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.

Risk of Myocarditis After Sequential Doses of COVID-19 Vaccine and SARS-CoV-2 Infection by Age and Sex.

BACKGROUND: Myocarditis is more common after severe acute respiratory syndrome coronavirus 2 infection than after COVID-19 vaccination, but the risks in younger people and after sequential vaccine doses are less certain. METHODS: A self-controlled case series study of people ages 13 years or older vaccinated for COVID-19 in England between December 1, 2020, and December 15, 2021, evaluated the association between vaccination and myocarditis, stratified by age and sex. The incidence rate ratio and excess number of hospital admissions or deaths from myocarditis per million people were estimated for the 1 to 28 days after sequential doses of adenovirus (ChAdOx1) or mRNA-based (BNT162b2, mRNA-1273) vaccines, or after a positive SARS-CoV-2 test. RESULTS: In 42 842 345 people receiving at least 1 dose of vaccine, 21 242 629 received 3 doses, and 5 934 153 had SARS-CoV-2 infection before or after vaccination. Myocarditis occurred in 2861 (0.007%) people, with 617 events 1 to 28 days after vaccination. Risk of myocarditis was increased in the 1 to 28 days after a first dose of ChAdOx1 (incidence rate ratio, 1.33 [95% CI, 1.09-1.62]) and a first, second, and booster dose of BNT162b2 (1.52 [95% CI, 1.24-1.85]; 1.57 [95% CI, 1.28-1.92], and 1.72 [95% CI, 1.33-2.22], respectively) but was lower than the risks after a positive SARS-CoV-2 test before or after vaccination (11.14 [95% CI, 8.64-14.36] and 5.97 [95% CI, 4.54-7.87], respectively). The risk of myocarditis was higher 1 to 28 days after a second dose of mRNA-1273 (11.76 [95% CI, 7.25-19.08]) and persisted after a booster dose (2.64 [95% CI, 1.25-5.58]). Associations were stronger in men younger than 40 years for all vaccines. In men younger than 40 years old, the number of excess myocarditis events per million people was higher after a second dose of mRNA-1273 than after a positive SARS-CoV-2 test (97 [95% CI, 91-99] versus 16 [95% CI, 12-18]). In women younger than 40 years, the number of excess events per million was similar after a second dose of mRNA-1273 and a positive test (7 [95% CI, 1-9] versus 8 [95% CI, 6-8]). CONCLUSIONS: Overall, the risk of myocarditis is greater after SARS-CoV-2 infection than after COVID-19 vaccination and remains modest after sequential doses including a booster dose of BNT162b2 mRNA vaccine. However, the risk of myocarditis after vaccination is higher in younger men, particularly after a second dose of the mRNA-1273 vaccine.

Comparative effectiveness of BNT162b2 and ChAdOx1 nCoV-19 vaccines against COVID-19.

BACKGROUND: Both BNT162b2 (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines have shown high efficacy against COVID-19 in randomized controlled trials. However, their comparative effectiveness against COVID-19 is unclear in the real world. We evaluated the comparative effectiveness of the BNT162b2 and ChAdOx1 nCoV-19 vaccines against COVID-19 in the UK general population. METHODS: We emulated a target trial using IQVIA Medical Research Database (IMRD), an electronic primary care database from the UK (2021). We included 1,311,075 participants, consisting of 637,549 men and 673,526 women age≥18 years, who received vaccination with BNT162b2 or ChAdOx1 nCoV-19 between January 1 and August 31, 2021. The outcomes consisted of confirmed diagnosis of SARS-CoV-2 infection, hospitalisation for COVID-19 and death from COVID-19 in the IMRD. We performed a cox-proportional hazard model to compare the risk of each outcome variable between the two vaccines adjusting for potential confounders with time-stratified overlap weighting of propensity score (PS). RESULTS: During a mean of 6.7 months of follow-up, 20,070 confirmed SARS-CoV-2 infection occurred in individuals who received BNT162b2 vaccine (PS weighted incidence rate: 3.65 per 1000 person-months), and 31,611 SARS-CoV-2 infection occurred in those who received ChAdOx1 nCoV-19 vaccine (PS weighted incidence rate: 5.25 per 1000 person-months). The time-stratified PS weighted rate difference of SARS-CoV-2 infection for BNT162b2 group vs. ChAdOx1 nCoV-19 group was -1.60 per 1000 person-months (95% confidence interval [CI]: -1.76 to -1.43 per 1000 person-months), and the hazard ratio was 0.69 (95% CI: 0.68 to 0.71). The results were similar across the stratum of sex, age (<65 and ≥65 years), and study periods (i.e., alpha-variant predominance period and delta-variant predominance period). The PS weighted incidence of hospitalisation for COVID-19 was also lower in the BNT162b2 vaccine group than that in the ChAdOx1 vaccine group (RD: -0.09, 95%CI: -0.13 to -0.05 per 1000 person-months; HR: 0.65, 95%CI: 0.57 to 0.74). No significant difference in the risk of death from COVID-19 was observed between the two comparison groups. CONCLUSIONS: In this population-based study, the BNT162b2 vaccine appears to be more efficacious than the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2 infection and hospitalisation for COVID-19 but not death from COVID-19.

Inflammatory and cytotoxic mediators in COVID-19 patients and in ChAdOx1 nCoV-19 (AZD1222) vaccine recipients.

Immunological and cytotoxic mediators are induced in natural infection and are essential for the effectiveness of vaccination. Vaccination is useful to prevent the spread of SARS-CoV-2 and limit the morbidity/mortality of COVID-19. ChAdOx1 nCoV-19 is one of the most widespread vaccines in the world. We compared the detection of anti-S1 SARS-CoV2 IgG and the profile of inflammatory and cytotoxic responses of patients who developed different clinical outcomes of COVID-19 with individuals previously exposed or not to the virus received the first and booster doses of ChAdOx1 nCoV-19. Plasma from 35 patients with COVID-19 and 11 vaccinated were evaluated by multiplex assay. Here, no vaccinated subjects had serious adverse effects. Those vaccinated with a booster dose had higher anti-S1 IgG than mild/moderate and recovered patients. Critically ill and deceased patients had IgG levels like those immunized. By univariate analysis, IL-2, IL-17, and perforin do not differentiate between patients and vaccinated individuals. Granzyme A increased at dose 1, while patients had their levels reduced. High levels of granulysin, sFas, and IL-6 were detected in the deaths, but after vaccination, all were declined. The multivariate analysis supports the role of IL-6 and granulysin as associated and non-confounding variables related to the worst clinical outcome of COVID-19, but not sFas. Our data confirm the ability of the ChAdOx1 vaccine to produce specific antibody levels up to booster time. Furthermore, our data suggest that the vaccine can regulate both the hyper-production and the kinetics of the production of inflammatory and cytotoxic mediators involved in the cytokine storm, such as granulysin and IL-6.

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.

Amentoflavone derivatives significantly act towards the main protease (3CLPRO/MPRO) of SARS-CoV-2: in silico admet profiling, molecular docking, molecular dynamics simulation, network pharmacology.

SARS-CoV-2 is the foremost culprit of the novel coronavirus disease 2019 (nCoV-19 and/or simply COVID-19) and poses a threat to the continued life of humans on the planet and create pandemic issue globally. The 3-chymotrypsin-like protease (MPRO or 3CLPRO) is the crucial protease enzyme of SARS-CoV-2, which directly involves the processing and release of translated non-structural proteins (nsps), and therefore involves the development of virus pathogenesis along with outbreak the forecasting of COVID-19 symptoms. Moreover, SARS-CoV-2 infections can be inhibited by plant-derived chemicals like amentoflavone derivatives, which could be used to develop an anti-COVID-19 drug. Our research study is designed to conduct an in silico analysis on derivatives of amentoflavone (isoginkgetin, putraflavone, 4''''''-methylamentoflavone, bilobetin, ginkgetin, sotetsuflavone, sequoiaflavone, heveaflavone, kayaflavone, and sciadopitysin) for targeting the non-structural protein of SARS-CoV-2, and subsequently further validate to confirm their antiviral ability. To conduct all the in silico experiments with the derivatives of amentoflavone against the MPRO protein, both computerized tools and online servers were applied; notably the software used is UCSF Chimera (version 1.14), PyRx, PyMoL, BIOVIA Discovery Studio tool (version 4.5), YASARA (dynamics simulator), and Cytoscape. Besides, as part of the online tools, the SwissDME and pKCSM were employed. The research study was proposed to implement molecular docking investigations utilizing compounds that were found to be effective against the viral primary protease (MPRO). MPRO protein interacted strongly with 10 amentoflavone derivatives. Every time, amentoflavone compounds outperformed the FDA-approved antiviral medicine that is currently underused in COVID-19 in terms of binding affinity (- 8.9, - 9.4, - 9.7, - 9.1, - 9.3, - 9.0, - 9.7, - 9.3, - 8.8, and - 9.0 kcal/mol, respectively). The best-selected derivatives of amentoflavone also possessed potential results in 100 ns molecular dynamic simulation (MDS) validation. It is conceivable that based on our in silico research these selected amentoflavone derivatives more precisely 4''''''-methylamentoflavone, ginkgetin, and sequoiaflavone have potential for serving as promising lead drugs against SARS-CoV-2 infection. In consequence, it is recommended that additional in vitro as well as in vivo research studies have to be conducted to support the conclusions of this current research study.

Trends of humoral immune responses to heterologous antigenic exposure due to vaccination & omicron SARS-CoV-2 infection: Implications for boosting.

Background & objectives: Vaccination and natural infection can both augment the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how omicron infection has affected the vaccine-induced and hybrid immunity is not well studied in Indian population. The present study was aimed to assess the durability and change in responses of humoral immunity with age, prior natural infection, vaccine type and duration with a minimum gap of six months post-two doses with either ChAdOx1 nCov-19 or BBV152 prior- and post-emergence of the omicron variant. Methods: A total of 1300 participants were included in this observational study between November 2021 and May 2022. Participants had completed at least six months after vaccination (2 doses) with either ChAdOx1 nCoV-19 or an inactivated whole virus vaccine BBV152. They were grouped according to their age (≤ or ≥60 yr) and prior exposure of SARS-CoV-2 infection. Five hundred and sixteen of these participants were followed up after emergence of the Omicron variant. The main outcome was durability and augmentation of the humoral immune response as determined by anti-receptor-binding domain (RBD) immunoglobulin G (IgG) concentrations, anti-nucleocapsid antibodies and anti-omicron RBD antibodies. Live virus neutralization assay was conducted for neutralizing antibodies against four variants - ancestral, delta and omicron and omicron sublineage BA.5. Results: Before the omicron surge, serum anti-RBD IgG antibodies were detected in 87 per cent participants after a median gap of eight months from the second vaccine dose, with a median titre of 114 [interquartile range (IQR) 32, 302] BAU/ml. The levels increased to 594 (252, 1230) BAU/ml post-omicron surge (P<0.001) with 97 per cent participants having detectable antibodies, although only 40 had symptomatic infection during the omicron surge irrespective of vaccine type and previous history of infection. Those with prior natural infection and vaccination had higher anti-RBD IgG titre at baseline, which increased further [352 (IQR 131, 869) to 816 (IQR 383, 2001) BAU/ml] (P<0.001). The antibody levels remained elevated after a mean time gap of 10 months, although there was a decline of 41 per cent. The geometric mean titre was 452.54, 172.80, 83.1 and 76.99 against the ancestral, delta, omicron and omicron BA.5 variants in the live virus neutralization assay. Interpretation & conclusions: Anti-RBD IgG antibodies were detected in 85 per cent of participants after a median gap of eight months following the second vaccine dose. Omicron infection probably resulted in a substantial proportion of asymptomatic infection in the first four months in our study population and boosted the vaccine-induced humoral immune response, which declined but still remained durable over 10 months.

Effects of the second dose of COVID-19 vaccines in patients with autoimmune rheumatic diseases with hybrid immunity.

Patients with autoimmune rheumatic diseases with a previous infection by the SARS-CoV-2 virus have exaggerated responses to a single dose of COVID-19 vaccination as compared to fully vaccinated infection naive patients. The second dose is currently recommended at an extended gap after the infection, but the information available regarding response to the second dose in this subgroup is limited. Patients with AIRDs previously infected with COVID-19, who have received at least one dose of AZD1222/ChAdOx1 (n = 200) were included and stratified based on vaccine doses (V), and infection (I) into I + V, I + V + V, V + I, V + V + I. Anti-RBD (receptor binding domain) antibodies were compared across the four groups. In 49 patients of the I + V + V group (AZD12222), paired sera were compared for antibody levels and neutralization after each vaccine dose. Thirty patients with hybrid immunity after BBV152 and 25 with complete vaccination without infection were included as controls. The highest anti-RBD antibody levels were observed in the V + V + I group (18,219 ± 7702 IU/ml) with statistically similar titers in the I + V + V (10,392 ± 8514 IU/ml) and the I + V (8801 ± 8122 IU/ml). This was confirmed in the 49 paired samples that paradoxically showed a lowering of antibody titers after the second dose [9626 (IQR: 4575-18,785)-5781 (2484-11,906); p < 0.001]. Neutralization of the Delta variant was unaffected but Omicron neutralization was significantly reduced after the second dose [45.7 (5.3-86.53)-35% (7.3-70.9); p = 0.028]. Ancillary analyses showed that only the hybrid immune sera could neutralize the Omicron variant and AZD1222 hybrids performed better than BBV152 hybrids. The second dose of AZD1222 did not boost antibody titers in patients with RD who had COVID-19 previously. In the analysis of paired sera, the second dose led to a statistically significant reduction in antibody titers and also reduced neutralization of the Omicron variant.

Aortic thrombosis and acute limb ischemia after ChAdOx1 nCov-19 (Oxford-AstraZeneca) vaccination: a case of vaccine-induced thrombocytopenia and thrombosis (VITT).

INTRODUCTION: Vaccine-induced thrombocytopenia and thrombosis (VITT) is a rare but devastating adverse event associated with the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) adenoviral vaccine against the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2). METHODS: A 49-year-old man presented to the emergency department with acute right limb ischemia (Rutherford IIB) nine days after his ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccination. CT angiography revealed significant aortic thrombosis and right femoral artery occlusion. Severe thrombocytopenia (platelet count of 23 × 103/µL), promptly elevated D-dimers (37937 ng/mL) and a reduced fibrinogen level (176 mg/dL) were remarkable. ELISA testing for anti-PF4 antibodies confirmed the diagnosis of VITT. RESULTS: An emergency revascularization of the right leg was provided via thrombectomy. High-dose intravenous immunoglobulins were administered whereafter the platelet count restored gradually. Therapeutic anticoagulation was progressively started. The postoperative course was uneventful and follow-up imaging after four weeks showed an almost complete resolution of the significant aortic thrombosis. CONCLUSION: Early recognition and appropriate counseling of VITT is advocated to pursue a good clinical outcome. Our patient presenting with severe aortic thrombosis and acute limb ischemia was successfully treated by a vascular thrombectomy along with intravenous immunoglobulins and anticoagulation therapy as the mainstay therapy.

Immune Responses to the ChAdOx1 nCoV-19 and BNT162b2 Vaccines and to Natural Coronavirus Disease 2019 Infections Over a 3-Month Period.

BACKGROUND: There are limited data directly comparing immune responses to vaccines and to natural infections with coronavirus disease 2019 (COVID-19). This study assessed the immunogenicity of the BNT162b2 and ChAdOx1 nCoV-19 vaccines over a 3-month period and compared the immune responses with those to natural infections. METHOD: We enrolled healthcare workers who received BNT162b2 or ChAdOx1 nCoV-19 vaccines and patients with confirmed COVID-19 and then measured S1 immunoglobulin (Ig) G and neutralizing antibodies and T-cell responses. RESULTS: A total of 121 vaccinees and 26 patients with confirmed COVID-19 were analyzed. After the second dose, the BNT162b2 vaccine yielded S1 IgG antibody responses similar to those achieved with natural infections (mean IgG titer [standard deviation], 2241 [899] vs 2601 [5039]; P = .68) but significantly stronger than responses to the ChAdOx1 vaccine (174 [96]; P < .001). The neutralizing antibody titer generated by BNT162b2 was 6-fold higher than that generated by ChAdOx1 but lower than that by natural infection. T-cell responses persisted for 3 months with BNT162b2 and natural infection but decreased with ChAdOx1. CONCLUSIONS: Antibody responses after the second dose of BNT162b2 are higher than after the second dose of ChAdOx1 and like those occurring after natural infection. T-cell responses are maintained longer in BNT162b2 vaccinees than in ChAdOx1 vaccinees.

Postvaccination Multisystem Inflammatory Syndrome in Adult with No Evidence of Prior SARS-CoV-2 Infection.

Ten days after receiving the first dose of coronavirus disease vaccine, a 22-year-old woman in South Korea experienced myocarditis, myopathy, pericarditis, and gastroenteritis; rash subsequently developed. There was no evidence of prior infection with severe acute respiratory syndrome coronavirus 2. The diagnosis was multisystem inflammatory syndrome resulting from coronavirus disease vaccination.

Effectiveness of Booster and Influenza Vaccines against COVID-19 among Healthcare Workers, Taiwan.

Among previously uninfected healthcare workers in Taiwan, mRNA COVID-19 booster vaccine was associated with lower odds of COVID-19 after primary recombinant vaccine. Symptom-triggered testing revealed that tetravalent influenza vaccine was associated with higher odds of SARS-CoV-2 infection. COVID-19 vaccination continues to be most effective against SARS-CoV-2.

An additional dose of viral vector COVID-19 vaccine and mRNA COVID-19 vaccine in kidney transplant recipients: A randomized controlled trial (CVIM 4 study).

Immunogenicity following an additional dose of Coronavirus disease 2019 (COVID-19) vaccine was investigated in an extended primary series among kidney transplant (KT) recipients. Eighty-five KT participants were randomized to receive either an mRNA (M group; n = 43) or viral vector (V group; n = 42) vaccine. Among them, 62% were male, with a median (IQR) age of 50 (43-59) years and post-transplantation duration of 46 (26-82) months. At 2 weeks post-additional dose, there was no difference in the seroconversion rate between the M and V groups (70% vs. 65%, p = .63). A median (IQR) of anti-RBD antibody level was not statistically different between the M group compared with the V group (51.8 [5.1-591] vs. 28.5 [2.9-119.3] BAU/ml, p = .18). Furthermore, the percentage of participants with positive SARS-CoV-2 surrogate virus neutralization test results was not statistically different between groups (20% vs. 15%, p = .40). S1-specific T cell and RBD-specific B cell responses were also comparable between the M and V groups (230 [41-420] vs. 268 [118-510], p = .65 and 2 [0-10] vs. 2 [0-13] spot-forming units/106 peripheral blood mononuclear cells, p = .60). In conclusion, compared with an additional dose of viral vector COVID-19 vaccine, a dose of mRNA COVID-19 vaccine did not elicit significantly different responses in KT recipients, regarding either humoral or cell-mediated immunity. (TCTR20211102003).

Comparison of the immunogenicity of ChAdOx1 nCoV-19 vaccine against the wild-type and delta variants in kidney transplant recipients and healthy volunteers.

Little is known about immunogenicity after ChAdOx1 nCov-19 vaccination after transplantation. We assessed the vaccine response by antibody testing, surrogate neutralization test (sVNT) against wild-type (WT) and delta variant (DT), and T cell assay in 83 kidney transplant recipients (KTRs) and 52 healthy volunteers (HVs). For KTRs, a positive anti-RBD antibody was seen in 2.8% after one dose and 15.7% after two doses of the vaccine. After two doses, the positivity rate by sVNT was equal (4.9% each, for WT and DT) and was 13.4% by T cell response. Post two doses, KTRs had significantly lower geometric mean titer than HVs (1.93 [95% CI: 1.39-2.69] vs. 248.3 [95% CI: 203.7-302.6] BAU/ml, respectively, p < .001). Daily mycophenolate dose of ≥1000 mg significantly associated with negative seroconversion [risk ratio (RR) of 0.33, 95% CI: 0.15-0.72, p = .005]. Compared with cyclosporine, daily tacrolimus dose of ≤3 mg and >3 mg of tacrolimus significantly associated with negative seroconversion [RR = 0.38 (95% CI, 0.17-0.85, p = .018) and RR = 0.16 (95% CI, 0.37-0.73, p = .018)], respectively. The vaccine was safe and well-tolerated but the immune response after the two doses of ChAdOx1 nCov-19 vaccine in KTRs was very low.

Interdependencies of cellular and humoral immune responses in heterologous and homologous SARS-CoV-2 vaccination.

BACKGROUND: Homologous and heterologous SARS-CoV-2 vaccinations yield different spike protein-directed humoral and cellular immune responses. This study aimed to explore their currently unknown interdependencies. METHODS: COV-ADAPT is a prospective, observational cohort study of 417 healthcare workers who received vaccination with homologous ChAdOx1 nCoV-19, homologous BNT162b2 or with heterologous ChAdOx1 nCoV-19/BNT162b2. We assessed humoral (anti-spike-RBD-IgG, neutralizing antibodies, and avidity) and cellular (spike-induced T-cell interferon-γ release) immune responses in blood samples up to 2 weeks before (T1) and 2-12 weeks following secondary immunization (T2). RESULTS: Initial vaccination with ChAdOx1 nCoV-19 resulted in lower anti-spike-RBD-IgG compared with BNT162b2 (70 ± 114 vs. 226 ± 279 BAU/ml, p < .01) at T1. Booster vaccination with BNT162b2 proved superior to ChAdOx1 nCoV-19 at T2 (anti-spike-RBD-IgG: ChAdOx1 nCoV-19/BNT162b2 2387 ± 1627 and homologous BNT162b2 3202 ± 2184 vs. homologous ChAdOx1 nCoV-19 413 ± 461 BAU/ml, both p < .001; spike-induced T-cell interferon-γ release: ChAdOx1 nCoV-19/BNT162b2 5069 ± 6733 and homologous BNT162b2 4880 ± 7570 vs. homologous ChAdOx1 nCoV-19 1152 ± 2243 mIU/ml, both p < .001). No significant differences were detected between BNT162b2-boostered groups at T2. For ChAdOx1 nCoV-19, no booster effect on T-cell activation could be observed. We found associations between anti-spike-RBD-IgG levels (ChAdOx1 nCoV-19/BNT162b2 and homologous BNT162b2) and T-cell responses (homologous ChAdOx1 nCoV-19 and ChAdOx1 nCoV-19/BNT162b2) from T1 to T2. Additionally, anti-spike-RBD-IgG and T-cell response were linked at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2. CONCLUSIONS: Interdependencies between humoral and cellular immune responses differ between common SARS-CoV-2 vaccination regimes. T-cell activation is unlikely to compensate for poor humoral responses.

ADEM after ChAdOx1 nCoV-19 vaccine: A case report.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system (CNS), clinically defined by an acute polyfocal neurological syndrome usually with monophasic course. ADEM often occurs after infections, but 5%-10% of cases are preceded by vaccinations. Several cases of ADEM have been described after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, whereas no case has been reported after adenovirus-vectored or mRNA COVID-19 vaccine administration. Here we describe a case of ADEM presenting 2 weeks after receiving the first dose of ChAdOx1 nCoV-19 vaccine. Patient clinical/magnetic resonance imaging (MRI) status spontaneously improved and rapidly resolved with corticosteroids. A 4-month follow-up showed complete recovery and no relapses.

MOG-antibody-associated longitudinal extensive myelitis after ChAdOx1 nCoV-19 vaccination.

This case report describes a 59-year-old man with myelin oligodendrocyte glycoprotein (MOG)-positive longitudinal extensive transverse myelitis (LETM) after being vaccinated with the COVID-19 vaccine ChAdOx1 nCoV-19. He presented with urinary retention, gait disturbance, hypoesthesia and brisk reflexes in his lower extremities without paresis. Due to the ineffectiveness of high-dose intravenous methylprednisolone, therapeutic plasma exchange was performed, gradually improving the patient's condition. Vaccination as a trigger for an excessive immunological response seems plausible, though unspecific for the ChAdOx1 nCoV-19 vaccine.

Incidence and severity of COVID-19 infection post-vaccination: a survey among Indian doctors.

PURPOSE: The rollout of COVID-19 vaccines began in India in January 2021, with healthcare professionals being the first to receive vaccination. The purpose of this research was to study the incidence and severity of COVID-19 infections among Indian doctors, following vaccination with ChAdOx1 nCoV-19 or BBV152. METHODS: We conducted an online voluntary survey among Indian doctors who received one or two doses of ChAdOx1 nCoV-19 or BBV152. Questions pertaining to the incidence and severity of COVID-19 infection following vaccination were asked. Data thus obtained were analysed. RESULTS: 9146 doctors were included in this study. 8301 of these received ChAdOx1 nCoV-19, while 845 received BBV152. 2842 (31.07%) respondents reported having a COVID-19 infection following vaccination. Presence of pre-existing medical comorbidities was associated with a higher incidence, while prior COVID-19 infection and two doses of either vaccine were associated with a lower incidence of COVID-19 infection post-vaccination. Exposure to COVID-19 patients on a daily basis did not increase the incidence of COVID-19 infection among doctors who were vaccinated. Increasing age, male gender, presence of pre-existing medical comorbidities, and daily exposure to COVID-19 patients were associated with increased severity of COVID-19 infection after vaccination. Two doses of either vaccine resulted in less severity of disease compared to one dose. CONCLUSION: ChAdOx1 nCoV-19 and BBV152 confer immunity against severe forms of COVID-19 infections. COVID-19 infections prior to vaccination result in a lower incidence of breakthrough infection. Presence of pre-existing medical comorbidities is associated with increased incidence and severity of breakthrough infections.

A systematic review of vaccine-induced thrombotic thrombocytopenia in individuals who received COVID-19 adenoviral-vector-based vaccines.

Reports of thrombotic response after receiving COVID-19 Adenoviral-Vector Based Vaccines raise concerns about vaccine-induced thrombotic thrombocytopenia (VITT); therefore, we conduct this systematic review to report susceptible demographics outcomes, commonalities, and prognosis of reporting cases. We identified published articles by searching PubMed, SCOPUS, and Web of Science from December 2020 till May 2021, with an updated search in September 2021. All case reports and case series reporting thrombotic response after receiving COVID-19 Adenoviral-Vector Based Vaccines were eligible for including. In addition, two authors independently extracted data and assessed the quality of the included studies. A total of 157 patients with thrombotic events after the ChAdOx1 nCoV-19 vaccine and 16 patients with thrombotic events after Ad26.COV2. S vaccine was included in our study. 72% of the ChAdOx1 nCoV-19 cases were females, while in Ad26.COV2.S subgroup, all reported patients were females. The commonest presentations were deep vein thrombosis 20 (12.7%) and cerebral venous sinus thrombosis 18 (11.5%) in the ChAdOx1 nCoV-19 subgroup while cerebral venous sinus thrombosis 14 (87.5%) and pulmonary embolism 2 (12.5%) in the Ad26.COV2. S subgroup. In this study, we described the certain demographics associated with VITT and the clinical presentations of those cases in the ChAdOx1 nCoV-19 and Ad26.COV2. S vaccines. Young individuals, particularly females, may be more susceptible to VITT, and future studies should seek to confirm this association. In addition, the clinical presentation of VITT commonly includes cerebral thrombi, pulmonary embolism, and deep venous thrombosis, but other presentations are also possible, highlighting the importance of clinical vigilance in recent vaccine recipients.

Central nervous system adverse events after ChAdOx1 vaccination.

INTRODUCTION: Post-ChAdOx1 vaccine (AZD1222) adverse events following immunization (AEFI) are uncommon. Recently described neurological events include thrombocytopenia with thrombosis syndrome (TTS) with cerebral venous thrombosis and Guillain-Barré syndrome. There are very few AEFI reports following COVID vaccination from India, because of underreporting or other factors. A few cases of acute transverse myelitis (ATM) and post-vaccinal encephalitis have also been reported. MATERIALS AND METHODS: Over 11 months, in 2 districts of Kerala, India, 8.19 million people were vaccinated with the ChAdOx1 vaccine. RESULTS: During this period, we encountered five cases of autoimmune central nervous system (CNS) AEFI following ChAdOX1 (Oxford/AstraZeneca, Covishield™) vaccination. These included three cases of acute disseminated encephalomyelitis (ADEM), one case of opsoclonus myoclonus ataxia syndrome (OMAS), and one case of limbic encephalitis. The calculated crude incidence of post-ChAdOX1 autoimmune CNS AEFI was approximately 0.24 cases per million for encephalitis and 0.36 per million for ADEM. This was compared to the crude annual incidence of community-acquired ADEM worldwide (3.2-4 per million) and the crude annual incidence of community-acquired encephalitis in India (8.35-10 per million). CONCLUSION: There was no increase in the incidence of post-vaccination CNS AEFI (ADEM or encephalitis) as compared to the community incidence of ADEM or encephalitis. While this emphasizes the safety of ChAdOX1 nCoV-19 vaccination for COVID-19, it is important to recognize these post-vaccination autoimmune syndromes early to initiate immunosuppressive therapy.