Herbal Medicine Intervention for the Treatment of COVID-19: A Living Systematic Review and Cumulative Meta-Analysis.

Background: Integrative herbal medicine has been reported to have beneficial effects in the treatment of coronavirus disease 2019 (COVID-19). Aim: To compile up-to-date evidence of the benefits and risks of herbal medicine for the treatment of COVID-19 symptoms. Methods: Eleven databases, including PubMed, Cochrane Register of Controlled Trials (CENTRAL), Embase, Allied and Complementary Medicine Database (AMED), Chinese National Knowledge Infrastructure Database (CNKI), Wanfang Database, and Chinese Science and Technique Journals Database (VIP), Research Information Service System (RISS), Korean Medical database (KMBase), Korean Association of Medical Journal database (KoreaMed), and OASIS database, were searched from 15 June, 2020, until 28 March 2022. Randomized controlled trials (RCTs), published in any language, reporting the efficacy and safety outcomes of herbal medicine in patients of all ages with a PCR-confirmed diagnosis of COVID-19 were included in this analysis. Data extraction and quality assessments were performed independently. Results: Random-effects meta-analyses showed evidence of favorable effects of treatment with herbal medicine when added to standard treatment, versus standard treatment alone, on the total effective rate (p = 0.0001), time to remission from fever (p < 0.00001), rate of remission from coughing (p < 0.0001), fatigue (p = 0.02), sputum production (p = 0.004), improvement of manifestations observed on chest computed tomography scans (p < 0.00001), incidence of progression to severe COVID-19 (p = 0.003), all-cause mortality (p = 0.003), time to a negative COVID-19 coronavirus test (p < 0.0001), and duration of hospital stay (p = 0.0003). There was no evidence of a difference between herbal medicine added to standard treatment, versus standard treatment alone, on the rate of remission from symptoms such as a fever, sore throat, nasal congestion and discharge, diarrhea, dry throat, chills, and the rate of conversion to a negative COVID-19 coronavirus test. Meta-analysis showed no evidence of a significant difference in adverse events between the two groups. There was an unclear risk of bias across the RCTs included in this analysis, indicating that most studies had methodological limitations. Conclusion: Current evidence suggests that herbal medicine added to standard treatment has potential benefits in the treatment of COVID-19 symptoms but the certainty of evidence was low.

Association of frailty with outcomes in individuals with COVID-19: A living review and meta-analysis.

BACKGROUND AND OBJECTIVES: Frailty leaves older adults vulnerable to adverse health outcomes. Frailty assessment is recommended by multiple COVID-19 guidelines to inform care and resource allocation. We aimed to identify, describe, and synthesize studies reporting the association of frailty with outcomes (informed by the Institute for Healthcare Improvement's Triple Aim [health, resource use, and experience]) in individuals with COVID-19. DESIGN: Systematic review and meta-analysis. SETTING: Studies reporting associations between frailty and outcomes in the setting of COVID-19 diagnosis. PARTICIPANTS: Adults with COVID-19. MEASUREMENTS: Following review of titles, abstracts and full text, we included 52 studies that contained 118,373 participants with COVID-19. Risk of bias was assessed using the Quality in Prognostic studies tool. Our primary outcome was mortality, secondary outcomes included delirium, intensive care unit admission, need for ventilation and discharge location. Where appropriate, random-effects meta-analysis was used to pool adjusted and unadjusted effect measures by frailty instrument. RESULTS: The Clinical Frailty Scale (CFS) was the most used frailty instrument. Mortality was reported in 37 studies. After confounder adjustment, frailty identified using the CFS was significantly associated with mortality in COVID-19 positive patients (odds ratio 1.79, 95% confidence interval [CI] 1.49-2.14; hazard ratio 1.87, 95% CI 1.33-2.61). On an unadjusted basis, frailty identified using the CFS was significantly associated with increased odds of delirium and reduced odds of intensive care unit admission. Results were generally consistent using other frailty instruments. Patient-reported, cost and experience outcomes were rarely reported. CONCLUSION: Frailty is associated with a substantial increase in mortality risk in COVID-19 patients, even after adjustment. Delirium risk is also increased. Frailty assessment may help to guide prognosis and individualized care planning, but data relating frailty status to patient-reported outcomes are urgently needed to provide a more comprehensive overview of outcomes relevant to older adults.

The association of smoking status with SARS-CoV-2 infection, hospitalization and mortality from COVID-19: a living rapid evidence review with Bayesian meta-analyses (version 7).

AIMS: To estimate the association of smoking status with rates of (i) infection, (ii) hospitalization, (iii) disease severity and (iv) mortality from SARS-CoV-2/COVID-19 disease. DESIGN: Living rapid review of observational and experimental studies with random-effects hierarchical Bayesian meta-analyses. Published articles and pre-prints were identified via MEDLINE and medRxiv. SETTING: Community or hospital, no restrictions on location. PARTICIPANTS: Adults who received a SARS-CoV-2 test or a COVID-19 diagnosis. MEASUREMENTS: Outcomes were SARS-CoV-2 infection, hospitalization, disease severity and mortality stratified by smoking status. Study quality was assessed (i.e. 'good', 'fair' and 'poor'). FINDINGS: Version 7 (searches up to 25 August 2020) included 233 studies with 32 'good' and 'fair' quality studies included in meta-analyses. Fifty-seven studies (24.5%) reported current, former and never smoking status. Recorded smoking prevalence among people with COVID-19 was generally lower than national prevalence. Current compared with never smokers were at reduced risk of SARS-CoV-2 infection [relative risk (RR) = 0.74, 95% credible interval (CrI) = 0.58-0.93, τ = 0.41]. Data for former smokers were inconclusive (RR = 1.05, 95% CrI = 0.95-1.17, τ = 0.17), but favoured there being no important association (21% probability of RR ≥ 1.1). Former compared with never smokers were at somewhat increased risk of hospitalization (RR = 1.20, CrI = 1.03-1.44, τ = 0.17), greater disease severity (RR = 1.52, CrI = 1.13-2.07, τ = 0.29) and mortality (RR = 1.39, 95% CrI = 1.09-1.87, τ = 0.27). Data for current smokers were inconclusive (RR = 1.06, CrI = 0.82-1.35, τ = 0.27; RR = 1.25, CrI = 0.85-1.93, τ = 0.34; RR = 1.22, 95% CrI = 0.78-1.94, τ = 0.49, respectively), but favoured there being no important associations with hospitalization and mortality (35% and 70% probability of RR ≥ 1.1, respectively) and a small but important association with disease severity (79% probability of RR ≥ 1.1). CONCLUSIONS: Compared with never smokers, current smokers appear to be at reduced risk of SARS-CoV-2 infection, while former smokers appear to be at increased risk of hospitalization, increased disease severity and mortality from COVID-19. However, it is uncertain whether these associations are causal.

Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis.

BACKGROUND: Bacterial co-pathogens are commonly identified in viral respiratory infections and are important causes of morbidity and mortality. The prevalence of bacterial infection in patients infected with SARS-CoV-2 is not well understood. AIMS: To determine the prevalence of bacterial co-infection (at presentation) and secondary infection (after presentation) in patients with COVID-19. SOURCES: We performed a systematic search of MEDLINE, OVID Epub and EMBASE databases for English language literature from 2019 to April 16, 2020. Studies were included if they (a) evaluated patients with confirmed COVID-19 and (b) reported the prevalence of acute bacterial infection. CONTENT: Data were extracted by a single reviewer and cross-checked by a second reviewer. The main outcome was the proportion of COVID-19 patients with an acute bacterial infection. Any bacteria detected from non-respiratory-tract or non-bloodstream sources were excluded. Of 1308 studies screened, 24 were eligible and included in the rapid review representing 3338 patients with COVID-19 evaluated for acute bacterial infection. In the meta-analysis, bacterial co-infection (estimated on presentation) was identified in 3.5% of patients (95%CI 0.4-6.7%) and secondary bacterial infection in 14.3% of patients (95%CI 9.6-18.9%). The overall proportion of COVID-19 patients with bacterial infection was 6.9% (95%CI 4.3-9.5%). Bacterial infection was more common in critically ill patients (8.1%, 95%CI 2.3-13.8%). The majority of patients with COVID-19 received antibiotics (71.9%, 95%CI 56.1 to 87.7%). IMPLICATIONS: Bacterial co-infection is relatively infrequent in hospitalized patients with COVID-19. The majority of these patients may not require empirical antibacterial treatment.