Use of Andrographis paniculata (Burm.f.) Wall. ex Nees and risk of pneumonia in hospitalised patients with mild coronavirus disease 2019: A retrospective cohort study

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Abstract

Andrographis paniculata (Burm.f.) Wall. ex Nees (AP) has been widely used in Thailand to treat mild COVID-19 infections since early 2020; however, supporting evidence is scarce and ambiguous. Thus, this study aimed to examine whether the use of AP is associated with a decreased risk of pneumonia in hospitalised mild COVID-19 patients.

Materials and methods

We collected data between March 2020 and August 2021 from COVID-19 patients admitted to one hospital in Thailand. Patients whose infection was confirmed by real-time polymerase chain reaction, had normal chest radiography and did not receive favipiravir at admission were included and categorised as either AP (deriving from a dried and ground aerial part of the plant), given as capsules with a total daily dose of 180 mg andrographolide for 5 days or standard of care. They were followed for pneumonia confirmed by chest radiography. Multiple logistic regression was used for the analysis controlling for age, sex, diabetes, hypertension, statin use, and antihypertensive drug use.

Results

A total of 605 out of 1,054 patients (mostly unvaccinated) were included in the analysis. Of these, 59 patients (9.8%) developed pneumonia during the median follow-up of 7 days. The incidence rates of pneumonia were 13.93 (95% CI 10.09, 19.23) and 12.47 (95% CI 8.21, 18.94) per 1,000 person-days in the AP and standard of care groups, respectively. Compared to the standard of care group, the odds ratios of having pneumonia in the AP group were 1.24 (95% CI 0.71, 2.16; unadjusted model) and 1.42 (95% CI 0.79, 2.55; fully adjusted model). All sensitivity analyses were consistent with the main results.

Conclusion

The use of AP was not significantly associated with a decreased risk of pneumonia in mild COVID-19 patients. While waiting for insights from ongoing trials, AP’s use in COVID-19 should be done with caution.

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  1. SciScore for 10.1101/2022.01.01.22268609: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIACUC: The ethical committee for clinical research of Phrae hospital approved this study (no. 70/2564).
    Sex as a biological variableIn addition, we also excluded those who recently received AP prior to hospital admission, had a history of allergy to AP, had elevated liver enzyme, or were pregnant or breastfeeding from the analysis.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisTherefore, sample size calculation was unnecessary, and we planned to calculate statistical power afterwards.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All analyses were performed using STATA version 16.1MP
    STATA
    suggested: (Stata, RRID:SCR_012763)
    P (StataCorp LLC, College Station, Texas) and R version 3.3 with a two-sided alpha error of 5%.
    StataCorp
    suggested: (Stata, RRID:SCR_012763)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Strengths and limitations: To the best of our knowledge, this is the first cohort study of AP’s use in treating mild COVID-19. Admittedly, Thailand was confronted with the favipiravir and vaccine shortages at the beginning of the second wave of the pandemic crisis, leading to the unproven AP’s use for this condition. Consequently, a pharmacovigilance study is required since the real-world data from using AP has been already available so that its efficacy and safety can be clinically ensured. However, there are some limitations worth noticing. First, we cannot avoid residual confounders embedded in an observational study design. For instance, smoking status and mental disorders (e.g., depression) were suggested to be risk factors for developing severe COVID-19 (Centers for Disease Control and Prevention, 2021b, 2021a), and this can be prevalent in people in their 30s and 40s. In addition, patients receiving AP may have a higher risk of developing pneumonia than those who do not (i.e., confounding by indication). Therefore, the observed association might result from residual confounders instead, and the causality cannot be inferred. However, baseline characteristics between groups were mostly similar in terms of statistical (i.e., p-values) and nonstatistical (i.e., eyeballing) consideration. Furthermore, since our study populations were relatively young, many medical conditions that can increase the risk of severe COVID-19, such as cancer, chronic lung disease, and chronic kid...

    Results from TrialIdentifier: No clinical trial numbers were referenced.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.


    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.