3.2. Tolerance, Reactogenicity and Safety
myalgia, rhinorrhea, viral infections, cardiosclerosis, chills, sore throat, dyspnea, infections, insomnia, hepatitis, arthralgia, asthenia, anaphylaxis, fatigue, syncope, cough, myocardial hypertrophy, nasal congestion, somnolence, oropharyngeal pain, dilated cardiomyopathy, Guillain–Barré syndrome, musculoskeletal and connective disorders, pain, dizziness, headache, upper limb fracture, deaths
CIRCULATORY DISORDER, NERVOUS SYSTEM DISORDERS, VIRAL INFECTION, CARDIOSCLEROSIS, PATHOLOGY, SORE THROAT, PHARYNGEAL EDEMA, UPPER RESPIRATORY TRACT INFECTIONS, GENERALIZED SEIZURES, THROMBOCYTOPENIA, INFECTIONS, HEPATITIS, ANAPHYLAXIS, ADVERSE EVENTS, COAGULOPATHY, HERPES ZOSTER, DILATED CARDIOMYOPATHY, HYPERTENSIVE CRISIS, RESPIRATORY DISORDERS, ORAL HERPES
In the 18–60 age cohort, participants were monitored for AEs until Day 42–45 after the 1st vaccination (Day 28–31 after the 2nd vaccination). The studied vaccine has shown good tolerability and safety. No deaths, serious AEs, or other significant AEs related to vaccination have been reported. All observed severe adverse events (SAEs) were classified as unlikely to be related or unrelated to the tested vaccine.In total, during the study period, 244 AEs were recorded in 136 (34.2%) participants, of which 189 AEs were observed in 105 (35.2%) of the Vaccine Group participants and 55 AEs in 31 (31%) of the Placebo Group participants (The most common AE in the Vaccine Group was pain at the injection site. It was registered in the Placebo Group as well but was significantly less common (Changes in the parameters of clinical blood tests, biochemical blood tests and general urine analysis, observed at different time points, in most cases, were regarded as clinically insignificant and unrelated to the vaccination (One participant (0.3%, 0.1–1.9 95% CI) from the Vaccine Group died on Day 29 of the observation period as a result of an acute circulatory disorder. Autopsy examination revealed signs of chronic mild hepatitis, pre-existing stromal cardiosclerosis and dilated cardiomyopathy manifested by myocardial hypertrophy. The character of the lesions observed at histological examination indicated long-lasting pathology of the myocardium. As the participant had no clinically significant deviations in any of the clinical parameters throughout the observation period, including physical condition, body temperature, vital signs, urine analysis, biochemical parameters of blood, complete blood count, coagulation parameters and ECG, and had no local or systemic reactions after each vaccination, the relation of this SAE to vaccination was classified by the treating physician as unlikely.In the 60+ age cohort, participants were monitored for AEs until Day 21 after the 3rd vaccination. Overall, in the 60+ age cohort, 827 AEs were observed in 184 (92%) volunteers throughout the observation period up to 21 days after 3rd vaccination. 317 AEs in 132 (66.3%) volunteers, 223 AEs in 110 (55.3%) volunteers and 287 AEs in 117 (58.5%) volunteers were observed over 21 days after the administration of the first, second and third doses of the vaccine, correspondingly (The studied vaccine has shown good tolerability and safety. The most frequent AEs reported by volunteers in 32.3% of cases were systemic reactions (mild asthenia, chills or fatigue) and pain at the vaccine injection site, which resolved within 3 days after vaccination in 85% of cases. Clinically significant abnormalities in the laboratory and instrumental analyses accounted for 38.5% of registered AE cases, nervous system disorders (insomnia, headache, dizziness, head discomfort, syncope, somnolence) for 8% cases, viral infections (COVID-19, other upper respiratory tract infections, herpes zoster, nasal and oral herpes) for 3.7% cases, respiratory disorders not associated with infections (oropharyngeal pain, nasal congestion, cough, dyspnea, pharyngeal edema, sore throat, rhinorrhea and sneezing) for 4.6% cases, musculoskeletal and connective disorders (arthralgia, pain in the extremities, back pain, myalgia, musculoskeletal discomfort) for 4.6% cases.In total, out of 827 registered AEs, 81% were classified as mild, 15.2% moderate and 3.7% severe. The outcome of AEs was “recovery without consequences” in 86.5% of all cases, “recovery with consequences” in 0.2% of cases, “have not yet recovered” in 4% of cases and “consequences unknown” in 9.2% of cases.No deaths or other AEs that were considered of special concern due to their clinical significance were reported. Of the 827 AEs in 184 (92%) volunteers, 22 (11%) volunteers had 22 serious AEs. COVID-19 accounted for 81.8% of serious AEs, and the remaining AEs were positive tests for SARS-CoV-2, hypertensive crisis, and upper limb fracture. 41% of the registered serious AEs were mild, 31.8% moderate and 27.2% severe. The observed serious AEs were considered by investigators as unrelated (91%) or unlikely to be related (9%) to vaccination (Changes in the parameters of clinical and biochemical blood tests and general urine analysis, registered in the dynamics of observation, were considered by the principal investigator in most cases as clinically insignificant and unrelated to vaccination, indicating the safety of the vaccine. Clinically significant changes in clinical and biochemical blood tests were noted in a few cases for each parameter, and in general, urine analysis only for erythrocyte and leukocyte levels.Routine observations revealed no cases of clinically significant deviations in physical examination parameters among the study participants in the 60+ age cohort.Most of the reported AEs where the relation to vaccination was considered “definite”, “probable” or “possible”, were the AEs typically expected after vaccination due to the effect of the vaccine. No vaccine-related AEs of particular concern, which were previously reported for other COVID-19 vaccine preparations (Guillain–Barré syndrome, generalized seizures, anaphylaxis, thrombocytopenia, coagulopathy, etc.) were reported in the volunteers that received CoviVac in the 60+ age cohort.