Abstract
Objective
Coronavirus disease 2019 (COVID-19) is still spreading worldwide. COVID-19 close contact is a key point of this epidemic. However, no medication is now available for close contact. This study aims to evaluate the beneficial effect and safety of the Lianhua Qingwen capsule (LHQW) on COVID-19 close contacts via a large, retrospective cohort study.
Methods
A total of 25,002 close contacts from 199 quarantine sites in Changchun, Jilin, who underwent medical observation, were included. The information about these close contacts were collected for further epidemiological research. Moreover, subjects were divided into an exposure group (LHQW group, oral, 4 capsules/time, t.i.d.; 18,579 subjects) and a non-exposure group (control group; 6,423 subjects). Inverse probability of treatment weighting (IPTW) with propensity score was employed to evaluate the positive rate of the SARS-CoV-2 nucleic acid test in nasal and throat swabs confirmed by polymerase chain reaction (PCR).
Results
A total of 22,975 subjects were included in the analysis, 17,286 cases in the LHQW group and 5,689 cases in the control group. The positive rate of nucleic acid testing in the LHQW group was 5.12%, and that in the control group was 9.70% before the adjustment of IPTW of the propensity score; the difference between the two groups was -4.58% (95% CI -5.44- -3.77%, p < 0.001). After adjusting IPTW, the positive rate of nucleic acid testing in the LHQW group and the control group was 5.10% and 9.80%, respectively; the difference between the two groups was -4.70% (95% CI -5.18- -4.23, p < 0.001). The conclusions before and after the IPTW adjustment were consistent. No test drug-related adverse reactions were observed during the study period.
Conclusion
LHQW has a beneficial effect and safety on the close contacts of SARS-CoV-2 who are under medical observation at the quarantine sites and can be used as an optional drug for those close contacts.
Keywords: Covid-19, Close contacts, Epidemiology, Positive rate, Lianhua Qingwen
Abbreviations: COVID-19, coronavirus disease 2019; CMH, Cochran-Mantel Haenszel test; CI, confidence interval; IQR, interquartile range; IPTW, inverse probability of treatment weighting; ICU, intensive care unit; LHQW, Lianhua Qingwen capsule; PCR, polymerase chain reaction; TCM, traditional Chinese medicine
Graphical abstract
Introduction
Since December 2019, coronavirus disease 2019 (COVID-19) has spread to more than 200 countries and regions worldwide, resulting in more than 600 million confirmed cases and 6.5 million confirmed deaths (World Health Organization, WHO, www.covid19.who.int). Over the years, several SARS-CoV-2 subtypes have emerged, including the Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529) variants. So far, several drugs and medications for COVID-19 have been presented; however, (World Health Organization guidance) (Forni and Mantovani, 2021). Moreover, many patients remain asymptomatic when carrying the virus, which significantly increases the difficulty of prevention and control of the COVID-19 epidemic.
Case tracing, isolation, quarantining, social distancing, and controlling personal hygiene are currently the most effective means to control the COVID-19 pandemic (Hussain et al., 2022; Wilder-Smith and Freedman, 2020). Close contact is an important node in the chain of transmission of COVID-19 (Hussain et al., 2022). A study involving 49,623 close contacts showed 4006 infections based on positive PCR test results (Denford et al., 2022). Therefore, isolation of close contacts of positive cases and regular nucleic acid testing during the isolation period can help with the timely detection of secondary cases, especially those without obvious clinical manifestations. However, no current treatment strategies are available for close contacts. Also, whether medication may help decrease the risk of potential COVID-19 infection and reduce the burden of the medical resource remains unclear.
Lianhua Qingwen Capsules (LHQW) is a traditional Chinese medicine (TCM) initially designed for treating influenza infection. It was patented in 2003 in China and was approved for Phase II clinical trial by US FDA in 2015 (Huang et al., 2021). During the COVID-19 epidemic, LHQW has been recommended for patients in medical observation and early stage of infection, with fatigue and fever as the primary clinical manifestations (Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia). According to recent studies, LHQW showed definite therapeutic effects in treating COVID-19 patients of mild and common types (Gravagnuolo et al., 2021; Hu et al., 2021). However, the effect of LHQW on close contact with COVID-19 patients has not been well investigated.
In this study, we evaluated the beneficial effect and safety of LHQW on close contacts via a large, retrospective cohort study. These results may provide new prevention and control options for close contacts of COVID-19 and curtail the transmission of the epidemic.
Methods
Data and study design
Information on 25,002 centralized medical isolated close contacts from 199 isolation places during the outbreak of COVID-19 in Changchun, Jilin Province, were collected from March 2022 to May 2022. The information included participant's name, age, gender, name of isolation place, date of starting isolation, date of ending isolation, close contact status/isolation reasons, date of starting taking LHQW, and date of ending of taking LHQW.
Subjects were then divided into an exposure group (LHQW group) and a non-exposure group (control group). All the participants in the LHQW group were given only LHQW capsules (4 capsules per time, 3 times a day) until the nucleic acid test was positive or the isolation was terminated; the longest time taking medication was 14 days. The participants of the control group were given no treatment. Both groups were under quarantine measures for the common population at the isolation points published by the National Health Commission and the local health departments. The study compared the two groups' positive conversion rates of nucleic acid.
Inclusion criteria were patients who required centralized medical isolation after the epidemiological investigation of the novel coronavirus pneumonia. The main groups of people to be quarantined included close contacts and secondary contacts based on the Diagnosis and Treatment Program for Novel Coronavirus Infection Pneumonia (Trial Ninth Edition) released by the National Health Commission of China.
The ethical approval of this study was approved by the Ethics Committee of Medicine of Jilin province people's hospital (ID: 2,022,025). The study has been registered in the Chinese Clinical Trial Registry (ChiCTR2200063524). Additionally, all personal identifying information was anonymized to ensure the contacts' privacy.
Definition of outcome indicators
Primary outcomes were nucleic acid test positive rate of nasal and throat swabs during the isolation medical observation period confirmed by PCR. LHQW is now widely used in patients with influenza and COVID-19 with a good safety profile for nearly 20 years. However, considering the current epidemic prevention and control measures for isolated persons, the main analysis of safety outcomes was based on adverse events during the medication.
Statistical analysis
Descriptive statistical methods were adopted to analyze continuous variables and categorical variables. We fitted parametric (Weibull, gamma, and log-normal) and nonparametric (kernel density) distributions to the time from isolation to case confirmed diagnosis, and time from taking LHQW to confirmed diagnosis, and isolation end. Model fitness was visually examined by comparing a fitted density curve to the observed frequencies, and, when necessary, parametric distributions were compared using the Akaike information criterion. In addition, we used inverse probability of treatment weighting (IPTW) with propensity score, a propensity score weighting method that mimics matching analysis, to eliminate bias. This method allows the use of all available data and does not require a specified matching algorithm. The propensity score model uses age and gender as covariates. After inverse probability weighting, we used a logistic regression model to calculate the OR and its 95% CI of the positive rate of nucleic acid testing in the LHQW group and control group. Afterward, the Cochran-Mantel-Haenszel (CMH) chi-square test was used for the difference in nucleic acid positive rate between groups, considering the bias of the isolation point effect. Moreover, Newcombe–Wilson test was used to evaluate the D-value of nucleic acid positive rate between the LHQW and the control groups and its 95% confidence interval. Subgroup analysis was conducted by age (≤65 years, >65 years) and gender (male and female) to further elucidate the effect of LHQW on the positive rate of nucleic acid test in different subgroups of the population.
SAS, version 9.4 (SAS Institute, USA) and R, version 3.6.0 (R Project for Statistical Computing) were used for data management and analysis. All statistical tests were two-tailed with a significance level of p < 0.05.
Results
Demographic characteristics
A total of 25,002 close contacts in 199 isolated sites were reported from March 2022 to May 2022, and 22,975 (91.9%) contacts were enrolled for the final analysis (Fig. 1 ). Among these, 14,026 (56.1%) contacts were male, and the overall male-to-female ratio was 1.28:1. The vast majority (31.3%) of contacts were adults (aged 30–44 years old), with a median age of 37 years [interquartile range (IQR), 25–51years]. In detail, we analyzed the age and sex of the close contacts by the laboratory result.
Fig. 1.
Study flowchart.
A total of 1595/22,975 (6.9%) of close contacts were confirmed with COVID-19. The proportion of males in the positive group was lower than that in the negative group (55.8% vs. 56.1%), although the difference was not statistically significant (p = 0.823). In addition, the median age of positive contacts [43, IQR: (29–55)] was higher compared to those with negative PCR results [37, IQR: (25–51)]; a total of 32.8% of positive contacts were 45–59 years old, while 7.7% were younger than 15 years. Correspondingly, the highest number of negative contacts was seen in the 30–44 years group (31.6%), followed by the 15–29 years group (27.5%) and the 45–59 years group (25.8%) (Table 1 ).
Table 1.
Characteristics of COVID-19 contacts confirmed in Jilin province, China, between March 2022 and May 2022.
| Characteristics | All (N = 25,002) | Positive group (n = 1595, 6.4%) | Negative group (n = 23,407, 93.6%) |
P-value |
|---|---|---|---|---|
| Sex | ||||
| Male | 14,026 (56.1) | 890 (55.8) | 13,136 (56.1) | 0.823 |
| Female | 10,976 (43.9) | 705 (44.2) | 10,271 (43.9) | |
| Age, median (IQR), y | 37 (25–51) | 43 (29–54) | 37 (25–51) | <0.001 |
| Age group, y | <0.001 | |||
| 0–14 | 1389 (5.6) | 123 (7.7) | 1266 (5.4) | |
| 15–29 | 6615 (26.5) | 285 (17.9) | 6330 (27.0) | |
| 30–44 | 7832 (31.3) | 437 (27.4) | 7395 (31.6) | |
| 45–59 | 6571 (26.3) | 523 (32.8) | 6048 (25.8) | |
| ≥60 | 2595 (10.4) | 227 (14.2) | 2368 (10.1) | |
| Received LHQW | 18,579 (74.3) | 956 (59.9) | 17,623 (75.3) | <0.001 |
We also found that the proportion of subjects who received LHQW in the positive group was lower than in the negative group (59.9% vs. 75.4%, p<0.001). In addition, we divided the close contacts into two groups based on whether they took LHQW, and we found that the LHQW group included 17,286 cases with a median age of 41years (IQR: 18–92), among which 9772 cases (56.5%) were males and7,514 cases (43.5%) were females; the control group included 5689 cases with a median age of 40 years (IQR: 18–95), among which 3279 cases (57.6%) were males and 2410 cases (42.4%) were females.
The time interval from isolation to different event nodes
The time interval from isolation to positive confirmation was 3 days (IQR:1–6 days); however, the time interval from isolation to the positive transfer of contacts was 7 days (IQR: 3–11 days). Subsequently, the contacts were transferred to the designated hospitals for treatment. In addition, the median isolation time interval of negative contacts was 12 days (IQR: 7–14 days), and the time interval was 7 days (IQR: 4–10 days) from receiving LHQW to the end of isolation. Moreover, we found that the median time interval from isolation to receiving the first LHQW dose was 0 days (IQR: 0–1 days) in the positive group, and the time interval from receiving LHQW to positive confirmation was 2 days (IQR: 1–4 days) (Fig. 2 ).
Fig. 2.
The time intervals from isolation to different events points.
Analysis of the positive rate of nucleic acid testing before and after IPTW of the propensity score
IPTW with propensity score was used to balance the differences in age and gender between groups, with standardized differences all < 0.05 and variance ratios close to 1. The difference between the LHQW group and the control group was −4.58% (95% CI −5.44- −3.77%), and the difference was statistically significant (p < 0.001) before the IPTW adjustment of the propensity score. After the adjustment of IPTW, the positive rate of nucleic acid testing in the LHQW group was 5.10%, and that in the control group was 9.80%. The difference between the two groups was −4.70% (95% CI −5.18- −4.23). The difference between the two groups was still statistically significant (p < 0.001) (Table 2 ). The balance evaluation of IPTW is shown in the Supplementary file.
Table 2.
Comparison of nucleic acid test positive rates before and after inverse probability processing weighting (IPTW) of propensity scores.
| IPTW crude | IPTW adjusted | |||
|---|---|---|---|---|
| LHQW group (N = 17,286) | Control group (N = 5689) | LHQW group (N = 22,974.8) | Control group (N = 22,976.6) | |
| The positive nucleic acid test, N (%) | 885 (5.12%) | 552 (9.70%) | 1171.89 (5.10%) | 2252.57 (9.80%) |
| p-value [1] | <0.001 | <0.001 | ||
| The difference in the positivity of nucleic acid tests (95% CI) [2] | −4.58 (−5.44, −3.77) | −4.70 (−5.18, −4.23) | ||
| OR (95% CI) [3] | 0.502 (0.449, 0.561) | 0.495 (0.460, 0.532) | ||
The Cochran-Mantel-Haenszel test was used to compare differences between groups.
The Newcombe-Wilson method was used to calculate the difference between the positive nucleic acid test rate of the LHQW group and the control group and its 95% CI.
The logistic regression model was used to calculate the OR and its 95% CI for the positive rate of nucleic acid testing in the test and control groups.
Analysis of the positive rate of nucleic acid test for different subgroups
Before IPTW adjustment for age, the positive nucleic acid test rate in the male subgroup was 5.21% in the LHQW group and 9.36% in the control group (p < 0.001), while in the female subgroup, the positive nucleic acid test rate was 5.00% and 10.17%, respectively (p < 0.001). After adjusting IPTW, the positive nucleic acid test rate in the male subgroup was 5.19% in the LHQW group and 9.46% in the control group (p < 0.001); in the female subgroup, the positive nucleic acid test rate was 4.99% and 10.25%, respectively (p < 0.001). The findings were consistent across gender before and after IPTW adjustment, with lower positive rates of nucleic acid test found in the LHQW group compared to the control group. Similarly, after IPTW adjustment for gender, the results for different ages were all lower in the LHQW group than in the control group for the positive rate of nucleic acid test before and after IPTW adjustment (Fig. 3 ).
Fig. 3.
Positive rate of nucleic acid test in different subgroups.
Discussion
The breakout of COVID-19 and the subsequent spread of the pandemic, which have been ongoing since 2019, severely affected the global economy and financial markets and led to a public health crisis. According to recent statistical results provided by a Harvard research team, humanity is expected to coexist with the SARS-CoV-2 virus for the next 5 years (Kissler et al., 2020). Although most COVID-19 patients are mild or common types, 5–10% are likely to develop severe and critical illness courses (Gavriatopoulou et al., 2021). The approximate mortality rate from COVID-19 is 1%, which inevitably poses a substantial challenge to medical systems, especially the intensive care unit (ICU) capacity. Since the beginning of the epidemic, the global scientific community has made a rapid and robust response to uncover the clinical features and pathological process of COVID-19, including typical manifestations and multisystem inflammatory syndromes (Hu et al., 2021; Huang and Li, 2022; Wiersinga et al., 2020). Yet, there are still no effective methods to treat COVID-19, i.e.,
The vaccine is the most effective method to prevent infectious diseases. A recent study summarized the efficacy/effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 Alpha and Beta infections, with 80–90% efficacy in both symptomatic and asymptomatic individuals (Harder et al., 2021). However, the protective effect of vaccines showed a significant decrease due to the enhanced immune escape ability of the Omicron variant (Andrews et al., 2022). Thus, considering the recent resurge of COVID-19 caused by the spread of the Omicron variant, validated methods and medicines for close contact with symptomatic and asymptomatic individuals are urgently needed. Our study indicated that 6.4% of contacts were confirmed with COVID-19 infection; therefore, good screening and isolating strategies for close contacts are important to control the transmission of the epidemic. In China, the management measure of “seven days of centralized isolated medical observation plus three days of home health surveillance” was required for close contacts before November 12, 2022. After November 12, 2022, the management measure for close contacts in China has been adjusted from “7+3″ to “5+3″; this adjustment of this measure is consistent with our study results. Our study found that the median time interval from isolation to confirmation for contacts was only 3 days. The adjustment of measures can greatly reduce the input of human, material, and financial resources. In addition, the median age of the confirmed contacts was 43 years (IQR: 29–54 years), which indicates that contacts at this age should be properly monitored.
Chinese studies have shown that TCM treatment combined with western medicines has an encouraging therapeutic effect on COVID-19 patients (Huang et al., 2021; Ni et al., 2020; Shah et al., 2022; Zhu et al., 2022). The main principle of TCM theory in treating infectious diseases is strengthening the body's resistance to eliminate pathogenic factors. However, except for the pointed effect on confirmed patients with overt clinical signs, we still lack large-scale evidence for the effectiveness of TCM in asymptomatic individuals, especially close contacts. LHQW, formulated as a recipe of herbal extracts, is recommended as a COVID-19 treatment option by the National Health Commission & State Administration of Traditional Chinese Medicine in China. Four ingredients of LHQW, including emodin, forsythiaside A, forsythiaside I, and neochlorogenic acid, block the interaction of spike protein and ACE2 by embedding into the SARS-ACE2 complex and thus prohibiting the invasion of the virus (Chen et al., 2021). A recent study suggested that LHQW is effective for mild and common types of COVID-19 patients and can reduce the mortality of severe cases (Hu et al., 2021). However, only a few studies have reported on the effect of LHQW in close contact. A previous prospective trial found that the positive rate of SARS-CoV-2 in the LHQW treatment group was significantly lower than that in a non-LHQW group. However, limitations such as small research dimensions and low incidence of positivity (13 in a total of 1976 subjects) suggested that further studies on a larger scale are necessary to validate LHQW as an effective and safe option for COVID-19 close contacts (Gong et al., 2021). Therefore, we performed this large-scale study to further validate the effect of LHQW. The results indicate the significant effect of LHQW on decreasing the positive rate of COVID-19 among close contacts (5.10% vs. 9.80%).
The present study has some limitations. First, this is a retrospective clinical study in isolation points; some information, such as the outcome of positive cases, were not collected. Second, factors that may influence the results, such as the vaccination rate, underlying diseases, and environmental changes in different quarantine sites, were not analyzed. Third, all the subjects were from Jilin province, China. Fourth, due to the large scale of participants and the policy of close contact isolation, the types of variables analyzed are small. Finally, the effect of LHQW on other ethnic groups needs further verification.
To sum up, 6.9% of contacts in Changchun, Jilin Province, China, were confirmed with COVID-19 between March 2022 to May 2022, and the proportion of positive contacts was especially high for those between adults (45 and 59 years old). The median time interval from isolation to positive confirmation was 3 days. In addition, LHQW treatment decreased the positive rate of COVID-19 among close contacts. Considering current spread of COVID-19 epidemic and the importance of close contact in the chain of transmission, appropriate treatment and medication for close contact could predictably reduce the risk of disease development and the gloom of the pandemic. Our study first suggests that LHQW may provide a potential option for treating close contacts affected by COVID-19.
Patient consent for publication
Not applicable.
CRediT authorship contribution statement
Yunfeng Qiao: Methodology, Data curation, Resources, Writing – original draft. Xiaolong Xu: Formal analysis, Investigation, Methodology, Software, Writing – original draft, Writing – review & editing. Fangfang Zhou: Data curation, Formal analysis, Software, Validation, Visualization. Ke Wang: Data curation, Investigation, Resources. Mingxian Li: Data curation, Investigation, Resources. Chaoying Liu: Data curation, Investigation, Resources. Zhiying Chen: Data curation, Investigation. Ping Yin: Data curation, Formal analysis, Software. Yifan Shi: Data curation, Formal analysis, Software. Yongjie Wang: Conceptualization, Investigation, Supervision, Project administration. Qingquan Liu: Conceptualization, Funding acquisition, Investigation, Project administration, Resources, Supervision, Validation.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
Funding
This work was funded by the National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine (No. ZYYCXTD-D-202201) and the National Key Research and Development Plan of China (No. 2021YFC1712901).
Acknowledgements
We thank Shijiazhuang Yiling Pharmaceutical Co., Ltd. (Shijiazhuang, People's Republic of China) for their provision of the LHQW capsules.
Footnotes
Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.phymed.2023.154690.
Appendix. Supplementary materials
References
- Andrews N., Stowe J., Kirsebom F., Toffa S., Rickeard T., Gallagher E., Gower C., Kall M., Groves N., O'Connell A.M., Simons D., Blomquist P.B., Zaidi A., Nash S., Iwani B.A.A.N., Thelwall S., Dabrera G., Myers R., Amirthalingam G., Gharbia S., Barrett J.C., Elson R., Ladhani S.N., Ferguson N., Zambon M., Campbell C., Brown K., Hopkins S., Chand M., Ramsay M., Lopez B.J. Covid-19 Vaccine effectiveness against the omicron (B.1.1.529) Variant. N Engl J Med. 2022;386:1532–1546. doi: 10.1056/NEJMoa2119451. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen X., Wu Y., Chen C., Gu Y., Zhu C., Wang S., Chen J., Zhang L., Lv L., Zhang G., Yuan Y., Chai Y., Zhu M., Wu C. Identifying potential anti-COVID-19 pharmacological components of traditional Chinese medicine Lianhuaqingwen capsule based on human exposure and ACE2 biochromatography screening. Acta Pharm. Sin. B. 2021;11:222–236. doi: 10.1016/j.apsb.2020.10.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Denford S., Martin A.F., Towler L., Mowbray F., Essery R., Bloomer R., Ready D., Love N., Amlot R., Oliver I., Rubin G.J., Yardley L. A qualitative process analysis of daily contact testing as an alternative to self-isolation following close contact with a confirmed carrier of SARS-CoV-2. BMC Public Health. 2022;22:1373. doi: 10.1186/s12889-022-13800-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Forni G., Mantovani A. COVID-19 vaccines: where we stand and challenges ahead. Cell Death Differ. 2021;28:626–639. doi: 10.1038/s41418-020-00720-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gavriatopoulou M., Ntanasis-Stathopoulos I., Korompoki E., Fotiou D., Migkou M., Tzanninis I.G., Psaltopoulou T., Kastritis E., Terpos E., Dimopoulos M.A. Emerging treatment strategies for COVID-19 infection. Clin. Exp. Med. 2021;21:167–179. doi: 10.1007/s10238-020-00671-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gong X., Yuan B., Yuan Y., Li F. Efficacy and safety of lianhuaqingwen capsules for the prevention of Coronavirus Disease 2019: a prospective open-label controlled trial. Evid. Based Complement. Alternat. Med. 2021;2021 doi: 10.1155/2021/7962630. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gravagnuolo A.M., Faqih L., Cronshaw C., Wynn J., Klapper P., Wigglesworth M. High throughput diagnostics and dynamic risk assessment of SARS-CoV-2 variants of concern. EBioMedicine. 2021;70 doi: 10.1016/j.ebiom.2021.103540. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harder T., Koch J., Vygen-Bonnet S., Kulper-Schiek W., Pilic A., Reda S., Scholz S., Wichmann O. Efficacy and effectiveness of COVID-19 vaccines against SARS-CoV-2 infection: interim results of a living systematic review, 1 January to 14 May 2021. Euro Surveill. 2021;26 doi: 10.2807/1560-7917.ES.2021.26.28.2100563. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hu B., Huang S., Yin L. The cytokine storm and COVID-19. J. Med. Virol. 2021;93:250–256. doi: 10.1002/jmv.26232. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huang K., Zhang P., Zhang Z., Youn J.Y., Wang C., Zhang H., Cai H. Traditional Chinese Medicine (TCM) in the treatment of COVID-19 and other viral infections: efficacies and mechanisms. Pharmacol. Ther. 2021;225 doi: 10.1016/j.pharmthera.2021.107843. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huang N., Li S. High-quality trials and pharmacological studies needed as translational evidence for the application of traditional Chinese medicine Lianhua Qingwen against COVID-19. Phytother. Res. 2022;36:4295–4298. doi: 10.1002/ptr.7574. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hussain T., Jawed N., Mughal S., Shafique K. Public perception of isolation, quarantine, social distancing and community containment during COVID-19 pandemic. BMC Public Health. 2022;22:528. doi: 10.1186/s12889-022-12970-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kissler S.M., Tedijanto C., Goldstein E., Grad Y.H., Lipsitch M. Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period. Science. 2020;368:860–868. doi: 10.1126/science.abb5793. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ni L., Chen L., Huang X., Han C., Xu J., Zhang H., Luan X., Zhao Y., Xu J., Yuan W., Chen H. Combating COVID-19 with integrated traditional Chinese and Western medicine in China. Acta Pharm. Sin. B. 2020;10:1149–1162. doi: 10.1016/j.apsb.2020.06.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shah M.R., Fatima S., Khan S.N., Ullah S., Himani G., Wan K., Lin T., Lau J., Liu Q., Lam D. Jinhua Qinggan granules for non-hospitalized COVID-19 patients: a double-blind, placebo-controlled, and randomized controlled trial. Front. Med. (Lausanne) 2022;9 doi: 10.3389/fmed.2022.928468. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wiersinga W.J., Rhodes A., Cheng A.C., Peacock S.J., Prescott H.C. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020;324:782–793. doi: 10.1001/jama.2020.12839. [DOI] [PubMed] [Google Scholar]
- Wilder-Smith A., Freedman D.O. Isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus (2019-nCoV) outbreak. J. Travel Med. 2020;27:taaa020. doi: 10.1093/jtm/taaa020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhu H., Li M., Tian C., Lai H., Zhang Y., Shi J., Shi N., Zhao H., Yang K., Shang H., Sun X., Liu J., Ge L., Huang L. Efficacy and safety of chinese herbal medicine for treating mild or moderate COVID-19: a systematic review and meta-analysis of randomized controlled trials and observational studies. Front. Pharmacol. 2022;13 doi: 10.3389/fphar.2022.988237. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.