Postvaccination infections among staff of a tertiary care hospital after vaccination with severe acute respiratory syndrome coronavirus 2 vector and mRNA-based vaccines

ObjectivesThe identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen or RNA in respiratory specimens ≥14 days after administration of all recommended doses of authorized coronavirus disease 2019 (COVID-19) vaccines is defined as breakthrough infection. In the present investigation, mRNA and vector-based SARS-CoV-2 vaccines were analysed with respect to postvaccination infections in vaccinated hospital employees.MethodsA total of 8553 staff members were vaccinated with BNT162b2 (47%) or ChAdOx1-S (53%) between January and May 2021. In a retrospective observational cohort study, incidence of SARS-CoV-2 postvaccination infections was analysed in relation to demographic data, viral load, virus variants, vaccine brand and vaccination status at time of positive PCR test (fully vaccinated: ≥14 days since second dose; partially vaccinated: >21 days since first, but <14 days after second dose; insufficiently vaccinated: <22 days since first dose).ResultsWithin the follow-up period, ending on 31 July 2021, person-time at risk-adjusted monthly rates for SARS-CoV-2 postvaccination infections were 0.18% (BNT162b2) and 0.57% (ChAdOx1-S) for insufficiently vaccinated, 0.34% (BNT162b2) and 0.32% (ChAdOx1-S) for partially vaccinated and 0.06% (BNT162b2) and 0.04% (ChAdOx1-S) for fully vaccinated participants. The two vaccine types did not differ with respect to hazard ratios for any of the respective postvaccination infection types. No cases of COVID-19-related hospitalizations or deaths were reported. Genotyping of positive PCR specimens revealed 42 variants of concern: B.1.1.7 (Alpha variant; n = 34); B.1.351 (Beta variant; n = 2), B.1.617.2 (Delta variant; n = 6).ConclusionsBNT162b2 and ChAdOx1-S are both effective in preventing breakthrough infections; however, it seems important, that all recommended vaccine doses are administered.     

Nationwide effectiveness of five SARS-CoV-2 vaccines in Hungary—the HUN-VE study

ObjectivesThe Hungarian vaccination campaign was conducted with five different vaccines during the third wave of the coronavirus disease 2019 (COVID-19) pandemic in 2021. This observational study (HUN-VE: Hungarian Vaccine Effectiveness) estimated vaccine effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related mortality in 3.7 million vaccinated individuals.MethodsIncidence rates of SARS-CoV-2 infection and COVID-19-related mortality were calculated using data from the National Public Health Centre surveillance database. Estimated vaccine effectiveness was calculated as 1 – incidence rate ratio ≥7 days after the second dose for each available vaccine versus an unvaccinated control group using mixed-effect negative binomial regression controlling for age, sex and calendar day.ResultsBetween 22 January 2021 and 10 June 2021, 3 740 066 Hungarian individuals received two doses of the BNT162b2 (Pfizer-BioNTech), HB02 (Sinopharm), Gam-COVID-Vac (Sputnik-V), AZD1222 (AstraZeneca), or mRNA-1273 (Moderna) vaccines. Incidence rates of SARS-CoV-2 infection and COVID-19-related death were 1.73–9.3/100 000 person-days and 0.04–0.65/100 000 person-days in the fully vaccinated population, respectively. Estimated adjusted effectiveness varied between 68.7% (95% CI 67.2%–70.1%) and 88.7% (95% CI 86.6%–90.4%) against SARS-CoV-2 infection, and between 87.8% (95% CI 86.1%–89.4%) and 97.5% (95% CI 95.6%–98.6%) against COVID-19-related death, with 100% effectiveness in individuals aged 16–44 years for all vaccines.ConclusionsOur observational study demonstrated the high or very high effectiveness of five different vaccines in the prevention SARS-CoV-2 infection and COVID-19-related death.     

Assessment of BIV1-CovIran inactivated vaccine–elicited neutralizing antibody against the emerging SARS-CoV-2 variants of concern

ObjectivesThe BIV1-CovIran vaccine is highly effective against COVID-19. The neutralizing potency of all SARS-CoV-2 vaccines seems to be decreased against variants of concern. We assessed the sensitivity of the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants to neutralizing antibodies (NAbs) present in sera from individuals who had received the BIV1-CovIran candidate vaccine compared with an original Wuhan-related strain.MethodsThe ability of vaccine serum to neutralize the variants was measured using the conventional virus neutralization test. The correlation of spike (S) protein antibody and anti-receptor binding domain with neutralizing activity was investigated.ResultsThe current study demonstrated that 29 of 32 (90.6%; 95% CI: 75.0–98.0) of the vaccinees developed NAbs against a Wuhan-related strain. It is noteworthy that 28 (87.50%) and 24 of 32 (75%) of the recipients were able to produce NAbs against Alpha, Beta, and Delta variants, respectively. Serum virus-neutralizing titres for different SARS-CoV-2 strains were weakly correlated with anti–receptor binding domain antibodies (Spearman r = 36-42, p < 0.05), but not S-binding antibodies (p > 0.05).DiscussionAlthough there was a reduction in neutralization titres against the Alpha, Beta, and Delta variants compared with the Wuhan strain, BIV1-CovIran still exhibited potent neutralizing activity against the SARS-CoV-2 variants of concern.     

Enhanced SARS-CoV-2 IgG durability following COVID-19 mRNA booster vaccination and comparison of BNT162b2 with mRNA-1273

BackgroundBNT162b2 (Pfizer/BioNTech, Comirnaty) and mRNA-1273 (Moderna, Spikevax) are messenger RNA (mRNA) vaccines that elicit antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (S-RBD) and have been approved by the US Food and Drug Administration to combat the coronavirus disease 2019 (COVID-19) pandemic. Because vaccine efficacy and antibody levels waned over time after the 2-shot primary series, the US Food and Drug Administration authorized a booster (third) dose for both mRNA vaccines to adults in the fall of 2021.ObjectiveTo evaluate the magnitude and durability of S-RBD immunoglobulin (Ig)G after the booster mRNA vaccine dose in comparison to the primary series. We also compared S-RBD IgG levels after BNT162b2 and mRNA-1273 boosters and explored effects of age and prior infection.MethodsSurrounding receipt of the second and third homologous mRNA vaccine doses, adults in an employee-based cohort provided serum and completed questionnaires, including information about previous COVID-19 infection. The IgG to S-RBD was measured using an ImmunoCAP-based system. A subset of samples were assayed for IgG to SARS-CoV-2 nucleocapsid by commercial assay.ResultsThere were 228 subjects who had samples collected between 7 and 150 days after their primary series vaccine and 117 subjects who had samples collected in the same time frame after their boost. Antibody levels from 7 to 31 days after the primary series and booster were similar, but S-RBD IgG was more durable over time after the boost, regardless of prior infection status. In addition, mRNA-1273 post-boost antibody levels exceeded BNT162b2 out to 5 months.ConclusionThe COVID-19 mRNA vaccine boosters increase antibody durability, suggesting enhanced long-term clinical protection from SARS-CoV-2 infection compared with the 2-shot regimen.     

Efficient recall of SARS-CoV-2 variant-reactive B cells and T responses in the elderly upon heterologous mRNA vaccines as boosters

Waning antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern highlight the need for booster vaccinations. This is particularly important for the elderly population, who are at a higher risk of developing severe coronavirus disease 2019 (COVID-19) disease. While studies have shown increased antibody responses following booster vaccination, understanding the changes in T and B cell compartments induced by a third vaccine dose remains limited. We analyzed the humoral and cellular responses in subjects who received either a homologous messenger RNA(mRNA) booster vaccine (BNT162b2 + BNT162b2 + BNT162b2; ‘‘BBB”) or a heterologous mRNA booster vaccine (BNT162b2 + BNT162b2 + mRNA-1273; ‘‘BBM”) at Day 0 (prebooster), Day 7, and Day 28 (postbooster). Compared with BBB, elderly individuals (≥60 years old) who received the BBM vaccination regimen display higher levels of neutralizing antibodies against the Wuhan and Delta strains along with a higher boost in immunoglobulin G memory B cells, particularly against the Omicron variant. Circulating T helper type 1(Th1), Th2, Th17, and T follicular helper responses were also increased in elderly individuals given the BBM regimen. While mRNA vaccines increase antibody, T cell, and B cell responses against SARS-CoV-2 1 month after receiving the third dose booster, the efficacy of the booster vaccine strategies may vary depending on age group and regimen combination.     

Investigation of an outbreak of symptomatic SARS-CoV-2 VOC 202012/01-lineage B.1.1.7 infection in healthcare workers,Italy

ObjectivesIn December 2020, Italy began a national immunization campaign using the BNT162b2 coronavirus disease 2019 (COVID-19) mRNA vaccine, prioritizing healthcare workers (HCWs). Immune serum from vaccinated subjects seems (largely) to retain titres of neutralizing antibodies, even against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) VOC 202012/01-lineage B.1.1.7. Here, we describe an outbreak of SARS-CoV-2 lineage B.1.1.7 infection in three HCWs in a hospital setting; two of the HCWs were fully vaccinated (i.e. had received two doses).MethodsTwo physicians and one nurse working on the same shift on 20th February 2021 were involved in the outbreak. Real-time PCR, antigen tests, and serological tests for the IgG anti-spike protein of SARS-CoV-2 were performed, along with whole-genome sequencing (WGS).ResultsSARS-CoV-2 infection was confirmed in all three HCWs; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE).ConclusionsThis mini-outbreak highlights some important issues about the efficacy of vaccines against transmission of SARS-CoV-2 variants, the high risk of exposure among HCWs, and the need for optimized implementation of PPE in hospitals. The wide circulation of VOC 202012/01 in Europe and Italy highlights the need to improve surveillance and genetic sequencing.     

Humoral and cell-mediated response against SARS-CoV-2 variants elicited by mRNA vaccine BNT162b2 in healthcare workers: a longitudinal observational study

ObjectivesTo assess the humoral and cell-mediated response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicited by the mRNA BNT162b2 vaccine in SARS-CoV-2-experienced and -naive subjects against a reference strain and SARS-CoV-2 variants.MethodsThe humoral response (including neutralizing antibodies) and T-cell-mediated response elicited by BNT162b2 vaccine in 145 healthcare workers (both naive and positive for previous SARS-CoV-2 infection) were evaluated. In a subset of subjects, the effect of SARS-CoV-2 variants on antibody level and cell-mediated response was also investigated.ResultsOverall, 125/127 naive subjects (98.4%) developed both neutralizing antibodies and specific T cells after the second dose of vaccine. Moreover, the antibody and T-cell responses were effective against viral variants since SARS-CoV-2 NT Abs were still detectable in 55/68 (80.9%) and 25/29 (86.2%) naive subjects when sera were challenged against β and δ variants, respectively. T-cell response was less affected, with no significant difference in the frequency of responders (p 0.369). Of note, two doses of vaccine were able to elicit sustained neutralizing antibody activity against all the SARS-CoV-2 variants tested in SARS-CoV-2-experienced subjects.ConclusionsBNT162b2 vaccine elicited a sustained humoral and cell-mediated response in immunocompetent subjects after two-dose administration of the vaccine, and the response seemed to be less affected by SARS-CoV-2 variants, the only exceptions being the β and δ variants. Increased immunogenicity, also against SARS-CoV-2 variant strains, was observed in SARS-CoV-2-experienced subjects. These results suggest that triple exposure to SARS-CoV-2 antigens might be proposed as valuable strategy for vaccination campaigns.     

Humoral and cellular immunity in three different types of COVID-19 vaccines against SARS-CoV-2 variants in a real-world data analysis

BackgroundAn effective vaccine response is currently a critical issue in the control of COVID-19. Little is known about humoral and cellular immunity comparing protein-based vaccine with other types of vaccines. The relevance of basal immunity to antibody production is also unknown.MethodsSeventy-eight individuals were enrolled in the study. The primary outcome were the level of spike-specific antibodies and neutralizing antibodies measured by ELISA. Secondary measures included memory T cells and basal immunity estimated by flow cytometry and ELISA. Correlations for all parameters were calculated using the nonparametric Spearman correlation method.ResultsWe observed that two doses of mRNA-based Moderna mRNA-1273 (Moderna) vaccine produced the highest total spike-binding antibody and neutralizing ability against the wild-type (WT), Delta, and Omicron variants. The protein-based MVC-COV1901 (MVC) vaccine developed in Taiwan produced higher spike-binding antibodies against Delta and Omicron variants and neutralizing ability against the WT strain than the adenovirus-based AstraZeneca-Oxford AZD1222 (AZ) vaccine. Moderna and AZ vaccination produced more central memory T cells in PBMC than the MVC vaccine. However, the MVC vaccine had the lowest adverse effects compared to the Moderna and AZ vaccines. Surprisingly, the basal immunity represented by TNF-α, IFN-γ, and IL-2 prior to vaccination was negatively correlated with the production of spike-binding antibodies and neutralizing ability.ConclusionThis study compared memory T cells, total spike-binding antibody levels, and neutralizing capacity against WT, Delta, and Omicron variants between the MVC vaccine and the widely used Moderna and AZ vaccines, which provides valuable information for future vaccine development strategies.     

Case Reports of Acute Transverse Myelitis Associated With mRNA Vaccine for COVID-19

Acute transverse myelitis (ATM) has been reported as rare complication of vaccination. Herein, we report 2 cases of ATM after the administration of an mRNA vaccine for coronavirus disease 2019 (COVID-19). The first one is an 81-year-old man who received the BNT162b2 vaccine. He presented with bilateral hand weakness. Spine magnetic resonance imaging (MRI) showed high signal intensity from the C1 to C3 vertebrae. The second is a 23-year-old woman who received the BNT162b2 vaccine and experienced tingling in her legs. Spine MRI showed a high signal intensity lesion at the conus medullaris. These patients were treated with intravenous methylprednisolone and their symptoms improved slightly. Careful follow-up is needed to identify adverse events after the administration of mRNA vaccines for COVID-19.     

COVID-19 vaccination and myocarditis: A review of current literature

Vaccination for coronavirus disease 2019 (COVID-19) is a critical strategy in controlling the current pandemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). After widespread COVID-19 vaccine imple-mentation, isolated case reports about myocarditis as a potential adverse reaction started coming. As of November 12, 2021, Centers for Disease Control and Prevention (CDC) has reported 1793 cases of myocarditis or pericarditis among young people with age 12-29 years, most cases have been reported in the male adolescent age group after the second dose of mRNA COVID-19 vaccines. It is very important to monitor the safety standards and adverse reactions of vaccines to effectively implement the vaccination policies. The CDC and the United States Food and Drug Administration actively monitor vaccine-associated adverse reactions a well-known platform such as Vaccine Adverse Event Reporting System. CDC continues to recommend COVID-19 vaccines and booster doses for eligible individuals (age limit according to the type of vaccine) after careful consideration from risk-benefit assessment and favorable outcomes from vaccination. Mechanisms behind COVID-19 vaccine-induced myocarditis are not clear yet but several possibilities such as molecular mimicry between the spike protein of SARS-CoV-2 and self-antigens, immune response to mRNA, and activation of host immunological system, trigger of the pre-existing dysregulated immunological system have been documented in the literature. Overall, data suggests a good prognosis, especially in young patients. In this review article, we cover currently available data on COVID-19 vaccine-related myocarditis incidence, concerns, possible mechanisms of myocarditis, current treatment, and outcome trends, risk vs benefit assessment of COVID-19 vaccination in this current pandemic.     

SARS-CoV-2 evolves to reduce but not abolish neutralizing action

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) have prolonged coronavirus disease 2019 (COVID-19) pandemic by escaping pre-existing immunity acquired by natural infection or vaccination. Elucidation of VOCs' mutation trends and evasion of neutralization is required to update current control measures. Mutations and the prevalence of VOCs were analyzed in the global immunization coverage rate context. Lentivirus-based pseudovirus neutralization analysis platforms for SARS-CoV-2 prototype strain (PS) and VOCs, containing Alpha, Beta, Gamma, Delta, and Omicron, were constructed based on the spike protein of each variant and HEK 293T cell line expressing the human angiotensin-converting enzyme 2 (hACE2) receptor on the surface, and an enhanced green fluorescent protein reporter. Serum samples from 65 convalescent individuals and 20 WIBP-CorV vaccine recipients and four therapeutic monoclonal antibodies (mAbs) namely imdevimab, casirivimab, bamlanivimab, and etesevimab were used to evaluate the neutralization potency against the variants. Pseudovirus-based neutralization assay platforms for PS and VOCs were established, and multiplicity of infection (MOI) was the key factor influencing the assay result. Compared to PS, VOCs may enhance the infectivity of hACE2-293T cells. Except for Alpha, other VOCs escaped neutralization to varying degrees. Attributed to favorable and emerging mutations, the current pandemic Omicron variant of all VOCs demonstrated the most significant neutralization-escaping ability to the sera and mAbs. Compared with the PS pseudovirus, Omicron had 15.7- and 3.71-fold decreases in the NT50 value (the highest serum dilution corresponding to a neutralization rate of 50%); and correspondingly, 90% and 43% of immunization or convalescent serum samples lost their neutralizing activity against the Omicron variant, respectively. Therefore, SARS-CoV-2 has evolved persistently with a strong ability to escape neutralization and prevailing against the established immune barrier. Our findings provide important clues to controlling the COVID-19 pandemic caused by new variants.     

Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine breakthrough infections: a multicentre cohort study

ObjectivesHighly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed but variants of concerns are worrisome, especially B.1.617.2 (Delta) which has rapidly spread across the world. We aim to study if vaccination alters virological and serological kinetics in breakthrough infections.MethodsWe conducted a multicentre retrospective cohort study of patients in Singapore who had received a licensed mRNA vaccine and been admitted to hospital with B.1.617.2 SARS-CoV-2 infection. We compared clinical features, virological and serological kinetics (anti-nucleocapsid, anti-spike and surrogate virus neutralization titres) between fully vaccinated and unvaccinated individuals.ResultsOut of 218 individuals with B.1.617.2 infection, 84 received an mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and four received a non-mRNA vaccine. Despite significantly older age in the vaccine breakthrough group, only 2.8% (2/71) developed severe COVID-19 requiring oxygen supplementation compared with 53.1% (69/130) in the unvaccinated group (p < 0.001). Odds of severe COVID-19 following vaccination were significantly lower (adjusted odds ratio 0.07 95% CI 0.015–0.335, p 0.001). PCR cycle threshold values were similar between vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals. Early, robust boosting of anti-spike protein antibodies was observed in vaccinated patients; however, these titres were significantly lower against B.1.617.2 than the wildtype vaccine strain.DiscussionThe mRNA vaccines are highly effective at preventing symptomatic and severe COVID-19 associated with B.1.617.2 infection. Vaccination is associated with faster decline in viral RNA load and a robust serological response. Vaccination remains a key strategy for control of the COVID-19 pandemic.     

Cross neutralization of SARS-CoV-2 omicron subvariants after repeated doses of COVID-19 mRNA vaccines

We have measured the humoral response to messenger RNA (mRNA) vaccines in COVID-19 naïve and convalescent individuals. Third doses of mRNA COVID-19 vaccines induced a significant increase in potency and breadth of neutralization against SARS-CoV-2 variants of concern (VoC) including Omicron subvariants BA.1, BA.2, and BA.2.12.1, that were cross-neutralized at comparable levels and less for BA.4/5. This booster effect was especially important in naïve individuals that only after the third dose achieved a level that was comparable with that of vaccinated COVID-19 convalescents except for BA.4/5. Avidity of RBD-binding antibodies was also significantly increased in naïve individuals after the third dose, indicating an association between affinity maturation and cross neutralization of VoC. These results suggest that at least three antigenic stimuli by infection or vaccination with ancestral SARS-CoV-2 sequences are required to induce high avidity cross-neutralizing antibodies. Nevertheless, the circulation of new subvariants such as BA.4/5 with partial resistance to neutralization will have to be closely monitored and eventually consider for future vaccine developments.     

Successful mRNA COVID-19 Vaccination and Colonoscopy After Oral Desensitization in a Patient With Polyethylene Glycol Allergy

Anaphylaxis to polyethylene glycol (PEG) is rare and mainly occurs with the use of laxatives containing PEG. Recently, an increasing number of PEG allergies have been reported, particularly those related to coronavirus disease 2019 (COVID-19) vaccines. mRNA COVID-19 vaccines, such as the BNT162b2 (Pfizer–BioNTech) and mRNA-1273 (Moderna) vaccines, contain PEG2000 as an excipient and are contraindicated when allergy to a vaccine component exist. We report a 55-year-old woman’s history as a case of successful mRNA COVID-19 vaccination and colonoscopy after oral desensitization to PEG in a patient with PEG allergy who required both COVID-19 vaccination and colon evaluation. Allergy to PEG was diagnosed based on clinical history, skin test results, and basophil histamine release testing. Oral desensitization effectively suppressed histamine release from basophils in response to PEG stimulation, suggesting that oral desensitization using PEG-based laxatives may be an effective treatment option for patients with allergy to the substance.     

The impact of COVID-19 vaccination programme in the Republic of San Marino: Focus on effectiveness of Gam-Covid-Vac

ObjectiveThe adenovirus-based vaccine Gam-COVID-Vac (Sputnik V) showed promising effectiveness in a phase 3 clinical trial; however, data concerning its impact at a population level are scarce. The Republic of San Marino (RSM) conducted a SARS-CoV-2 vaccination programme mainly based (>80%) on Gam-COVID-Vac. Our aims were to investigate the impact of Gam-COVID-Vac vaccination programme and its effectiveness in a retrospective observational study based on the entire RSM population aged ≥12 years.MethodsWe calculated the incidence rate and the vaccine effectiveness (VE) in the entire RSM population not previously infected, against SARS-CoV-2 infection and COVID-19–related hospitalization, from 25 February to 1 October 2021, considering any vaccine and separately according to the vaccine used. Vaccine effectiveness was calculated using a multivariable negative binomial regression model as 1-Incidence Rate Ratio.ResultsDuring the study period, 21 568/28 791 (74.9%) not previously infected subjects received at least one dose of the Gam-COVID-Vac (84%) or BNT162b2, vaccines with 98% completing the vaccination schedule. Overall, 1634 SARS-CoV-2 infections and 166 COVID-19-related hospitalizations were observed with 17 COVID-19-related deaths reported. Incidence rates of SARS-CoV-2 infection and COVID-19-related hospitalization were 7.11 and 0.49/100 000 person-days in the fully vaccinated population, respectively. The adjusted overall VE was 67.6% (95% CI: 61.8–72.5) against SARS-CoV-2 infection and 87.9% (95% CI: 77.4–93.5) against COVID-19-related hospitalizations.Gam-COVID-Vac against SARS-CoV-2 infection VE peaked 91.8% (95% CI: 86.3–95.1) in the first bimester from the second dose, declining to 57.8% (95% CI: 42.2–69.2) at 6 months. Protection against hospitalization with COVID-19 was overall 91.6% (95% CI: 81.5–96.2), with no relevant waning trend over time.DiscussionOur study demonstrated the effectiveness of overall vaccination (Gam-COVID-Vac [84%] and BNT162b2 [16%]) in the prevention SARS-CoV-2 infection (pre-Omicron variant), waning over time but still with sustainable effectiveness against COVID-19-related hospitalization in the Republic of San Marino.     

Relevance of immune response and vaccination strategies of SARS-CoV-2 in the phase of viral red queen dynamics

BackgroundFollowing a relatively mild first wave of coronavirus disease 2019 (COVID-19) in India, a deadly second wave of the pandemic overwhelmed the healthcare system due to the emergence of fast-transmitting SARS-CoV-2 genetic variants. The emergence and spread of the B.1.617.2/Delta variant considered to be driving the devastating second wave of COVID-19 in India. Currently, the Delta variant has rapidly overtaken the previously circulating variants to become the dominant strain. Critical mutations in the spike/RBD region of these variants have raised serious concerns about the virus's increased transmissibility and decreased vaccine effectiveness. As a result, significant scientific and public concern has been expressed about the impact of virus variants on COVID-19 vaccines.ObjectivesThe purpose of this article is to provide an additional explanation in the context of the evolutionary trajectory of SARS-CoV-2 variants in India, the vaccine-induced immune response to the variants of concern (VOC), and various vaccine deployment strategies to rapidly increase population immunity.ContentPhylogenetic analysis of SARS-CoV-2 isolates circulating in India suggests the emergence and spread of B.1.617 variant. The immunogenicity of currently approved vaccines indicates that the majority of vaccines elicit an antibody response and some level of protection. According to current data, vaccines in the pre-fusion configuration (2p substitution) have an advantage in terms of nAb titer, but the duration of vaccine-induced immunity, as well as the role of T cells and memory B cells in protection, remain unknown. Since vaccine efficacy on virus variants is one of the major factors to be considered for achieving herd immunity, existing vaccines need to be improved or effective next-generation vaccines should be developed to cover the new variants of the virus.     

Risk of myocarditis and pericarditis following coronavirus disease 2019 messenger RNA Vaccination—A nationwide study

BackgroundAn extended interval between the two primary doses may reduce the risk of myocarditis/pericarditis after COVID-19 mRNA vaccination. Taiwan has implemented a two-dose regimen with a 12-week interval for adolescents. Here we present nationwide data of myocarditis/pericarditis following COVID-19 vaccinations.MethodsData on adverse events of myocarditis/pericarditis were from the Taiwan Vaccine Adverse Events Reporting System between March 22, 2021, and February 9, 2022. The reporting rates according to sex, age, and vaccine type were calculated. We investigated the rates among young individuals under different two-dose intervals and among those who received two doses of different vaccines.ResultsAmong 204 cases who met the case definition of myocarditis/pericarditis, 75 cases occurred after the first dose and 129 after the second. The rate of myocarditis/pericarditis after COVID-19 vaccination varied across sex and age groups and was highest after the second dose in males aged 12–17 years (126.79 cases per million vaccinees) for the BNT162b2 vaccine and in males aged 18–24 years (93.84 cases per million vaccinees) for the mRNA-1273 vaccine. The data did not suggest an association between longer between-dose interval and lower rate of myocarditis/pericarditis among males and females aged 18–24 or 25–29 years who received two doses of the BNT162b2 or mRNA-1273 vaccine. Rates of myocarditis/pericarditis in males and females aged 18–49 years after receiving ChAdOx1-S - mRNA-1273 vaccination was significantly higher than after ChAdOx1-S - ChAdOx1-S vaccination.ConclusionsMyocarditis and pericarditis are rare following mRNA vaccination, with higher risk occurring in young males after the second dose.     

An Outbreak of Breakthrough Infections by the SARS-CoV-2 Delta Variant in a Psychiatric Closed Ward

BackgroundA rapid decline in immunity and low neutralizing activity against the delta variant in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinees has been observed. This study describes an outbreak of coronavirus disease 2019 (COVID-19) breakthrough infections caused by the SARS-CoV-2 delta variant in a psychiatric closed ward.MethodsData from epidemic intelligence service officers were utilized to obtain information regarding demographic, vaccination history, and clinical data along with SARS-CoV-2 PCR test results for a COVID-19 outbreak that occurred in a closed psychiatric ward.ResultsAmong the 164 residents, 144 (87.8%) received two doses of vaccines and 137 (95.1%) of them received ChAdOx1 nCoV-19 vaccine. The mean interval between the second vaccination and COVID-19 diagnosis was 132.77 ± 40.68 days. At the time of detection of the index case, SARS-CoV-2 had spread throughout the ward, infecting 162 of 164 residents. The case-fatality ratio was lower than that in the previously reported outbreak before the vaccination (1.2%, 2/162 vs. 6.9%, P = 0.030). Prolonged hospitalization occurred in 17 patients (11.1%) and was less prevalent in the vaccinated group than in the unvaccinated group (8.5% vs. 25.0%, P = 0.040).ConclusionThe findings of this study highlight that while vaccination can reduce mortality and the duration of hospitalization, it is not sufficient to prevent an outbreak of the SARS-CoV-2 delta variant in the present psychiatric hospital setting.     

Association between a low response to rubella vaccination and reduced anti-severe acute respiratory syndrome coronavirus 2 immune response after vaccination with BNT162b2: a cross-sectional study

ObjectivesSome vaccinated individuals fail to acquire an adequate immune response against infection. We aimed to determine whether mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination could induce a sufficient immune response against SARS-CoV-2 in low responders to other vaccinations.MethodsUsing data from health-care workers who received two doses of the BNT162b2 vaccine (BioNTech/Pfizer), we conducted a single-centre, cross-sectional study to determine whether low responders to measles, rubella, and hepatitis B virus (HBV) vaccinations could acquire sufficient antibodies after SARS-CoV-2 vaccination. From May 2021 to June 2021, participants were tested for anti-SARS-CoV-2 spike (anti-S) IgG antibodies at least 2 weeks after the second dose of BNT162b2. The association between a low response to measles, rubella, and HBV vaccinations and the post-vaccination anti-S IgG titre was evaluated using the multivariable linear regression analysis.ResultsAll 714 participants were positive for the anti-S IgG titre (≥50.0 AU/mL) after two doses of BNT162b2 (median, 7126.8 AU/mL; interquartile range, 4496.2–11 296.8). There were 323 (45.2%), 131 (18.3%), and 43 (6.0%) low responders to measles, rubella, and HBV vaccinations, respectively. In the multivariable linear regression analysis, low responders to rubella vaccination had significantly low acquisition of the anti-S IgG titre after two doses of the BNT162b2 vaccine (standardized coefficient β, ?0.110; 95% CI, ?0.175 to ?0.044).ConclusionsA low response to rubella vaccination is a potential predictor of a reduced response to SARS-CoV-2 vaccination. Further studies are needed to determine whether a low response to rubella vaccination is associated with the durability of SARS-CoV-2 vaccination-induced immune response.