Characterization of Adaptive Immune Responses to SARS-CoV-2 Updated Bivalent Booster

Bivalent COVID-19 vaccines that contain two mRNAs encoding Wuhan-1 and Omicron BA.4/5 spike proteins are successful in preventing infection from the original strain and Omicron variants, but the quality of adaptive immune responses is still not well documented. This study aims at characterizing adaptive immune responses to the bivalent booster vaccination in 46 healthy participants. Plasma and PBMC were collected prior and three weeks after bivalent booster. We measured anti-N, anti-S, and RBD IgM, IgA, IgG plasma titers against original, Omicron BA.1, and BA.5 variants (pending) as well as total anti-S IgG titers and surrogate Virus Neutralization capacity against the Alpha, Delta, and BA.1 variant. With spectral flow-cytometry we identified peripheral blood B-cells specific for the RBD of the S-protein of the original and BA.1 variants. T-cell-specific responses were assessed by cytokine release assay after stimulation with SARS-CoV-2 peptides from the original, BA.1, BA.4, and BA.5 variants (pending). Finally, we performed TRB and IGH repertoire studies on sorted CD4+, CD8+, CD19+ lymphocytes, to study breadth of SARS-CoV-2 specific clonotypes (pending). 27/46 participants were analyzed;9 had SARS-CoV-2 infection (COVID+), while 18 are infection naive (COVID-). In both groups, median time since last dose of SARS-CoV-2 vaccine (3rd or 4th) was 11 months. All subjects were positive for anti-S IgG prior to bivalent booster. The COVID + group displayed anti-S IgG pre-booster levels and neutralization against BA.1 higher than the COVID- group. Significant increase post-boost of total anti-S IgG and BA.1 neutralizing activity was detected in the COVID- but not in the COVID+ group;however, no difference in neutralization activity post-boost was detected between the two groups. Furthermore, the COVIDgroup showed significant increase in the frequency of CD19+ and CD27+ switched memory B-cells specific for BA.1 RBD in post-boost compared to pre-boost samples. However, post-boost frequencies of the same B-cells were higher in the COVID+ compared to the COVID- group. These preliminary findings confirm that among individual immunized with the original COVID-19 mRNAvaccine, prior COVID infection provides increased protection against SARS-CoV-2 variants. They also demonstrate that booster immunization with the bivalent vaccine induces robust adaptive immune responses against Omicron variant.[Formula presented][Formula presented]Copyright © 2023 Elsevier Inc.

COVID-19 Vaccine and Booster Shots Compatibility Analyzer using CMOS-based Monochrome Encoding

The continuous increase in COVID-19 positive cases in the Philippines might further weaken the local healthcare system. As such, an efficient system must be implemented to further improve the immunization efforts of the country. In this paper, a contactless digital electronic device is proposed to assess the vaccine and booster brand compatibility. Using Logisim 2.7.1, the logic diagrams were designed and simulated with the help of truth tables and Boolean functions. Moreover, the finalized logic circuit design was converted into its equivalent complementary metal-oxide semiconductor (CMOS) and stick diagrams to help contextualize how the integrated circuits will be designed. Results have shown that the proposed device was able to accept three inputs of the top three COVID-19 vaccine brands (Sinovac, AstraZeneca, and Pfizer) and assess the compatibility of heterologous vaccinations. With the successful results of the circuit, it can be concluded that this low-power device can be used to manufacture a physical prototype for use in booster vaccination sites. © 2022 IEEE.

Phytochemicals: an immune booster against the pathogens

Phytochemicals are chemical compounds produced by plants. Actually, it is produced by primary and secondary metabolism. Vegetables, fruits, whole grains, nuts, seeds, etc., are rich with phytochemicals and impart aroma, colors, and flavors. There are many phytochemicals like polyphenols, flavonoids, carotenoids, phytoestrogens, phytosterols, etc. They act as antioxidants against diseases related to lungs, urinal, stomach, and heart and can be used as nutraceuticals to control various metabolic disorders. Medicinal plants have been regarded as beneficial for many centuries. In India, Himalayas and Western Ghat regions are diverse in such plants. It has many beneficial effects on human health and boosts up immunity. Tens of thousands of phytochemicals have been identified, and many more are yet to be discovered. Synthetic medicine is known to cause many side effects on human health, and having such natural medicinal plants in diet is believed to be beneficial without side effects. They may increase immunity to fight against today's diseases like SARS, MERS, and Coronavirus (CoV) infections. The phytotherapy or the phytomedicines are effective immunity boosters and have the potential to eliminate bacterial as well as viral infections. Phytochemicals like phenolic compounds, vegetables, and fruits containing such compounds in the human diet may be effective against coronaviruses and people cure due to having it in their diet too. Still more research and identification of such compounds are required to get more information regarding its benefits. The phytotherapy-based research and developing phytotherapic medicines could cure many more chronic as well as acute diseases. This chapter deals with comprehensive information on phytochemicals and its importance. © 2023 Elsevier Inc. All rights reserved.

The pattern from the first three rounds of vaccination: declining vaccination rates.

Introduction: Vaccination rates for the COVID-19 vaccine have recently been stagnant worldwide. We aim to analyze the potential patterns of vaccination development from the first three doses to reveal the possible trends of the next round of vaccination and further explore the factors influencing vaccination in the selected populations. Methods: On July 2022, a stratified multistage random sampling method in the survey was conducted to select 6,781 people from 4 provinces China, who were above the age of 18 years. Participants were divided into two groups based on whether they had a chronic disease. The data were run through Cochran-Armitage trend test and multivariable regression analyses. Results: A total of 957 participants with chronic disease and 5,454 participants without chronic disease were included in this survey. Vaccination rates for the first, second and booster doses in chronic disease population were93.70% (95% CI: 92.19-95.27%), 91.12% (95%CI: 94.43-95.59%), and 83.18% (95%CI: 80.80-85.55%) respectively. By contrast, the first, second and booster vaccination rates for the general population were 98.02% (95% CI: 97.65-98.39%), 95.01% (95% CI: 94.43-95.59%) and 85.06% (95% CI: 84.11-86.00%) respectively. The widening gap in vaccination rates was observed as the number of vaccinations increases. Higher self-efficacy was a significant factor in promoting vaccination, which has been observed in all doses of vaccines. Higher education level, middle level physical activity and higher public prevention measures play a positive role in vaccination among the general population, while alcohol consumption acts as a significant positive factor in the chronic disease population (p < 0.05). Conclusion: As the number of vaccinations increases, the trend of decreasing vaccination rate is becoming more pronounced. In future regular vaccinations, we may face low vaccination rates as the increasing number of infections and the fatigue associated with the prolonged outbreak hamper vaccination. Measures need to be found to counter this downward trend such as improving the self-efficacy of the population.

Long-term real-world protection afforded by third mRNA doses against symptomatic SARS-COV-2 infections, COVID-19-related emergency attendances and hospitalizations amongst older Singaporeans during an Omicron XBB wave.

BACKGROUND: Literature on long-term real-world vaccine effectiveness of SARS-CoV-2 booster vaccines (up to and beyond 360 days) is scarce. We report estimates of protection against symptomatic infection, emergency department (ED) attendances and hospitalizations up to and beyond 360 days post-receipt of booster mRNA vaccines amongst Singaporeans aged ≥60 years during an Omicron XBB wave. METHODS: We conducted a population-based cohort study including all Singaporeans aged ≥60 years with no documented prior SARS-CoV-2 infection who had previously received ≥3 doses of mRNA vaccines (BNT162b2/mRNA-1273), over a 4-month period during transmission of Omicron XBB. We reported the adjusted incidence-rate-ratio (IRR) for symptomatic infections, ED attendances and hospitalizations at different time-intervals from both first and second boosters, using Poisson regression; with the reference group being those who received their first booster 90 to 179 days prior. RESULTS: 506,856 boosted adults were included, contributing 55,846,165 person-days of observation. Protection against symptomatic infections among those who received a third vaccine dose (first booster) waned after 180 days with increasing adjusted IRRs; however, protection against ED attendances and hospitalizations held up, with comparable adjusted IRRs with increasing time from third vaccine doses [≥360 days from third dose: adjusted IRR (ED attendances) = 0.73, 95%CI = 0.62-0.85; adjusted IRR (hospitalization) = 0.58, 95%CI = 0.49-0.70]. CONCLUSIONS: Our results highlight the benefit of a booster dose in reducing ED attendances and hospitalizations amongst older adults aged ≥60 years with no documented prior SARS-CoV-2 infection, during an Omicron XBB wave; up to and beyond 360 days post-booster. A second booster provided further reduction.

Relapse of minimal change disease following the third mRNA COVID-19 vaccination: a case report and literature review.

Mass vaccination is the most important strategy to terminate the coronavirus disease 2019 (COVID-19) pandemic. Reports suggest the potential risk of the development of new-onset or relapse of minimal change disease (MCD) following COVID-19 vaccination; however, details on vaccine-associated MCD remain unclear. A 43-year-old man with MCD, who had been in remission for 29 years, developed nephrotic syndrome 4 days after receiving the third dose of the Pfizer-BioNTech vaccine. His kidney biopsy revealed relapsing MCD. Intravenous methylprednisolone pulse therapy followed by oral prednisolone therapy was administered, and his proteinuria resolved within 3 weeks. This report highlights the importance of careful monitoring of proteinuria after COVID-19 vaccination in patients with MCD, even if the disease is stable and no adverse events occurred during previous vaccinations. Our case report and literature review of COVID-19 vaccine-associated MCD indicated that MCD relapse tends to occur later after vaccination and slightly more often following the second and subsequent vaccine doses than new-onset MCD.

Varying Cellular Immune Response against SARS-CoV-2 after the Booster Vaccination: A Cohort Study from Fukushima Vaccination Community Survey, Japan.

Booster vaccination reduces the incidence of severe cases and mortality related to COVID-19, with cellular immunity playing an important role. However, little is known about the proportion of the population that has achieved cellular immunity after booster vaccination. Thus, we conducted a Fukushima cohort database and assessed humoral and cellular immunity in 2526 residents and healthcare workers in Fukushima Prefecture in Japan through continuous blood collection every 3 months from September 2021. We identified the proportion of people with induced cellular immunity after booster vaccination using the T-SPOT.COVID test, and analyzed their background characteristics. Among 1089 participants, 64.3% (700/1089) had reactive cellular immunity after booster vaccination. Multivariable analysis revealed the following independent predictors of reactive cellular immunity: age < 40 years (adjusted odds ratio: 1.81; 95% confidence interval: 1.19-2.75; p-value: 0.005) and adverse reactions after vaccination (1.92, 1.19-3.09, 0.007). Notably, despite IgG(S) and neutralizing antibody titers of ≥500 AU/mL, 33.9% (349/1031) and 33.5% (341/1017) of participants, respectively, did not have reactive cellular immunity. In summary, this is the first study to evaluate cellular immunity at the population level after booster vaccination using the T-SPOT.COVID test, albeit with several limitations. Future studies will need to evaluate previously infected subjects and their T-cell subsets.

Severe acute respiratory syndrome coronavirus-2 antibody response after Moderna vaccine booster on healthcare providers.

INTRODUCTION: As an endeavor to control SARS-CoV-2 infection, the Moderna vaccine booster was given to healthcare workers to prevent reinfection and reduce the risk of complications from COVID-19. A heterologous booster vaccine is also thought to provide better protection against the current SARS-CoV-2 variants of concern. However, research that evaluates the effectiveness of the Moderna vaccine booster and the resulting SARS-CoV-2 antibody concentration is needed. OBJECTIVE: To evaluate the concentration of SARS-CoV-2 antibodies after the Moderna vaccine booster and the severity of SARS-CoV-2 infection before and after the Moderna vaccine booster. RESULTS: A total of 93 healthcare providers who received Moderna vaccine booster were included in the study. Examination of antibody concentration 3 months after the booster showed an average concentration of 10081.65 U/mL. There was an increase in antibody concentration before the booster and 3 months after, from a median of 1.7 U/mL to 9540 U/mL. Every subject showed a statistically significant increment of antibody concentration 3 months after the booster (p < 0.01). Thirty-seven (39.8%) subjects received two doses of the Sinovac vaccine and were confirmed to have COVID-19 with the Delta variant. After the booster, 26 (28%) subjects were infected with the Omicron Variant. Among the subjects who received two doses of the Sinovac vaccine and were confirmed with COVID-19, 36 (30.1%) had mild symptoms, and 1 (1.1%) was asymptomatic. CONCLUSIONS: Heterologous Moderna vaccine booster effectively increases antibody response against SARS-CoV-2 variants and shows mild symptoms of COVID-19 infection.

Predictors of second COVID-19 booster dose or new COVID-19 vaccine hesitancy among nurses: A cross-sectional study.

AIMS AND OBJECTIVES: To assess the levels of second COVID-19 booster dose/new COVID-19 vaccine hesitancy among nurses and explore the potential predictors of vaccine hesitancy. BACKGROUND: COVID-19 full vaccination seems to be highly effective against highly contagious variants of SARS-CoV-2. Healthcare workers are at high-risk group since they have experienced high levels of COVID-19-associated morbidity and mortality. DESIGN: An on-line cross-sectional study was carried out in Greece in May 2022, using a self-administered questionnaire. METHODS: The study population included nurses in healthcare services who were fully vaccinated against COVID-19 at the time of study. We considered socio-demographic characteristics, COVID-19-related variables, and attitudes toward COVID-19 vaccination and pandemic as potential predictors of vaccine hesitancy. We applied the STROBE checklist in our study. RESULTS: Among 795 nurses, 30.9% were hesitant toward a second booster dose or a new COVID-19 vaccine. Independent predictors of hesitancy included lower educational level, absence of a chronic condition, good/very good self-perceived physical health, lack of flu vaccination during 2021, front-line nurses that provided healthcare to COVID-19 patients, nurses that had not been diagnosed with COVID-19 and nurses that had at least one relative/friend that has died from COVID-19. Moreover, increased compliance with hygiene measures, increased fear of a second booster dose/new COVID-19 vaccine and decreased trust in COVID-19 vaccination were associated with increased hesitancy. CONCLUSIONS: Our study shows that a significant percentage of nurses are hesitant toward a second booster dose/new COVID-19 vaccine. This initial hesitancy could be a barrier to efforts to control the COVID-19 pandemic. RELEVANCE TO CLINICAL PRACTICE: Nurses' role during the COVID-19 pandemic is essential since they are the front-line healthcare workers empowering the public with their passion and empathy. There is a need to communicate COVID-19 vaccine science in a way that is accessible to nurses in order to decrease COVID-19 vaccine hesitancy. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Immunogenicity and safety of COVID-19 BNT162b2 booster vaccine in end-stage kidney disease patients receiving haemodialysis in Yogyakarta, Indonesia: a cohort prospective study.

BACKGROUND: A significant decrease in antibody titres several months after COVID-19 primary vaccination in end-stage kidney disease (ESKD) patients receiving maintenance haemodialysis has recently been reported. The waning in antibody titres has led to the recommendations for a booster dose to increase the antibody titres after vaccination. Consequently, it is crucial to analyse the long-term humoral immune responses after COVID-19 primary vaccination and assess the immunogenicity and safety of booster doses in haemodialysis (HD) patients. METHODS: Patients on maintenance haemodialysis who received the primary vaccine of CoronaVac (Sinovac) vaccine were administered with BNT162b2 (Pfizer-BioNTech) as the booster dose. The immunogenicity was assessed before (V1), one month (V2) and eight months (V3) after the primary vaccination, as well as one month after the booster dose (V4). Patients were followed up one month after the booster dose to assess the adverse events (AEs). RESULTS: The geometric mean titre (GMT) of anti-SARS-CoV-2 S-RBD IgG antibody at 8 months after the primary vaccination increased significantly to 5,296.63 (95%CI: 2,930.89-9,571.94) U/mL (p = < 0.0001) compared to before the primary vaccination. The GMT also increased significantly to 19,142.56 (95% CI: 13,489.63-27,227.01) U/mL (p < 0.0001) 1 month after the booster vaccine. Meanwhile, the median inhibition rate of neutralizing antibodies (NAbs) at 8 months after the primary vaccine and 1 month after the booster dose were not significantly different (p > 0.9999). The most common AEs after the booster dose included mild pain at the injection site (55.26%), mild fatigue (10.53%), and swelling at the injection site (10.53%). No serious AEs were reported. CONCLUSIONS: The majority of ESKD patients on haemodialysis mounted a good antibody response to the BNT162b2 booster vaccination with tolerable adverse events.

Functional CVIDs phenotype clusters identified by the integration of immune parameters after BNT162b2 boosters.

Introduction: Assessing the response to vaccinations is one of the diagnostic criteria for Common Variable Immune Deficiencies (CVIDs). Vaccination against SARS-CoV-2 offered the unique opportunity to analyze the immune response to a novel antigen. We identify four CVIDs phenotype clusters by the integration of immune parameters after BTN162b2 boosters. Methods: We performed a longitudinal study on 47 CVIDs patients who received the 3rd and 4th vaccine dose of the BNT162b2 vaccine measuring the generation of immunological memory. We analyzed specific and neutralizing antibodies, spike-specific memory B cells, and functional T cells. Results: We found that, depending on the readout of vaccine efficacy, the frequency of responders changes. Although 63.8% of the patients have specific antibodies in the serum, only 30% have high-affinity specific memory B cells and generate recall responses. Discussion: Thanks to the integration of our data, we identified four functional groups of CVIDs patients with different B cell phenotypes, T cell functions, and clinical diseases. The presence of antibodies alone is not sufficient to demonstrate the establishment of immune memory and the measurement of the in-vivo response to vaccination distinguishes patients with different immunological defects and clinical diseases.

Impact of Health Workers' Choice of COVID-19 Vaccine Booster on Immunization Levels in Istanbul, Turkey.

BACKGROUND: There are limited data regarding short- and medium-term IgG antibody levels after the CoronaVac and BNT162b2 vaccines. This study aimed to investigate the antibody responses of health workers who initially received two doses of CoronaVac one month apart followed by a booster dose of either CoronaVac or BNT162b2, as well as determine whether either vaccine provided superior results. METHODS: This research represents the second phase of a mixed-methods vaccine cohort study and was conducted between July 2021 and February 2022. The participants (n = 117) were interviewed in person and blood samples were collected before and at 1 and 6 months after the booster vaccination. RESULTS: BNT162b2 was found to have greater immunogenic potential than CoronaVac (p < 0.001). Health workers without chronic disease exhibited statistically significant increases in antibody levels after both vaccines (p < 0.001), whereas only BNT162b2 caused a significant increase in antibody levels in participants with chronic disease (p < 0.001). Samples obtained before and at 1 and 6 months after the booster vaccination revealed no age- or sex-based differences in IgG-inducing potential for either vaccine (p > 0.05). Antibody levels were comparable in both vaccine groups before the booster regardless of COVID-19 history (p > 0.05); however, antibody levels were significantly higher after the BNT162b2 booster at 1 month (<0.001) and at 6 months, except among participants who had a positive history of COVID-19 infection (p < 0.001). CONCLUSIONS: Our results suggest that even a single booster dose of BNT162b2 after initial vaccination with CoronaVac provides a protective advantage against COVID-19, especially for risk groups such as health workers and those with chronic diseases.

COVID-19 booster vaccination during pregnancy enhances maternal binding and neutralizing antibody responses and transplacental antibody transfer to the newborn.

The immune response to COVID-19 booster vaccinations during pregnancy for mothers and their newborns and the functional response of vaccine-induced antibodies against Omicron variants are not well characterized. We conducted a prospective, multicenter cohort study of participants vaccinated during pregnancy with primary or booster mRNA COVID-19 vaccines from July 2021 to January 2022 at 9 academic sites. We determined SARS-CoV-2 binding and live virus and pseudovirus neutralizing antibody (nAb) titers pre- and post-vaccination, and at delivery for both maternal and infant participants. Immune responses to ancestral and Omicron BA.1 SARS-CoV-2 strains were compared between primary and booster vaccine recipients in maternal sera at delivery and in cord blood, after adjusting for days since last vaccination. A total of 240 participants received either Pfizer or Moderna mRNA vaccine during pregnancy (primary 2-dose series: 167; booster dose: 73). Booster vaccination resulted in significantly higher binding and nAb titers, including to the Omicron BA.1 variant, in maternal serum at delivery and in cord blood compared to a primary 2-dose series (range 0.44-0.88 log10 higher, p < 0.0001 for all comparisons). Live virus nAb to Omicron BA.1 were present at delivery in 9 % (GMT ID50 12.7) of Pfizer and 22 % (GMT ID50 14.7) of Moderna primary series recipients, and in 73 % (GMT ID50 60.2) of mRNA boosted participants (p < 0.0001), although titers were significantly lower than to the D614G strain. Transplacental antibody transfer was efficient for all regimens with median transfer ratio range: 1.55-1.77 for IgG, 1.00-1.78 for live virus nAb and 1.79-2.36 for pseudovirus nAb. COVID-19 mRNA vaccination during pregnancy elicited robust immune responses in mothers and efficient transplacental antibody transfer to the newborn. A booster dose during pregnancy significantly increased maternal and cord blood binding and neutralizing antibody levels, including against Omicron BA.1. Findings support the use of a booster dose of COVID-19 vaccine during pregnancy.

An omicron-based vaccine booster elicits potent neutralizing antibodies against emerging SARS-CoV-2 variants in adults.

SARS-CoV-2 Omicron subvariants have become the predominantly strain in most countries. However, the neutralizing activity of the human serum after Omicron-based vaccine booster against different SARS-CoV-2 variants is poorly understood. Here, we developed an update Omicron vaccine (SCoK-Omicron), based on the RBD-Fc fusion protein vaccine (SCoK) and RBD domain of Omicron BA.1. To assess cross-variant neutralizing activity in adults, 25 volunteers that have received three doses of SCoK and 25 volunteers with two doses of CoronaVac (inactive vaccine) were further boosted with a dose updated vaccine (SCoK-Omicron). The results of pseudovirus neutralization assays demonstrated that the booster potently induced the high-level of neutralizing antibody against SARS-CoV-2 Wild type, Delta and Omicron subvariants in adults. Further assays of single point mutations showed that K444T, L452R, N460K, or F486V was key mutations to cause immune evasion. Together, these data suggest that SCOK-Omicron can be used as a booster vaccine candidate in adults receiving subunit protein or inactivated vaccine in response to the epidemic of COVID-19 Omicron subvariants, and the mutation K444T, L452R, N460K, or F486V needs to be considered in future vaccine design.

The Psychology of COVID-19 Booster Hesitancy, Acceptance and Resistance in Australia.

COVID-19 booster vaccinations have been recommended as a primary line of defence against serious illness and hospitalisation. This study identifies and characterises distinct profiles of attitudes towards vaccination, particularly the willingness to get a booster dose. A sample of 582 adults from Australia completed an online survey capturing COVID-related behaviours, beliefs and attitudes and a range of sociodemographic, psychological, political, social and cultural variables. Latent Profile Analysis (LPA) identified three subgroups: Acceptant (61%), Hesitant (30%) and Resistant (9%). Compared to the Acceptant group, the Hesitant and Resistant groups were less worried about catching COVID-19, used fewer official COVID-19 information sources, checked the news less, were lower on the agreeableness personality dimension and reported more conservatism, persecutory thinking, amoral attitudes and need for chaos. The Hesitant group also reported checking the legitimacy of information sources less, scored lower on the openness to new experiences personality dimension and were more likely than the Resistant and Acceptant groups to report regaining freedoms (e.g., travel) and work requirements or external pressures as reasons to get a booster. The Resistant group were higher on reactance, held more conspiratorial beliefs and rated their culture as being less tolerant of deviance than the Hesitant and Acceptant groups. This research can inform tailored approaches to increasing booster uptake and optimal strategies for public health messaging.

Thrombocytopenia Secondary to COVID-19 Vaccination: Side Effect or Coincidence?

  While widespread coronavirus disease 2019 (COVID-19) vaccination has helped achieve some control of the pandemic, vaccines have presented with side effects of their own, both common and rare. We present an unusual case of a 66-year-old who presented with severe thrombocytopenia following vaccination with the Pfizer-BioNTech mRNA vaccine. Our patient is a 66-year-old African American female with a known history of Sjogren's syndrome and hepatitis C who presented to our facility as a direct admit from our affiliated infusion clinic where routine lab work revealed a platelet count of 14,000. On arrival, she reported a one-month history of progressive tiredness, intermittent epistaxis, and bruising on her legs. Her physical exam was notable for multiple petechiae and non-palpable purpura on all four extremities. Further questioning revealed that she had received her COVID-19 vaccine booster (Pfizer-BioNTech) three weeks prior to presentation and that is when all the symptoms had started. Rheumatology was consulted and the patient was started on intravenous immunoglobulin infusion for two days and pulse dose prednisone. Her platelet count showed improvement after treatment, and she was discharged home with a platelet count of 42,000. Though largely safe and efficacious, COVID-19 vaccines can present with rare systemic side effects and physicians must have a high index of suspicion and report these cases so that more data is available for interpretation.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection History and Antibody Response to 3 Coronavirus Disease 2019 Messenger RNA Vaccine Doses.

BACKGROUND: Data on antibody kinetics are limited among individuals previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). From a cohort of healthcare personnel and other frontline workers in 6 US states, we assessed antibody waning after messenger RNA (mRNA) dose 2 and response to dose 3 according to SARS-CoV-2 infection history. METHODS: Participants submitted sera every 3 months, after SARS-CoV-2 infection, and after each mRNA vaccine dose. Sera were tested for antibodies and reported as area under the serial dilution curve (AUC). Changes in AUC values over time were compared using a linear mixed model. RESULTS: Analysis included 388 participants who received dose 3 by November 2021. There were 3 comparison groups: vaccine only with no known prior SARS-CoV-2 infection (n = 224); infection prior to dose 1 (n = 123); and infection after dose 2 and before dose 3 (n = 41). The interval from dose 2 and dose 3 was approximately 8 months. After dose 3, antibody levels rose 2.5-fold (95% confidence interval [CI] = 2.2-3.0) in group 2 and 2.9-fold (95% CI = 2.6-3.3) in group 1. Those infected within 90 days before dose 3 (and median 233 days [interquartile range, 213-246] after dose 2) did not increase significantly after dose 3. CONCLUSIONS: A third dose of mRNA vaccine typically elicited a robust humoral immune response among those with primary vaccination regardless of SARS-CoV-2 infection >3 months prior to boosting. Those with infection <3 months prior to boosting did not have a significant increase in antibody concentrations in response to a booster.

Clinical Characteristics of Mild Patients with Breakthrough Infection of Omicron Variant in China after Relaxing the Dynamic Zero COVID-19 Policy.

For SARS-CoV-2 mutants, the effectiveness of the COVID-19 vaccines is still controversial. In this study, we aimed to investigate the clinical characteristics of Omicron-infected patients who completed primary immunization and booster immunization, respectively, during the rapid propagation of the Omicron variant in China. A total of 932 patients with confirmed SARS-CoV-2 infection from 18 December 2022 to 1 January 2023 were included in this survey by filling out questionnaires online. The enrolled patients were divided into the primary immunization group and the booster immunization group according to their vaccination status. During the whole course of disease, the most frequent symptoms were fever (90.6%), cough (84.3%), weakness (77.4%), headache and dizziness (76.1%), and myalgia (73.9%). Nearly 90% of the patients had symptoms lasting for less than 10 days, and 39.8% of the patients ended the course of the disease in 4-6 days. A total of 58.8% of these patients had a fever with a maximum body temperature of over 38.5 °C. Moreover, 61.4% of the patients had a fever that lasted less than 2 days. There were no obvious differences in initial symptoms, cardinal symptoms, symptom duration time, maximum body temperature, and fever duration time between the two groups of patients. In addition, no significant difference was found in the positive or negative conversion time of SARS-CoV-2 antigen/nucleic acid between the two groups of patients. For mild patients with Omicron breakthrough infection, enhanced immunization has no significant impact on the clinical performance and duration of viral infection compared with primary immunization. The reasons behind the different clinical manifestations of patients with mild symptoms after the breakthrough infection of the Omicron strain are still worth further research. Heterologous vaccination may be a better strategy for enhanced immunization, which can help improve the immune protection ability of the population. Further research should be carried out on vaccines against mutant strains and spectral anti-COVID-19 vaccines.

Future COVID-19 Booster Vaccine Refusal in Healthcare Workers after a Massive Breakthrough Infection Wave, a Nationwide Survey-Based Study.

Background: An unprecedented coronavirus disease 2019 (COVID-19) wave occurred in China between December 2022 and January 2023, challenging the efficacy of the primary series of COVID-19 vaccines. The attitudes toward future COVID-19 booster vaccines (CBV) after the massive breakthrough infection among healthcare workers remain unknown. This study aimed to explore the prevalence and determinants of future CBV refusal after the unprecedented COVID-19 wave among healthcare workers. Methods: Between 9 and 19 February 2023, a cross-sectional nationwide online survey was conducted using a self-administered questionnaire vaccine among healthcare workers in China. Sociodemographics, profession, presence of chronic medical conditions, previous COVID-19 infection, attitudes towards future CBV, and reasons for future CBV refusal were collected. We estimated odds ratio [OR] with 95% confidence interval [CI] using a multivariable logistic regression model to explore the factors associated with future CBV refusal. Results: Among the 1618 participants who completed the survey, 1511 respondents with two or more doses of COVID-19 vaccines were analyzed. A total of 648 (41.8%) of respondents were unwilling to receive a future CBV. Multivariable logistic regression analysis revealed the association of CBV refusal with profession (vs. other staff, physician-adjusted OR 1.17, 95%CI 0.79-1.72, nurse-adjusted OR 1.88, 95%CI 1.24-2.85, p = 0.008), history of allergy (adjusted OR 1.72, 95%CI 1.05-2.83, p = 0.032), a lower self-perceived risk of future COVID-19 infection (p < 0.001), and a lower belief in CBV effectiveness (p = 0.014), safety (p < 0.001), and necessities for healthcare workers and the public (p < 0.001, respectively). Conclusions: Our findings highlight that a considerable proportion of healthcare workers were against a future booster dose after an unprecedented COVID-19 wave. Self-perception of future COVID-19 risk, and potential harm or doubtful efficacy of vaccines are the main determinants. Our findings may help public health authorities to establish future COVID-19 vaccination programs.

Humoral Response after a Fourth Dose with mRNA-1273 in Healthcare Workers with and without a History of SARS-CoV-2 Infection and Previously Vaccinated with Two Doses of BBIBP-CorV Plus BNT162b2 Vaccine.

There is limited information on the kinetics of the humoral response elicited by a fourth dose with a heterologous mRNA1273 booster in patients who previously received a third dose with BNT162b2 and two doses of BBIBP-CorV as the primary regimen. We conducted a prospective cohort study to assess the humoral response using Elecsys® anti-SARS-CoV-2 S (anti-S-RBD) of 452 healthcare workers (HCWs) in a private laboratory in Lima, Peru at 21, 120, 210, and 300 days after a third dose with a BNT162b2 heterologous booster in HCW previously immunized with two doses of BBIBP-CorV, depending on whether or not they received a fourth dose with the mRNA1273 heterologous vaccine and on the history of previous SARS infection -CoV-2. Of the 452 HCWs, 204 (45.13%) were previously infected (PI) with SARS-CoV-2, and 215 (47.57%) received a fourth dose with a heterologous mRNA-1273 booster. A total of 100% of HCWs presented positive anti-S-RBD 300 days after the third dose. In HCWs receiving a fourth dose, GMTs 2.3 and 1.6 times higher than controls were observed 30 and 120 days after the fourth dose. No statistically significant differences in anti-S-RBD titers were observed in those HCWs PI and NPI during the follow-up period. We observed that HCWs who received a fourth dose with the mRNA1273 and those previously infected after the third dose with BNT162b2 (during the Omicron wave) presented higher anti-S-RBD titers (5734 and 3428 U/mL, respectively). Further studies are required to determine whether patients infected after the third dose need a fourth dose.