Efficacy and safety of AP-Bio®(KalmCold®) in participants with uncomplicated upper respiratory tract viral infection (common cold) - A phase III, double-blind, parallel group, randomized placebo-controlled trial.

INTRODUCTION: Kalmegh (Andrographis paniculata) is commonly used for treating uncomplicated Upper Respiratory Tract Infection (URTI) in complementary and alternative system of medicine. AP-Bio®(KalmCold®) is a standardized extract derived from the leaves of A. paniculata. This study was proposed to evaluate its efficacy using validated scales and objective measures. METHODS: Participants were randomized in a ratio of 1:1:1 to receive either AP-Bio® 200 mg/day, AP-Bio® 400 mg/day or placebo for 7 days. The primary outcome measure was Wisconsin Upper Respiratory Symptom Survey (WURSS-21) score. The secondary outcome measures were nasal mucous weight, nasal muco-ciliary clearance function and Interleukin-8 in nasal wash, as well as safety and tolerability. RESULTS: A total of n = 331 participants were screened and N = 300 participants were enrolled. The absolute WURSS-21 global score [mean (Standard Deviation - SD)] in the AP-Bio® 400 mg group [5.70 (5.31)] was less than the AP-Bio® 200 mg group [5.81 (4.83)] on Day-3. However, it was much higher in the placebo group [9.55 (14.27)]. AP-Bio® 400 mg group (Mean Difference - MD [Standard Error - SE] = -3.85 [1.52]; 95% CI = -6.85, - 0.85; adjusted p = 0.034) and 200 mg group (MD [SE] = -3.74 [1.51]; 95% CI = -6.73, - 0.76; adjusted p = 0.038) had significantly lower score than placebo. Similarly, on Day-3, the change in global score from baseline was significantly better in the AP-Bio® 400 mg group (MD [SE] = -3.91; [1.82] 95% CI = -7.50, - 0.32; adjusted p = 0.038) and AP-Bio® 200 mg group (MD [SE] = -3.84 [1.97]; 95% CI = -7.72, - 0.04; adjusted p = 0.044) in comparison to the placebo group. Nasal mucous weight, tissue paper counts used, and interleukin-8 showed a trend towards AP-Bio® groups having a favourable outcome when compared with placebo but did not reach statistical significance due to a small sample size. None of the study participants complained of any adverse physical symptoms. However, incident eosinophilia was noted in n = 20 participants on day 3. (n = 6 in AP-Bio® 200 mg group, n = 7 in Ap-Bio® 400 mg group and n = 13 in placebo group; p = 0.181). CONCLUSIONS: Participants in both the AP-Bio® dose groups showed positive tendency towards resolution of URTI symptoms when compared with placebo on Day-3 but not on Day-5 and Day-7.

COVID-19 associated Rhino-Orbito-Cerebral Mucormycosis: Imaging spectrum and Clinico-radiological correlation- a single Centre experience.

PURPOSE: The study aims to depict the radiological features of Cov-ROCM, depict the common routes of spread to orbits and intracranial compartment and look for an association of the risk factors with radiological severity of the disease. METHODS: 96 patients who had COVID-19 infection in the past 3 months and were diagnosed with ROCM underwent CECT PNS examinations which were assessed by two experienced radiologists. They were divided into three groups based on the intraorbital and intracranial involvement and were correlated with various risk factors. RESULTS: The incidence of bony erosions which was the commonest finding (75%) was double in Cov-ROCM than the ROCM cases of pre COVID era (33-40%). The most common route of spread to orbit was through angioinvasion(52%) with intact orbital walls; and intracranial extension was via erosion of the cribriform plate(52%). Sphenoid sinus involvement is strongly associated with intracranial and intraorbital involvement.(p-value = .0004). History of longer ICU stays and being on mechanical ventilation as a part of COVID management is associated with aggressive disease pattern(p-value = .002). Similarly, poor glycaemic control signified by raised HbA1c levels showed statistically significant correlation with severe Cov-ROCM(intraorbital/intracranial extension) (p-value = .040). CONCLUSION: Amidst the COVID pandemic, it is pertinent to look at bony erosions in case of any sinusitis, especially bony maxillary walls and the turbinates. The intraorbital compartment must be viewed thoroughly even in the absence of bony erosions due to the angioinvasive nature of these fungi. Aggressive follow-up for patients with ICU stays for COVID and for glycaemic control would help reduce the morbidity.