A nationwide survey on the management of the COVID-19 pandemic and respiratory disease in South Korea.

Background: This study aimed to explore individual prevalence of respiratory symptoms and to describe the Korean population's treatment approaches, preventive health behaviors, and mental health conditions during the pandemic. Methods: We analyzed responses from an online nationwide survey, conducted between February 2021 to May 2021, about people's experiences during the pandemic. Statistical analysis was also performed to see if there were any significant differences in treatment and prevention strategies between different groups of respondents (between those had respiratory symptoms, compared with those who did not, and between those tested positive for COVID-19, compared with those who did not). Results: A total of 2,177 survey respondents completed the survey and, of these, only 142 had experienced symptoms. The most frequently reported respiratory infections related symptoms were runny or blocked nose (47.6%), cough (45.5%), fever (44.1%), sore throat (42.0%), and fatigue (30.1%). More than half of the respondents (53.1%) used complementary and alternative medicine (CAM) approaches as means of preventive measures. In terms of preventive behaviors, the more emphasized behaviors were mask-wearing (58.9%) and hand-washing after coming home (42.7%). The majority of the respondents (64.9%) did not show signs of mental health issues. Conclusion: In South Korea, conventional medicine was mainly used for COVID-19 treatment whereas CAM was commonly used as preventive measures. COVID-19 was also found to have less impact on the general population's mental health. The findings of this study may shed light on how the pandemic impacted the general population.

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.

Delayed generation of functional virus-specific circulating T follicular helper cells correlates with severe COVID-19 (preprint)

Effective humoral immune responses require well-orchestrated cellular interactions between B and T follicular helper (Tfh) cells. Whether this interaction is impaired and associated with COVID-19 disease severity is unknown. Here, longitudinal acute and convalescent blood samples from 49 COVID-19 patients across mild to severe disease were analysed. We found that during acute infection activated and SARS-CoV-2-specific circulating Tfh (cTfh) cell frequencies expanded with increasing disease severity. The frequency of activated and SARS-CoV-2-specific cTfh cells correlated with plasmablast frequencies and SARS-CoV-2 antibody titers, avidity and neutralization. Furthermore, cTfh cells but not other memory CD4 T cells, isolated from severe patients induced more pronounced differentiation of autologous plasmablast and antibody production in vitro compared to cTfh cells isolated from mild patients. However, the development of virus-specific cTfh cells was delayed in patients that displayed or later developed severe disease compared to those that maintained a mild or moderate disease. This correlated with a delayed induction of high-avidity and neutralizing virus-specific antibodies. Our study therefore suggests that impaired generation of functional virus-specific cTfh cells delays the production of high-quality antibodies to combat the infection at an early stage and thereby enabling progression to more severe COVID-19 disease.

Use of Traditional, Complementary and Integrative Medicine During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

Background: Traditional, Complementary and Integrative Medicine (TCIM) has been reported to use for symptom management of coronavirus disease 2019 (COVID-19). The objective of this review was to identify the overall usage prevalence of TCIM interventions for COVID-19. Methods: Surveys on the general population and observational studies on the COVID-19 patient chart review were located in the search of PubMed, EMBASE and Cochrane Central Register of Controlled Trials databases in September 2021. Observational studies, such as cross-sectional studies, surveys, cohort studies and hospital-based patient case reviews, published in any language, reporting the usage of TCIM in the patients with COVID-19 or the general population during the COVID-19 pandemic were included in this review. Data screening and extraction were performed independently by two reviewers. The reporting quality of the included studies was assessed with the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement. To conduct a meta-analysis of the usage prevalence of various TCIM interventions, the effect size of the proportion for each intervention was calculated with the inverse variance method. The main outcome was usage prevalence of TCIM interventions among patients with COVID-19 or the general population during the COVID-19 pandemic. Results: A total of 62 studies were included in this review. The overall TCIM usage prevalence was estimated to be 0.64 (95% CI 0.54-0.73). The overall prevalence did not differ between the population-based survey (0.65, 95% CI 0.48-0.81) and the hospital-based patient case review (0.63, 95% CI 0.52-0.73). Statistical heterogeneity and comparatively low quality in reporting were observed, which should be cautiously considered when interpreting the results. Conclusion: Various TCIM interventions were reported to be used with comparatively high frequency. Future international collaborative research might overcome the main limitation of this study, i.e., the heterogeneity of the included data. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278452, identifier: CRD42021278452.

Herbal medicine for COVID-19: An overview of systematic reviews and meta-analysis.

BACKGROUND: As coronavirus disease 2019 (COVID-19) continues to spread throughout countries, researchers and scientific groups have published a large number of scientific papers examining effective treatments and prevention strategies for COVID-19, including herbal medicine. It has become difficult to navigate the increasing volume of scientific material on the pandemic, and critical appraisal of these outcomes is needed. This overview of systematic reviews (SRs) aims to synthesize evidence from SRs and summarize the effects of herbal medicine interventions in the treatment of COVID-19. METHODS: Four databases were searched from inception up to October 20, 2021. SRs analyzing primary studies of the efficacy of herbal medications for treating COVID-19 were included. Two reviewers selected the studies and retrieved the data independently. The AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) was used to assess the methodological quality of the included SRs. RESULTS: A total of 21 SRs on herbal medicine treatments for COVID-19 were included. All SRs were published between May 2020 and September 2021. Thirteen of the SRs included only randomized controlled trials (RCTs), whereas the remaining eight included evidence from nonrandomized trials in addition to RCTs, with a significant overlap identified across the RCTs. Twelve SRs concluded that existing evidence was insufficient to form a definite judgment, nine found that herbal therapy was useful, and none indicated that herbal medicine had no benefit. The AMSTAR 2 tool revealed that the methodological quality of the included SRs was generally low. CONCLUSION: In this overview of SRs, we reviewed herbal medicine-related evidence from 21 SRs that were published after the outbreak of COVID-19. This study shows that while there is considerable evidence demonstrating the advantages of herbal medicine interventions, the quality of the evidence is inadequate to provide solid and accurate judgments about the effectiveness of herbal medicine therapies for COVID-19. Despite the crisis caused by the pandemic, clinical studies and SRs should comply with established methodological standards.

Complementary and alternative medicine (CAM) interventions for COVID-19: An overview of systematic reviews.

Background: Since the beginning of the Coronavirus disease 2019 (COVID-19) pandemic, various complementary and alternative medicines (CAMs) have been used in clinical practice. In this overview, we summarized the evidence for CAM interventions in the treatment of COVID-19 patients. Methods: For this overview, PubMed, Embase and Cochrane Library were searched from inception to October 2021. Systematic reviews (SRs) on the effectiveness and safety of CAM interventions for COVID-19 patients were located, and the MeaSurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) was used to evaluate the reporting quality of the included SRs. Keywords including COVID-19 and CAM interventions were used for locating SRs. For evidence mapping, we created a two-dimensional bubble plot that included the width and strength of the evidence for each CAM intervention and specific outcome. Results: In this overview, we identified 24 SRs (21 for Traditional Chinese Medicine (TCM) medications, two for vitamin D and one for home-based activity). From the included SRs, TCM herbal medications were reported to show good results in decreasing the rate of disease progression (relative risk (RR) 0.30, 95% confidence intervals (CI) [0.20, 0.44]), time to the resolution of fever (standard mean difference (SMD) -0.98, 95% CI [-1.78, -0.17]) and rate of progression to severe COVID-19 cases (RR 0.34, 95% CI [0.18, 0.65]), but the evidence for other interventions did not show effectiveness with certainty. Gastric disturbance was a major adverse event of TCM medications. Conclusion: There is evidence that TCM medications are effective in the symptom management of COVID-19 patients. However, evidence for the effectiveness of most CAM interventions still needs evaluation.

Randomized controlled trials of traditional, complementary, and integrative medicine-based interventions for coronavirus disease 2019 (COVID-19): A bibliometric analysis and review of study designs.

BACKGROUND: To date, the coronavirus disease 2019 (COVID-19) pandemic remains ongoing and continues to affect millions of people worldwide. In the effort of fighting this pandemic, there has been an increasing interest in the potential of traditional, complementary, and integrative medicines (TCIMs) in engaging COVID-19. This study presents a bibliometric analysis of the research trends of TCIMs for COVID-19. METHODS: Six databases were searched on July 15, 2021, to retrieve all the citations on TCIM-focused randomized controlled trials (RCTs) available on COVID-19. Only RCTs that mentioned at least one TCIMs for the treatment and/or management or COVID-19 were eligible. Data such as number and countries of trials conducted, publication journal, research focus, study design, and sample size were extracted for analysis. RESULTS: The resulting 56 articles were authored by 553 unique authors, and included 28 English articles, 19 Chinese articles with English abstracts, and 9 Chinese articles without English abstract. Analyses had shown that China was the dominant country with TCIM related RCT publications, followed by India and the United States. The included articles were published across 24 English journals and 22 Chinese journals with a wide range of impact factors from 0.220 to 56.272. The most commonly studied TCIM modalities included Chinese herbal decoction (n=12) and Chinese patent medicine (n=16). In terms of study designs, TCIM interventions were integrated with standard medicine across the trials with most trials having a small to medium sample size and open-labeled. CONCLUSION: This bibliometric analysis of RCTs demonstrated the research trends and characteristics of TCIM utilized in COVID-19 research. Although there are still many research gaps and limitations for pandemic research, the publication of TCIM-focused RCTs is anticipated to show a continuously increasing trend.

Network Analysis of Herbs Recommended for the Treatment of COVID-19.

PURPOSE: In this study, we aimed to identify the pattern and combination of herbs used in the formulae recommended for treating different stages of COVID-19 using a network analysis approach. METHODS: The herbal formulae recommended by official guidelines for the treatment of COVID-19 are included in the present analysis. To describe the tendency of herbs to form a "herb pair", we computed the mutual information (MI) value and distance-based mutual information model (DMIM) score. We also performed modularity, degree, betweenness, and closeness centrality analysis. Network analyses were performed and visualized for each disease stage. RESULTS: A total of 142 herbal formulae comprising 416 herbs were analyzed. All possible herbal pairs were examined, and the top frequently used herbal pairs were identified for each disease stage. The herb Glycyrrhizae radix et rhizoma is only identified in one herb pair, even though this herb is identified as one of the herbs with high frequency of use for every disease stage. This suggests that the DMIM score could be used to identify the optimal combination rule of herbal formulae by achieving a balance among the herbs' frequency and relative distance in herbal formulae. CONCLUSION: Our results presented the prescription patterns and herbal combinations of the herbal formulae recommended for the treatment of COVID-19. This study may provide new insights and ideas for clinical research in the future.

Heterologous vaccination strategy for containing COVID-19 pandemic (preprint)

An unequitable vaccine allocation and continuously emerging SARS-CoV-2 variants pose challenges to contain the pandemic, which underscores the need for licensing more vaccine candidates, increasing manufacturing capacity and implementing better immunization strategy. Here, we report data from a proof-of-concept investigation in two healthy individuals who received two doses of inactivated whole-virus COVID-19 vaccines, followed by a single heterologous boost vaccination after 7 months with an mRNA vaccine candidate (LPP-Spike-mRNA) developed by Stemirna Therapeutics. Following the boost, Spike-specific antibody (Ab), memory B cell and T cell responses were significantly increased. These findings indicate that a heterologous immunization strategy combining inactivated and mRNA vaccines can generate robust vaccine responses and therefore provide a rational and effective vaccination regimen.

Functional myeloid-derived suppressor cells expand in blood but not airways of COVID-19 patients and predict disease severity (preprint)

The immunopathology of COVID-19 remains enigmatic, exhibiting immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSC) are T cell suppressors that expand in inflammatory conditions, but their role in acute respiratory infections remains unclear. We studied blood and airways of COVID-19 patients across disease severity at multiple timepoints. M-MDSC frequencies were elevated in blood but not in nasopharyngeal or endotracheal aspirates of COVID-19 patients compared to controls. M-MDSCs isolated from COVID-19 patients suppressed T cell proliferation and IFN{gamma} production partly via an arginase-1 (Arg-1) dependent mechanism. Furthermore, patients showed increased Arg-1 and IL-6 plasma levels. COVID-19 patients had fewer T cells, and displayed downregulated expression of the CD3{zeta} chain. Ordinal regression showed that early M-MDSC frequency predicted subsequent disease severity. In conclusion, M-MDSCs expand in blood of COVID-19 patients, suppress T cells and strongly associate with disease severity, suggesting a role for M-MDSCs in the dysregulated COVID-19 immune response.

Herbal medicine for the management of COVID-19 during the medical observation period: A review of guidelines.

BACKGROUND: Medical observation period is a period of 14 days after any exposure to coronavirus disease 2019 (COVID-19) occurred. This review aimed to summarize and analyze the herbs and herbal formulae recommended by available guidelines. METHODS: A total of 14 sources were searched for potential guidelines that provide herbal medicine treatment for the medical observation period of COVID-19. We summarized and analyzed the recommended herbal formulae and performed a network analysis to identify the relationship between herbs. RESULTS: We found 9 guidelines that provide herbal formula for medical observation based on clinical manifestation. There are 12 herbal formulae with a total of 53 herbs recommended by the guidelines. The result of our network analysis showed that the herb Citri Reticulatae Pericarpium (Chen Pi) strongly paired with the herb Glycyrrhizae Radix et Rhizoma (Gan Cao). CONCLUSION: This review briefly summarized the usage of herbal medicine for the medical observation period of COVID-19 and may serve as a reference for future studies. More research is needed in the future to provide evidence on the usage of herbal medicine in various phases of COVID-10.

Herbal Medicine for the Treatment of Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused a worldwide outbreak of respiratory illness. This review aims to evaluate the effectiveness and adverse events of herbal medicines for the treatment of COVID-19. METHODS: Twelve databases were searched through 12 May 2020. Randomized controlled trials (RCTs) and quasi-RCTs assessing the effects of herbal medicines for the treatment of COVID-19 were eligible. The study selection and data extraction were performed by two independent reviewers. The Cochrane risk of bias tool was used for the assessment of the risk of bias in all included RCTs. Mean differences (MDs), risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and the effect sizes of the studies were pooled. RESULTS: Seven RCTs with a total of 855 patients were included. All included trials compared the combined therapy of herbal medicine with Western medicine to Western medicine alone. The combined therapy significantly improved the total effective rate (RR 1.23, 95% CI 1.13 to 1.34, p < 0.001), cough symptom disappearance rate (RR 1.45, 95% CI 1.12 to 1.89, p = 0.005), and sputum production symptom disappearance rate (RR 1.73, 95% CI 1.19 to 2.50, p = 0.004). Beneficial effects of the combined therapy were also seen in TCM syndrome score of cough (MD -1.18, 95% CI -1.34 to -1.03, p < 0.001), fever (MD -0.62, 95% CI -0.79 to -0.45, p < 0.001), dry and sore throat (MD -0.83, 95% CI -1.45 to -0.20, p = 0.009), and fatigue (MD -0.60, 95% CI -1.04 to -0.17, p = 0.007). The overall risk of bias of the included studies was unclear. No serious adverse events were reported. CONCLUSION: Significant effects of the combined therapy of herbal medicine with Western medicine were found, and revealed the potential role of herbal medicine in treating COVID-19. More high-quality RCTs are needed to further validate the effectiveness and adverse events of herbal medicine in the treatment of COVID-19.

Herbal medicine for treatment of children diagnosed with COVID-19: A review of guidelines.

This review aimed to summarize and analyze the pattern identification (PI), herbal formulae, and composition of herbs provided by recent guidelines for the treatment of pediatric COVID-19. Seven data sources were reviewed until March 25, 2020. We analyzed the herbal formulae included in the guidelines and performed a network analysis to identify the frequency of herbs recommended in the herbal formulae. All 3 guidelines were provincial guidelines from China. Our results showed that there were 4 stages, 12 PIs, and 13 herbal formulae recommended by the provincial guidelines. These herbal formulae included a total of 56 herbs. Based on our network analysis, Scutellariae Radix was paired with Artemisiae Annuae Herba in one cluster. In another cluster, Armeniacae Semen was paired with Coicis Semen and Ephedrae Herba was paired with Gypsum Fibrosum. This review serves as a reference for the use of traditional medicine in the treatment of pediatric COVID-19.

Herbal medicine and pattern identification for treating COVID-19: a rapid review of guidelines.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is pandemic and has caused illness to many people worldwide. This review aimed to summarize and analyze the herbal formulae provided by the guidelines for their pattern identifications (PIs) and compositions of herbs to treat patients with COVID-19. METHODS: We searched 7 data sources for eligible traditional medicine guidelines up to March 6, 2020 and found a total of 28 traditional medicine guidelines that provide treatment measures for COVID-19. RESULTS: Of the 28 guidelines, there were 26 government-issued Chinese guidelines and 2 Korean guidelines. After standardizing the terminology of the PIs and herbal formulae, there were 8 PIs and 23 herbal formulae for the mild stage, 11 PIs and 31 herbal formulae for the moderate stage, 8 PIs and 21 herbal formulae for the severe stage, and 6 PIs and 23 herbal formulae for the recovery stage in the Chinese guidelines. In the Korean guidelines, there were 4 PIs and 15 herbal formulae for the mild stage, 3 PIs and 3 herbal formulae for the severe stage, and 2 PIs and 2 herbal formulae for the recovery stage. In the frequency analysis of herbs, Glycyrrhizae Radix et Rhizoma was found to be the herb with the highest frequency of usage in the Chinese guidelines. CONCLUSION: This review can be used as guidance for the traditional medicine treatment of COVID-19. Clinical evidence is needed in the future to evaluate the efficacy of traditional medicine.