepoints using a quantitative S1/S2 IgG assay. All HCWs with suspected coronavirus disease 2019 (COVID-19) were polymerase chain reaction (PCR) tested. We described trends in circulating IgG geometric mean concentration (GMC) by age, ethnicity, timing of boosting, and previous infection status and compared strata using Kruskall-Wallis tests. RESULTS: Among 985 vaccinated HCWs, IgG titers between 1 month post 2nd dose to pre-boosting gradually decreased in all age groups. Younger or previously infected individuals had higher initial post-vaccination IgG levels (P < .001 in both cases); differences substantially decreased or disappeared at 7-9 months, before boosting. The proportion of individuals infected prior to initiating vaccination and re-infected after dose 1 was comparable to the proportion of breakthrough infection post-dose 2 in those not previously infected (4.2 vs 4.7%). Pre-infection IgG levels in the 40 participants with breakthrough infection after dose 2 were similar to levels measured at the same timepoint in vaccinated HCWs who remained uninfected (P > .3). Post-dose3 IgG levels were more than 10-fold those 1 month post-dose 2. CONCLUSIONS: Immunity waned in all age groups and previously infected individuals, reversed by boosting. IgG titers decrease and reinfections in individuals with hybrid immunity (infection + vaccination) suggests they may also require further doses. Our study also highlights the difficulty in determining protective IgG levels.

Cycle threshold responses in SARS-COV2 PCR tests depend on the method by which the samples were obtained and require strict global standardization.

PURPOSE: Since 2020, a SARS-COV2 epidemic has been raging worldwide. The cycle of the PCR test in which the virus is detected is called cycle threshold (CT). The method of obtaining the sample is not detailed in any published study and is based on general guidelines of the CDC. Our contention is that the manner in which the sample is obtained has a dramatic effect on CT values. METHODS: For each person suspected of having Covid-19 who arrives at the emergency room, two swabs are taken in succession, one according to CDC guidelines and the other according to "Ziv" guidelines. The Ziv method sample collection guidelines determine the depth of penetration, the number of rotations of the swab, and their direction. Each double sample was sent for analysis. RESULTS: Analysis of the CT results of the sample to results methods and of the Seegene platform clearly found (p = 0.003 and p = 0.001, respectively) that more rigorous sample collection yielded lower CT values. CONCLUSION: The method of obtaining the samples had a dramatic effect on CT results. Any publication that includes CT results, and certainly studies that discuss CT kinetics, must describe in detail the method by which the samples were obtained. In places where it is also important to detect the onset of illness (airports, hospitals, schools, etc.), it is important to use the Ziv method to reduce the risk of false negatives.

SARS-CoV-2 immunogenicity in individuals infected before and after COVID-19 vaccination: Israel, January-March 2021.

Between December 2020 and March 2021, we measured anti-SARS-CoV-2 IgG titres among 725 Israeli hospital workers vaccinated against COVID-19. Infection post-dose 1 vaccination did not increase IgG titres, and individuals infected post-dose 1 had IgG levels comparable to never-infected individuals who received a single dose, lower than fully vaccinated, never-infected individuals. This suggests dose 2, currently not offered to those infected post-dose 1, may be required in these individuals. Larger studies should confirm whether individuals infected post-dose 1 need the second.

Impact of age, ethnicity, sex and prior infection status on immunogenicity following a single dose of the BNT162b2 mRNA COVID-19 vaccine: real-world evidence from healthcare workers, Israel, December 2020 to January 2021.

The BNT162b2 mRNA COVID-19 vaccine showed high efficacy in clinical trials but observational data from populations not included in trials are needed. We describe immunogenicity 21 days post-dose 1 among 514 Israeli healthcare workers by age, ethnicity, sex and prior COVID-19 infection. Immunogenicity was similar by ethnicity and sex but decreased with age. Those with prior infection had antibody titres one magnitude order higher than naïve individuals regardless of the presence of detectable IgG antibodies pre-vaccination.