"COAGULATION FACTORS, INFLUENCED OR NOT, IN THE REPEATED DOSE TOXICITY TEST OF A CANDIDATE VACCINE AGAINST SARS-COV-2?"

"SARS-CoV-2 infection increases the risk of multi-organ systemic complications and venous and arterial thromboembolism. The development of vaccines has proven to be an effective method to combat severe forms of infection. Adverse effects reported after COVID-19 vaccination consisted of local injection site reaction, fatigue, myalgia, or fever as well as sporadic cases of vaccine-induced thrombotic immune thrombocytopenia, especially viral vector vaccines. Objectives: The aim of the study was to evaluate the repeated dose toxicity of a candidate vaccine against SARS-CoV-2, a test in which several parameters were analyzed, including coagulation factors. Materials and methods: The test included 120 rats, of both sexes, divided into six groups (main group, recovery group and control group) at which the human dose, 10X human dose and 1 control adjuvant were tested. The vaccine was administered intranasally, 4 times every two weeks. The final day was after the last administration to the main group and another 30 days from the last administration to the recovery group. On day 0 and the final day, blood was collected for hematological, biochemical, immunological examinations and coagulation tests (Fibrinogen, Prothrombin Time-PT, Activated Partial Thromboplastin Time-aPTT and Thrombin Time-TT). Results: Fibrinogen, in the case of all groups, increased on the final day, except for females from the recovery groups where this parameter decreased by 25%. PT, aPTT and TT, regardless of group or sex, had low values ​​compared to the initial time of the study. On day 0, the values ​​of the coagulation factors were homogeneous, the fibrinogen being between 155-347mg / dL, PT 25.5-57.8 sec, aPTT 61.9-120 sec and TT values ​​of 53-60 sec. On the final day, the group analysis also showed unit values. Fibrinogen increased between 90-116%, PT decreased by 48-71%, aPTT decreased by 59-80%, and TT had values ​​lower by 10-14% compared to the initial day. Conclusions: Increased fibrinogen associated with decreased PT and aPTT is common in human clinical pathology. Fibrinogen, PT, aPTT and TT are the standard parameters of blood clotting assessed in toxicity tests. The results obtained in the study represent a preliminary phase which, corroborated with the results of the other tests, supports the conclusion that the candidate vaccine does not have toxicological potential, the coagulation factors not being influenced after its repeated administration. Keywords: SARS-CoV-2, coagulation factors, rat, vaccine"