The winding 12-month journey of the AstraZeneca COVID-19 vaccine since its first administration to humans.

The deficiently designed and conducted initial clinical development plan and the occurrence of thrombotic thrombocytopenia cases, have marked the 12-month journey of the AstraZeneca coronavirus disease 2019 (COVID-19) vaccine after it was first administered to humans. When it was authorized, there were no available efficacy data in the elderly. However, this age group was included in the product labelling based on immunogenicity data. The lack of safety and efficacy data in the elderly that was acknowledged in the product information, triggered most European Union (EU) countries to limit the administration of this vaccine to certain age groups. In February-March/2021, after the results of observational studies supported the vaccine effectiveness in the elderly, several countries broadened its use to this age group. When trust on the vaccine was ramping up, unusual blood clot cases were described in Europe, which led 24 countries around the world to temporarily halt its administration. These cases were first described as thrombotic thrombocytopenia in late March. In mid-April, the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA) updated the product information and confirmed the positive benefit/risk ratio of the vaccine, recommending its use with no age restrictions. The World Health Organization (WHO) coincided with this approach. However, several countries decided to limit its use to certain age groups. The EMA listed thrombotic thrombocytopenia as a "very rare" adverse reaction. Although, the AstraZeneca vaccine was conceived in early 2020 to be a worldwide leader in the fight against COVID-19, its use was abandoned by the African Union, Denmark, and Israel. However, this vaccine has shown its usefulness in many settings across the world.

Comparison of Immunogenicity and Reactogenicity of Five Primary Series of COVID-19 Vaccine Regimens against Circulating SARS-CoV-2 Variants of Concern among Healthy Thai Populations.

To compare immunogenicity and reactogenicity of five COVID-19 vaccine regimens against wild-type SARS-CoV-2 and variants of concern (VoCs) among Thai populations, a prospective cohort study was conducted among healthy participants aged ≥18 years who had never been infected with COVID-19 and were scheduled to get one of the five primary series of COVID-19 vaccine regimens, including CoronaVac/CoronaVac, AZD1222/AZD1222, CoronaVac/AZD1222, AZD1222/BNT162b2, and BNT162b2/BNT162b2. Anti-receptor binding domain (anti-RBD-WT) IgG and neutralizing antibody (NAb-WT) against wild-type SARS-CoV-2 were measured at pre-prime, post-prime, and post-boost visits. NAb against VoCs (NAb-Alpha, NAb-Beta, NAb-Delta, and NAb-Omicron) were assessed at the post-boost visit. Adverse events (AEs) following vaccination were recorded. A total of 901 participants (CoronaVac/CoronaVac: 332, AZD1222/AZD1222: 221, CoronaVac/AZD1222: 110, AZD1222/BNT162b2: 128, and BNT162b2/BNT162b2: 110) were enrolled. Anti-RBD-WT IgG and NAb-WT levels increased substantially after each vaccine dose. At the post-boost visit, BNT162b2/BNT162b2 induced the highest GMC of anti-RBD-WT IgG level (1698 BAU/mL), whereas AZD1222/BNT162b2 induced the highest median NAb-WT level (99% inhibition). NAb levels against VoCs, particularly the Omicron strain, were markedly attenuated for all vaccine regimens (p < 0.001). Overall, no serious AEs following vaccination were observed. All five primary series of COVID-19 vaccine regimens were well-tolerated and elicited robust antibody responses against wild-type SARS-CoV-2 but had attenuated responses against VoCs, particularly the Omicron strain, among healthy Thai populations.

Side Effects Associated With Homologous and Heterologous COVID-19 Vaccines: A Cross-Sectional Study in Saudi Arabia.

BACKGROUND: Numerous studies on coronavirus disease 2019 (COVID-19) vaccination safety have been conducted in Saudi Arabia. Even though there is less evidence comparing the side effects of different vaccines and a few of them studied the side effects of mixing different platforms of vaccines. OBJECTIVES: This study aimed to evaluate the type and severity of adverse effects following COVID-19 vaccination based on the type and platform of received vaccine and to determine factors that contribute to the occurrence of these side effects. METHODS: This cross-sectional comparative study was conducted in Saudi Arabia from January to the end of February 2022 among COVID-19 vaccine recipients through an online survey. Based on the type of vaccines received, we categorized our participants into two groups - those who received two doses of either the Pfizer or the AstraZeneca COVID-19 vaccines, and those who received mixed vaccination regimen (one dose of Pfizer and one dose of AstraZeneca). RESULTS: The study included 1,340 participants, of which 56.3% received two doses of the Pfizer vaccine while (7%) received two doses of the AstraZeneca vaccine, and 8.8% received mixed vaccines (one dose of the Pfizer vaccine and one dose of the AstraZeneca vaccine). Pain at the injection site was the most frequent local symptom (37.9%) followed by swelling±redness (27.6%). The local adverse reactions were nearly equal in AstraZeneca and Pfizer vaccines, whereas these were significantly lower in those who received mixed doses (p<0.001). Fever was significantly higher in mixed vaccination regimens compared to other types (p<0.001). The male gender who received the Pfizer vaccine were at higher risk of developing an adverse reaction following vaccination. Unusual side effects (sleep disorders, menstrual irregularities, and symptoms suggestive of diabetic neuropathy) were also reported. CONCLUSION: The results suggest the overall safety of Pfizer and AstraZeneca vaccines as well as the mixed vaccination protocol. A heterologous regimen was associated with fewer side effects compared to homologous vaccines. Further studies are needed to assess the long-term side effects.

Cerebral venous sinus thrombosis following intracerebral hemorrhage after COVID-19 AstraZeneca vaccination: A case report.

The patient was a 55-year-old female patient who presented with sudden onset of left hemiplegia, facial hemiparesis, and hypoesthesia. She has received her first dose of the AstraZeneca COVID-19 vaccine. This case indicates that vaccination may raise the hypercoagulable state even in a condition of post-ICH and anticoagulant prophylaxis.

COVID-19 vaccination and male fertility issues: Myth busted. Is taking COVID-19 vaccine the best choice for semen protection and male fertility from risky infection hazards?

The emerging coronavirus illness (COVID-19) pandemic is posing a global health hazard, with men being at a larger risk than women. There have been few publications on the andrological consequences of COVID-19 and its vaccines so far. To assuage vaccine fear stemming from concerns about fertility, the effect of inactivated whole-virus and viral vector vaccines on semen quality was investigated in 100 Egyptian men. The safety of COVID-19 vaccines on semen parameters was validated with no significant change in pre- and post-vaccination semen analyses in either type of vaccine. Following COVID-19 vaccination, we can declare male semen parameters as unaffected.

Self-Reported COVID-19 Vaccines' Side Effects among Patients Treated with Biological Therapies in Saudi Arabia: A Multicenter Cross-Sectional Study.

OBJECTIVE: The aim of this study was to explore the side effects of COVID-19 vaccines among a mixed gender sample of patients on monoclonal antibody biologics (mAbs) in Saudi Arabia. METHODS: This was a prospective questionnaire-based cross-sectional study in which adult patients (≥18 years) on mAbs who had received at least one dose of COVID-19 vaccine from three tertiary care centers in Saudi Arabia were included. Descriptive statistics and univariate logistic regressions were conducted to present the vaccine side effects and examine the association between the reported side effects and vaccine type. RESULTS: Four-hundred and seventeen patients, with a mean age of 39 years, consented to participate. Approximately 82% and 18% of the participants received Pfizer-BioNTech and Oxford-AstraZeneca vaccines, respectively, and nearly 71% received two doses of the vaccine. Diarrhea (9.59%), fever (51.32%), headache (32.13%), hypotension (13.67%), palpitation (9.11%), and temporary loss of smell (5.28%) were the most commonly reported side effects. CONCLUSION: COVID-19 vaccines are generally safe for patients treated with mAbs. Future studies should examine the rates of side effects across different COVID-19 vaccines among patients on mAbs using more robust study designs and representative samples.

Concomitant myocarditis and painless thyroiditis after AstraZeneca coronavirus disease 2019 vaccination: a case report.

BACKGROUND: Incidence of myocarditis following messenger RNA coronavirus disease 2019 vaccination has been widely described, but this clinical scenario after adenoviral vector coronavirus disease 2019 vaccination has only been rarely reported. In addition, a few case reports of thyroiditis after adenoviral vector coronavirus disease 2019 vaccination have been published. CASE PRESENTATION: A 55-year-old Thai woman presented with palpitation without neck pain 14 days after receiving AstraZeneca coronavirus disease 2019 vaccination. Electrocardiography revealed sinus tachycardia. Her blood tests showed elevation of cardiac troponin and free triiodothyronine with suppressed serum thyroid stimulating hormone, reflecting a hyperthyroid status. Evidence of myocardial inflammation and necrosis from cardiac magnetic resonance imaging supported the diagnosis of recent myocarditis. Laboratory results and imaging findings were consistent with thyroiditis. After 3 weeks of symptomatic treatment, her symptom and blood tests had returned to normal. CONCLUSIONS: This case demonstrates that the adenoviral vector coronavirus disease 2019 vaccine could possibly cause myocarditis and painless thyroiditis. Clinicians should have a high index of suspicion and promptly evaluate these conditions, despite minimal symptoms.

AstraZeneca COVID-19 vaccine induces robust broadly cross-reactive antibody responses in Malawian adults previously infected with SARS-CoV-2.

BACKGROUND: Binding and neutralising anti-Spike antibodies play a key role in immune defence against SARS-CoV-2 infection. Since it is known that antibodies wane with time and new immune-evasive variants are emerging, we aimed to assess the dynamics of anti-Spike antibodies in an African adult population with prior SARS-CoV-2 infection and to determine the effect of subsequent COVID-19 vaccination. METHODS: Using a prospective cohort design, we recruited adults with prior laboratory-confirmed mild/moderate COVID-19 in Blantyre, Malawi, and followed them up for 270 days (n = 52). A subset of whom subsequently received a single dose of the AstraZeneca COVID-19 vaccine (ChAdOx nCov-19) (n = 12). We measured the serum concentrations of anti-Spike and receptor-binding domain (RBD) IgG antibodies using a Luminex-based assay. Anti-RBD antibody cross-reactivity across SARS-CoV-2 variants of concern (VOC) was measured using a haemagglutination test. A pseudovirus neutralisation assay was used to measure neutralisation titres across VOCs. Ordinary or repeated measures one-way ANOVA was used to compare log10 transformed data, with p value adjusted for multiple comparison using Sídák's or Holm-Sídák's test. RESULTS: We show that neutralising antibodies wane within 6 months post mild/moderate SARS-CoV-2 infection (30-60 days vs. 210-270 days; Log ID50 6.8 vs. 5.3, p = 0.0093). High levels of binding anti-Spike or anti-RBD antibodies in convalescent serum were associated with potent neutralisation activity against the homologous infecting strain (p < 0.0001). A single dose of the AstraZeneca COVID-19 vaccine following mild/moderate SARS-CoV-2 infection induced a 2 to 3-fold increase in anti-Spike and -RBD IgG levels 30 days post-vaccination (both, p < 0.0001). The anti-RBD IgG antibodies from these vaccinated individuals were broadly cross-reactive against multiple VOCs and had neutralisation potency against original D614G, beta, and delta variants. CONCLUSIONS: These findings show that the AstraZeneca COVID-19 vaccine is an effective booster for waning cross-variant antibody immunity after initial priming with SARS-CoV-2 infection. The potency of hybrid immunity and its potential to maximise the benefits of COVID-19 vaccines needs to be taken into consideration when formulating vaccination policies in sub-Saharan Africa, where there is still limited access to vaccine doses.

The risk of confusion between AstraZeneka COVID-19 vaccine side effects and signs of COVID-19 infection: a case report.

Post-vaccination side effects of AstraZeneca (AZ) coronavirus disease 2019 (COVID-19) vaccine are common. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection immediately after the first dose of AZ COVID-19 vaccine has not been reported. In this case, a 30-year-old female without a past medical history of SARS-CoV2 infection presented to an outpatient clinic with lightheadedness and weakness 2 hours after getting the first dose of the AZ COVID-19 vaccine. Blood pressure (BP) was 80/60 mm Hg, and oxygen saturation (SpO2) was 98%. After administering normal saline intravenous fluid, the BP was 110/80 mm Hg. On the first day, fever (oral temperature of 39℃), sweating, dry cough, sore throat, and injection-site pain were presented. On the second day, diarrhea, productive cough, and hypotension occurred in addition to fever (oral temperature of 39.9℃). The fever did not stop and productive cough, change in smell, and fatigue were reported. SpO2 was 96%. On the third day, no abnormality of the spiral lung computed tomography and the positive reverse transcriptase-polymerase chain reaction (RT-PCR) test were reported. Simultaneously, two out of three members of the family became symptomatic on the second day and their RT-PCR tests were positive. Dexamethasone ampule, Cefixime tablet, Acetaminophen tablet, and Diphenhydramine syrup were prescribed. After a week, fever subsided and SpO2 was 98%. After 3 weeks of self-quarantine at home, her general condition improved. Despite the similarity between SARS-CoV2 infection signs and symptoms and AZ COVID-19 vaccine side effects, none of the approved vaccines contain the live virus that causes disease. Therefore, any unusual post-vaccination signs and symptoms should not be attributed to the vaccine itself and need to be considered for further evaluations and early actions in order to prevent the spread of the disease in society.

Demographic Characteristics and Status of Vaccinated Individuals with a History of COVID-19 Infection Pre- or Post-Vaccination: A Descriptive Study of a Nationally Representative Sample in Saudi Arabia.

BACKGROUND: Saudi Arabia expedited the approval of some COVID-19 vaccines and launched mass vaccination campaigns. The aim of this study was to describe the demographics of vaccinated COVID-19 cases and compare the mortality rates of COVID-19 cases who were infected post-vaccination in Saudi Arabia. METHODS: This was a retrospective cohort study. We retrieved data for COVID-19 cases who were infected pre- or post-vaccination and had received at least one injection of the Oxford-AstraZeneca or Pfizer-BioNTech vaccine from 4 December 2020 to 15 October 2021. RESULTS: The number of patients who were infected and had received at least one dose of a COVID-19 vaccine was 281,744. Approximately 45% of subjects were infected post-vaccination, and 75% of subjects had received the Pfizer-BioNTech vaccine. Only 0.342% of the patients who were infected post-vaccination died, and 447 patients were admitted to ICUs. Most of the patients who were infected with COVID-19 post-vaccination and were admitted to ICUs (69.84%) had received only one dose of the vaccine (p < 0.0001). The mean time to infection for patients who had received one and two doses of the Oxford-AstraZeneca vaccine were 27 and 8 days longer than their counterparts who had received one and two doses of Pfizer-BioNTech vaccine, respectively. No difference in the odds of mortality between the Pfizer-BioNTech and Oxford-AstraZeneca vaccines was found (OR = 1.121, 95% CI = [0.907-1.386], p-value = 0.291). Patients who had received two doses of the vaccine had significantly lower odds of mortality compared to those who had received one dose (p < 0.0001). CONCLUSIONS: Vaccines are vital in combating the COVID-19 pandemic. The results of this study show no difference between the Pfizer-BioNTech and Oxford-AstraZeneca vaccines in the rate of mortality. However, the number of vaccine doses was significantly associated with a lower risk of mortality. Future studies should examine the effectiveness of different COVID-19 vaccines using real-world data and more robust designs.

Adverse Events following AstraZeneca COVID-19 Vaccine in Saudi Arabia: A Cross-Sectional Study among Healthcare and Nonhealthcare Workers.

INTRODUCTION: Many COVID-19 vaccines have been emerging with different efficacy and safety profiles. So far, very little attention has been paid to severity and reactogenicity of COVID-19 vaccine among healthcare workers. Thus, the aim of this study is to investigate the side effects associated with the first dose of AstraZeneca COVID-19 vaccine among healthcare workers (HCWs) and nonhealthcare workers (non-HCWs). METHOD: This is an observational cross-sectional study conducted at King Abdullah bin AbdulAziz University Hospital, Saudi Arabia, between February 28 and March 12, 2021. The major outcomes were the reported side effects of day 1, day 2, and day 3 after vaccination among HCWs and non-HCWs. Other outcomes included the onset and the duration of the reactions or the side effects that were reported. RESULTS: A total of 526 participants completed the survey with 173 (32.8%) HCWs and the remaining majority were non-HCWs. Some of the most frequently reported side effects among the participants on the first day were muscle aches (49%), followed by fever (42%) and headache (40%). HCWs experienced more muscle aches, headache, sore throat, and abdominal pain, which were statically significant, compared to non-HCWs. The mean onset of symptoms was 16 (±15.3) h in the HCW arm compared with 12.2 (±10.2) h in non-HCWs (p = 0.0024). Furthermore, the mean duration of symptoms in the HCW group was 37 (±19) h compared with 32.3 (±13) h in the non-HCW group (p = 0.067). CONCLUSION: The reported side effects were common but not pressing in both groups. HCW respondents appeared to have more COVID-19 vaccine-associated symptoms.

Reported adverse effects following COVID-19 vaccination at a tertiary care hospital, focus on cerebral venous sinus thrombosis (CVST).

Objectives: Several cases of unusual thrombotic events with thrombocytopenia were reported in several countries, in association with AstraZeneca's COVID-19 vaccine. The European medicines agency conducted a detailed review and concluded that there was no evidence to suggest an association of thrombotic events with the use of COVID-19 vaccine AstraZeneca.Methods: King Abdulaziz Medical City is a 1500 bed tertiary care hospital in Riyadh, Saudi Arabia; this study describes spontaneously reported vaccine adverse effects received through the hospital's internal electronic safety reporting system from December 2020 to 13 April 2021.We assessed each report for causality association utilizing the world health organization's (WHO) causality assessment of an adverse event following immunization (AEFI) classification 2nd Edition 2019.Results: The majority of the reported events were mild to moderate, there were five serious events, one reported cardiac arrest, two cerebral venous sinus thrombosis, and two pulmonary embolism. Clinical and laboratory summary of the five patients are presented in detail.Conclusions: Efforts of pharmacovigilance in mediating the rare risk of thrombosis associated with COVID-19 vaccine are crucial in providing awareness on the possible risk factors and signs/symptoms that should raise red flags.