Abstract
Two hundred and fifty-seven patients presenting mild to moderate symptoms of COVID-19, confirmed through Reverse Transcription Polymerase Chain Reaction (RT-PCR) within 72 hours, were enrolled in this randomized controlled trial. The patients were divided into two groups: the first group received standard treatment in addition to standardized Andrographis paniculata powder capsules (AP), containing an equivalent of andrographolide at a dosage of 180 mg/day. The second group received standard treatment along with placebo capsules (PB). The treatment course spanned a duration of 5 days. Safety and efficacy assessments were conducted within the hospital ward over a 10-day period. The primary objective of this study was to assess the incidence of pneumonia. Secondary outcomes aimed to ascertain the severity of symptoms through the evaluation of various parameters, including: 1) Oxygen saturation 2) Respiratory rate 3) C-reactive protein levels 4) Viral load quantification 5) Adverse events, specifically assessed through blood tests for liver and renal function, as well as monitoring blood pressure, heart rate, and potassium levels. 6) Plasma profiling utilizing proteomic methodologies. Statistical analyses were conducted utilizing either the Independent t-test or the Wilcoxon Rank Sum Test for continuous data, depending on the nature of the variables. Categorical variables underwent analysis through the Chi-square test. Representation of the plasma profile involved the utilization of a Venn diagram and a Volcano plot. A difference value exceeding 2 log units was employed for the subsequent analysis of KEGG pathways, facilitating an exploration of the pathway interactions among genes, proteins, and enzymes. This meticulous approach allowed for a nuanced understanding of the underlying mechanisms and interactions within the biological systems under investigation. The investigation unveiled four cases within the study of 132 cases afflicted with pneumonia in the AP group. Conversely, the placebo group exhibited four cases out of 125 cases, representing proportions of 3.03% and 3.20%, respectively. Regarding secondary outcomes, there was no discernible difference between the groups in terms of oxygen saturation, respiratory rate, and viral load quantification among the 131 cases. The AP group exhibited a markedly higher proportion of patients with C-reactive protein (CRP) levels below 10 mg/ml, demonstrating statistical significance (p = 0.038). No serious adverse effects were identified in the study, and both renal function and blood pressure were observed to be within normal ranges in both groups. In the AP group, elevations in Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) were noted, albeit not exceeding three times the normal values in 13 cases. Conversely, in the placebo group, such elevations were observed in 7 cases. However, no statistically significant difference was observed between the two groups (p = 0.248). On days 5 and 10, the median ALT level in the AP was significantly higher than that in the PB. Notwithstanding, the ALT levels remained within the normal range. Furthermore, the number of patients with ALT values exceeding three times the normal range was 2 in the AP group and 1 in the PB group, respectively. Importantly, in all cases where ALT levels rose, there were no clinical symptoms indicative of hepatitis. By day 28, all cases demonstrated a return of ALT levels to the normal range. No significant difference was observed in the incidence of hypertension between both groups. Additionally, no instances were found of a heart rate lower than 60 times per minute. There were no discernible differences in the incidence of hypotension between the two groups. Furthermore, there were no significant disparities in median potassium levels between the AP and PB groups. Upon conducting plasma profiling using proteomic analysis, our investigation identified distinct disparities between the two groups in terms of 1) Complement and coagulation cascades, 2) Staphylococcus aureus infection, and 3) Coronavirus disease, with these alterations being evident in the AP group. Proteins expressed in the Complement and coagulation cascades were found to potentially mitigate blood coagulation. In conclusion, the administration of AP at a dosage of 180 mg/day may serve as a preventive measure against pneumonia in individuals exhibiting mild to moderate symptoms of COVID-19, not different from comparable to standard treatment protocols. These findings may diverge from prior research due to the inclusion of a vaccinated population and the overall lower severity of viral infections in our study cohort. Notably, the AP group demonstrated a higher proportion of patients with C-reactive protein (CRP) levels below 10 mg/ml
