Protection of natural infection against reinfection with SARS-CoV-2 JN.1 variant (preprint)

This study investigated the effectiveness of natural infection in preventing reinfection with the JN.1 variant during a large JN.1 wave in Qatar, using a test-negative case-control study design. The overall effectiveness of previous infection in preventing reinfection with JN.1 was estimated at only 1.8% (95% CI: -9.3-12.6%). This effectiveness demonstrated a rapid decline over time since the previous infection, decreasing from 82.4% (95% CI: 40.9-94.7%) within 3 to less than 6 months after the previous infection to 50.9% (95% CI: -11.8-78.7%) in the subsequent 3 months, and further dropping to 18.3% (95% CI: -34.6-56.3%) in the subsequent 3 months. Ultimately, it reached a negligible level after one year. The findings show that the protection of natural infection against reinfection with JN.1 is strong only among those who were infected within the last 6 months, with variants such as XBB*. However, this protection wanes rapidly and is entirely lost one year after the previous infection. The findings support considerable immune evasion by JN.1.

Population immunity of natural infection, primary-series vaccination, and booster vaccination in Qatar during the COVID-19 pandemic: An observational study (preprint)

Background: Waning of natural infection protection and vaccine protection highlight the need to evaluate changes in population immunity over time. Population immunity of previous SARS-CoV-2 infection or of COVID-19 vaccination are defined, respectively, as the overall protection against reinfection or against breakthrough infection at a given point in time in a given population. Methods: We estimated these population immunities in Qatar population between July 1, 2020 and November 30, 2022, to discern generic features of the epidemiology of SARS-CoV-2. Effectiveness of previous infection, mRNA primary-series vaccination, and mRNA booster (third-dose) vaccination in preventing infection were estimated, month by month, using matched, test-negative, case-control studies. Findings: Previous-infection effectiveness against reinfection was strong before emergence of Omicron, but declined with time after a wave and rebounded after a new wave. Effectiveness dropped immediately after Omicron emergence from 88.3% (95% CI: 84.8-91.0%) in November 2021 to 51.0% (95% CI: 48.3-53.6%) in December 2021. Primary-series effectiveness against infection was 84.0% (95% CI: 83.0-85.0%) in April 2021, soon after introduction of vaccination, before waning gradually to 52.7% (95% CI: 46.5-58.2%) by November of 2021. Effectiveness declined linearly by ~1 percentage point every 5 days. After Omicron emergence, effectiveness dropped suddenly from 52.7% (95% CI: 46.5-58.2%) in November 2021 to negligible levels in December 2021. Booster effectiveness dropped immediately after Omicron emergence from 83.0% (95% CI: 65.6 -91.6%) in November 2021 to 32.9% (95% CI: 26.7-38.5%) in December 2021, and continued to decline thereafter. Effectiveness of previous infection and vaccination against severe, critical, or fatal COVID-19 were generally >80% throughout the study duration. Interpretation: High population immunity may not be sustained beyond a year. This creates fertile grounds for repeated waves of infection to occur, but these waves may increasingly exhibit a benign pattern of infection. Funding: The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, Qatar University Biomedical Research Center, and Qatar University Internal Grant ID QUCG-CAS-23/24-114.

Short- and longer-term all-cause mortality among SARS-CoV-2- infected persons and the pull-forward phenomenon in Qatar (preprint)

Background: Risk of short- and long-term all-cause mortality after a primary SARS-CoV-2 infection is inadequately understood. Methods: A national, matched, retrospective cohort study was conducted in Qatar to assess the risk of all-cause mortality in the national cohort of people infected with SARS-CoV-2 compared with a reference national control cohort of uninfected persons. Associations were estimated using Cox proportional-hazards regression models. Results: Among unvaccinated persons, within 90 days after primary infection, adjusted hazard ratio (aHR) comparing incidence of death in the primary-infection cohort with the infection-naive cohort was 1.19 (95% CI: 1.02-1.39). The aHR was 1.34 (95% CI: 1.11-1.63) in persons more clinically vulnerable to severe COVID-19 and 0.94 (95% CI: 0.72-1.24) in those less clinically vulnerable to severe COVID-19. In subsequent follow-up, the aHR was 0.50 (95% CI: 0.37-0.68). The aHR was 0.41 (95% CI: 0.28-0.58) in months 3-7 after the primary infection and 0.76 (95% CI: 0.46-1.26) in subsequent months. The aHR was 0.37 (95% CI: 0.25-0.54) in persons more clinically vulnerable to severe COVID-19 and 0.77 (95% CI: 0.48-1.24) in those less clinically vulnerable to severe COVID-19. Among vaccinated persons, no evidence was found for differences in incidence of death in the primary-infection versus infection-naive cohorts, even among persons more clinically vulnerable to severe COVID-19. Conclusions: COVID-19 mortality in Qatar appears primarily driven by forward displacement of deaths of individuals with relatively short life expectancy and more clinically vulnerable to severe COVID-19. Vaccination negated the mortality displacement by preventing early deaths.

Dynamics of anti-S IgG antibodies titers after the second dose of COVID 19 mRNA and non-mRNA vaccines in the manual and craft worker population of Qatar (preprint)

Background: There is limited sero epidemiological evidence on the magnitude and long-term durability of antibody titers of mRNA and non-mRNA vaccines in the Qatari population. This study was conducted to generate evidence on long-term anti-S IgG antibodies titers and their dynamics in individuals who have completed a primary COVID-19 vaccination schedule. Methods: A total of 300 participants who received any of the following vaccines BNT162b2/Comirnaty or mRNA-1273 or ChAdOx1-S/Covishield or COVID-19 Vaccine Janssen/Johnson or BBIBP-CorV or Covaxin were enrolled in our study. All sera samples were tested by chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of IgG antibodies to SARS-CoV-2, receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2. Antibodies against SARS-CoV-2 nucleocapsid (SARS-CoV-2 N-protein IgG) were also determined. Kaplan-Meier survival curves were used to compare the time from the last dose of the primary vaccination schedule to the time by which anti-S IgG antibodies titers fell into the lowest quartile (range of values collected) for the mRNA and non-mRNA vaccines. Results: Participants vaccinated with mRNA vaccines had higher median anti-S IgG antibody titers. Participants vaccinated with the mRNA-1273 vaccine had the highest median anti-S-antibody level of 13720.9 AU/mL (IQR 6426.5 to 30185.6 AU/mL) followed by BNT162b2 (median, 7570.9 AU/ml; IQR, 3757.9 to 16577.4 AU/mL); while the median anti-S antibody titer for non-mRNA vaccinated participants was 3759.7 AU/mL (IQR, 2059.7-5693.5 AU/mL). The median time to reach the lowest quartile was 3.53 months (IQR, 2.2-4.5 months) and 7.63 months (IQR, 6.3-8.4 months) for the non-mRNA vaccine recipients and Pfizer vaccine recipients, respectively. However, more than 50% of the Moderna vaccine recipients did not reach the lowest quartile by the end of the follow-up period. Conclusions: This evidence on anti-S IgG antibody titers, their durability and decay over time should be considered for the utility of these assays in transmission dynamics after the full course of primary vaccination.

Immune protection against SARS-CoV-2 re-reinfection and immune imprinting (preprint)

We investigated epidemiological evidence for immune imprinting by comparing incidence of re-reinfection in the national cohort of individuals with a documented Omicron (BA.1/BA.2) reinfection after a pre-Omicron primary infection (designated as the reinfection cohort), to incidence of reinfection in the national cohort of individuals with a documented Omicron (BA.1/BA.2) primary infection (designated as the primary-infection cohort). This was done using a matched, retrospective cohort study that emulated a randomized target trial. Vaccinated individuals were excluded. Associations were estimated using Cox proportional-hazard regression models. Cumulative incidence of infection was 1.1% (95% CI: 0.8-1.4%) for the reinfection cohort and 2.1% (95% CI: 1.8-2.3%) for the primary-infection cohort, 135 days after the start of follow-up. The adjusted hazard ratio (aHR) for infection was 0.52 (95% CI: 0.40-0.68), comparing incidence in the reinfection cohort to that in the primary-infection cohort. The aHR was 0.59 (95% CI: 0.40-0.85) in a subgroup analysis in which primary infection in the reinfection cohort was restricted to only the index virus or Alpha variant. In the first 70 days of follow-up, when incidence was dominated by BA.2, the aHR was 0.92 (95% CI: 0.51-1.65). However, cumulative incidence curves diverged when BA.4/BA.5 subvariants dominated incidence (aHR, 0.46 (95% CI: 0.34-0.62)). There was no evidence that immune imprinting compromises protection against Omicron subvariants. However, there was evidence that having two infections, one with a pre-Omicron variant followed by one with an Omicron subvariant, elicits stronger protection against future Omicron-subvariant reinfection than having had only one infection with an Omicron subvariant.