SARS-CoV-2 Breakthrough Infections According to the Immune Response Elicited after mRNA Third Dose Vaccination in COVID-19-Naïve Hospital Personnel.

BACKGROUND: Vaccine-induced SARS-CoV-2-anti-spike antibody (anti-S/RBD) titers are often used as a marker of immune protection and to anticipate the risk of breakthrough infections, although no clear cut-off is available. We describe the incidence of SARS-CoV-2 vaccine breakthrough infections in COVID-19-free personnel of our hospital, according to B- and T-cell immune response elicited one month after mRNA third dose vaccination. METHODS: The study included 487 individuals for whom data on anti-S/RBD were available. Neutralizing antibody titers (nAbsT) against the ancestral Whuan SARS-CoV-2, and the BA.1 Omicron variant, and SARS-CoV-2 T-cell specific response were measured in subsets of 197 (40.5%), 159 (32.6%), and 127 (26.1%) individuals, respectively. RESULTS: On a total of 92,063 days of observation, 204 participants (42%) had SARS-CoV-2 infection. No significant differences in the probability of SARS-CoV-2 infection for different levels of anti-S/RBD, nAbsT, Omicron nAbsT, or SARS-CoV-2 T cell specific response, and no protective thresholds for infection were found. CONCLUSIONS: Routine testing for vaccine-induced humoral immune response to SARS-CoV-2 is not recommended if measured as parameters of 'protective immunity' from SARS-CoV-2 after vaccination. Whether these findings apply to new Omicron-specific bivalent vaccines is going to be evaluated.

Breakthrough infections and acceptance of COVID-19 vaccine boosters: A survey analysis.

Objective: This Short Communication explores the effect of COVID-19 breakthrough infections (defined as a COVID-19 diagnosis after vaccination) on the willingness of previously vaccinated individuals to receive ongoing vaccine boosters. Specifically, we examine unique effects for three different breakthrough infection experiences, including the participant themselves, a close member of their family, and a friend/coworker. Methods: A representative, web-based survey of 600 adults in the state of Florida was fielded in March/April of 2022. Among the respondents, 455 had been vaccinated against COVID-19. Their responses were analyzed for this study using both descriptive and inferential statistical methods. Results: Individuals who have experienced a personal breakthrough infection are two times less likely to receive annual vaccine boosters, ceteris paribus. However, there is not a statistically significant relationship between vaccine acceptance and breakthrough infections among close family members or friends/coworkers. We also found a very strong relationship between vaccine decisions and confidence in public health guidance. Conclusion: Our findings show that confidence in public health guidelines is the most compelling determinant of vaccine acceptance, but breakthrough infections also have a significant impact on individual decision making when it comes to ongoing vaccination. Going forward, public health messaging should directly account for this correlation in order to effectively maintain vaccination levels. Innovation: The COVID-19 pandemic marked a turning point in the development and deployment of mRNA vaccines. This study contributes to innovation in health communication research by examining how breakthrough infections in these vaccinated individuals impacts ongoing booster shot acceptance. The findings of this study contribute to the nascent and ongoing development of baseline research in this area.

Breakthrough infections due to SARS-CoV-2 Delta variant: relation to humoral and cellular vaccine responses.

Introduction: COVID-19 vaccines are expected to provide effective protection. However, emerging strains can cause breakthrough infection in vaccinated individuals. The immune response of vaccinated individuals who have experienced breakthrough infection is still poorly understood. Methods: Here, we studied the humoral and cellular immune responses of fully vaccinated individuals who subsequently experienced breakthrough infection due to the Delta variant of SARS-CoV-2 and correlated them with the severity of the disease. Results: In this study, an effective humoral response alone was not sufficient to induce effective immune protection against severe breakthrough infection, which also required effective cell-mediated immunity to SARS-CoV-2. Patients who did not require oxygen had significantly higher specific (p=0.021) and nonspecific (p=0.004) cellular responses to SARS-CoV-2 at the onset of infection than those who progressed to a severe form. Discussion: Knowing both humoral and cellular immune response could allow to adapt preventive strategy, by better selecting patients who would benefit from additional vaccine boosters. Trial registration numbers: https://clinicaltrials.gov, identifier NCT04355351; https://clinicaltrials.gov, identifier NCT04429594.

Vaccination Ameliorates Cellular Inflammatory Responses in SARS-CoV-2 Breakthrough Infections.

BACKGROUND: Data on cellular immune responses in persons with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection following vaccination are limited. The evaluation of these patients with SARS-CoV-2 breakthrough infections may provide insight into how vaccinations limit the escalation of deleterious host inflammatory responses. METHODS: We conducted a prospective study of peripheral blood cellular immune responses to SARS-CoV-2 infection in 21 vaccinated patients, all with mild disease, and 97 unvaccinated patients stratified based on disease severity. RESULTS: We enrolled 118 persons (aged 50 years [SD 14.5 years], 52 women) with SARS-CoV-2 infection. Compared to unvaccinated patients, vaccinated patients with breakthrough infections had a higher percentage of antigen-presenting monocytes (HLA-DR+), mature monocytes (CD83+), functionally competent T cells (CD127+), and mature neutrophils (CD10+); and lower percentages of activated T cells (CD38+), activated neutrophils (CD64+), and immature B cells (CD127+CD19+). These differences widened with increased disease severity in unvaccinated patients. Longitudinal analysis showed that cellular activation decreased over time but persisted in unvaccinated patients with mild disease at 8-month follow-up. CONCLUSIONS: Patients with SARS-CoV-2 breakthrough infections exhibit cellular immune responses that limit the progression of inflammatory responses and suggest mechanisms by which vaccination limits disease severity. These data may have implications for developing more effective vaccines and therapies. Clinical Trials Registration. NCT04401449.

Patients' Post-/Long-COVID Symptoms, Vaccination and Functional Status-Findings from a State-Wide Online Screening Study.

(1) Background: Better understanding of post-/long-COVID and limitations in daily life due to the symptoms as well as the preventive potential of vaccinations is required. It is unclear whether the number of doses and timepoint interrelate with the trajectory of post-/long-COVID. Accordingly, we examined how many patients positively screened with post-/long-COVID were vaccinated and whether the vaccination status and the timepoint of vaccination in relation to the acute infection were related to post-/long-COVID symptom severity and patients' functional status (i.e., perceived symptom severity, social participation, workability, and life satisfaction) over time. (2) Methods: 235 patients suffering from post-/long-COVID were recruited into an online survey in Bavaria, Germany, and assessed at baseline (T1), after approximately three weeks (T2), and approximately four weeks (T3). (3) Results: 3.5% were not vaccinated, 2.3% were vaccinated once, 20% twice, and 53.3% three times. Overall, 20.9% did not indicate their vaccination status. The timepoint of vaccination was related to symptom severity at T1, and symptoms decreased significantly over time. Being vaccinated more often was associated with lower life satisfaction and workability at T2. (4) Conclusions: This study provides evidence to get vaccinated against SARS-CoV-2, as it has shown that symptom severity was lower in those patients who were vaccinated prior to the infection compared to those getting infected prior to or at the same time of the vaccination. However, the finding that being vaccinated against SARS-CoV-2 more often correlated with lower life satisfaction and workability requires more attention. There is still an urgent necessity for appropriate treatment for overcoming long-/post-COVID symptoms efficiently. Vaccination can be part of prevention measures, and there is still a need for a communication strategy providing objective information about the usefulness and risks of vaccinations.

Clinical features and severe outcome predictors of COVID-19 vaccine breakthrough infection among hospitalized patients: results from Egypt severe acute respiratory infections sentinel surveillance, 2021-2022.

BACKGROUND: COVID-19 vaccines are effective against infections and outcomes; however, breakthrough infections (VBT) are increasingly reported, possibly due to waning of vaccine-induced immunity or emerging variants. Most studies have focused on determining VBT rate based on antibody levels. This study aims at describing clinical features, risks, time trends, and outcomes of COVID-19 VBT among hospitalized patients in Egypt. METHODS: Data of SARS-CoV-2 confirmed patients hospitalized in 16 hospitals was obtained from the severe acute respiratory infections surveillance database, September 2021-April 2022. Data includes patients' demographics, clinical picture, and outcomes. Descriptive analysis was performed and patients with VBT were compared to not fully vaccinated (UPV). Bivariate and multivariate analyses were performed using Epi Info7 with a significance level < 0.05 to identify VBT risk factors. RESULTS: Overall, 1,297 patients enrolled, their mean age 56.7 ± 17.0 years, 41.5% were males, 64.7% received inactivated, 25.% viral vector, and 7.7% mRNA vaccine. VBT was identified in 156(12.0%) patients with an increasing trend over time. VBT significantly was higher in (16-35 years) age, males, in those who received inactivated vaccine compared to corresponding groups of UPV (14.1 vs. 9.0%, p < 0.05 and 57.1 vs. 39.4%, p < 0.001 and 64.7 vs. 45.1, p < 0.01 respectively). Whereas receiving mRNA vaccine was significantly protective against VBT (7.7 vs. 21.6%, p < 001). VBT patients tend to have shorter hospital stays and lower case fatality (mean hospital days = 6.6 ± 5.5 vs. 7.9 ± 5.9, p < 0.01 and CFR = 28.2 vs. 33.1, p < 0.01 respectively). MVA identified younger ages, male gender, and inactivated vaccines as risks for VBT. CONCLUSION: The study indicated that COVID-19 vaccines significantly reduce hospital days and fatality. VBT trend is on the rise and males, young ages, and inactivated vaccine receivers are at higher risk. Caution regarding relaxation of personal preventive measures in areas with higher or increasing incidences of COVID-19, particularly for the at-risk group even if they are vaccinated. The vaccination strategy should be revised to reduce VBT rate and increase vaccine effectiveness.

Variants of SARS-CoV-2: Influences on the Vaccines' Effectiveness and Possible Strategies to Overcome Their Consequences.

The immune response elicited by the current COVID-19 vaccinations declines with time, especially among the immunocompromised population. Furthermore, the emergence of novel SARS-CoV-2 variants, particularly the Omicron variant, has raised serious concerns about the efficacy of currently available vaccines in protecting the most vulnerable people. Several studies have reported that vaccinated people get breakthrough infections amid COVID-19 cases. So far, five variants of concern (VOCs) have been reported, resulting in successive waves of infection. These variants have shown a variable amount of resistance towards the neutralising antibodies (nAbs) elicited either through natural infection or the vaccination. The spike (S) protein, membrane (M) protein, and envelope (E) protein on the viral surface envelope and the N-nucleocapsid protein in the core of the ribonucleoprotein are the major structural vaccine target proteins against COVID-19. Among these targets, S Protein has been extensively exploited to generate effective vaccines against COVID-19. Hence, amid the emergence of novel variants of SARS-CoV-2, we have discussed their impact on currently available vaccines. We have also discussed the potential roles of S Protein in the development of novel vaccination approaches to contain the negative consequences of the variants' emergence and acquisition of mutations in the S Protein of SARS-CoV-2. Moreover, the implications of SARS-CoV-2's structural proteins were also discussed in terms of their variable potential to elicit an effective amount of immune response.

COVID-19 Breakthrough Infection Among Vaccinated Population in the United Arab Emirates.

BACKGROUND: Despite significant efforts to contain the Coronavirus Disease 2019 (COVID-19) pandemic through mass vaccination, numerous nations throughout the world have recorded breakout infections. The incidence and severity of COVID-19 breakthrough infections in the United Arab Emirates (UAE) remain unknown despite extensive COVID-19 vaccine coverage. The goal of this research is to establish the characteristics of COVID-19 breakthrough infections in the UAE's vaccinated population. METHODS: Between February and March 2022, we conducted a descriptive cross-sectional study in the UAE with 1533 participants to examine the characteristics of COVID-19 breakthrough infection among the vaccinated population. RESULTS: The vaccination coverage was 97.97%, and the COVID-19 breakthrough infection rate was 32.1%, requiring hospitalization in 7.7% of cases. The bulk of the 492 COVID-19 breakthrough infections reported was among young adults (67%), with the majority experiencing mild to moderate symptoms (70.7%) or remaining asymptomatic (21.5%). CONCLUSIONS: COVID-19 breakthrough infection were reported in younger age, male sex, non-healthcare professions, vaccination with inactivated whole virus vaccine (Sinopharm), and not receiving a booster dose. Information on breakthrough infection in the UAE might influence public health decisions and motivate measures such as providing additional booster doses of the vaccines to the people.

Severe acute respiratory syndrome coronavirus 2 vaccine breakthrough infections: A single metro-based testing network experience.

Objectives: Understanding the incidence and characteristics that influence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infections (VBIs) is imperative for developing public health policies to mitigate the coronavirus disease of 2019 (COVID-19) pandemic. We examined these factors and post-vaccination mitigation practices in individuals partially and fully vaccinated against SARS-CoV-2. Materials and methods: Adults >18 years old were voluntarily enrolled from a single metro-based SARS-CoV-2 testing network from January to July 2021. Participants were categorized as asymptomatic or symptomatic, and as unvaccinated, partially vaccinated, or fully vaccinated. All participants had confirmed SARS-CoV-2 infection based on standard of care (SOC) testing with nasopharyngeal swabs. Variant analysis by rRT-PCR was performed in a subset of time-matched vaccinated and unvaccinated individuals. A subgroup of partially and fully vaccinated individuals with a positive SARS-CoV-2 rRT-PCR was contacted to assess disease severity and post-vaccination mitigation practices. Results: Participants (n = 1,317) voluntarily underwent testing for SARS-CoV-2 during the enrollment period. A total of 29.5% of the population received at least one SARS-CoV-2 vaccine (n = 389), 12.8% partially vaccinated (n = 169); 16.1% fully vaccinated (n = 213). A total of 21.3% of partially vaccinated individuals tested positive (n = 36) and 9.4% of fully vaccinated individuals tested positive (n = 20) for SARS-CoV-2. Pfizer/BioNTech mRNA-1273 was the predominant vaccine received (1st dose = 66.8%, 2nd dose = 67.9%). Chronic liver disease and immunosuppression were more prevalent in the vaccinated (partially/fully) group compared to the unvaccinated group (p = 0.003, p = 0.021, respectively). There were more asymptomatic individuals in the vaccinated group compared to the unvaccinated group [n = 6 (10.7%), n = 16 (4.1%), p = 0.045]. CT values were lower for the unvaccinated group (median 24.3, IQR 19.1-30.5) compared to the vaccinated group (29.4, 22.0-33.7, p = 0.004). In the vaccinated group (n = 56), 18 participants were successfully contacted, 7 were lost to follow-up, and 2 were deceased. A total of 50% (n = 9) required hospitalization due to COVID-19 illness. Adherence to nationally endorsed mitigation strategies varied post-vaccination. Conclusion: The incidence of SARS-CoV-2 infection at this center was 21.3% in the partially vaccinated group and 9.4% in the fully vaccinated group. Chronic liver disease and immunosuppression were more prevalent in the vaccinated SARS-CoV-2 positive group, suggesting that these may be risk factors for VBIs. Partially and fully vaccinated individuals had a higher incidence of asymptomatic SARS-CoV-2 and higher CT values compared to unvaccinated SARS-CoV-2 positive individuals.

Resident Factors Associated With Breakthrough SARS-CoV-2 Infections.

OBJECTIVE: To examine incidence of and resident characteristics associated with breakthrough infections (BTIs) and severe illness among residents with 2 messenger RNA (mRNA) vaccinations. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Nursing home (NH) residents who completed their primary series of mRNA COVID-19 vaccination by March 31, 2021. METHODS: Electronic health records and Minimum Data Set assessments from a multistate NH data consortium were used to identify BTI and severe illness (a composite measure of hospitalization and/or death within 30 days of BTI) occurring prior to November 24, 2021. A t test for differences in means was used to compare covariates for residents with and without BTI. Finally, we estimated incidence rate ratios (IRRs) for BTI with 95% CIs using a modified Poisson regression approach, comparing residents with BTI vs residents without. We adjusted for facility fixed effects in our model. RESULTS: Our sample included 23,172 residents from 984 NHs who were at least 14 days past their second mRNA vaccine dose. Of those, 1173 (5%) developed an incident COVID-19 BTI (mean follow-up time: 250 days). Among residents with BTI, 8.6% were hospitalized or died within 30 days of BTI diagnosis. Factors associated with severe illness included age ≥85 years (IRR 2.08, 95% CI 1.08-4.02, reference age <65 years), bowel incontinence (IRR 1.73, 95% CI 1.01-2.99), coronary artery disease (IRR 1.96, 95% CI 1.31-2.94), chronic kidney disease (IRR 1.65, 95% CI 1.07-2.54), and schizophrenia (IRR 2.38, 95% CI 1.19-4.75). CONCLUSIONS AND IMPLICATIONS: Among vaccinated NH residents, BTIs and associated severe illness are rare. Residents aged ≥85 years and with certain comorbidities appear to be the most vulnerable. Given that the pandemic continues and testing policies have relaxed, these data provide prognostic information for NH facilities faced with continued outbreaks.

Effect of a Fourth Dose of mRNA Vaccine and of Immunosuppression in Preventing SARS-CoV-2 Breakthrough Infections in Heart Transplant Patients.

Patients with heart transplantation (HT) have an increased risk of COVID-19 disease and the efficacy of vaccines on antibody induction is lower, even after three or four doses. The aim of our study was to assess the efficacy of four doses on infections and their interplay with immunosuppression. We included in this retrospective study all adult HT patients (12/21-11/22) without prior infection receiving a third or fourth dose of mRNA vaccine. The endpoints were infections and the combined incidence of ICU hospitalizations/death after the last dose (6-month survival rate). Among 268 patients, 62 had an infection, and 27.3% received four doses. Following multivariate analysis, three vs. four doses, mycophenolate (MMF) therapy, and HT < 5 years were associated with an increased risk of infection. MMF ≥ 2000 mg/day independently predicted infection, together with the other variables, and was associated with ICU hospitalization/death. Patients on MMF had lower levels of anti-RBD antibodies, and a positive antibody response after the third dose was associated with a lower probability of infection. In HT patients, a fourth dose of vaccine against SARS-CoV-2 reduces the risk of infection at six months. Mycophenolate, particularly at high doses, reduces the clinical effectiveness of the fourth dose and the antibody response to the vaccine.

SARS-CoV-2 Breakthrough Infections after Third Doses Boost IgG Specific Salivary and Blood Antibodies.

SARS-CoV-2 breakthrough infections, associated with waning immunity, increase systemic antibody levels. In this study, we analyzed the impact of the infection timing on the magnitude of the systemic humoral response and whether breakthrough infections also boost antibody levels in the salivary compartment. We observed that the combination of infection plus vaccination, regardless of infection timing, produced a sharp increase in systemic antibodies, which were higher in subjects infected after third doses. Moreover, despite high systemic antibody levels, breakthrough infections after dose three occurred and boosted antibody levels in the salivary compartment. These results suggest that current vaccination strategies against COVID-19 should be improved. Results also showed that determination of salivary antibodies against SARS-CoV-2 could be a valuable tool in disease prevalence studies, for the follow-up of vaccinated individuals, and to assist vaccination strategies against COVID-19, especially in settings where blood sampling cannot be fulfilled.

COVID-19 breakthrough infections and hospitalizations among vaccinated patients with dementia in the United States between December 2020 and August 2021.

INTRODUCTION: There is lack of data on COVID-19 breakthrough infections in vaccinated patients with dementia in the United States. METHODS: This is a retrospective cohort study of 262,847 vaccinated older adults (age 73.8 ± 6.81 years old) between December 2020 and August 2021. RESULTS: Among the fully vaccinated patients with dementia, the overall risk of COVID-19 breakthrough infections ranged from 8.6% to 12.4%. Patients with dementia were at increased risk for breakthrough infections compared with patients without dementia, with the highest odds for patients with Lewy body dementia (LBD) (adjusted odds ratio or AOR: 3.06, 95% confidence interval or CI [1.45 to 6.66]), followed by vascular dementia (VD) (AOR: 1.99, 95% CI [1.42 to 2.80]), Alzheimer's disease (AD) (1.53, 95% CI [1.22 to 1.92]), and mild cognitive impairment (MCI) (AOR: 1.78, 95% CI [1.51 to 2.11]). The incidence rate of breakthrough infections among fully vaccinated patients with dementia increased since December 2020 and accelerated after May 2021. The overall risk for hospitalization after breakthrough infections in patients with dementia was 39.5% for AD, 46.2% for VD, and 30.4% for MCI. DISCUSSION: These results highlight the need to continuously monitor breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and outcomes in vaccinated patients with dementia.

Molecular epidemiology of SARS-CoV-2 in healthcare workers and identification of viral genomic correlates of transmissibility and vaccine break through infection: A retrospective observational study from a cancer hospital in eastern India.

PURPOSE: Despite COVID vaccination with ChAdOx1 ncov-19 (COVISHIELD®) (ChAdOx1 ncov-19) a large number of healthcare workers (HCWs) were getting infected in wave-2 of the pandemic in a cancer hospital of India. It was important therefore to determine the genotypes responsible for vaccine breakthrough infections. METHODS & OBJECTIVES: Retrospective observational study of HCWs. Whole genome sequencing of SARS CoV-2 using Illumina NovaSeq was done. Mutations from both waves were compared to identify genomic correlates of transmissibility and vaccine breakthrough infections. RESULTS: Vaccine breakthrough infections were seen in 127 HCWs out of 1806 fully vaccinated staff (7.03%). Median number of HCWs infected per day in wave-1 was 0.92 versus 3.25 in wave-2. Majority of wave-1 samples belonged to B.1 and B.1.1 lineage. Variant of concern- Delta variant (90%), and variant of interest- Kappa variant (10%), was seen in only wave-2 samples. Total mutation observed in wave-2 samples (median â€‹= â€‹44) was 1.8 times than wave-1 sample (median â€‹= â€‹24). Spike protein in wave-2 samples had 13 non-synonymous mutation as compared to 8 seen in wave-1 samples. E484Q-vaccine escape mutant was detected in five samples of wave-2; T478K - highly infectious mutation was seen in 31 samples of wave-2. We identified a novelcoding disruptive in-frame deletion (c.467_472delAGTTCA, p. Glu156_Arg158delinsGly) in the Spike protein. This mutation was seen only in wave-2 (78%, n â€‹= â€‹39) samples. CONCLUSION: The circulating virus strains in wave-2 infections demonstrated a greater degree of infectivity. There was a significant change in the genotypes observed in wave-1 and wave-2 infections along with almost twice the number of mutations. We noted that vaccine breakthrough infections (although mostly mild).

Impact of Omicron Variant Infection on Assessment of Spike-Specific Immune Responses Using the EUROIMMUN Quan-T-Cell SARS-CoV-2 Assay and Roche Elecsys Anti-SARS-CoV-2-S.

The currently prevailing variants of SARS-CoV-2 are subvariants of the Omicron variant. The aim of this study was to analyze the effect of mutations in the Spike protein of Omicron on the results Quan-T-Cell SARS-CoV-2 assays and Roche Elecsys anti-SARS-CoV-2 anti-S1. Omicron infected subjects ((n = 37), vaccinated (n = 20) and unvaccinated (n = 17)) were recruited approximately 3 weeks after a positive PCR test. The Quan-T-Cell SARS-CoV-2 assays (EUROIMMUN) using Wuhan and the Omicron adapted antigen assay and a serological test (Roche Elecsys anti-SARS-CoV-2 anti-S1) were performed. Using the original Wuhan SARS-CoV-2 IGRA TUBE, in 19 of 21 tested Omicron infected subjects, a positive IFNy response was detected, while 2 non-vaccinated but infected subjects did not respond. The Omicron adapted antigen tube resulted in comparable results. In contrast, the serological assay detected a factor 100-fold lower median Spike-specific RBD antibody concentration in non-vaccinated Omicron infected patients (n = 12) compared to patients from the pre Omicron era (n = 12) at matched time points, and eight individuals remained below the detection threshold for positivity. For vaccinated subjects, the Roche assay detected antibodies in all subjects and showed a 400 times higher median specific antibody concentration compared to non-vaccinated infected subjects in the pre-Omicron era. Our results suggest that Omicron antigen adapted IGRA stimulator tubes did not improve detection of SARS-CoV-2-specific T-cell responses in the Quant-T-Cell-SARS-CoV-2 assay. In non-vaccinated Omicron infected individuals, the Wuhan based Elecsys anti-SARS-CoV-2 anti-S1 serological assay results in many negative results at 3 weeks after diagnosis.

Significant neutralizing escapes of Omicron and its sublineages in SARS-CoV-2-infected individuals vaccinated with inactivated vaccines.

In China, most SARS-CoV-2-infected individuals had been vaccinated with inactivated vaccines. However, little is known about their immune resistances to the previous variants of concerns (VOCs) and the current Omicron sublineages. Here, we collected convalescent serum samples from SARS-CoV-2-infected individuals during the ancestral, Delta, and Omicron BA.1 waves, and evaluated their cross-neutralizing antibodies (nAbs) against the previous VOCs and the current Omicron sublineages using VSV-based pseudoviruses. In the convalescents who had been unvaccinated and vaccinated with two doses of inactivated vaccines, we found infections from either the ancestral or the Delta strain elicited moderate cross-nAbs to previous VOCs, but very few cross-nAbs to the Omicron sublineages, including BA.1, BA.2, BA.3, and BA.4/5. The individuals who had been vaccinated with two doses of inactivated vaccines before Omicron BA.1 infection had moderate nAbs to Omicron BA.1, but weak cross-nAbs to the other Omicron sublineages. While three doses of inactivated vaccines followed Omicron BA.1 infection induced elevated and still weak cross-nAbs to other Omicron sublineages. Our results indicate that the Omicron sublineages show significant immune escape in the previously SARS-CoV-2-infected individuals and thus highlights the importance of vaccine boosters in this population.

Breakthrough Sars-Cov-2 infection after Covid-19 vaccination - A retrospective observational clinico-epidemiological study from North-Western India

Introduction: Mass vaccination is considered one of the most crucial weapons in fighting against the ongoing COVID-19 pandemic. However, the occurrence of breakthrough infections (BTIs) has questioned the vaccine effectiveness of the currently available vaccines. The present study aimed to determine the breakthrough SARS-CoV-2 infections in the vaccinated population and to compare the clinic-epidemiological profile and outcomes between breakthrough cases and unvaccinated SARS-CoV-2 positive cases. Methods: This retrospective case-control study was conducted between April 15, 2021, and June 15, 2021, in a zonal military hospital in Jaipur. We evaluated individuals with BTI as cases which were SARS-CoV-2 positive after 14 days of the second dose of vaccine and unvaccinated SARS-CoV-2-positive individuals as control. The clinical and demographic data was collected from the Indian Council of Medical Research and specimen referral forms were filled out for all persons who had undergone testing for SARS-CoV-2. The outcome of positive cases in terms of discharge and deaths were collected from hospital records. Results: A total of 162 breakthrough COVID 19 infections and 925 unvaccinated positive confirmed controls were recorded within the study duration. The majority of cases presented with mild infection in both case (80.2%) and control groups (72.4%). The risk of hospitalization and occurrence of moderate to severe disease was 2.3 and 4 times more in the non-vaccinated group as compared to the vaccinated group, respectively. No mortality was reported among the breakthrough cases. Interpretation and Conclusions: Despite the occurrence of BTIs, the benefits of vaccines are far greater. Our findings suggest that vaccination is associated with a lower risk of hospital admission, severe disease, and mortality against COVID-19. © 2022 Medical Journal of Dr. D.Y. Patil Vidyapeeth ;Published by Wolters Kluwer - Medknow.

Upper respiratory tract mucosal immunity for SARS-CoV-2 vaccines.

SARS-CoV-2 vaccination significantly reduces morbidity and mortality, but has less impact on viral transmission rates, thus aiding viral evolution, and the longevity of vaccine-induced immunity rapidly declines. Immune responses in respiratory tract mucosal tissues are crucial for early control of infection, and can generate long-term antigen-specific protection with prompt recall responses. However, currently approved SARS-CoV-2 vaccines are not amenable to adequate respiratory mucosal delivery, particularly in the upper airways, which could account for the high vaccine breakthrough infection rates and limited duration of vaccine-mediated protection. In view of these drawbacks, we outline a strategy that has the potential to enhance both the efficacy and durability of existing SARS-CoV-2 vaccines, by inducing robust memory responses in the upper respiratory tract (URT) mucosa.

SARS-CoV-2 Breakthrough Infections in Health Care Workers: An Italian Retrospective Cohort Study on Characteristics, Clinical Course and Outcomes.

BACKGROUND: The aim of this study was to determine the characteristics, clinical course and outcomes of COVID-19 breakthrough infections (BIs) among healthcare workers (HCWs) of an Italian University Hospital. METHODS: A retrospective observational study was conducted on 6111 HCWs, from January 2021 to February 2022. The study population was offered the full vaccination with BNT162b2 mRNA COVID-19 vaccine. To allow return to work after BI, the protocol required one negative nasopharyngeal RT-PCR swab followed by a medical examination to assess the HCW's health status. Laboratory tests, instrumental tests and specialist evaluations were carried out if necessary. RESULTS: The cases of BIs observed numbered 582 (9.7%). The frequency of BIs was significantly higher in females than in males (67% vs. 33%; p = 0.03), and in nurses than in all other professional categories (p = 0.001). A total of 88% of the HCWs affected by BI were still symptomatic after the negative swab. None of the instrumental tests carried out showed any new findings of pathological significance. All cases showed progressive disappearance of symptoms, such that no cases of long COVID and no hospitalization or deaths were recorded. CONCLUSIONS: Our results confirm that SARS-CoV-2 infections occur even after a full vaccination course; however, the clinical course is favorable and severe outcomes are reduced.

Investigating SARS-CoV-2 breakthrough infections per variant and vaccine type.

Breakthrough SARS-CoV-2 infections have been reported in fully vaccinated individuals, in spite of the high efficacy of the currently available vaccines, proven in trials and real-world studies. Several variants of concern (VOC) have been proffered to be associated with breakthrough infections following immunization. In this study, we investigated 378 breakthrough infections recorded between January and July 2021 and compared the distribution of SARS-CoV-2 genotypes identified in 225 fully vaccinated individuals to the frequency of circulating community lineages in the region of South Limburg (The Netherlands) in a week-by-week comparison. Although the proportion of breakthrough infections was relatively low and stable when the Alpha variant was predominant, the rapid emergence of the Delta variant lead to a strong increase in breakthrough infections, with a higher relative proportion of individuals vaccinated with Vaxzevria or Jcovden being infected compared to those immunized with mRNA-based vaccines. A significant difference in median age was observed when comparing fully vaccinated individuals with severe symptoms (83 years) to asymptomatic cases (46.5 years) or individuals with mild-to-moderate symptoms (42 years). There was no association between SARS-CoV-2 genotype or vaccine type and disease symptoms. Furthermore, the majority of adaptive mutations were concentrated in the N-terminal domain of the Spike protein, highlighting its role in immune evasion. Interestingly, symptomatic individuals harbored significantly higher SARS-CoV-2 loads than asymptomatic vaccinated individuals and breakthrough infections caused by the Delta variant were associated with increased viral loads compared to those caused by the Alpha variant. In addition, we investigated the role of the Omicron variant in causing breakthrough infections by analyzing 135 samples that were randomly selected for genomic surveillance during the transition period from Delta to Omicron. We found that the proportion of Omicron vs. Delta infections was significantly higher in individuals who received a booster vaccine compared to both unvaccinated and fully vaccinated individuals. Altogether, these results indicate that the emergence of the Delta variant and in particular Omicron has lowered the efficiency of particular vaccine types to prevent SARS-CoV-2 infections and that, although rare, the elderly are particularly at risk of becoming severely infected as the consequence of a breakthrough infection.