A randomised trial of Mycobacterium w in critically ill patients with COVID-19 (ARMY-1)

Singh Sehgal, Inderpaul; Guleria, Randeep; Singh, Sarman; Sabah Siddiqui, Mohammad; Agarwal, Ritesh; Singh Sehgal, Inderpaul; Guleria, Randeep; Singh, Sarman; Siddiqui, Mohammad Sabah; Mohan, Anant; Jindal, Atul; Bhalla, Ashish; Kajal, Kamal; Malhotra, Pankaj; Puri, Goverdhan Dutt; Khadanga, Sagar; Joshi, Rajnish; Saigal, Saurabh; Nagarkar, Nitin M.; Suri, Vikas; Bhatnagar, Sushma; Tiwari, Pawan; Singh, Mini P.; Yaddanapudi, Laxmi Narayana; Mittal, Sourab; Agarwal, Ritesh

PURPOSE: We investigate whether Mycobacterium w (Mw), an immunomodulator, would improve clinical outcomes in coronavirus infectious disease 19 (COVID-19). METHODS: We conducted an exploratory, randomised, double-blind, placebo-controlled trial of hospitalised subjects with severe COVID-19 (pulmonary infiltrates and oxygen saturation ≤94% on room air) conducted at four tertiary care centers in India. Patients were randomised 1:1 to receive either 0.3 mL·day(−1) of Mw intradermally or a matching placebo for three consecutive days. The primary outcome of the study was the distribution of clinical status assessed on a seven-point ordinal scale ranging from discharged (category 1) to death (category 7) on study days 14, 21, and 28. The co-primary outcome was a change in SOFA score on days 7 and 14 compared to the baseline. The secondary outcomes were 28-day mortality, time to clinical recovery, time to RT-PCR negativity, adverse events, and others RESULTS: We included 42 subjects (22 Mw, 20 placebo). On days 14 (OR, 30.4; 95% CI, 3.3–276.4) and 21 (OR, 14.9; 95% CI, 1.8–128.4), subjects in the Mw arm had a better clinical status distribution than placebo. There was no difference in the SOFA score change on days 7 and 14 between the two groups. We did not find any difference in the mortality, or other secondary outcomes. We observed no adverse events related to the use of Mw. CONCLUSIONS: The use of Mw results in better clinical status distribution on days 14 and 21 compared to placebo in critically ill patients with COVID-19.