Adverse events following COVID-19 vaccination in Kwara State, North-central Nigeria.

Safe and effective vaccination remains the mainstay of control of COVID-19 because there is still no universally recommended treatment. This strategy is however being threatened by vaccine hesitancy and resistance due to fear of adverse events and safety concerns. It is, therefore, necessary to study post-vaccination adverse events (AE) in various populations and geographical areas. The objective of this study was to analyze the adverse events following COVID-19 vaccination in five major immunization centers of Kwara State Nigeria. A retrospective descriptive study of the adverse events following AstraZeneca COVID-19 vaccination that were reported from five immunization centers of Kwara State, North-central Nigeria from March to July 2021 was carried out. Statistical Package for Social Science version 26 was used for analysis. Adverse event classification and severity were compared based on age, gender, and time to onset of adverse event and vaccine dose type using the Chi-square test. The incidence of COVID-19 vaccine AE was 1.6%. There was female predominance (51.6%) and a mean age of 41.6±13.7 years. Most of the AE (95.8%) were systemic and mild (81.1%) without a requirement for any therapeutic intervention. Fatal outcome was not reported in any of the AE and the time to outcome of AE was 2 days in most cases (45.3%). No significant association was found between the variables studied and the adverse event type and severity. The low incidence and mild nature of adverse events reported in this study will add to the body of knowledge regarding vaccine adverse events and may eventually impact vaccine uptake.

Therapeutic Potentials of Selected Antihypertensive Agents and Their Fixed-Dose Combinations Against Trastuzumab-Mediated Cardiotoxicity.

Trastuzumab (TZM) is useful in the clinical management of HER2-positive metastatic breast, gastric, and colorectal carcinoma but has been limited by its off-target cardiotoxicity. This study investigates the therapeutic potentials of 0.25 mg/kg/day amlodipine, 0.035 mg/kg/day lisinopril, 5 mg/kg/day valsartan, and their fixed-dose combinations in TZM-intoxicated Wistar rats that were randomly allotted into 10 groups of 6 rats for each group. Group I rats were treated with 10 ml/kg/day sterile water orally and 1 ml/kg/day sterile water intraperitoneally; Groups II, III, and IV rats were orally gavaged with 5 mg/kg/day valsartan and 1 ml/kg/day sterile water intraperitoneally, 0.25 mg/kg/day amlodipine and 1 ml/kg/day sterile water via the intraperitoneal route, 0.035 mg/kg/day lisinopril and 1 ml/kg/day sterile water administered intraperitoneally, respectively. Group V rats were orally treated with 10 ml/kg/day of sterile water prior to intraperitoneal administration of 2.25 mg/kg/day of TZM. Groups VI-VIII rats were equally pretreated with 5 mg/kg/day valsartan, 0.25 mg/kg/day amlodipine, and 0.035 mg/kg/day lisinopril before intraperitoneal 2.25 mg/kg/day TZM treatment, respectively; Groups IX and X rats were orally pretreated with the fixed-dose combinations of 0.25 mg/kg/day amlodipine +0.035 mg/kg/day lisinopril and 5 mg/kg/day valsartan +0.035 mg/kg/day lisinopril, respectively, before TZM treatment. Cardiac injury and tissue oxidative stress markers, complete lipids profile, histopathological, and immunohistochemical assays were the evaluating endpoints. Results showed that repeated TZM treatments caused profound increases in the serum TG and VLDL-c levels, serum cTnI and LDH levels, and cardiac tissue caspase-3 and -9 levels but decreased BCL-2 expression. TZM also profoundly attenuated CAT, SOD, GST and GPx activities, and increased MDA levels in the treated tissues. In addition, TZM cardiotoxicity was characterized by marked vascular and cardiomyocyte congestion and coronary artery microthrombi formation. However, the altered biochemical, histopathological, and immunohistochemical changes were reversed with amlodipine, lisinopril, valsartan, and fixed-dose combinations, although fixed-dose valsartan/lisinopril combination was further associated with hyperlipidemia and increased AI and CRI values and coronary artery cartilaginous metaplasia. Thus, the promising therapeutic potentials of amlodipine, lisinopril, valsartan and their fixed-dose combinations in the management of TZM cardiotoxicity, majorly mediated via antiapoptotic and oxidative stress inhibition mechanisms were unveiled through this study.