Inflawell® improves neutrophil-to-lymphocyte ratio and shortens hospitalization in patients with moderate COVID-19, in a randomized double-blind placebo-controlled clinical trial

Abstract

Aims: COVID-19 is a significant global threat to public health. Despite the availability of vaccines and anti-viral drugs, there is an urgent need for alternative treatments to help prevent and/or manage COVID-19 symptoms and the underlying dysregulated immune response. We hypothesized that administration of Inflawell^® syrup, a Boswellia extract formulation enriched for boswellic acids (BAs), can reduce the excessive or persistent inflammation and thereby prevent disease progression. BAs are medicinally activated triterpenoids found in the resins of Boswellia spp., and possess an immense therapeutic potential due to their anti-inflammatory and immunoregulatory activities. We investigated the effect of Inflawell^® syrup, on moderate COVID-19 patients along with the current standard of care treatment.

Methods: A randomized placebo-controlled double-blind clinical trial was conducted, following definitive confirmation of COVID-19. Forty-seven hospitalized patients with moderate COVID-19 were enrolled and received either the Inflawell^® syrup or placebo. Clinical symptoms and markers of inflammation were evaluated at baseline and completion of the trial.

Results: Our clinical trial revealed an increase in the percentage of oxygen saturation level in patients that received the BAs compared to placebo (P < 0.0001). In addition, the average duration of hospitalization was significantly shorter in the BAs group compared with the placebo group (P < 0.04). Concomitantly, some improvement in the clinical symptoms including cough, dyspnea, myalgia, headache, and olfactory and gustatory dysfunction were detected in the BAs group. Hematologic findings showed a significant decrease in the percentage of neutrophils (P < 0.006) and neutrophil-to-lymphocyte ratio (NLR) levels (P < 0.003), associated with a significant increase in the percentage of lymphocytes in the BAs group compared with the placebo (P < 0.002). Additionally, a significant decrease in CRP, LDH, IL - 6 and TNF - α levels was detected in the BAs group. Following the intervention, fewer patients in the BAs group were PCR-positive for COVID-19 compared to placebo, though not statistically significant.

Conclusion: Overall, the treatment with Inflawell^® resulted in shorter hospital stay, alleviation of COVID-19 clinical symptoms and decline in the level of pro-inflammatory cytokines.

Trial registration: The trial has been registered in https://www.irct.ir with unique identifier: IRCT20170315033086N10 ( https://en.irct.ir/trial/51631 ). IRCT is a primary registry in the WHO registry network ( https://www.who.int/clinical-trials-registry-platform/network/primary-registries ).

Keywords: Boswellic acids; COVID-19; Clinical trial; Inflammation; Inflawell® syrup; NLR.

Fig. 1

Flow diagram of participants in a Randomized Clinical Trial of BAs group vs placebo group

Fig. 2

Change of oxygen saturation in BAs group and placebo group after the intervention (day 14). Data is presented as mean ± SEM and was analyzed using ANCOVA test. P < 0.05 was considered significant

Fig. 3

Comparison of the length of hospital stay in BAs and placebo groups. Data are presented as mean ± SEM and was analyzed using t test. P < 0.05 was considered significant

Fig. 4

A Neutrophil percent, B Lymphocyte percent, C NLR D the levels of CRP, and E LDH, day 14 post-intervention in both BAs group and placebo group. Data are presented as mean ± SEM and were analyzed using ANCOVA test. P < 0.05 was considered significant

Fig. 5

Levels of inflammatory cytokines at day 14 post-intervention in both BAs and placebo groups. Data are presented as mean ± SEM and were analyzed using ANCOVA test. P < 0.05 was considered significant