Temporal changes in biomarkers of neutrophil extracellular traps and NET-promoting autoantibodies following adenovirus-vectored, mRNA, and recombinant protein COVID-19 vaccination.

Neutrophil extracellular traps (NETs) play a role in innate pathogen defense and also trigger B-cell response by providing antigens. NETs have been linked to vaccine-induced thrombotic thrombocytopenia. We postulated a potential link between NET biomarkers, NET-promoting autoantibodies, and adverse events (AEs) after COVID-19 vaccine boosters. Healthy donors (HDs) who received ChAdOx1-S (A), mRNA-1273 (M), or recombinant protein (MVC-COV1901) vaccines at the National Taiwan University Hospital between 2021 and 2022 were recruited. We measured serial NET-associated biomarkers, citrullinated-histone3 (citH3), and myeloperoxidase (MPO)-DNA. Serum citH3 and MPO-DNA were significantly or numerically higher in HDs who reported AEs (n = 100, booster Day 0/Day 30, p = 0.01/p = 0.03 and p = 0.30/p = 0.35, respectively). We also observed a positive correlation between rash occurrence in online diaries and elevated citH3. A linear mixed model also revealed significantly higher citH3 levels in mRNA-1273/ChAdOx1-S recipients than MVC-COV1901 recipients. Significant positive correlations were observed between the ratios of anti-heparin platelet factor 4 and citH3 levels on Booster Day 0 and naïve and between the ratios of anti-NET IgM and citH3 on Booster Day 30/Day 0 in the AA-M and MM-M group, respectively. The increased levels of citH3/MPO-DNA accompanied by NET-promoting autoantibodies suggest a potential connection between mRNA-1273/ChAdOx1-S vaccines and cardiovascular complications. These findings provide insights for risk assessments of future vaccines.

A natural experiment during lockdown and on-going care-home COVID-19 outbreaks showed a single dose of vaccine reduced hospitalisation and deaths of care-home residents in North West England.

OBJECTIVE: To examine the effectiveness of one dose of the COVID-19 vaccine on care-home residents. STUDY DESIGN: Natural experiment. METHODS: We compared the effectiveness of single doses of Pfizer/BioNTech BNT162b2 (effective at 10 days) and AstraZeneca ChAdOx1 (effective at 14 days) vaccines in vaccinated and control (unvaccinated) homes. Using routine data, all care-homes reporting COVID-19 outbreaks between 11/12/2020 and 12/3/2021 in a sub-region of North West England were included. RESULTS: Of 126 care-homes (4042 residents), with outbreaks, 55 (44%, 1686 residents) reported onset dates before vaccination commenced; 38 (30%, 1304 residents) reported onset < 10 (BNT162b2) and < 14 days (ChAdOx1) after vaccine administration; and 33 (26%, 1052 residents) reported onset > 10 (BNT162b2) and > 14 (ChAdOx1) days after vaccination. Eighty-nine (71%) homes used ChAdOx1 vaccine. A single dose of vaccine before the outbreak onset significantly lowered the risk of symptoms (reduced by 48%), positivity (by 65%), hospitalisation (by 68%), and death (by 81%). Some vaccine effectiveness was also noted in care-homes that received one dose of vaccine within 10-14 days of outbreak onset. The number needed to vaccinate to prevent one resident from COVID-19-related hospitalisation was 34, and death was 17. CONCLUSIONS: This real-world, natural experiment adds to the evidence of COVID-19 vaccine effectiveness from different studies using varying designs. In the context of lockdown's impact on infection rates and on-going care-home outbreaks, a single dose of either ChAdOx1 or BNT162b2 vaccine had a significant impact on reducing COVID-19 related hospitalisation and death in care-home residents. Natural experiments should be used more in public health.

Evaluation of humoral immune response after ChAdOx1 nCoV-19 vaccination among health care workers.

We assessed the immunogenicity of ChAdOx1 nCoV-19 vaccination by evaluating the levels of SARS-CoV-2 IgG after vaccination and investigated the effect of diverse factors such as gender, age, and adverse reactions after vaccination. The study included a total of 1028 serum samples from 452 healthcare workers. SARS-CoV-2 IgG levels were assessed using the SARS-CoV-2 IgG II Quant assay. Participants completed a questionnaire regarding the intensity and duration of adverse reactions after vaccination. The seropositive rates after the first and second doses were 95.5% and 100%, respectively. The median antibody levels after the second dose showed a 4.2-fold increase compared with the first. Five months after the second dose, the median antibody levels decreased by 3.5-fold. The antibody levels in men were lower than those in women after the first dose and were higher after the second dose. There was no difference according to age groups after the first dose, but after the second dose, in subjects aged 50 and above, the rise in antibody levels was less than that in other age groups. The antibody levels among participants with moderate or severe symptoms were significantly higher than those among participants with mild symptoms after the first dose. There were no statistically significant differences according to the duration of symptoms. We could assume that different age groups and genders might have different immunogenicity following vaccination. The intensity of adverse symptoms was positively correlated with the antibody levels, implying that higher immunogenicity is related to the intensity of adverse symptoms after vaccination.

Comparative safety analysis of mRNA and adenoviral vector COVID-19 vaccines: a nationwide cohort study using an emulated target trial approach.

OBJECTIVE: This nationwide cohort study compared the incidence of adverse events of special interest (AESIs) between adenoviral vector-based (ChAdOx1) and mRNA-based (BNT162b2 or mRNA-1273) coronavirus disease 2019 (COVID-19) vaccines. METHODS: A targeted trial emulation study was conducted using data from the National Health Insurance Service database. Vaccinees aged 18-85 years who had received at least one dose of ChAdOx1 or an mRNA-based vaccine were identified. The 42-day risks of AESIs were calculated. RESULTS: A total of 1 767 539 ChAdOx1 vaccinees were matched exactly with mRNA vaccinees according to their risk factors. The 42-day risks of adverse events were low (∼0 to 176 events per 100 000 persons in both vaccine groups), and the incidence rates of AESIs were comparable between the two platforms, except for a higher occurrence of acute cardiac injury (incidence rate ratio [IRR], 1.22; 95% CI, 1.10-1.35), myocarditis or pericarditis (IRR, 2.14; 95% CI, 1.14-4.04), and arrhythmia (IRR, 1.46; 95% CI, 1.24-1.71) in mRNA vaccinees. The incidence of Guillain-Barré syndrome (IRR, 0.20; 95% CI, 0.06-0.69), vasovagal syncope (IRR, 0.77; 95% CI, 0.62-0.97), radiculopathy (IRR = 0.59, 95% CI, 0.41-0.84), and aseptic arthritis (IRR, 0.81; 95% CI, 0.70-0.93) was significantly lower in mRNA-based vaccinees compared with ChAdOx1 vaccinees. DISCUSSION: A remarkable platform-dependent difference was observed in the safety profiles of COVID-19 vaccines, particularly for myocarditis or pericarditis and Guillain-Barré syndrome. However, the overall risk of AESIs was low for both vaccine platforms.

AZD1222 effectiveness against severe COVID-19 in individuals with comorbidity or frailty: The RAVEN cohort study.

OBJECTIVES: Despite being prioritized during initial COVID-19 vaccine rollout, vulnerable individuals at high risk of severe COVID-19 (hospitalization, intensive care unit admission, or death) remain underrepresented in vaccine effectiveness (VE) studies. The RAVEN cohort study (NCT05047822) assessed AZD1222 (ChAdOx1 nCov-19) two-dose primary series VE in vulnerable populations. METHODS: Using the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub, linked to secondary care, death registration, and COVID-19 datasets in England, COVID-19 outcomes in 2021 were compared in vaccinated and unvaccinated individuals matched on age, sex, region, and multimorbidity. RESULTS: Over 4.5 million AZD1222 recipients were matched (mean follow-up ∼5 months); 68% were ≥50 years, 57% had high multimorbidity. Overall, high VE against severe COVID-19 was demonstrated, with lower VE observed in vulnerable populations. VE against hospitalization was higher in the lowest multimorbidity quartile (91.1%; 95% CI: 90.1, 92.0) than the highest quartile (80.4%; 79.7, 81.1), and among individuals ≥65 years, higher in the 'fit' (86.2%; 84.5, 87.6) than the frailest (71.8%; 69.3, 74.2). VE against hospitalization was lowest in immunosuppressed individuals (64.6%; 60.7, 68.1). CONCLUSIONS: Based on integrated and comprehensive UK health data, overall population-level VE with AZD1222 was high. VEs were notably lower in vulnerable groups, particularly the immunosuppressed.

Covid Antibody Titers in Cancer Patients Following Vaccination with ChAdOx1 nCOV-19 Vaccine.

Dr. Vikram GotaCovid-19 has led to significant mortality worldwide, with an increased risk in cancer patients. Vaccination provides significant protection against the infection. The study focuses on the immunogenicity and effectiveness of ChAdOx1 nCoV-19 vaccine in cancer patients within a real-world setting. Blood samples for measuring Covid antibody titers against the receptor binding domain were collected according to a convenient sparse sampling strategy in a real-world setting, with the days of the collection coinciding with their hospital appointment. The antibody titers between different groups were analyzed descriptively. A total of 56 patients were enrolled in the study. There was no apparent effect in antibody titers between patients with solid tumors and hematological malignancies (mean ± standard deviation [SD]: 36.80 ± 41.18 vs. 52.02 ± 26.27), among patients who were undergoing chemotherapy, immunotherapy, or local therapy (mean ± SD: 42.50 ± 44.46 vs. 50.06 ± 51.39 vs. 28.70 ± 25.03), and in patients with up to 90 days and more than 90 days' interval between their last treatment and date of vaccination (mean ± SD: 38.96 ± 42.66 vs. 40.51 ± 38.65). Additionally, there were only 2/56 patients with breakthrough infection, which points out the effectiveness of this vaccine in cancer patients. The ChAdOx1 nCoV-19 vaccine has activity in cancer regardless of the tumor type, type of treatment, or time from the last treatment.

Comparison of Adverse Events and Antibody Responses Among Different COVID-19 Vaccination Schedules.

Global investment in developing COVID-19 vaccines has been substantial, but vaccine hesitancy has emerged due to misinformation. Concerns about adverse events, vaccine shortages, dosing confusion, mixing vaccines, and access issues contribute to hesitancy. Initially, the WHO recommended homologous vaccination (same vaccine for both doses), but evolving factors led to consideration of heterologous vaccination (different vaccines). The study compared reactogenicity and antibody response for both viral protein spike (S) and nucleocapsid (N) in 205 participants who received three vaccination regimens: same vaccine for all doses (Pfizer), two initial doses of the same vaccine (CoronaVac or AstraZeneca), and a Pfizer booster. ChAdOx1 and BNT162b2 vaccines were the most reactogenic vaccines, while CoronaVac vaccine was the least. ChAdOx1 and BNT162b2 achieved 100% of S-IgG seropositivity with one dose, while CoronaVac required two doses, emphasizing the importance of the second dose in achieving complete immunization across the population with different vaccine regimes. Pfizer recipients showed the highest S-IgG antibody titers, followed by AstraZeneca recipients, both after the first and second doses. A third vaccine dose was essential to boost the S-IgG antibodies and equalize the antibody levels among the different vaccine schedules. CoronaVac induced N-IgG antibodies, while in the Pfizer and AstraZeneca groups, they were induced by a natural infection, reinforcing the role of N protein as a biomarker of infection.

Adverse events following immunization of ChAdOx1 nCoV-19 vaccine among healthcare workers of a medicine-teaching institution of North India.

Objective: This study sought to assess the prevalence of adverse events following immunization (AEFI) and factors associated with AEFI of the ChAdOx1 nCoV-19 vaccine (Covishield) among healthcare workers (HCW) of a medicine-teaching institution of North India. Materials and Methods: A cross-sectional study was conducted in the months of June and July 2021 among HCW (N = 203) of 18 years and above, vaccinated with at least the first dose of Covishield. A semi-structured, prevalidated, and pretested questionnaire was used to collect information through an interview schedule. The questionnaire was divided into five sections: the sociodemographic profile, behavioral characteristics, past medical history, COVID-19 awareness, and past infection and COVID-19 vaccine related information. Chi-squared test was applied to check the association of different factors with AEFI. Results: In our study, 73.89% of participants suffered from at least one AEFI after the first dose of the vaccine, while 48.66% had at least one AEFI after the second dose. Females reported significantly high AEFI for both doses (P = 0.001, 0.000). We found a significant association between the occurrence of AEFI and occupation (first dose P = 0.015), substance abuse (first dose P = 0.002), diet (first dose P = 0.016), and allergy (first dose P = 0.027). Other significant findings were headaches among HCW ≥40 years of age (dose P = 0.034) and systemic AEFI in participants with comorbidity (first dose P = 0.020). Conclusion: More AEFI were reported after the first dose as compared to the second dose. AEFI were more among females after both the doses. Occupation, substance use, diet, and history of allergy were significantly associated with AEFI.

Probable secondary hemophagocytic lymphohistiocytosis manifesting as central nervous system lesions after COVID-19 vaccination: a case report.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare systemic inflammatory disease commonly characterized by histiocyte infiltration in multiple organs, such as the liver, spleen, lymph nodes, bone marrow, and central nervous system. The clinical features of HLH include fever, splenomegaly, cytopenia, hypertriglyceridemia, hypofibrinogenemia, and elevated blood ferritin levels. HLH is categorized as either primary or secondary. Coronavirus disease 2019 (COVID-19) vaccines may occasionally trigger secondary HLH, which is related to hyperinflammatory syndrome. Case presentation: A 58-year-old woman, previously diagnosed with Graves' disease, presented with cognitive decline 2 weeks after receiving the first dose of the ChAdOx1 nCoV-19 vaccine. Brain MRI revealed a hyperintense lesion on T2-weighted and fluid-attenuated inversion recovery images in the bilateral subcortical white matter and right periventricular area. Vaccination-associated acute disseminated encephalomyelitis was suspected and methylprednisolone and intravenous immunoglobulin (IVIg) were administered. From the 5th day of IVIg administration, the patient developed fever and pancytopenia. In the findings of bone marrow biopsy, hemophagocytosis was not observed; however, six of the eight diagnostic criteria for HLH-2004 were met, raising the possibility of HLH. Although there was no definitive method to confirm causality, considering the temporal sequence, suspicion arose regarding vaccine-induced HLH. Splenectomy was considered for therapeutic and diagnostic purposes; however, the patient died on the 28th day of hospitalization owing to multiple organ failure. Conclusion: To date, 23 cases of COVID-19 vaccine-related HLH have been reported. Additionally, HLH in COVID-19 patients has been reported in various case reports. To the best of our knowledge, this is the first reported case of central nervous system involvement in HLH related to any type of COVID-19 vaccine. This case suggests that even when there are no systemic symptoms after COVID-19 vaccination, HLH should be considered as a differential diagnosis if brain lesions are suggestive of CNS demyelinating disease.

Evaluation of SARS-CoV-2 Humoral Response Following Vaccination with ChAdOx1 nCoV-19 (Covishield™) and/or Sinopharm, BBIBP-CorV (Vero cell™).

BACKGROUND: Billions of doses of COVID-19 vaccine have been introducing in the world to prevent pandemic COVID-19. Higher efficacy but limited data are available for its longevity. We aimed to find out the IgG Anti-SARS Cov-2 antibody level among frontline healthcare workers after two doses of vaccines. METHODS: A cross-sectional study was carried among 170 HCPs of Seti Provincial Hospital of western Nepal, who were more than 18 years, and had taken two doses of either one of COVID 19 vaccine. All those participants, who were on leave during the data collection tenure (1st February 2022 to 28th February 2022) and/or did not consent to participate were excluded. Mindray SARS-CoV-2 S-RBD IgG assay kit based on CLIA method, was used whose target antigen is S-RBD (spike protein of receptor binding domain) antigen. The IgG immunoglobulin is detected and cut off value ≥10 AU/ml is considered positive. RESULTS: Based on the recommended cut off, the antibody was present in more than 90% across both groups of vaccinee i.e. the positive antibody titer at a mean duration of 7.31 months was 93.53% overall (93.75% and 93.44% in Vero cell™ and Covishield™ vaccinees respectively). There were 3.92 times high odds of high antibody titer (≥250 AU/ml) in Covishield™ group (OR: 3.92, 95% CI: 1.86-8.26, P-value: <0.001) than in Vero cell™ group of vaccinee. Similarly, there were significant difference of high titer of antibody across groups with more than six months of elapse of vaccination (OR: 2.18, 95% CI: 1.06-4.49, P-value: <0.001) than with less than six months of elapse of vaccination. CONCLUSIONS: The humoral response was higher among HCPs who received two-doses vaccination with ChAdOx1 nCoV-19 (Covishield™) and/or Sinopharm, BBIBP-CorV (Vero cell™) vaccine, and among those with six or more months of elapse of vaccination. The seroprevalence of SARS-CoV-2 following two-doses vaccination among HCPs was more than nine-tenths.

Monitoring of adaptive immune responses in healthcare workers who received a Coronavirus disease 2019 vaccine booster dose.

Background and Aims: Coronavirus disease 2019 (COVID-19) has become a global pandemic and led to increased mortality and morbidity. Vaccines against the etiologic agent; severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were approved for emergency use on different platforms. In the early phase of the pandemic, Thai healthcare workers (HCWs) received CoronaVac, an inactivated vaccine, as the first vaccine against SARS-CoV-2, followed by ChAdOx1 nCoV-19, a viral vector-based vaccine, or BNT162b2, an mRNA vaccine, as a booster dose. This preliminary study evaluated the immunogenicity of ChAdOx1 nCoV-19 and BNT162b2 as a booster dose in HCWs who previously received two doses of CoronaVac. Methods: Ten HCW participants received ChAdOx1 nCoV-19 and another 10 HCWs received BNT162b2 as a booster dose after two doses of CoronaVac. Anti-RBD IgG, neutralizing antibodies (NAb), and cellular immunity, including interferon-gamma (IFN-γ)-releasing CD4, CD8, double negative T cells, and NK cells, were measured at 3 and 5 months after the booster dose. Results: There was no significant difference in anti-RBD IgG levels at 3 and 5 months between the two different types of booster vaccine. The levels of anti-RBD IgG and NAb were significantly decreased at 5 months. HCWs receiving BNT162b2 had significantly higher NAb levels than those receiving ChAdOx1 nCoV-19 at 5 months after the booster dose. IFN-γ release from CD4 T cells was detected at 3 months with no significant difference between the two types of booster vaccines. However, IFN-γ-releasing CD4 T cells were present at 5 months in the ChAdOx1 nCoV-19 group only. Conclusion: ChAdOx1 nCoV-19 or BNT162b2 can be used as a booster dose after completion of the primary series primed by inactivated vaccine. Although the levels of immunity decline at 5 months, they may be adequate during the first 3 months after the booster dose.

Single ChAdOx1 nCoV-19 dose elicits stronger immune response in previously infected individuals than in SARS-CoV2 naive persons.

BACKGROUND: Current vaccines against COVID-19 effectively reduce morbidity and mortality and are vitally important for controlling the pandemic. Between December 2020 and February 2021, adenoviral vector vaccines such as ChAdOx1 (AstraZeneca-Oxford) were put in use. Recent reports demonstrate robust serological responses to a single dose of messenger RNA vaccines in individuals previously infected with SARS-CoV-2. We aimed to study the association between previous COVID-19 infection and antibody levels after a single dose of ChAdOx1 nCoV-19. METHODS: This cross-sectional study was conducted on 657 individuals who were either convalescent or SARS-CoV-2 naive and had received one dose of ChAdOx1 (AstraZeneca). A questionnaire was used to collect data on age, sex, and self-reported history of COVID-19 infection. We then compared the average levels of immunoglobulin G (IgG) between the previously infected and COVID-19-naive participants. RESULTS: We compared the antibody responses of individuals with confirmed prior COVID-19 infection with those of individuals without prior evidence of infection. The mean antibody levels in those who reported no history of COVID-19 infection were substantially lower than in those who were previously infected, in both males and females. Sex-related differences were observed when we compared antibody levels between men and women. In males, anti-S IgG antibody levels were higher in those who had been previously infected (156.1 vs. 87.69 AU/mL, p = .009), compared with the same pattern was observed in females (113.5 vs. 90.69 AU/mL, p = .005). CONCLUSIONS: Previous COVID-19 infection is associated with higher levels of SARS-CoV-2 antibodies following ChAdOx1 (AstraZeneca) vaccination. Our finding supports the notion that a single dose of ChAdOx1 nCoV-19 administered post-SARS-CoV-2 infection serves as an effective immune booster. This provides a possible rationale for a single-dose vaccine regimen for previously infected individuals.

Seropersistence of SII-ChAdOx1 nCoV-19 (COVID-19 vaccine): 6-month follow-up of a randomized, controlled, observer-blind, phase 2/3 immuno-bridging study in Indian adults.

AZD1222 (ChAdOx1 nCoV-19) is a replication-deficient adenoviral vectored coronavirus disease-19 (COVID-19) vaccine that is manufactured as SII-ChAdOx1 nCoV-19 by the Serum Institute of India Pvt Ltd following technology transfer from Oxford University/AstraZeneca. The non-inferiority of SII-ChAdOx1 nCoV-19 with AZD1222 was previously demonstrated in an observer-blind, phase 2/3 immuno-bridging study (trial registration: CTRI/2020/08/027170). In this analysis of immunogenicity and safety data 6 months post first vaccination (Day 180), 1,601 participants were randomized 3:1 to SII-ChAdOx1 nCoV-19 or AZD1222 (immunogenicity/reactogenicity cohort n = 401) and 3:1 to SII-ChAdOx1 nCoV-19 or placebo (safety cohort n = 1,200). Immunogenicity was measured by anti-severe acute respiratory syndrome coronavirus 2 spike (anti-S) binding immunoglobulin G and neutralizing antibody (nAb) titers. A decline in anti-S titers was observed in both vaccine groups, albeit with a greater decline in SII-ChAdOx1 nCoV-19 vaccinees (geometric mean titer [GMT] ratio [95% confidence interval (CI) of SII-ChAdOx1 nCoV-19 to AZD1222]: 0.60 [0.41-0.87]). Consistent similar decreases in nAb titers were observed between vaccine groups (GMT ratio [95% CI]: 0.88 [0.44-1.73]). No cases of severe COVID-19 were reported following vaccination, while one case was observed in the placebo group. No causally related serious adverse events were reported through 180 days. No thromboembolic or autoimmune adverse events of special interest were reported. Collectively, these data illustrate that SII-ChAdOx1 nCoV-19 maintained a high level of immunogenicity 6 months post-vaccination. SII-ChAdOx1 nCoV-19 was safe and well tolerated.

Safety and immunogenicity of CoronaVac and ChAdOx1 heterologous prime-boost vaccines in an overweight population in Chiang Mai, Thailand.

Background: In early 2021, the Ministry of Public Health of Thailand announced heterologous regimens for COVID-19 vaccines using CoronaVac as the first dose followed by ChAdOx1 nCoV-19 at 3 weeks apart. Priority was given to individuals above 60 years old and those who had seven underlying conditions, including obesity. The vaccine regimen was evaluated for safety and immunogenicity in overweight populations in Chiang Mai, Thailand. Methods: Participants who had a COVID-19 vaccination appointment for the heterologous prime-boost regimen were enrolled. Before each immunization and on day 28 following the second dosage, blood samples were taken, and were examined for anti-spike and neutralizing antibodies by using an indirect ELISA and virus neutralization assays. Safety profile of the vaccine regimen was assessed via a self-recorded diary of adverse events after each vaccination. Results: No serious adverse events related to vaccination were reported during study period and the majority of adverse reactions were fatigue and pain at the injection site. The levels of anti-spike IgG were 26.3, 56.4 and 1752.1 BAU/mL at baseline, 21 days after first dose and 28 days after second dose, respectively. At 4 weeks after complete vaccination, the median inhibition rates of neutralizing antibody determined by surrogate neutralization assay against wild type, Delta and Omicron variants were 95.2, 85.0 and 3.8, respectively. Moreover, the NT50 level against wild type and Delta variants determined by pseudotyped virus neutralization assay were 133.3 and 41.7, respectively. The neutralizing activity against Omicron variant was almost lower than cutoff level for detection. Conclusions: The heterologous CoronaVac-ChAdOx1vaccination was safe, well-tolerated and able to induce humoral immunity against wild-type and Delta variants but not against the Omicron variant in overweight population.

Long-Term Dynamic Changes in Hybrid Immunity over Six Months after Inactivated and Adenoviral Vector Vaccination in Individuals with Previous SARS-CoV-2 Infection.

Numerous studies have largely focused on short-term immunogenicity in recovered individuals post mRNA vaccination. However, understanding the long-term durability, particularly in inactivated and adenoviral vectored vaccines, remains limited. We evaluated antibody responses, omicron variant neutralization, and IFN-γ responses in 119 previously infected individuals vaccinated with CoronaVac or ChAdOx1 up to six months post-vaccination. Both vaccines elicited robust immune responses in recovered individuals, surpassing those who were infection-naïve, and these persisted above pre-vaccination levels for six months. However, antibody levels declined over time (geometric mean ratio (GMR) = 0.52 for both vaccines). Notably, neutralizing activities against omicron declined faster in ChAdOx1 (GMR = 0.6) compared to CoronaVac recipients (GMR = 1.03). While the first dose of ChAdOx1 adequately induced immune responses in recovered individuals, a second dose demonstrated advantages in omicron variant neutralization and slower decline. Although both vaccines induced T cell responses, the median IFN-γ level at six months returned to pre-vaccination levels. However, more individuals exhibited reactive T cell responses. Extending the interval (13-15 months) between infection and vaccination could enhance antibody levels and broaden neutralization. Together, these findings demonstrate a robust humoral and cellular response that was sustained for at least six months after vaccination, thus guiding optimal vaccination strategies based on prior infection and vaccine platforms.

Immunogenicity, safety, and reactogenicity of a half- versus full-dose BNT162b2 (Pfizer-BioNTech) booster following a two-dose ChAdOx1 nCoV-19, BBIBP-CorV, or Gam-COVID-Vac priming schedule in Mongolia: a randomised, controlled, non-inferiority trial.

Background: COVID-19 vaccine booster doses restore vaccine effectiveness lost from waning immunity and emerging variants. Fractional dosing may improve COVID-19 booster acceptability and uptake and will reduce the per-dose cost of COVID-19 booster programmes. We sought to quantify the immunogenicity, reactogenicity, and safety of a half-dose BNT162b2 (Pfizer-BioNTech) booster relative to the standard formulation. Methods: This randomised, controlled, non-inferiority trial recruited adults in Mongolia primed with a two-dose homologous ChAdOx1 nCov-19 (Oxford-AstraZeneca, n = 129 participants), BBIBP-CorV (Sinopharm (Beijing), n = 399), or Gam-COVID-Vac (Gamaleya, n = 70) schedule. Participants were randomised (1:1) to receive a 15 µg (half-dose) or 30 µg (full-dose) BNT162b2 booster. Participants and study staff assessing reactogenicity were blinded up to day 28. Co-primary endpoints were Wuhan-Hu-1 anti-spike S1 IgG seroresponse 28 days post-boosting and reactogenicity within 7 days of boosting. The non-inferiority margin for the absolute difference in seroresponse was -10%. Differences in seroresponse were estimated from logistic regression with marginal standardisation. Geometric mean ratios of IgG were also estimated. ClinicalTrials.gov Identifier: NCT05265065. Findings: Between May 27th and September 30th, 2022, 601 participants were randomized to full-dose BNT162b2 (n = 300) or half-dose (n = 301). 598 were included in safety analyses, and 587 in immunological analyses. The frequency of grade 3-4 reactions was similar between arms (half-dose: 4/299 [1.3%]; full-dose: 6/299 [2.0%]). Across all severity grades, half-dose recipients reported fewer local and systemic reactions (60% versus 72% and 25% versus 32%, respectively). Seroresponse was 84.7% (250/295) and 86.6% (253/292) in the half-dose and full-dose arms, respectively (Difference: -2.8%; 95% CI -7.7, 2.1). Geometric mean IgG titres were similar in those receiving full and half-dose boosters for the ChAdOx1 and BBIBP-CorV primed groups, but lower in the half-dose arm in Gam-COVID-Vac-primed participants (GMR: 0.71; 95% CI 0.54, 0.93). Interpretation: Half-dose BNT162b2 boosting elicited an immune response that was non-inferior to a full-dose, with fewer reactions, in adults primed with ChAdOx1 nCov-19 or BBIBP-CorV. Half-dose boosting may not be suitable in adults primed with Gam-COVID-Vac. Half-dose BNT162b2 boosting may be considered in populations primed with ChAdOx1 nCov-19 or BBIBP-CorV. Funding: Coalition for Epidemic Preparedness Innovations (CEPI).

Neurovascular Adverse Effects of Sars-Cov-2 Vaccination.

The global deployment of SARS-CoV-2 vaccines has been pivotal in curbing the COVID-19 pandemic, reducing morbidity and mortality associated with the virus. While most of these vaccines have demonstrated high efficacy and overall safety, emerging reports have highlighted potential neurovascular adverse effects, albeit uncommon, associated with these vaccinations. This review aims to assess and summarize the current knowledge on the neurovascular complications arising post-SARS-CoV-2 vaccination. We conducted an extensive literature review, focusing on clinical studies and case reports to identify reported neurovascular events, such as ischemic stroke, cerebral sinus venous thrombosis, intracerebral hemorrhage, pituitary apoplexy and primary CNS angiitis Despite the relative rarity of these events, their impact on affected individuals underscores the importance of ongoing surveillance, early detection, and management strategies. We aim to provide healthcare professionals with the latest evidence on neurovascular adverse effects, facilitating informed decision-making in the context of SARS-CoV-2 vaccination programs. Furthermore, we highlight areas requiring further research to understand the pathophysiology of these adverse events better and to develop targeted prevention and treatment strategies.

Randomised, double-blind, controlled phase 1 trial of the candidate tuberculosis vaccine ChAdOx1-85A delivered by aerosol versus intramuscular route.

BACKGROUND: A BCG booster vaccination administered via the respiratory mucosa may establish protective immune responses at the primary site of Mycobacterium tuberculosis infection. The primary objective of this trial was to compare the safety and immunogenicity of inhaled versus intramuscular administered ChAdOx1-85A. METHODS: We conducted a single-centre, randomised, double-blind, controlled phase 1 study (Swiss National Clinical Trials Portal number SNCTP000002920). After a dose-escalation vaccination in nine BCG-vaccinated healthy adults, a dose of 1 × 1010 vp of ChAdOx1-85A was administered to twenty BCG-vaccinated adults that were randomly allocated (1:1) into two groups: aerosol ChAdOx1-85A with intramuscular saline placebo or intramuscular ChAdOx1-85A with aerosol saline placebo, using block randomisation. A control group of ten BCG-naïve adults received aerosol ChAdOx1-85A at the same dose. Primary outcomes were solicited and unsolicited adverse events (AEs) up to day 16 post-vaccination and Serious AEs (SAEs) up to 24 weeks; secondary outcomes were cell-mediated and humoral immune responses in blood and bronchoalveolar lavage (BAL) samples. FINDINGS: Both vaccination routes were well tolerated with no SAEs. Intramuscular ChAdOx1-85A was associated with more local AEs (mostly pain at the injection site) than aerosol ChAdOx1-85A. Systemic AEs occurred in all groups, mainly fatigue and headaches, without differences between groups. Respiratory AEs were not different between BCG-vaccinated groups. Aerosol ChAdOx1-85A vaccination induced Ag85A BAL and systemic cellular immune responses with compartmentalisation of the immune responses: aerosol ChAdOx1-85A induced stronger BAL cellular responses, particularly IFNγ/IL17+CD4+ T cells; intramuscular ChAdOx1-85A induced stronger systemic cellular and humoral responses. INTERPRETATION: Inhaled ChAdOx1-85A was well-tolerated and induced lung mucosal and systemic Ag85A-specific T-cell responses. These data support further evaluation of aerosol ChAdOx1-85A and other viral vectors as a BCG-booster vaccination strategy.

Effectiveness of AstraZeneca vaccine against SARS-CoV-2 (ChAdox1-S) in reducing in-hospital mortality in individuals with COVID-19 and schizophrenia: A retrospective cohort study.

ChAdOx1-S is a viral vector vaccine developed by AstraZeneca. We aimed to assess the effectiveness of 1 and 2 doses of the ChAdOx1-S vaccine in reducing COVID-19-related in-hospital mortality in individuals with schizophrenia. This is a retrospective cohort study using a nationwide hospital database in Brazil. Individuals diagnosed with COVID-19 and schizophrenia were included in the study. The exposures were 0, 1, and 2 doses of ChAdOx1-S. The outcome of mortality was measured in hazard ratios (HR), calculated using multivariable Cox regression models. The study included 1,929 positive cases of COVID-19 in schizophrenia patients. After adjusting for age, socioeconomic factors, and comorbidities, we observed a significant 55% decrease in the hazard of mortality in the 2-dose vaccination group (HR 0.45, 95% CI: 0.310-0.652) compared to the unvaccinated. Surprisingly, our results did not show any significant reduction in the hazard of mortality in the 1 dose vaccination group (HR 1.278, 95% CI: 0.910-1.795). The effectiveness of two doses of ChAdOx1-S in individuals with schizophrenia aligns with findings from studies on the general population. That one dose was insignificant. Overall, these findings are important for informing public health decisions - prioritizing individuals with schizophrenia for vaccinations and managing acceptance of vaccines.

Association of the Magnitude of Anti-SARS-CoV-2 Vaccine Side Effects with Sex, Allergy History, Chronic Diseases, Medication Intake, and SARS-CoV-2 Infection.

Vaccination provides the best protection against the increasing infections of SARS-CoV-2. The magnitude and type of anti-SARS-CoV-2 vaccine side effects (SEs) depend on parameters that are not fully understood. In this cross-sectional study, the associations between different anti-SARS-CoV-2 vaccine SEs and age, sex, the presence of chronic diseases, medication intake, history of allergies, and infections with SARS-CoV-2 were investigated. Our survey used the Google platform and had 866 participants, contacted through e-mails, social media and chain referral sampling (margin of error ≈ 4.38%, 99% confidence). More than 99% of the participants received the BNT162b2 and ChAdOx1-S vaccines. Being female, having chronic diseases, taking medicines routinely and the presence of a SARS-CoV-2 infection (p < 0.05) were associated with strong SEs after the BNT162b2 vaccine second dose. Having a history of allergies and a female sex (p < 0.01) were associated with strong SEs after the ChAdOx1-S vaccine second dose. Furthermore, the results reveal, for the first time, the associations between having a history of allergies, chronic diseases, medication usage, and SEs of a strong magnitude for the BNT162b2 and ChAdOx1-S vaccines. Additionally, this study supports the association of the female sex and infection with SARS-CoV-2 with an increased potential of developing stronger SEs with certain anti-SARS-CoV-2 vaccines.