Risk of secondary bacterial infections during treatment with anti-inflammatory genetically engineered biological drugs in COVID-19 patients

The aim of the work was to identify the presence and strength of association between the use of anti-inflammatory genetically engineered biological drugs and the development of secondary bacterial infections in COVID-19 patients. Materials and methods. We used 1 296 medical records of patients hospitalized in the infectious diseases hospital of the Volgograd region with a diagnosis of COVID-19 in September 2020, March and September 2021, March, September and November 2022, have been analyzed. A matched case-control study was performed with 275 pairs identical in gender, age (±2 years), the severity of the lung damage according to computed tomography / chest X-ray, a COVID-19 outcome, concomitant carbohydrate metabolism disorders. Patients with the signs of the secondary bacterial infection (leukocytes ≥12×109/l, procalcitonin ≥0.5 ng/ml and/or viral-bacterial pneumonia according to the autopsy data) were presented as a case. The “control” group included patients without signs of any bacterial infection (leukocytes <11×109/l, procalcitonin <0.5 ng/ml, no description of clinical signs of the bacterial infection in the medical record during the hospitalization). The prescription of 6 anti-inflammatory genetically engineered biological drugs (tocilizumab, sarilumab, olokizumab, levilimab, netakimab, secukinumab) has been studied for these groups. Results. The use of any anti-inflammatory genetically engineered biological drug was associated with the development of the secondary bacterial infection signs (OR=2.41; 95% CI: from 1.54 to 3.77; p < 0.001): for levilimab, the OR was 3.44 (95% CI: from 1.64 to 7.23; p < 0.001), for tocilizumab – OR=1.75 (95% CI: from 0.73 to 4.17; p =0.201), for olokizumab – OR=1.28 (95% CI: from 0.81 to 2.03; p =0.292). Conclusion. Among the three drugs (tocilizumab, olokizumab, levilimab), the Russian biosimilar olokizumab, a monoclonal antibody to circulating interleukin-6, has shown itself as the safest drug in terms of preventing the secondary bacterial infection signs. Further studies of developing bacterial complications risk in COVID-19 patients receiving anti-inflammatory genetically engineered biological drugs are required.