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.

Analysis of COVID-19 Vaccine Adverse Drug Reactions Reported Among Sultan Qaboos University Hospital Staff.

Objectives: This study aimed to report any suspected adverse drug reactions (ADRs) experienced by all vaccinated staff and students in a tertiary teaching hospital following COVID-19 vaccination. Methods: This retrospective study was conducted during the COVID-19 vaccination campaign at Sultan Qaboos University and Hospital in Muscat, Oman, from August to September 2021. An online survey was generated and sent to all staff and students via email and text messages. An announcement was made on the hospital website with a link to the survey. Results: A total of 8,421 individuals reported being vaccinated at least once with a total of 11,468 doses administered from January to July 2021; 8,014 staff and students received the Pfizer-Biotech vaccine while 3,454 staff and students received the Oxford-AstraZeneca vaccine. The survey received a total of 3,275 responses (response rate = 38.8%). Of these, 741 individuals (22.6%) experienced an ADR after vaccination and 67.2% (n = 498) were females (P <0.001). The majority of the ADRs reported were fever and chills (19.7%) followed by localised pain and swelling at the injection site (18.8%). Other ADRs such as hair loss (0.5%) were reported, and one staff/student reported a clot in the right leg. Among the responders, 27.0% considered their ADRs as mild while 25.0% considered them as severe. Conclusions: In the study cohort, mild symptoms of COVID-19 vaccines were reported. Females experienced more ADRs compared to males. Long-term observation of ADRs to the vaccines and follow-up monitoring should be done on subjects to preclude any unwanted effects.

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.

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.

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.

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.

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.

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.

Spectrum of various CNS inflammatory demyelination diseases following COVID-19 vaccinations.

BACKGROUND AND PURPOSE: Although rare, neurological adverse events have been reported post-COVID-19 vaccination. This study reports 16 patients diagnosed with CNS inflammatory demyelinating diseases (CNS-IDD) within 6 weeks of COVID-19 vaccine administration. METHODOLOGY: A prospective observational study was conducted from June 2021 to May 2022. All patients were diagnosed according to the latest international guidelines with CNS-IDD within 6 weeks of COVID-19 vaccine exposure. Data regarding the demographic profile, clinical features, type of COVID-19 vaccination, radiological findings and occurrence of symptoms were noted and further analysed using descriptive statistics. RESULTS: We reported 16 cases (median age 40 years) of CNS demyelination: fourteen occurred in temporal association with ChAdOx1-S vaccine and two in association with BBV152 vaccine. Median time duration of presenting symptoms after vaccination was 19 days (3-40 days). The most common presentation was myelitis (7/16 patients), followed by optic neuritis (6/16 patients). Demyelination events were reported after first and second dose in thirteen and five patients respectively, although two patients reported such events after both vaccine dosages. Myelin oligodendrocyte glycoprotein (MOG) IgG antibodies were positive in eight patients. Tumefactive demyelination was seen in four patients. Management included high-dose methylprednisolone, PLEX, IVIG or a combination of those, with a favourable outcome in the majority of cases. CONCLUSION: Although a rare event, awareness regarding potential demyelinating episodes post-COVID-19 vaccination can help in early diagnosis. The presence of increased MOG-IgG antibodies with temporal association in post-COVID vaccine patients raises a possibility of an immunogenic phenomenon leading to demyelinating disorders.

A Generalized Lichen Planus Following COVID-19 Vaccination: A Case Report.

As part of the efforts to overcome the ongoing coronavirus disease 2019 (COVID-19) pandemic, mass vaccination programs against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been initiated. Since then, an increasing number of cutaneous adverse events associated with the COVID-19 vaccines have been reported. Lichen planus (LP) is a rare inflammatory mucocutaneous disease with various clinical presentations, although uncommon, occurring following vaccination. There have been several cases of LP reported following COVID-19 vaccination. However, there has been no report of generalized LP following the COVID-19 vaccine to our knowledge. Herein, we report a case of generalized LP following the Oxford/AstraZeneca (AZD1222) vaccine. A 68-year-old female presented with widespread, erythematous pruritic papules and plaques on the trunk and both limbs, which developed 2 to 3 days after administration of the AZD1222 vaccine. Histopathological examinations revealed cellular interface dermatitis. The patient was diagnosed with generalized LP and was successfully treated with systemic corticosteroid and cyclosporine. As the vaccination campaign against COVID-19 is ongoing and early recognition and treatment are essential to reduce the morbidity of this condition, clinicians should be aware that LP could follow COVID-19 vaccination regardless of the type of vaccine administered.

Assessment of humoral immune response to different COVID-19 vaccines in patients undergoing maintenance hemodialysis / Avaliação da resposta imune humoral a diferentes vacinas contra a COVID-19 em pacientes submetidos à hemodiálise de manutenção

ABSTRACT Introduction: The immune response to different Coronavirus Disease 2019 (COVID-19) vaccines is under-investigated in end-stage kidney disease (ESKD) patients, especially in the Middle East and North Africa. We carried out this research to estimate the effectiveness of COVID-19 immunization in ESKD patients on regular hemodialysis (HD). Methods: In this prospective observational study, we enrolled 60 ESKD patients on regular HD who had completed COVID-19 vaccination and 30 vaccinated healthy participants. Serum levels of severe acute respiratory syndrome coronavirus 2 immunoglobulin G (SARS-COV2 IgG) were quantified 1 month after completing the vaccination schedule, and all participants were followed up from October 2021 to March 2022. The vaccines used in the study were from Pfizer-BioNTech, AstraZeneca, and Sinopharm. Results: The median level of SARS-COV2 IgG was lower in HD patients than in healthy participants (p < 0.001). Regarding the type of COVID-19 vaccination, there was no statistical difference in SARS-COV2 IgG levels among HD patients. During the observation period, none of the HD patients had COVID-19. Conclusion: COVID-19 vaccination appeared to be protective in HD patients for 6 months and the side effects of vaccines were tolerable.

RESUMO Introdução: A resposta imune a diferentes vacinas contra a doença do coronavírus 2019 (COVID-19) é pouco investigada em pacientes com doença renal em estágio terminal (DRET), especialmente no Oriente Médio e norte da África. Realizamos esta pesquisa para estimar a eficácia da imunização contra a COVID-19 em pacientes com DRET em hemodiálise regular (HD). Métodos: Nesse estudo observacional prospectivo, inscrevemos 60 pacientes com DRET em HD regular que haviam concluído o esquema de vacinação contra a COVID-19 e 30 participantes saudáveis vacinados. Os níveis séricos de imunoglobulina G da síndrome respiratória aguda grave do coronavírus 2 (SARS-COV2 IgG) foram quantificados um mês após a conclusão do esquema vacinal, e todos os participantes foram acompanhados de outubro de 2021 a março de 2022. As vacinas utilizadas no estudo eram da Pfizer-BioNTech, AstraZeneca e Sinopharm. Resultados: O nível mediano de SARS-COV2 IgG foi menor em pacientes em HD do que em participantes saudáveis (p < 0,001). Com relação ao tipo de vacinação contra a COVID-19, não houve diferença estatística nos níveis de SARS-COV2 IgG entre pacientes em HD. Durante o período de observação, nenhum dos pacientes em HD teve COVID-19. Conclusão: A vacinação contra a COVID-19 pareceu ser eficaz na proteção de pacientes em HD por 6 meses e os efeitos colaterais das vacinas foram toleráveis.

Sex Differences in Serious Adverse Events Reported Following Booster Doses of COVID-19 Vaccination in Thailand: A Countrywide Nested Unmatched Case-Control Study.

A booster dose of a COVID-19 vaccine has been proven effective in restoring vaccine effectiveness and is currently recommended for use in some populations at risk of severe COVID-19 infection. Since sex differences in adverse events are significant in response to the vaccines, the safety of booster selection must be studied to avoid serious adverse events (SAE), such as life-threatening diseases. First, this study aimed to identify sex differences in SAE incidences using a prospective cohort design. Second, a nested unmatched case-control study was used to identify factors associated with reported SAE within 30 days after the booster shot. Multivariable logistic regression indicated the adjusted odds ratio by accounting for host and vaccine variables, thus, policy effects. The findings confirmed that SAE was rare and that age-sex-dominated disease classifications differed. Specific to SAE following the booster dose, we found that females aged 12-40 had a higher risk of being reported with SAE than males of the same age, while males over 50 had a higher risk than females. Other risk factors identified were the presence of metabolic syndrome and the use of certain vaccine brands. Mechanisms could be explained by individual host responses rather than the vaccines' direct effect. Therefore, SAE could be preventable by age-sex-specific vaccine selection, post-vaccination precautions, and early symptom detection. Future vaccine development should aim to limit host-specific reactogenicity for safety concerns.

Evaluation of SARS-CoV-2 infection risks after primary vaccination with BNT162b2, BBIBP-CorV, or ChAdOx1-nCOV-19 and after homologous and heterologous booster vaccinations with these vaccines and evaluation of SARS-CoV-2 reinfection profiles.

Background: The emergence of SARS-CoV-2 variants has significantly increased the number of cases of COVID-19 among vaccinated individuals, raising concerns about the effectiveness of current vaccines. The aim of this study was to analyze the SARS-CoV-2 infection risks after primary vaccination with BNT162b2, BBIBP-CorV, or ChAdOx1-nCOV-19 and after homologues and heterologous booster vaccinations with these vaccines, as well as the profiles of reinfected patients. Methods: We analyzed retrospectively 1082 patients vaccinated or unvaccinated with BNT162b2, BBIBP-CorV, and/or ChAdOx1nCoV-19 vaccines to determine their SARS-CoV2 infection statuses using the reverse transcription-polymerase chain reaction (RT-PCR) in addition to their clinical features. The infection risks of patients receiving the different vaccine regimens were compared using multivariate logistic regression analysis, comparing the adjusted OR of a positive COVID-19 test result. Results: Among 596 vaccinated patients, 53%(n = 286) tested positive for SARS-CoV-2 and 57%(n = 310) tested negative. Among positive cases, 10 were reinfection cases. The risk of SARS-CoV-2 infection was 1.6 (adj. OR) for patients who received one dose compared with those who received two doses (95% CI = 1.3-1.8; p < 0.01).The risk was 2.6 (adj. OR) for patients who received one dose compared with those who received three doses (95%CI = 2.1-3.3; p < 0.01), and 1.6 (adj. OR) for patients who received two doses compared with those who received three doses (95% CI = 1.3-2; p < 0.01). The patients who received two doses that were heterologous to that of the primary vaccine had the lowest risk of infection. Booster vaccinations (third dose) significantly reduced the number of positive cases with an acceptable safety profile. Higher cycle-threshold (Ct) values (indicative of viral load) were observed in vaccinated patients, whereas low Ct values were observed in unvaccinated patients. Conclusion: A complete cycle of vaccination with homologous vaccines or heterologous vaccines resulted in an acceptable reduction in SARS-CoV-2 infection. Further, vaccination was associated with a reduction in viral load.

Immunogenicity of ChAdOx1 (Covishield) Booster Dose in Healthcare Providers: A Pre-Post Study.

Background Worldwide, healthcare workers who face a higher risk of contracting coronavirus disease 2019 (COVID-19) were among the first to receive COVID-19 vaccinations. Following the initial two vaccine doses, health experts recommended a third booster shot to enhance protection against the severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) virus. However, limited information about how this booster dose affects antibody levels is available. This study assesses the immune response triggered by the ChAdOx1 (Covishield) booster dose. Methods We conducted a before and after study among 132 healthcare providers at a tertiary care hospital in India who had already received their initial COVID-19 vaccine doses and agreed to participate. A booster shot was administered nine months following their second vaccine dose per the prevalent norms. We collected blood samples to measure immunoglobulin-G (IgG) levels against the spike protein's receptor-binding domain of the SARS-CoV-2 virus. These blood samples were taken both when they received the booster shot and one month after the booster. We determined IgG levels using a chemiluminescence microparticle immunoassay. Result Among the participants, approximately 54% were females. Regarding occupation, about 36% were doctors, 30% were students, 20% were nursing officers, and the remaining 14% held grade-4 positions. The median age of the participants was 32 years. About 74% had no history of underlying health conditions. Before the booster dose, 29% of the participants tested negative for antibodies. However, all participants developed antibodies following the booster shot, and there was a significant increase in antibody levels, which was statistically meaningful with a p-value of less than 0.0001. Conclusion In conclusion, the administration of a booster dose effectively induced seroconversion and significantly increased antibody levels among healthcare providers, enhancing their immunity against COVID-19, essential in the face of a waning immune response to primary series vaccination.

Half dose ChAdOx1 nCoV-19 vaccine was equivalent to full doses to reduce moderate and severe COVID-19 cases.

Objectives: Previously, we presented the effectiveness of ChAdOx1 nCoV-19 half-dose (HD) immunization for preventing new COVID-19 cases. Here, we evaluated the administration of an HD of ChAdOx1 nCoV-19 in the primary immunization protocol (up to two doses) in reducing moderate and severe cases, hospitalizations, and deaths when compared to the administration of full doses (FD) after a long-term follow-up. Methods: We evaluated data from 29,469 participants between January 2021 and November 2022 who received an HD or FD vaccine and crossed this information with their medical records to identify those who developed moderate or severe cases. All participants were classified into four groups according to their immunization status and followed 500 days after the last vaccine administration. Results: The propensity-score matching analysis indicates that the administration of the two HDs of ChAdOx1 nCoV-19 was equivalent to the use of two FDs to reduce moderate and severe COVID-19 cases. The relative risk of being infected and developing moderate or severe conditions after the administration of at least one HD or FD was similar 150 or 500 days after the administration of the immunizers. Conclusion: Administering two HDs can be used safely as a cost-effective alternative to the primary immunization protocol.

ChAdOx1 nCoV-19 Vaccine and Thrombosis with Thrombocytopenia Syndrome among Adults: A Systematic Review.

Several vaccine-induced thrombotic thrombocytopenia syndrome (VITTS) cases have been reported after the ChAdOx1 nCov-19 vaccination. The current study systematically reviewed the reported post-ChAdOx1 nCoV-19 vaccination thrombotic thrombocytopenia cases. Their laboratory and clinical features, as well as the diagnostic and therapeutic measures, were investigated. Online databases were searched until 25 August 2021. Studies reporting post-ChAdOx1 nCov-19 vaccination thrombotic thrombocytopenia syndrome (TTS) were included. Overall, 167 cases (21-77 years old) from 53 publications were included showing a female dominance of 1.75 times. About 85% of the cases exhibited the primary symptoms within the first two weeks post-vaccination. Headache was the most common initial symptom (>44.2%), and hemorrhage/thrombotic problems (22.46%), as well as discoordination/weakness/numbness/ hemiparesis/cyanotic toes (19.6%), were the most prevalent uncommon initial symptoms. Prothrombin time (PT), D-dimers, and C-reactive protein were the most remarkable increased laboratory parameters in 50.6%, 99.1%, and 55.6% of cases, respectively. In comparison, platelet and fibrinogen were the most remarkable decreased laboratory parameters in 92.7% and 50.5% of cases, respectively. Most VITT cases presented with cerebral venous thrombosis/cerebral venous sinus thrombosis, supraventricular tachycardia, transverse sinus/cerebral thrombosis, pulmonary embolism, and cerebral hemorrhage. Anti-PF4 antibody measurement through immunoassays and functional assays were positive in 86.2% and 73% of cases, respectively. About 31% of the cases died. Early diagnosis and proper therapeutic measures are important in ChAdOx1 nCov-19 vaccine-induced VITTS patients. Therefore, experts are recommended to know the corresponding clinical and laboratory features, as well as diagnostic methods. Elucidation of the pathophysiologic mechanism of ChAdOx1 nCov-19 vaccine-induced TTS deserves further investigation.

Thyroid Eye Disease as Initial Manifestation of Graves' Disease Following Viral Vector SARS-CoV-2 Vaccine: Report of a Case and Review of the Literature.

COVID-19, a contagious disease caused by the novel coronavirus SARS-CoV-2, emerged in 2019 and quickly became a pandemic, infecting more than 700 million people worldwide. The disease incidence, morbidity and mortality rates have started to decline since the development of effective vaccines against the virus and the widespread immunization of the population. SARS-CoV-2 vaccines are associated with minor local or systemic adverse reactions, while serious adverse effects are rare. Thyroid-related disorders have been reported after vaccination for COVID-19, and Graves' disease (GD) is the second most common amongst them. Thyroid eye disease (TED), an extrathyroidal manifestation of GD, is rarely observed post-COVID-19 vaccination. All TED cases followed mRNA-based vaccinations, but two new onset mild TED cases post-viral vector vaccine (ChAdox1nCoV-19) have also been reported. We report the case of a 63-year-old woman who presented with new onset hyperthyroidism and moderate-to-severe and active TED 10 days after she received the first dose of a viral vector vaccine against SARS-CoV-2. This is the first case of moderate-to-severe TED after such a vaccine. Our patient was initially treated with intravenous glucocorticoids, and subsequently with intravenous rituximab, due to no response. The disease was rendered inactive after rituximab, but constant diplopia persisted, and the patient was referred for rehabilitative surgery.

NEURO-COVAX: An Italian Population-Based Study of Neurological Complications after COVID-19 Vaccinations.

OBJECTIVE: In this Italian population-based study, we aimed to evaluate the neurological complications after the first and/or second dose of COVID-19 vaccines and factors potentially associated with these adverse effects. METHODS: Our study included adults aged 18 years and older who received two vaccine doses in the vaccination hub of Novegro (Milan, Lombardy) between 7 and 16 July 2021. The NEURO-COVAX questionnaire was able to capture the neurological events, onset and duration. That data that were digitized centrally by the Lombardy region were used to match the demographic/clinical characteristics and identify a vulnerability profile. Associations between vaccine lines and the development of complications were assessed. Digital healthcare system matching was also performed to evaluate severe neurological complications (Guillain-Barrè syndrome, Bell's palsy, transverse myelitis, encephalitis) and the incidence of hospital admissions and/or the mortality rate after two doses of the vaccines. RESULTS: The NEURO-COVAX-cohort included 19.108 vaccinated people: 15.368 with BNT162b2, 2077 with mRNA-1273, 1651 with ChAdOx1nCov-19, and 12 with Ad26.COV2.S who were subsequently excluded. Approximately 31.2% of our sample developed post-vaccination neurological complications, particularly with ChAdOx1nCov-19. A vulnerable clinical profile emerged, where over 40% of the symptomatic people showed comorbidities in their clinical histories. Defining the neurological risk profile, we found an increased risk for ChAdOx1nCov-19 of tremors (vs. BNT162b2, OR: 5.12, 95% CI: 3.51-7.48); insomnia (vs. mRNA-1273, OR: 1.87, 95% CI: 1.02-3.39); muscle spasms (vs. BNT162b2, OR: 1.62, 95% CI: 1.08-2.46); and headaches (vs. BNT162b2, OR: 1.49, 95% CI: 0.96-1.57). For mRNA-1273, there were increased risks of parethesia (vs. ChAdOx1nCov-19, OR: 2.37, 95% CI: 1.48-3.79); vertigo (vs. ChAdOx1nCov-19, OR: 1.68, 95% CI: 1.20-2.35); diplopia (vs. ChAdOx1nCov-19, OR: 1.55, 95% CI: 0.67-3.57); and sleepiness (vs. ChAdOx1nCov-19, OR: 1.28, 95% CI: 0.98-1.67). In the period that ranged from March to August 2021, no one was hospitalized and/or died of severe complications related to COVID-19 vaccinations. DISCUSSION: This study estimates the prevalence and risk for neurological complications potentially associated with COVID-19 vaccines, thus improving the vaccination guidelines and loading in future personalized preventive medicine.

Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT)-Insights from Clinical Cases, In Vitro Studies and Murine Models.

An effective worldwide vaccination campaign started and is still being carried out in the face of the coronavirus disease 2019 (COVID-19) pandemic. While vaccines are great tools to confront the pandemic, predominantly adenoviral vector-based vaccines can cause a rare severe adverse effect, termed vaccine-induced immune thrombocytopenia and thrombosis (VITT), in about 1 in 100,000 vaccinated individuals. VITT is diagnosed 5-30 days post-vaccination and clinically characterized by thrombocytopenia, strongly elevated D-dimer levels, platelet-activating anti-platelet factor 4 (PF4) antibodies and thrombosis, especially at atypical sites such as the cerebral venous sinus and/or splanchnic veins. There are striking similarities between heparin-induced thrombocytopenia (HIT) and VITT. Both are caused by anti-PF4 antibodies, causing platelet and leukocyte activation which results in massive thrombo-inflammation. However, it is still to be determined why PF4 becomes immunogenic in VITT and which constituent of the vaccine triggers the immune response. As VITT-like syndromes are increasingly reported in patients shortly after viral infections, direct virus-PF4 interactions might be most relevant. Here we summarize the current information and hypotheses on the pathogenesis of VITT and address in vivo models, especially murine models for further studies on VITT.