Repurposing of Mycobacterium indicus pranii for the severe form of COVID-19 patients in India: A cohort study

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induces the production of proinflammatory cytokines, which results in a cytokine storm, and immune-modulators like Mycobacterium indicus pranii (MIP) might ameliorate coronavirus disease of 2019 (COVID-19) related cytokine storm. Therefore, the present study evaluates whether MIP offers an advantage in the treatment of severe COVID-19 patients infected with SARS-CoV-2. A prospective MIP cohort study was conducted in chest disease hospitals in Srinagar, Jammu and Kashmir, India. In the present prospective, randomized clinical study, critically severe COVID-19 patients were divided into two groups, the MIP group (n = 105) and the best standard treatment (BST) group (n = 210). Procalcitonin, ferritin, high-sensitive C-reactive protein, D-dimer levels, and interleukin levels on 5th-day posttreatment were significantly reduced in the MIP group compared to the BST group. Compared to the BST group, 105 consecutive patients with severe COVID-19 in the MIP group reported early weaning off ventilation, resolution of chest architecture (computed tomography [CT] scan), a significant increase in SpO₂ levels, and decreased mortality with a hazard ratio: 0.234 (95% confidence interval: 0.264-2.31) (p = 0.001). MIP restored SpO₂ , immune/inflammatory response, normalized lung abnormalities (chest CT scan), and reduced mortality without any serious complications. However, there is a need for placebo-controlled double-blind and controlled clinical trials to confirm the efficacy.

Keywords: COVID-19; Mycobacterium indicus pranii; interleukins; mechanical ventilation; proinflammatory response and oxygen saturation.

Figure 1

Associations between increased serum inflammatory factors, interleukins (IL‐1; IL‐2, IL‐4, IL‐6, IL‐10, and INF‐ γ) and TNF‐α levels with hospital stay in coronavirus disease of 2019 patients (Pearson's product‐moment correlations) correlation analyses were conducted between variables and were considered significant at p < 0.05; p < 0.01; p < 0.0001. Hs‐CRP, high‐sensitive C‐reactive protein

Figure 2

(A–D) The violin plots of interleukin‐1 (IL‐1), IL‐6, and TNF‐α level in patients with coronavirus disease of 2019 (COVID‐19) in severely ill COVID‐19 patients under best standard treatment (BST) arm and Mycobacterium indicus pranii (MIP) arm. The red dot in the violin is the median value, and the blue rectangle is the 25th and 75th percentiles. (A) On 5th day of treatment, a significant reduction was observed in values of IL‐1 in the MIP group (p = 0.03) while a nonsignificant reduction in values of IL‐1 was observed in the BST group. (B) Similarly in both groups IL‐2 was significantly reduced in MIP (0.05) and BST (0.05) groups. (C and D) Nonsignificant reduction in values of IL‐6 and TNF‐α was observed

Figure 3

(A–C) The box plots of interleukin‐4 (IL‐4), IL‐10, and INF‐γ level in patients with coronavirus disease of 2019 (COVID‐19) in severely ill COVID‐19 patients under best standard treatment (BST) arm and Mycobacterium indicus pranii (MIP) arm

Figure 4

(A–F) Dynamic changes of high‐sensitive C‐reactive protein (Hs‐CRP), D‐dimer, LDH, ferritin, procalcitonin. During hospitalization, the horizontal lines represent the median value in each group. On 5th‐day posttreatment, levels of procalcitonin (p = 0.02), ferritin (p = 0.09), Hs‐CRP (p = 0.05), and levels of D‐dimer (p < 0.001) were found to be decreased significantly in Mycobacterium indicus pranii (MIP) group. Significant reduction was observed in posttreatment values of LDH (p = 0.05) in best standard treatment (BST) group, but the gradient of reduction was below the gradient of reduction observed in the MIP group

Figure 5

Radiological findings in severe coronavirus disease of 2019 (COVID‐19) patients treated with Mycobacterium indicus pranii

Figure 6

Kaplan–Meier estimates of the time from intervention (administration of Mycobacterium indicus pranii [MIP] and best standard treatment [BST]) to death or to improvement. The ordinal scale ranging from Category 1 (death) to Category 0 (discharged with full return to baseline physical function)