Follow-Up and Comparative Assessment of SARS-CoV-2 IgA, IgG, Neutralizing, and Total Antibody Responses After BNT162b2 or mRNA-1273 Heterologous Booster Vaccination.

BACKGROUND: Priming with ChAdOx1 followed by heterologous boosting is considered in several countries. Nevertheless, analyses comparing the immunogenicity of heterologous booster to homologous primary vaccination regimens and natural infection are lacking. In this study, we aimed to conduct a comparative assessment of the immunogenicity between homologous primary vaccination regimens and heterologous prime-boost vaccination using BNT162b2 or mRNA-1273. METHODS: We matched vaccinated naïve (VN) individuals (n = 673) with partial vaccination (n = 64), primary vaccination (n = 590), and primary series plus mRNA vaccine heterologous booster (n = 19) with unvaccinated naturally infected (NI) individuals with a documented primary SARS-CoV-2 infection (n = 206). We measured the levels of neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA titers. RESULTS: Homologous primary vaccination with ChAdOx1 not only showed less potent NTAb, TAb, anti-S-RBD IgG, and anti-S1 IgA immune responses compared to primary BNT162b2 or mRNA-1273 vaccination regimens (p < 0.05) but also showed ~3-fold less anti-S1 IgA response compared to infection-induced immunity (p < 0.001). Nevertheless, a heterologous booster led to an increase of ~12 times in the immune response when compared to two consecutive homologous ChAdOx1 immunizations. Furthermore, correlation analyses revealed that both anti-S-RBD IgG and anti-S1 IgA significantly contributed to virus neutralization among NI individuals, particularly in symptomatic and pauci-symptomatic individuals, whereas among VN individuals, anti-S-RBD IgG was the main contributor to virus neutralization. CONCLUSION: The results emphasize the potential benefit of using heterologous mRNA boosters to increase antibody levels and neutralizing capacity particularly in patients who received primary vaccination with ChAdOx1.

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

Overall effectiveness of infection in preventing reinfection with SARS-CoV-2 JN.1 variant was estimated at 1.8% (95% CI: -9.3-12.6%), and demonstrated rapid decline over time since the previous infection, decreasing from 82.4% (95% CI: 40.9 to 94.7%) within 3 to less than 6 months, to a negligible level after one year.

Understanding dynamics and overlapping epidemiologies of HIV, HSV-2, chlamydia, gonorrhea, and syphilis in sexual networks of men who have sex with men.

Introduction: We aimed to investigate the overlapping epidemiologies of human immunodeficiency virus (HIV), herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhea, and syphilis in sexual networks of men who have sex with men (MSM), and to explore to what extent the epidemiology of one sexually transmitted infection (STI) relates to or differs from that of another STI. Methods: An individual-based Monte Carlo simulation model was employed to simulate the concurrent transmission of STIs within diverse sexual networks of MSM. The model simulated sexual partnering, birth, death, and STI transmission within each specific sexual network. The model parameters were chosen based on the current knowledge and understanding of the natural history, transmission, and epidemiology of each considered STI. Associations were measured using the Spearman's rank correlation coefficient (SRCC) and maximal information coefficient (MIC). Results: A total of 500 sexual networks were simulated by varying the mean and variance of the number of partners for both short-term and all partnerships, degree correlation, and clustering coefficient. HSV-2 had the highest current infection prevalence across the simulations, followed by HIV, chlamydia, syphilis, and gonorrhea. Threshold and saturation effects emerged in the relationship between STIs across the simulated networks, and all STIs demonstrated moderate to strong associations. The strongest current infection prevalence association was between HIV and gonorrhea, with an SRCC of 0.84 (95% CI: 0.80-0.87) and an MIC of 0.81 (95% CI: 0.74-0.88). The weakest association was between HSV-2 and syphilis, with an SRCC of 0.54 (95% CI: 0.48-0.59) and an MIC of 0.57 (95% CI, 0.49-0.65). Gonorrhea exhibited the strongest associations with the other STIs while syphilis had the weakest associations. Across the simulated networks, proportions of the population with zero, one, two, three, four, and five concurrent STI infections were 48.6, 37.7, 11.1, 2.4, 0.3, and < 0.1%, respectively. For lifetime exposure to these infections, these proportions were 13.6, 21.0, 22.9, 24.3, 13.4, and 4.8%, respectively. Conclusion: STI epidemiologies demonstrate substantial overlap and associations, alongside nuanced differences that shape a unique pattern for each STI. Gonorrhea exhibits an "intermediate STI epidemiology," reflected by the highest average correlation coefficient with other STIs.

Effectiveness of two and three doses of COVID-19 mRNA vaccines against infection, symptoms, and severity in the pre-omicron era: A time-dependent gradient.

BACKGROUND: Vaccines were developed and deployed to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to characterize patterns in the protection provided by the BNT162b2 and mRNA-1273 mRNA vaccines against a spectrum of SARS-CoV-2 infection symptoms and severities. METHODS: A national, matched, test-negative, case-control study was conducted in Qatar between January 1 and December 18, 2021, utilizing a sample of 238,896 PCR-positive tests and 6,533,739 PCR-negative tests. Vaccine effectiveness was estimated against asymptomatic, symptomatic, severe coronavirus disease 2019 (COVID-19), critical COVID-19, and fatal COVID-19 infections. Data sources included Qatar's national databases for COVID-19 laboratory testing, vaccination, hospitalization, and death. RESULTS: Effectiveness of two-dose BNT162b2 vaccination was 75.6% (95% CI: 73.6-77.5) against asymptomatic infection and 76.5% (95% CI: 75.1-77.9) against symptomatic infection. Effectiveness against each of severe, critical, and fatal COVID-19 infections surpassed 90%. Immediately after the second dose, all categories-namely, asymptomatic, symptomatic, severe, critical, and fatal COVID-19-exhibited similarly high effectiveness. However, from 181 to 270 days post-second dose, effectiveness against asymptomatic and symptomatic infections declined to below 40%, while effectiveness against each of severe, critical, and fatal COVID-19 infections remained consistently high. However, estimates against fatal COVID-19 often had wide 95% confidence intervals. Analogous patterns were observed in three-dose BNT162b2 vaccination and two- and three-dose mRNA-1273 vaccination. Sensitivity analyses confirmed the results. CONCLUSION: A gradient in vaccine effectiveness exists and is linked to the symptoms and severity of infection, providing higher protection against more symptomatic and severe cases. This gradient intensifies over time as vaccine immunity wanes after the last vaccine dose. These patterns appear consistent irrespective of the vaccine type or whether the vaccination involves the primary series or a booster.

Antibody-dependent enhancement (ADE) of SARS-CoV-2 in patients exposed to MERS-CoV and SARS-CoV-2 antigens.

This study evaluated the potential for antibody-dependent enhancement (ADE) in serum samples from patients exposed to Middle East respiratory syndrome coronavirus (MERS-CoV). Furthermore, we evaluated the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination on ADE in individuals with a MERS infection history. We performed ADE assay in sera from MERS recovered and SARS-CoV-2-vaccinated individuals using BHK cells expressing FcgRIIa, SARS-CoV-2, and MERS-CoV pseudoviruses (PVs). Further, we analyzed the association of ADE to serum IgG levels and neutralization. Out of 16 MERS patients, nine demonstrated ADE against SARS-CoV-2 PV, however, none of the samples demonstrated ADE against MERS-CoV PV. Furthermore, out of the seven patients exposed to SARS-CoV-2 vaccination after MERS-CoV infection, only one patient (acutely infected with MERS-CoV) showed ADE for SARS-CoV-2 PV. Further analysis indicated that IgG1, IgG2, and IgG3 against SARS-CoV-2 S1 and RBD subunits, IgG1 and IgG2 against the MERS-CoV S1 subunit, and serum neutralizing activity were low in ADE-positive samples. In summary, samples from MERS-CoV-infected patients exhibited ADE against SARS-CoV-2 and was significantly associated with low levels of neutralizing antibodies. Subsequent exposure to SARS-CoV-2 vaccination resulted in diminished ADE activity while the PV neutralization assay demonstrated a broadly reactive antibody response in some patient samples.

Epidemiology of gonorrhoea: systematic review, meta-analyses, and meta-regressions, World Health Organization European Region, 1949 to 2021.

BackgroundEpidemiology of Neisseria gonorrhoeae (NG) infection remains inadequately understood.AimWe aimed to characterise NG epidemiology in Europe.MethodsWe used Cochrane and PRISMA guidelines to systematically review, report, synthesise and analyse NG prevalence data from 1949 to 30 September 2021. Random-effects meta-analyses estimated pooled prevalence. Meta-regression analyses investigated associations and sources of heterogeneity.ResultsThe 844 included publications yielded 1,573 prevalence measures. Pooled prevalence of current urogenital infection was 1.0% (95% CI: 0.7-1.2%) among general populations, 3.2% (95% CI: 1.8-4.8%) among female sex workers, 4.9% (95% CI: 4.2-5.6%) among sexually transmitted infection clinic attendees and 12.1% (95% CI: 8.8-15.8%) among symptomatic men. Among men who have sex with men, pooled prevalence was 0.9% (95% CI: 0.5-1.4%), 5.6% (95% CI: 3.6-8.1%), and 3.8% (95% CI: 2.5-5.4%), respectively, for current urogenital, anorectal or oropharyngeal infection. Current urogenital, anorectal or oropharyngeal infection was 1.45-fold (95% CI: 1.19-1.77%), 2.75-fold (95% CI: 1.89-4.02%) and 2.64-fold (95% CI: 1.77-3.93%) higher among men than women. Current urogenital infection declined 0.97-fold (95% CI: 0.96-0.98%) yearly, but anorectal and oropharyngeal infection increased (1.02-fold; 95% CI: 1.01-1.04% and 1.02-fold; 95% CI: 1.00-1.04%), respectively.ConclusionsNeisseria gonorrhoeae epidemiology in Europe has distinct and contrasting epidemiologies for vaginal sex transmission in heterosexual sex networks vs anal and oral sex transmission in MSM sexual networks. Increased transmission may facilitate drug-resistant strain emergence. Europe is far from achieving the World Health Organization target of 90% incidence reduction by 2030.

SARS-CoV-2 infection triggers more potent antibody-dependent cellular cytotoxicity (ADCC) responses than mRNA-, vector-, and inactivated virus-based COVID-19 vaccines.

Neutralizing antibodies (NAbs) are elicited after infection and vaccination and have been well studied. However, their antibody-dependent cellular cytotoxicity (ADCC) functionality is still poorly characterized. Here, we investigated ADCC activity in convalescent sera from infected patients with wild-type (WT) severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or omicron variant compared with three coronavirus disease 2019 (COVID-19) vaccine platforms and postvaccination breakthrough infection (BTI). We analyzed ADCC activity targeting SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in convalescent sera following WT SARS-CoV-2-infection (n = 91), including symptomatic and asymptomatic infections, omicron-infection (n = 8), COVID-19 vaccination with messenger RNA- (mRNA)- (BNT162b2 or mRNA-1273, n = 77), adenovirus vector- (n = 41), and inactivated virus- (n = 46) based vaccines, as well as post-mRNA vaccination BTI caused by omicron (n = 28). Correlations between ADCC, binding, and NAb titers were reported. ADCC was elicited within the first month postinfection and -vaccination and remained detectable for ≥3 months. WT-infected symptomatic patients had higher S-specific ADCC levels than asymptomatic and vaccinated individuals. Also, no difference in N-specific ADCC activity was seen between symptomatic and asymptomatic patients, but the levels were higher than the inactivated vaccine. Notably, omicron infection showed reduced overall ADCC activity compared to WT SARS-CoV-2 infection. Although post-mRNA vaccination BTI elicited high levels of binding and NAbs, ADCC activity was significantly reduced. Also, there was no difference in ADCC levels across the four vaccines, although NAbs and binding antibody titers were significantly higher in mRNA-vaccinated individuals. All evaluated vaccine platforms are inferior in inducing ADCC compared to natural infection with WT SARS-CoV-2. The inactivated virus-based vaccine can induce N-specific ADCC activity, but its relevance to clinical outcomes requires further investigation. Our data suggest that ADCC could be used to estimate the extra-neutralization level against COVID-19 and provides evidence that vaccination should focus on other Fc-effector functions besides NAbs. Also, the decreased susceptibility of the omicron variant to ADCC offers valuable guidance for forthcoming efforts to identify the specific targets of antibodies facilitating ADCC.

Addressing bias in the definition of SARS-CoV-2 reinfection: implications for underestimation.

Introduction: Reinfections are increasingly becoming a feature in the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, accurately defining reinfection poses methodological challenges. Conventionally, reinfection is defined as a positive test occurring at least 90 days after a previous infection diagnosis. Yet, this extended time window may lead to an underestimation of reinfection occurrences. This study investigated the prospect of adopting an alternative, shorter time window for defining reinfection. Methods: A longitudinal study was conducted to assess the incidence of reinfections in the total population of Qatar, from February 28, 2020 to November 20, 2023. The assessment considered a range of time windows for defining reinfection, spanning from 1 day to 180 days. Subgroup analyses comparing first versus repeat reinfections and a sensitivity analysis, focusing exclusively on individuals who underwent frequent testing, were performed. Results: The relationship between the number of reinfections in the population and the duration of the time window used to define reinfection revealed two distinct dynamical domains. Within the initial 15 days post-infection diagnosis, almost all positive tests for SARS-CoV-2 were attributed to the original infection. However, surpassing the 30-day post-infection threshold, nearly all positive tests were attributed to reinfections. A 40-day time window emerged as a sufficiently conservative definition for reinfection. By setting the time window at 40 days, the estimated number of reinfections in the population increased from 84,565 to 88,384, compared to the 90-day time window. The maximum observed reinfections were 6 and 4 for the 40-day and 90-day time windows, respectively. The 40-day time window was appropriate for defining reinfection, irrespective of whether it was the first, second, third, or fourth occurrence. The sensitivity analysis, confined to high testers exclusively, replicated similar patterns and results. Discussion: A 40-day time window is optimal for defining reinfection, providing an informed alternative to the conventional 90-day time window. Reinfections are prevalent, with some individuals experiencing multiple instances since the onset of the pandemic.

Impact of price reductions, subsidies, or financial incentives on healthy food purchases and consumption: a systematic review and meta-analysis.

Poor diets are a global concern and are linked with various adverse health outcomes. Healthier foods such as fruit and vegetables are often more expensive than unhealthy options. This study aimed to assess the effect of price reductions for healthy food (including fruit and vegetables) on diet. We performed a systematic review and meta-analysis on studies that looked at the effects of financial incentives on healthy food. Main outcomes were change in purchase and consumption of foods following a targeted price reduction. We searched electronic databases (MEDLINE, EconLit, Embase, Cinahl, Cochrane Library, and Web of Science), citations, and used reference screening to identify relevant studies from Jan 1, 2013, to Dec 20, 2021, without language restrictions. We stratified results by population targeted (low-income populations vs general population), the food group that the reduction was applied to (fruit and vegetables, or other healthier foods), and study design. Percentage price reduction was standardised to assess the effect in meta-analyses. Study quality was assessed using the Cochrane Risk of Bias tool and Newcastle-Ottawa Scale. 34 studies were eligible; 15 took place in supermarkets and eight took place in workplace canteens in high-income countries, and 21 were targeted at socioeconomically disadvantaged communities. Pooled analyses of 14 studies showed a price reduction of 20% resulted in increases in fruit and vegetable purchases by 16·62% (95% CI 12·32 to 20·91). Few studies had maintained the price reduction for over 6 months. In conclusion, price reductions can lead to increases in purchases of fruit and vegetables, potentially sufficient to generate health benefits, if sustained.

Estimating protection afforded by prior infection in preventing reinfection: Applying the test-negative study design.

The COVID-19 pandemic has highlighted the need to use infection testing databases to rapidly estimate effectiveness of prior infection in preventing reinfection ($P{E}_S$) by novel SARS-CoV-2 variants. Mathematical modeling was used to demonstrate a theoretical foundation for applicability of the test-negative, case-control study design to derive $P{E}_S$. Apart from the very early phase of an epidemic, the difference between the test-negative estimate for $P{E}_S$ and true value of $P{E}_S$ was minimal and became negligible as the epidemic progressed. The test-negative design provided robust estimation of $P{E}_S$ and its waning. Assuming that only 25% of prior infections are documented, misclassification of prior infection status underestimated $P{E}_S$, but the underestimate was considerable only when >50% of the population was ever infected. Misclassification of latent infection, misclassification of current active infection, and scale-up of vaccination all resulted in negligible bias in estimated $P{E}_S$. The test-negative design was applied to national-level testing data in Qatar to estimate $P{E}_S$ for SARS-CoV-2. $P{E}_S$ against SARS-CoV-2 Alpha and Beta variants was estimated at 97.0% (95% CI: 93.6-98.6) and 85.5% (95% CI: 82.4-88.1), respectively. These estimates were validated using a cohort study design. The test-negative design offers a feasible, robust method to estimate protection from prior infection in preventing reinfection.

Patterns and trends of hepatitis C virus infection in Jordan: an observational study.

Background: Hepatitis C virus (HCV) infection levels in Jordan remain uncertain. No HCV national population-based survey has ever been conducted in the country. To meet the World Health Organization's target of reducing HCV incidence to ≤5 per 100,000 people per year by 2030, it is essential to determine the infection levels, identify affected individuals and populations, and provide appropriate treatment using direct-acting antivirals to individuals carrying the virus. Methods: The study utilized the HCV testing database of 28,798 attendees of Biolab Diagnostic Laboratories in Jordan, covering the period from January 19, 2010, to May 26, 2023. Cross-sectional and cohort study analyses were conducted, including estimating HCV antibody (Ab) prevalence, examining associations with HCV Ab positivity, determining the HCV viremic rate, and estimating HCV incidence rate using a retrospective cohort study design. Results: A total of 27,591 individuals, with a median age of 31.3 and 52.9% being females, underwent HCV Ab testing, while 1,450 individuals, with a median age of 42.2 and 32.8% being females, underwent HCV RNA PCR testing. The study sample HCV Ab prevalence was 4.0% (95% CI: 3.7-4.2%). After applying probability weights, the weighted HCV Ab prevalence was 5.8% (95% CI: 4.6-7.3%). Age was strongly associated with HCV Ab positivity, particularly among individuals aged 50 years or older, who had 10-fold higher odds of being HCV Ab positive compared to those aged 10-19 years. Males had 2.41-fold higher odds of testing positive for HCV Ab compared to females. The HCV viremic rate was 54.1% (95% CI: 43.0-65.0%). The cumulative incidence of HCV infection, after 5 years of follow-up, was estimated to be 0.41% (95% CI: 0.17-0.99%). The HCV incidence rate was calculated at 1.19 per 1,000 person-years (95% CI, 0.50-2.87). Conclusion: Prevalence and incidence of HCV infection were substantial, estimated at ~5% and 1 per 1,000 person-years, respectively, and highlighting the presence of core groups actively engaged in the virus' acquisition and transmission. The high observed viremic rate indicates the need for expanding HCV treatment efforts to effectively control HCV transmission in Jordan. Utilizing quality diagnostic laboratories and innovative testing strategies is key to identifying infection carriers and facilitating linkage to treatment and care.

Vaccine value profile for Neisseria gonorrhoeae.

Neisseria gonorrhoeae infection (gonorrhoea) is a global public health challenge, causing substantial sexual and reproductive health consequences, such as infertility, pregnancy complications and increased acquisition or transmission of HIV. There is an urgency to controlling gonorrhoea because of increasing antimicrobial resistance to ceftriaxone, the last remaining treatment option, and the potential for gonorrhoea to become untreatable. No licensed gonococcal vaccine is available. Mounting observational evidence suggests that N. meningitidis serogroup B outer membrane vesicle-based vaccines may induce cross-protection against N. gonorrhoeae (estimated 30%-40% effectiveness using the 4CMenB vaccine). Clinical trials to determine the efficacy of the 4CMenB vaccine against N. gonorrhoeae are underway, as are Phase 1/2 studies of a new gonococcal-specific vaccine candidate. Ultimately, a gonococcal vaccine must be accessible, affordable and equitably dispensed, given that those most affected by gonorrhoea are also those who may be most disadvantaged in our societies, and most cases are in less-resourced settings. This vaccine value profile (VVP) provides a high level, holistic assessment of the current data to inform the potential public health, economic and societal value of pipeline vaccines. This was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations. All contributors have extensive expertise on various elements of the N. gonorrhoeae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using published data obtained from peer-reviewed journals or reports.

Seroprevalence of hepatitis E virus (HEV) among male craft and manual workers in Qatar (2020-2021).

Background: The rapid growth of Qatar in the last two decades has attracted a large influx of immigrant craft and manual workers (CMWs) seeking employment in jobs associated with food handling, domestic service, and construction. Nearly 60 % of Qatar's population are expatriates CMWs, including many from hyperendemic countries for HEV. Thus, estimating the seroprevalence of HEV in Qatar and understanding its epidemiology is essential for public health efforts to control HEV transmission in Qatar. Methods: Blood samples from 2670 CMWs were collected between 2020 and 2021. All samples were tested for HEV-IgG antibodies. Positive HEV-IgG samples were tested for HEV-IgM antibodies, and those positives were also tested for viral antigens using an HEV-Ag ELISA kit and HEV-RNA by RT-PCR to confirm current HEV infections. Results: The seroprevalence of HEV-IgG was 27.3 % (729/2670; 95 % CI: 25.6-29.0). Of those HEV-IgG positive, 8.23 % (60/729; 95 % CI: 6.30-10.5) were HEV-IgM positive. Of the IgM-positive samples, 2 were HEV-RNA positive (3.39 %; 95 % CI: 0.40-11.7), and 1 was HEV-Ag positive (1.69 %; 95 % CI: 0.04-9.09). In addition, HEV-IgG seroprevalence was associated with age and nationality, with the highest seroprevalence in participants from Egypt (IgG 60.0 %; IgM 5.56 %), Pakistan (IgG 59.0 %; IgM 2.24 %), Nepal (IgG 29.3 %; IgM 2.70 %), Bangladesh (IgG 27.8 %; IgM 2.45 %), and India (IgG 23.9 %; IgM 2.43 %). Conclusion: In this study, we showed that the seroprevalence of HEV among CMWs was slightly higher than what was previously reported among the urban population in Qatar (2013-2016).

SARS-CoV-2 infection and effects of age, sex, comorbidity, and vaccination among older individuals: A national cohort study.

BACKGROUND: We investigated the contribution of age, coexisting medical conditions, sex, and vaccination to incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of severe, critical, or fatal COVID-19 in older adults since pandemic onset. METHODS: A national retrospective cohort study was conducted in the population of Qatar aged ≥50 years between February 5, 2020 and June 15, 2023. Adjusted hazard ratios (AHRs) for infection and for severe coronavirus disease 2019 (COVID-19) outcomes were estimated through Cox regression models. RESULTS: Cumulative incidence was 25.01% (95% confidence interval [CI]: 24.86-25.15%) for infection and 1.59% (95% CI: 1.55-1.64%) for severe, critical, or fatal COVID-19 after a follow-up duration of 40.9 months. Risk of infection varied minimally by age and sex but increased significantly with coexisting conditions. Risk of infection was reduced with primary-series vaccination (AHR: 0.91, 95% CI: 0.90-0.93) and further with first booster vaccination (AHR: 0.75, 95% CI: 0.74-0.77). Risk of severe, critical, or fatal COVID-19 increased exponentially with age and linearly with coexisting conditions. AHRs for severe, critical, or fatal COVID-19 were 0.86 (95% CI: 0.7-0.97) for one dose, 0.15 (95% CI: 0.13-0.17) for primary-series vaccination, and 0.11 (95% CI: 0.08-0.14) for first booster vaccination. Sensitivity analysis restricted to only Qataris yielded similar results. CONCLUSION: Incidence of severe COVID-19 in older adults followed a dynamic pattern shaped by infection incidence, variant severity, and population immunity. Age, sex, and coexisting conditions were strong determinants of infection severity. Vaccine protection against severe outcomes showed a dose-response relationship, highlighting the importance of booster vaccination for older adults.

History of primary-series and booster vaccination and protection against Omicron reinfection.

Laboratory evidence suggests a possibility of immune imprinting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated the differences in the incidence of SARS-CoV-2 reinfection in a cohort of persons who had a primary Omicron infection, but different vaccination histories using matched, national, retrospective, cohort studies. Adjusted hazard ratio for reinfection incidence, factoring adjustment for differences in testing rate, was 0.43 [95% confidence interval (CI): 0.39 to 0.49] comparing history of two-dose vaccination to no vaccination, 1.47 (95% CI: 1.23 to 1.76) comparing history of three-dose vaccination to two-dose vaccination, and 0.57 (95% CI: 0.48 to 0.68) comparing history of three-dose vaccination to no vaccination. Divergence in cumulative incidence curves increased markedly when the incidence was dominated by BA.4/BA.5 and BA.2.75* Omicron subvariants. The history of primary-series vaccination enhanced immune protection against Omicron reinfection, but history of booster vaccination compromised protection against Omicron reinfection. These findings do not undermine the public health utility of booster vaccination.

Follow up and comparative assessment of IgG, IgA, and neutralizing antibody responses to SARS-CoV-2 between mRNA-vaccinated naïve and unvaccinated naturally infected individuals over 10 months.

BACKGROUND: Evidence on the effectiveness of vaccination-induced immunity compared to SARS-CoV-2 natural immunity is warranted to inform vaccination recommendations. AIM: In this study, we aimed to conduct a comparative assessment of antibody responses between vaccinated naïve (VN) and unvaccinated naturally infected individuals (NI) over 10 Months. METHOD: The study comprised fully-vaccinated naïve individuals (VN; n = 596) who had no history of SARS-CoV-2 infection, and received two doses of either BNT162b2 or mRNA-1273, and naturally infected individuals who had a documented history of SARS-CoV-2 infection and no vaccination record (NI cohort; n = 218). We measured the levels of neutralizing total antibodies (NtAbs), anti-S-RBD IgG, and anti-S1 IgA titers among VN and NI up to ∼10 months from administration of the first dose, and up to ∼7 months from SARS-CoV-2 infection, respectively. To explore the relationship between the antibody responses and time, Spearman's correlation coefficient was computed. Furthermore, correlations between the levels of NtAbs/anti-S-RBD IgG and NtAbs/anti-S1 IgA were examined through pairwise correlation analysis. RESULTS: Up to six months, VN individuals had a significantly higher NtAb and anti-S-RBD IgG antibody responses compared to NI individuals. At the 7th month, there was a significant decline in antibody responses among VN individuals, but not NI individuals, with a minimum decrease of 3.7-fold (p < 0.001). Among VN individuals, anti-S1 IgA levels began to decrease significantly (1.4-fold; p = 0.007) after two months, and both NtAb and S-RBD IgG levels began to decline significantly (NtAb: 2.0-fold; p = 0.042, S-RBD IgG: 2.4-fold; p = 0.035) after three months. After 10 months, the most significant decline among VN individuals was observed for S-RBD-IgG (30.0-fold; P < 0.001), followed by NtAb (15.7-fold; P < 0.001) and S-IgA (3.7-fold; P < 0.001) (most stable). Moreover, after 5 months, there was no significant difference in the IgA response between the two groups. CONCLUSION: These findings have important implications for policymakers in the development of vaccination strategies, particularly in the consideration of booster doses to sustain long-lasting protection against COVID-19.

Short- and longer-term all-cause mortality among SARS-CoV-2- infected individuals and the pull-forward phenomenon in Qatar: a national cohort study.

OBJECTIVES: We assessed short-, medium-, and long-term all-cause mortality risks after a primary SARS-CoV-2 infection. METHODS: A national, matched, retrospective cohort study was conducted in Qatar to assess risk of all-cause mortality in the national SARS-CoV-2 primary infection cohort compared with the national infection-naïve cohort. Associations were estimated using Cox proportional-hazards regression models. Analyses were stratified by vaccination status and clinical vulnerability status. RESULTS: Among unvaccinated persons, within 90 days after primary infection, the adjusted hazard ratio (aHR) comparing mortality incidence in the primary-infection cohort with the infection-naïve cohort was 1.19 (95% confidence interval 1.02-1.39). aHR was 1.34 (1.11-1.63) in persons more clinically vulnerable to severe COVID-19 and 0.94 (0.72-1.24) in those less clinically vulnerable. Beyond 90 days after primary infection, aHR was 0.50 (0.37-0.68); aHR was 0.41 (0.28-0.58) at 3-7 months and 0.76 (0.46-1.26) at ≥8 months. The aHR was 0.37 (0.25-0.54) in more clinically vulnerable persons and 0.77 (0.48-1.24) in less clinically vulnerable persons. Among vaccinated persons, mortality incidence was comparable in the primary-infection versus infection-naïve cohorts, regardless of clinical vulnerability status. CONCLUSIONS: COVID-19 mortality was primarily driven by an accelerated onset of death among individuals who were already vulnerable to all-cause mortality, but vaccination prevented these accelerated deaths.