Molnupiravir for treatment of adults with mild or moderate COVID-19: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The effects of molnupiravir in treating patients with non-severe COVID-19 remain uncertain. OBJECTIVES: To evaluate the efficacy and safety of molnupiravir in adult patients with mild or moderate COVID-19. DATA SOURCES: PubMed, Embase, CENTRAL, Web of Science, and WHO COVID-19 database up to 27 December 2022. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials with no language restrictions. PARTICIPANTS: Adults with mild or moderate COVID-19. INTERVENTIONS: Molnupiravir against standard care or placebo. ASSESSMENT OF RISK OF BIAS: We used a revision of RoB-2 criteria. METHODS OF DATA SYNTHESIS: Outcomes were mortality, hospital admission, viral clearance, time to viral clearance, time to symptom resolution or clinical improvement, any adverse events, and serious adverse events. We performed DerSimonian-Laird random-effects meta-analyses to summarize the evidence and evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Nine randomized controlled trials enrolling 30 472 patients proved eligible. Majority of patients were outpatients, with a mean age ranging from 35 to 56.6 years. In adult patients with mild or moderate COVID-19, molnupiravir probably reduces mortality (relative risk [RR], 0.43; 95% CI, 0.20-0.94; risk difference [RD], 0.1% fewer; moderate certainty) and the risk of hospital admission (RR, 0.67; 95% CI, 0.45-0.99; RD, 1.4% fewer; moderate certainty) and may reduce time to viral clearance (mean difference, -1.81 days; 95% CI, -3.31 to -0.31; low certainty) and time to symptom resolution or clinical improvement (mean difference, -2.39 days; 95% CI, -3.71 to -1.07; low certainty). Molnupiravir probably increases the rate of viral clearance (RR, 3.47; 95% CI, 2.43-4.96; RD 16.1% more; moderate certainty) at 7 days (±3 days) and likely does not increase serious adverse events (RR, 0.84; 95% CI, 0.61-1.15; RD 0.1% fewer; moderate certainty). CONCLUSIONS: In adult patients with mild or moderate COVID-19, molnupiravir likely reduces mortality and risk of hospital admission probably without increasing serious adverse events.

Effects of therapies for Ebola virus disease: a systematic review and network meta-analysis.

BACKGROUND: Specific treatments targeting Ebola virus are crucial in managing Ebola virus disease. To support the development of clinical practice guidelines on medications for Ebola virus disease, we aimed to evaluate the efficacy and safety of therapies for patients with Ebola virus disease. METHODS: In this systematic review and network meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, Global Health, African Index Medicus, World Health Organization Global Index Medicus, the Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, Epistemonikos, bioRxiv, medRxiv, and SSRN without language restrictions for randomised controlled trials (RCTs) published between database inception and Jan 1, 2022, comparing at least one therapeutic agent for Ebola virus disease against standard care or another therapeutic agent for Ebola virus disease. Two reviewers assessed study eligibility and extracted summary data independently using a standardised form. Our outcomes of interest were mortality, adverse maternal outcomes, risk of onward transmission, duration of admission to a health-care facility, functional status after Ebola virus disease, serious adverse events from medication, adverse perinatal outcomes, time to symptom resolution, and time to viral clearance. We did frequentist network meta-analyses to estimate the effect of all interventions and applied the Grading of Recommendations Assessment, Development and Evaluation approach to rate the certainty of the evidence. We registered the protocol with PROSPERO, CRD42022296539. FINDINGS: We identified 7840 records through database searches, of which two RCTs with a total of 753 patients proved eligible. Only data on mortality, the duration of admission, serious adverse events, and time to viral clearance were available for meta-analysis. Compared with standard care, REGN-EB3 (relative risk [RR] 0·40, 95% CI 0·18 to 0·89; moderate certainty) and mAb114 (0·42, 0·19 to 0·93; moderate certainty) probably reduce mortality. Whether ZMapp (0·60, 0·28 to 1·26; very low certainty) and remdesivir (0·64, 0·29 to 1·39; very low certainty) reduce mortality compared with standard care is uncertain. With high certainty, REGN-EB3 reduces mortality compared with ZMapp (0·67, 0·52 to 0·88) and remdesivir (0·63, 0·49 to 0·82). With high certainty, mAb114 also reduces mortality compared with ZMapp (0·71, 0·55 to 0·91) and remdesivir (0·66, 0·52 to 0·84). Compared with standard care, REGN-EB3, mAb114, ZMapp, and remdesivir might have little or no effect on the time to viral clearance (mean difference ranged from -0·25 days to -1·14 days; low certainty). ZMapp might reduce the duration of admission compared with standard care (mean difference -2·02 days, 95% CI -4·05 to 0·01; low certainty). Findings for all comparisons suggested that there might be little or no difference in the prevalence of serious adverse events, but certainty was low or very low in all comparisons but one. INTERPRETATION: REGN-EB3 and mAb114 separately reduce mortality compared with ZMapp, remdesivir, or standard care in patients with Ebola virus disease. These findings suggest that health-care workers should prioritise the use of REGN-EB3 and mAb114 for patients with Ebola virus disease during future outbreaks. FUNDING: WHO.

Micronutrient perspective on COVID-19: Umbrella review and reanalysis of meta-analyses.

INTRODUCTION: Micronutrients are clinically important in managing COVID-19, and numerous studies have been conducted, but inconsistent findings exist. OBJECTIVE: To explore the association between micronutrients and COVID-19. METHODS: PubMed, Web of Science, Embase, Cochrane Library and Scopus for study search on July 30, 2022 and October 15, 2022. Literature selection, data extraction and quality assessment were performed in a double-blinded, group discussion format. Meta-analysis with overlapping associations were reconsolidated using random effects models, and narrative evidence was performed in tabular presentations. RESULTS: 57 reviews and 57 latest original studies were included. 21 reviews and 53 original studies were of moderate to high quality. Vitamin D, vitamin B, zinc, selenium, and ferritin levels differed between patients and healthy people. Vitamin D and zinc deficiencies increased COVID-19 infection by 0.97-fold/0.39-fold and 1.53-fold. Vitamin D deficiency increased severity 0.86-fold, while low vitamin B and selenium levels reduced severity. Vitamin D and calcium deficiencies increased ICU admission by 1.09 and 4.09-fold. Vitamin D deficiency increased mechanical ventilation by 0.4-fold. Vitamin D, zinc, and calcium deficiencies increased COVID-19 mortality by 0.53-fold, 0.46-fold, and 5.99-fold, respectively. CONCLUSION: The associations between vitamin D, zinc, and calcium deficiencies and adverse evolution of COVID-19 were positive, while the association between vitamin C and COVID-19 was insignificant.REGISTRATION: PROSPERO CRD42022353953.

Prevalence of anxiety, depressive and insomnia symptoms among the different groups of people during COVID-19 pandemic: An overview of systematic reviews and meta-analyses

Since the pandemic of the novel 2019 coronavirus disease (COVID-19), in addition to the harm caused by the disease itself, the psychological damage caused to the public by the pandemic is also a serious problem. The aim of our study was to summarize the systematic reviews/meta-analyses (SRs/MAs) of the prevalence of anxiety, depression and insomnia in different populations during the COVID-19 pandemic and to qualitatively evaluate these SRs/MAs. We searched the Cochrane Library, PubMed and Web of Science to obtain SRs/MAs related to anxiety, depression, and insomnia in different populations during the COVID-19 pandemic. The main populations we studied were healthcare workers (HCWs), college students (CSs), COVID-19 patients (CPs), and the general populations (GPs). A subgroup analysis was performed of the prevalence of psychological disorders. A total of 42 SRs/MAs (8,200,330 participants) were included in calculating and assessing the prevalence of anxiety, depression, and insomnia in these populations. The results of subgroup analysis showed that the prevalence of anxiety in different populations were: HCWs (20–44%), CSs (24–41%), CPs (15–47%), and GPs (22–38%). The prevalence of depression were: HCWs (22–38%), CSs (22–52%), CPs (38–45%), and GPs (16–35%), statistically significant differences between subgroups (p < 0.05). The prevalence of insomnia were: HCWs (28–45%), CSs (27–33%), CPs (34–48%), and GPs (28–35%), statistically significant differences between subgroups (p < 0.05). The comparison revealed a higher prevalence of psychological disorders in the CP group, with insomnia being the most pronounced. The methodological quality of the included SRs/MAs was then evaluated using AMSTAR 2 tool. The results of the methodological quality evaluation showed that 13 SRs/MAs were rated “medium,” 13 were rated “low,” and 16 were rated “very low.” Through the subgroup analysis and evaluation of methodological quality, we found a higher prevalence of insomnia than anxiety and depression among the psychological disorders occurring in different populations during the pandemic, but the sample size on insomnia is small and more high-quality studies are needed to complement our findings.

Past, present and future of living systematic review: a bibliometrics analysis.

INTRODUCTION: In recent years, the concept of living systematic review (LSR) has attracted the attention of many scholars and institutions. A growing number of studies have been conducted based on LSR methodology, but their focus direction is unclear. The objective of this study was to provide a comprehensive review of existing LSR-related studies and to analyse their whole picture and future trends with bibliometrics. METHODS: A comprehensive search strategy was used to construct a representative dataset of LSRs up to October 2021. GraphPad V.8.2.1 and Mindmaster Pro presented the basic information of the included studies and the timeline of LSR development, respectively. The author and country cooperation network, hotspot distribution clustering, historical citation network and future development trend prediction related to LSR were visualised by VOSviewer V.1.6.16 and R-Studio V.1.4. RESULTS: A total of 213 studies were eventually included. The concept of LSR was first proposed in 2014, and the number of studies has proliferated since 2020. There was a closer collaboration between author teams and more frequent LSR research development and collaboration in Europe, North America and Australia. Numerous LSR studies have been published in high-impact journals. COVID-19 is the predominant disease of concern at this stage, and the rehabilitation of its patients and virological studies are possible directions of research in LSR for a long time to come. A review of existing studies found that more than half of the LSR series had not yet been updated and that the method needed to be more standardised in practice. CONCLUSION: Although LSR has a relatively short history, it has received much attention and currently has a high overall acceptance. The LSR methodology was further practised in COVID-19, and we look forward to seeing it applied in more areas.

Risk of incident diabetes after COVID-19 infection: A systematic review and meta-analysis.

BACKGROUND: COVID-19 might be a risk factor for various chronic diseases. However, the association between COVID-19 and the risk of incident diabetes remains unclear. We aimed to meta-analyze evidence on the relative risk of incident diabetes in patients with COVID-19. METHODS: In this systematic review and meta-analysis, the Embase, PubMed, CENTRAL, and Web of Science databases were searched from December 2019 to June 8, 2022. We included cohort studies that provided data on the number, proportion, or relative risk of diabetes after confirming the COVID-19 diagnosis. Two reviewers independently screened studies for eligibility, extracted data, and assessed risk of bias. We used a random-effects meta-analysis to pool the relative risk with corresponding 95 % confidence intervals. Prespecified subgroup and meta-regression analyses were conducted to explore the potential influencing factors. We converted the relative risk to the absolute risk difference to present the evidence. This study was registered in advance (PROSPERO CRD42022337841). MAIN FINDINGS: Ten articles involving 11 retrospective cohorts with a total of 47.1 million participants proved eligible. We found a 64 % greater risk (RR = 1.64, 95%CI: 1.51 to 1.79) of diabetes in patients with COVID-19 compared with non-COVID-19 controls, which could increase the number of diabetes events by 701 (558 more to 865 more) per 10,000 persons. We detected significant subgroup effects for type of diabetes and sex. Type 2 diabetes has a higher relative risk than type 1. Moreover, men may be at a higher risk of overall diabetes than women. Sensitivity analysis confirmed the robustness of the results. No evidence was found for publication bias. CONCLUSIONS: COVID-19 is strongly associated with the risk of incident diabetes, including both type 1 and type 2 diabetes. We should be aware of the risk of developing diabetes after COVID-19 and prepare for the associated health problems, given the large and growing number of people infected with COVID-19. However, the body of evidence still needs to be strengthened.

Artificial intelligence model on chest imaging to diagnose COVID-19 and other pneumonias: A systematic review and meta-analysis.

Objectives: When diagnosing Coronavirus disease 2019(COVID-19), radiologists cannot make an accurate judgments because the image characteristics of COVID-19 and other pneumonia are similar. As machine learning advances, artificial intelligence(AI) models show promise in diagnosing COVID-19 and other pneumonias. We performed a systematic review and meta-analysis to assess the diagnostic accuracy and methodological quality of the models. Methods: We searched PubMed, Cochrane Library, Web of Science, and Embase, preprints from medRxiv and bioRxiv to locate studies published before December 2021, with no language restrictions. And a quality assessment (QUADAS-2), Radiomics Quality Score (RQS) tools and CLAIM checklist were used to assess the quality of each study. We used random-effects models to calculate pooled sensitivity and specificity, I2 values to assess heterogeneity, and Deeks' test to assess publication bias. Results: We screened 32 studies from the 2001 retrieved articles for inclusion in the meta-analysis. We included 6737 participants in the test or validation group. The meta-analysis revealed that AI models based on chest imaging distinguishes COVID-19 from other pneumonias: pooled area under the curve (AUC) 0.96 (95 % CI, 0.94-0.98), sensitivity 0.92 (95 % CI, 0.88-0.94), pooled specificity 0.91 (95 % CI, 0.87-0.93). The average RQS score of 13 studies using radiomics was 7.8, accounting for 22 % of the total score. The 19 studies using deep learning methods had an average CLAIM score of 20, slightly less than half (48.24 %) the ideal score of 42.00. Conclusions: The AI model for chest imaging could well diagnose COVID-19 and other pneumonias. However, it has not been implemented as a clinical decision-making tool. Future researchers should pay more attention to the quality of research methodology and further improve the generalizability of the developed predictive models.

Evidence Mapping of 23 Systematic Reviews of Traditional Chinese Medicine Combined With Western Medicine Approaches for COVID-19

Background: Coronavirus disease 2019 (COVID-19) has already spread around the world. The modality of traditional Chinese medicine (TCM) combined with Western medicine (WM) approaches is being used to treat COVID-19 patients in China. Several systematic reviews (SRs) are available highlighting the efficacy and safety of TCM combined with WM approaches in COVID-19 patients. However, their evidence quality is not completely validated. Purpose: We aimed to assess the methodological quality and the risk of bias of the included SRs, assess the evidence quality of outcomes, and present their trends and gaps using the evidence mapping method. Methods: PubMed, Cochrane Library, Embase, CNKI, CBM, and Wanfang Data were searched from inception until March 2021 to identify SRs pertaining to the field of TCM combined with WM approaches for COVID-19. The methodological quality of the SRs was assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2), the risk of bias of the included SRs was assessed with the Risk of Bias in Systematic Review (ROBIS) tool, and the evidence quality of outcomes was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: In total, 23 SRs were found eligible. Twenty-one were rated of moderate confidence by AMSTAR 2, while 12 were rated at low risk using the ROBIS tool. In addition, most outcomes were graded as having moderate quality using the GRADE system. We found that the combined use of TCM and WM approaches could improve the CT recovery rate, effective rate, viral nucleic acid negative conversion rate, and the disappearance rate of fever, cough, and shortness of breath. Also, these approaches could decrease the conversion rate from mild to critical, white blood cell counts, and lymphocyte counts and shorten the time to viral assay conversion and the length of hospital stay. Conclusion: TCM combined with WM approaches had advantages in efficacy, laboratory, and clinical symptom outcomes of COVID-19, but the methodological deficiencies of SRs should be taken into consideration. Therefore, to better guide clinical practice in the future, the methodological quality of SRs should still be improved, and high-quality randomized controlled trials (RCTs) and observational studies should also be carried out.

Caution in underrepresentation of older adults in clinical trials on COVID-19 vaccines.

We read with great interest the article "Underrepresentation of older adults in clinical trials on COVID-19 vaccines: A systematic review" written by Nicola Veronese et al. This important work demonstrated that medications and vaccines commonly used in older adults have not been adequately evaluated. Concerning this systematic review, we shall like to mention some certain points deserved to be attended by the authors.

A Comparison of Lung Ultrasound and Computed Tomography in the Diagnosis of Patients with COVID-19: A Systematic Review and Meta-Analysis.

Background Lung ultrasound (LUS) and computed tomography (CT) can both be used for diagnosis of interstitial pneumonia caused by coronavirus disease 2019 (COVID-19), but the agreement between LUS and CT is unknown. Purpose to compare the agreement of LUS and CT in the diagnosis of interstitial pneumonia caused by COVID-19. Materials and Methods We searched PubMed, Cochrane library, Embase, Chinese Biomedicine Literature, and WHO COVID-19 databases to identify studies that compared LUS with CT in the diagnosis of interstitial pneumonia caused by COVID-19. We calculated the pooled overall, positive and negative percent agreements, diagnostic odds ratio (DOR) and the area under the standard receiver operating curve (SROC) for LUS in the diagnosis of COVID-19 compared with CT. Results We identified 1896 records, of which nine studies involving 531 patients were finally included. The pooled overall, positive and negative percentage agreements of LUS for the diagnosis of interstitial pneumonia caused by COVID-19 compared with CT were 81% (95% confidence interval [CI] 43-99%), 96% (95% CI, 80-99%, I2 = 92.15%) and 80% (95%CI, 60-92%, I2 = 92.85%), respectively. DOR was 37.41 (95% CI, 9.43-148.49, I2 = 63.9%), and the area under the SROC curve was 0.94 (95% CI, 0.92-0.96). The quality of evidence for both specificity and sensitivity was low because of heterogeneity and risk of bias. Conclusion The level of diagnostic agreement between LUS and CT in the diagnosis of interstitial pneumonia caused by COVID-19 is high. LUS can be therefore considered as an equally accurate alternative for CT in situations where molecular tests are not available.

Efficacy and Safety of Integrated Traditional Chinese and Western Medicine for Corona Virus Disease 2019 (COVID-19): a systematic review and meta-analysis.

Corona virus disease (COVID-19) has now spread to all parts of the world and almost all countries are battling against it. This study aimed to assess the efficacy and safety of Integrated Traditional Chinese and Western Medicine (Hereinafter referred to as "Integrated Medicine") to COVID-19. We searched six major Chinese and English databases to identify randomized controlled trials (RCTs) and case-control studies (CCSs) of Integrated Medicine on COVID-19. Two reviewers independently screened, identified studies, and extracted data. Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale were used to assess the quality of included RCTs and CCSs, respectively. Stata (version 13.0; StataCorp) was used to perform meta-analyses with the random-effects model. Risk ratio (RR) was used for dichotomous data while the weighted mean difference (WMD) was adopted for continuous variables as effect size, both of which were demonstrated in effect size and 95% confidence intervals (CI). A total of 11 studies were included. Four were RCTs and seven were CCSs. The sample size of including studies ranged from 42 to 200 (total 982). The traditional Chinese medicine included Chinese medicine compound drugs (QingFei TouXie FuZhengFang) and Chinese patent medicine (e.g. Shufeng Jiedu Capsule, Lianhua Qingwen granules). Compared with the control group, the overall response rate [RR = 1.230, 95%CI (1.113, 1.359), P = 0.000], cure rate [RR = 1.604, 95%CI (1.181, 2.177), P = 0.002], severity illness rate [RR = 0.350, 95%CI (0.154, 0.792), P = 0.012], and hospital stay [WMD = -1.991, 95%CI (-3.278, -0.703), P = 0.002] of the intervention group were better. In addition, Integrated Medicine can improve the disappearance rate of fever, cough, expectoration, fatigue, chest tightness and anorexia and reduce patients' fever, and fatigue time (P < 0.05). This review found that Integrated Medicine had better effects and did not increase adverse drug reactions for COVID-19. More high-quality RCTs are needed in the future.

Characteristics of systematic reviews evaluating treatments for COVID-19 registered in PROSPERO.

Characteristics and research collaboration of registered systematic reviews (SRs) on treatment modalities for coronavirus disease-2019 (COVID-19) remain unclear. This study analysed research collaboration, interventions and outcome measures in registered SRs on COVID-19 treatments and pointed out the relevant problems. PROSPERO (international prospective register of systematic reviews) was searched for SRs on COVID-19 treatments as of 2 June 2020. Excel 2016 was used for descriptive analyses of the extracted data. VOSviewer 1.6.14 software was used to generate network maps for collaborations between countries and institutions. A total of 189 SRs were included, which were registered by 301 institutions from 39 countries. China (69, 36.50%) exhibited the highest output. Cooperation between countries was not close enough. As an institution, the Chengdu University of Traditional Chinese Medicine (7, 3.70%) had the highest output. There was close cooperation between institutions. Interventions included antiviral therapy (81, 42.86%), respiratory support (16, 8.47%), circulatory support (11, 5.82%), plasma therapy for convalescent patients (11, 5.82%), immunotherapy (9, 4.76%), TCM (traditional Chinese medicine) treatment (9, 4.76%), rehabilitation treatment (5, 2.65%), anti-inflammatory treatment (16, 8.47%) and other treatments (31, 16.40%). Concerning antiviral therapy (81, 42.86%), the most commonly used antiviral agents were chloroquine/hydroxychloroquine (26, 13.76%), followed by remdesivir (12, 6.35%), lobinavir/ritonavir (11, 5.82%), favipiravir (5, 2.65%), ribavirin (5, 2.65%), interferon (5, 2.65%), abiron (4, 2.12%) and abidor (4, 2.12%). The most frequently used primary and secondary outcomes were the mortality rate (92, 48.68%) and hospital stay length (48, 25.40%), respectively. The expression of the outcomes was not standardised. Many COVID-19 SRs on treatment modalities have been registered, with a low completion rate. Although there was some collaboration between countries and institutions in the currently registered SRs on treatment modalities for COVID-19 on PROSPERO, cooperation between countries should be further enhanced. More attention should be directed towards identifying deficiencies of outcome measures, and the standardisation of results should be maximised.

Nervous system diseases are associated with the severity and mortality of patients with COVID-19: a systematic review and meta-analysis.

Coronavirus disease 2019 (COVID-19) has become a global pandemic. Previous studies showed that comorbidities in patients with COVID-19 are risk factors for adverse outcomes. This study aimed to clarify the association between nervous system diseases and severity or mortality in patients with COVID-19. We performed a systematic literature search of four electronic databases and included studies reporting the prevalence of nervous system diseases in COVID-19 patients with severe and non-severe disease or among survivors and non-survivors. The included studies were pooled into a meta-analysis to calculate the odds ratio (OR) with 95% confidence intervals (95%CI). We included 69 studies involving 17 879 patients. The nervous system diseases were associated with COVID-19 severity (OR = 3.19, 95%CI: 2.37 to 4.30, P < 0.001) and mortality (OR = 3.75, 95%CI: 2.68 to 5.25, P < 0.001). Specifically, compared with the patients without cerebrovascular disease, patients with cerebrovascular disease infected with COVID-19 had a higher risk of severity (OR = 3.10, 95%CI: 2.21 to 4.36, P < 0.001) and mortality (OR = 3.45, 95% CI: 2.46 to 4.84, P < 0.001). Stroke was associated with severe COVID-19 disease (OR = 1.95, 95%CI: 1.11 to 3.42, P = 0.020). No significant differences were found for the prevalence of epilepsy (OR = 1.00, 95%CI: 0.42 to 2.35, P = 0.994) and dementia (OR = 2.39, 95%CI: 0.55 to 10.48, P = 0.247) between non-severe and severe COVID-19 patients. There was no significant association between stroke (OR = 1.79, 95%CI: 0.76 to 4.23, P = 0.185), epilepsy (OR = 2.08, 95%CI: 0.08 to 50.91, P = 0.654) and COVID-19 mortality. In conclusion, nervous system diseases and cerebrovascular disease were associated with severity and mortality of patients with COVID-19. There might be confounding factors that influence the relationship between nervous system diseases and COVID-19 severity as well as mortality.

COVID-19 vaccine research focusses on safety, efficacy, immunoinformatics, and vaccine production and delivery: a bibliometric analysis based on VOSviewer.

Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has affected tens of millions of people globally since it was declared a pandemic by the World Health Organization (WHO) on March 11, 2020. There is an urgent need for safe and effective preventive vaccines to curb this pandemic. A growing amount of related research has been published. This study aimed to provide the current status of COVID-19 vaccine using bibliometric analysis. We searched Embase.com and MEDLINE comprehensively and included articles, articles in press, reviews, short surveys, conference abstracts and conference papers about COVID-19 vaccine. VOSviewer1.6.11 (Leiden University, Leiden, Netherlands) was applied to perform the bibliometric analysis of these papers. A total of 1,312 papers were finally included. The BMJ has been the most popular journal in this field. The United States maintained a top position worldwide and has provided a pivotal influence, followed by China, India and United Kingdom. Among all the institutions, Harvard University was regarded as a leader for research collaboration. We analyzed the keywords and identified seven COVID-19 vaccine research hotspot clusters. COVID-19 vaccine research hotspots focus on clinical trials on vaccine safety and efficacy, research on vaccine immunology and immunoinformatics, and vaccine hesitancy. Our analysis results demonstrated that cooperation between countries, institutions, and authors were insufficient. The results suggested that clinical trials on vaccine safety, efficacy, immunology, immunoinformatics, production and delivery are research hotspots. Furthermore, we can predict that there will be a lot of research focusing on vaccine adverse reactions.

Prevalence of delirium, depression, anxiety, and post-traumatic stress disorder among COVID-19 patients: protocol for a living systematic review.

BACKGROUND: Previous studies on the impact of corona virus disease 2019 (COVID-19) on the mental health of the patients has been limited by the lack of relevant data. With the rapid and sustained growth of the publications on COVID-19 research, we will perform a living systematic review (LSR) to provide comprehensive and continuously updated data to explore the prevalence of delirium, depression, anxiety, and post-traumatic stress disorder (PTSD) among COVID-19 patients. METHODS: We will perform a comprehensive search of the following databases: Cochrane Library, PubMed, Web of Science, EMBASE, and Chinese Biomedicine Literature to identify relevant studies. We will include peer-reviewed cross-sectional studies published in English and Chinese. Two reviewers will independently assess the methodological quality of included studies using the Joanna Briggs Institute Prevalence Critical Appraisal tool and perform data extraction. In the absence of clinical heterogeneity, the prevalence estimates with a 95% confidence interval (CI) of delirium, depression, anxiety, and post-traumatic stress disorder (PTSD) will be calculated by using random-effects model to minimize the effect of between-study heterogeneity separately. The literature searches will be updated every 3 months. We will perform meta-analysis if any new eligible studies or data are obtained. We will resubmit an updated review when there were relevant changes in the results, i.e., when outcomes became statistically significant (or not statistically significant anymore) or when heterogeneity became substantial (or not substantial anymore). DISCUSSION: This LSR will provide an in-depth and up-to-date summary of whether the common neuropsychiatric conditions observed in patients hospitalized for severe acute respiratory syndrome (SARS-CoV) and Middle East respiratory syndrome (MERS) are also prevalent in a different stage of COVID-19 patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020196610.

Research Collaboration and Outcome Measures of Interventional Clinical Trial Protocols for COVID-19 in China.

Background: Research collaboration of registered clinical trials for Coronavirus Disease 2019 (COVID-19) remains unclear. This study aimed to analyze research collaboration and distribution of outcome measures in registered interventional clinical trials (ICTs) of COVID-19 conducted in China. Methods: The International Clinical Trials Registry Platform, China Clinical Trials Registry, and Clinicaltrials.gov were searched to obtain COVID-19-registered ICTs up to May 25, 2020. Excel 2016 was used to perform a descriptive statistical analysis of the extracted information. VOSviewer 1.6.14 software was used to generate network maps for provinces and institutions and create density maps for outcomes. Results: A total of 390 ICTs were included, and the number of daily registrations fluctuated greatly. From 29 provinces in China, 430 institutions contributed to the registration of ICTs. The top three productive provinces were Hubei (160/390, 41.03%), Shanghai (60/390, 15.38%), and Beijing (59/390, 15.13%). The top three productive institutions were Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (30/390, 7.69%), Zhongnan Hospital of Wuhan University (18/390, 4.62%), and Wuhan Jinyintan Hospital (18/390, 4.62%). Collaborations between provinces and institutions were not close enough. There were many interventions, but many trials did not provide specific drugs and their dosage and treatment duration. The most frequently used primary outcome was Chest/lung CT (53/390, 13.59%), and the most frequently used secondary outcome was hospital stay (33/390, 8.46%). There was a large difference in the number of outcomes, the expression of some outcomes was not standardized, the measurement time and tools for some outcomes were not clear, and there was a lack of special outcomes for trials of traditional Chinese medicine. Conclusions: Although there were some collaborations between provinces and institutions of the current COVID-19 ICT protocols in China, cooperation between regions should be further strengthened. The identified deficiencies in interventions and outcome measures should be given more attention by future researchers of COVID-19.

Bibliometric Analysis on COVID-19: A Comparison of Research Between English and Chinese Studies.

Background: As an emerging infectious disease, COVID-19 has garnered great research interest. We aimed to explore the differences between English language and Chinese language Medical/Scientific journals publications, particularly aiming to explore the efficacy/contents of the literature published in English and Chinese in relation to the outcomes of management and characterization of COVID-19 during the early stage of COVID-19 pandemic. Methods: Publications on COVID-19 research were retrieved from both English and Chinese databases. Bibliometric analyses were performed using VOSviewer 1.6.14, and CiteSpace V software. Network maps were generated to evaluate the collaborations between different authors, countries/provinces, and institutions. Results: A total of 143 English and 721 Chinese original research articles and reviews on COVID-19 were included in our study. Most of the authors and institutions of the papers were from China before March 1st, 2020, however, the distribution of authors and institutions were mainly in developed countries or more wealthy areas of China. The range of the keywords in English publications was more extensive than those in Chinese. Traditional Chinese Medicine was seen more frequently in Chinese papers than in English. Of the 143 articles published in English, 54 articles were published by Chinese authors only and 21 articles were published jointly by Chinese and other overseas authors. Conclusions: The publications in English have enabled medical practitioners and scientists to share/exchange information, while on the other hand, the publications in the Chinese language have provided complementary educational approaches for the local medical practitioners to understand the essential and key information to manage COVID-19 in the relatively remote regions of China, for the general population with a general level of education.