Epidemiological Characteristics of COVID-19 Deaths In China: An Analysis of Environmental Factors (preprint)

Background: As of April 2020, most of the confirmed cases outside Hubei province have been cured or confirmed dead in China. We aimed to understand environmental factors leading to COVID-19-related mortality in non-Hubei region. Methods: : We collected spatial-temporal and environmental data of 99 cases of COVID-19-related deaths outside of Hubei province in Mainland China between January 22, 2020 and April 6, 2020. A descriptive analysis, including a spatial-temporal distribution of daily reported diagnosed cases and related deaths, was conducted. We analyzed the possible environmental factors that affect the provincial-level case fatality rate (CFR) of COVID-19 outside Hubei, China. Results: Among the 99 reported deaths, 59 (59.6%) were male and 40 (40.4%) were female. The mean age at death was 71.30 (SD 12.98) years and 74 deaths were among those 65 years or older. The CFR was negatively correlated with temperature (r=-0.679, P <0.001) and humidity (r=-0.607, P =0.002), while latitude was positively correlated with the CFR (r=0.636, P =0.001). There were no statistically significant associations between CFR and the social environment factors. Conclusion: Higher CFR of COVID-19 was associated with lower temperature, lower humidity, and higher latitude. Continual analysis of daily reported diagnoses and mortality data can help healthcare professionals and policy makers understand the trends within a country in order to better prepare nationwide prevention and care guidelines, along with adequately appropriate funds accordingly.

Potentially Effective Drugs for the Treatment of COVID-19 or MIS-C in Children: A Systematic Review (preprint)

Introduction: The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. Methods: : We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. Results: : A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that, after the treatment, 54.7% (95%CI, 10.3% to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2% to 10.1%) died, 27.0% (95%CI, 0% to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone. Conclusions: : Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines.

Risk of COVID-19 Transmission Aboard Aircraft: An Epidemiological Analysis Based on the National Health Information Platform (preprint)

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the type of coronavirus that causes the Coronavirus Disease 2019 (COVID-19), is mainly spread by respiratory droplets and aerosols. This study aims to investigate the risk of COVID-19 transmission on aircraft. This in turn provides the scientific basis for the return of air travel from pandemic to normal conditions.Methods: We obtained data on all international flights to Lanzhou, China, from June 1 to August 1, 2020, through the Gansu Province National Health Information Platform and the official website of the Gansu Provincial Center for Disease Control and Prevention. We calculated the period prevalence rate of COVID-19 among the passengers of all flights during the 14-day period following the flight, and stratified the prevalence by the seat positions (aisle, middle, window), and the relationship to other confirmed cases (1-2 rows ahead, same row, 1-2 rows behind). Results: Three international flights arrived in Lanzhou, China, during the study period, from Riyadh (MU7792), Jeddah (MU7790), and Moscow (CA608) each. The flights had a total of 700 passengers, of whom 405 (57.9%) were male and 80 (11.4%) were children below age fourteen. Twenty-seven (3.9%) passengers were confirmed to have COVID-19. There were no fatalities and all patients were cured. We identified three family clusters of cases. Confirmed patients were primarily male (n=17, 65.4%) with a median age of 27.0 years. The majority of confirmed cases were seated in the middle rows of the economy class, or near public facility areas such as restrooms and galleys. The prevalence of COVID-19 did not differ between passengers sitting on window, aisle or middle seats. Compared with passengers sitting on the same row up to two rows behind a confirmed case, passengers seated in the two rows ahead a confirmed case were at a slightly higher risk of being infected. Conclusions: COVID-19 may possibly be transmitted during a passenger flight, although there is still no direct evidence.

Safety, Immunogenicity, and Efficacy of COVID-19 Vaccine in Children and Adolescents: A Systematic Review (preprint)

AimTo identify the safety, immunogenicity, and protective efficacy of COVID-19 vaccine in children and adolescents. MethodsWe conducted a systematic review. Databases including PubMed, Web of Science, WHO COVID-19 database, and CNKI were searched on 23 July 2021. International Clinical Trials Registry Platform (ICTRP) was also searched to collect ongoing trials. We included published researches or ongoing clinical trials related to the safety, immunogenicity, and efficacy of COVID-19 vaccine in children or adolescents (aged [≤]18 years). Meta-analysis was performed if the consistency of the included studies was high. If not, descriptive analyses were performed. ResultsEight published studies with 2851 children or adolescents and 28 ongoing clinical trials were included. Among eight published studies, two (25.0%) were RCTs, two (25.0%) case series, and four (50.0%) case reports. The results showed selected COVID-19 vaccines had a good safety profile in children and adolescents. Injection site pain, fatigue, headache, and chest pain were the most common adverse events. Some studies reported a few cases of myocarditis and pericarditis. Two RCTs showed that the immune response to BNT162b2 in adolescents aged 12-15 years was non-inferior to that in young people aged 16-25 years, while a stronger immune response was detected with 3g CoronaVac injection. Only one single RCT showed the efficacy of BNT162b2 was 100% (95% CI: 75.3 to 100). Of the 28 ongoing clinical trials, twenty-three are interventional studies. Fifteen countries are conducting interventional clinical trials of COVID-19 vaccines in children and adolescents. Among them, China (10, 43.5%) and United Stated (9, 39.1%) were the top two countries with the most trials. BNT162b2 was the most common vaccine, which is under testing. ConclusionSome of the COVID-19 vaccines have potential protective effects in children and adolescents, but awareness is needed to monitor possible adverse effects after injection. Clinical trials of the COVID-19 vaccine in children and adolescents with long follow-up, large sample size, and different vaccines are still urgently needed.

Associations Between the Use of Non-Steroidal Anti-Inflammatory Drugs and Adverse Outcomes Among Patients with COVID-19: A Systematic Review and Meta-Analysis (preprint)

Background: There are concerns that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of adverse outcomes in COVID-19 patients. Therefore, this study aimed to synthesize the existing evidence on associations between the use of NSAIDs and adverse outcomes among patients with COVID-19.Methods: Systematic search of WHO COVID-19 Database, Medline, The Cochrane Library, Web of Science, Embase, China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Database for all articles published from January 1, 2020, to August 10, 2021, as well as a supplementary search of Google Scholar. We included comparative observational studies and randomized controlled trials that enrolled patients with COVID-19 who took NSAIDs before or after diagnosis of COVID-19. Data extraction and quality assessment of methodology of included studies were completed by two reviewers independently. We conducted a meta-anlysis on the main outcomes, as well as selected subgroup analyses stratified by the type of NSAID.Fingings: Fifteen non-randomized studies evaluating 24700 adult COVID-19 patients were identified. The use of NSAIDs in patients with COVID-19, compared with no use of NSAIDs, was not significantly associated with an elevated mortality (odds ratio [OR]=0.94, 95% confidence interval [CI]: 0.87 to 1.02), or an increased probability of ICU admission (OR=1.35, 95% CI: 0.73 to 2.49), requiring mechanical ventilation (OR=1.23, 95% CI: 0.71 to 2.13), or administration of supplemental oxygen (OR=0.99, 95% CI: 0.91 to 1.08). The subgroup analyses revealed that the use of ibuprofen (OR=1.22, 95% CI: 0.32 to 4.60), etoricoxib (OR=0.36, 95% CI: 0.02 to 6.49) or celecoxib (zero deaths in both groups) were not associated with an increased risk of death in COVID-19 patients, compared with not using any NSAID.Interpretation: Fever is one of the main clinical symptoms of COVID-19. According to our findings, NSAIDs such as ibuprofen can be used to treat fever in COVID-19 patients safely.Funding: None to declare. Declaration of Interest: None to declare.

Potentially effective drugs for the treatment of COVID-19 in children: a systematic review (preprint)

Background: The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19 is unclear. Methods: We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to March 2, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19. Findings: A total of six cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that, after the treatment, 37.1% (95%CI, 0.0% to 74.5%) experienced adverse events, 5.9% (95%CI, 1.5% to 10.2%) died, 37.2% (95%CI, 0% to 76.0%) needed extracorporeal membrane oxygenation (ECMO) or invasive mechanical ventilation (IMV). As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio (OR) for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, the two included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone. Interpretation: Overall, the current evidence in the included studies is insignificant and of low quality, which does not adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C.

Risk Factors for Poor Prognosis in Children and Adolescents With COVID-19: A Systematic Review and Meta Analysis (preprint)

Background: The prognosis of children and adolescents with COVID-19 obtain increasing attention worldwide. This study provides the first systematic review and meta-analysis to identify risk factors which predict poor prognosis in this group.Methods: Electronic databases from inception to March, 2021 were searched for cohort studies, case-control studies and case series that investigated risk factors for poor prognosis of children and adolescents with COVID-19. We estimated the summary effect size by use of random-effects models and the 95% confidential interval (CI).Findings: We identified 33 studies, comprising 32,225 individuals. The risk of bias were generally high. In children and adolescents with COVID-19, risk of death was significantly increased in patients with MIS-C complication (odds ratio [OR]=58.00, 95% CI 6.39 to 526.79) and in need for intensive care (OR=15.25, 95% CI 1.98 to 117.44). Congenital heart disease (OR=2.90, 95% CI 1.26 to 6.67), chronic pulmonary disease (OR=3.45, 95% CI 1.47 to 8.07), and gastrointestinal symptoms (OR=2.11, 95% CI 1.43 to 3.12) increased the odds to be admitted to ICU; MIS-C complication (OR=70.00, 95% CI 6.51 to 752.27) and neurological diseases (OR=2.51, 95% CI 1.03 to 6.15) increased the odds of respiratory support; neurological diseases (OR=4.59, 95% CI 1.99 to 10.61), obesity (OR=2.51, 95% CI 2.02 to 3.12), C-reactive protein (CRP) level ≥80mg/L (OR=11.70, 95% CI 4.37 to 31.37) and D-dimer level ≥0.5ug/mL (OR=20.40, 95% CI 1.76 to 236.44) on admission increased the odds of progression to severe/critical disease.Interpretation: Very low to moderate quality evidence found that MIS-C, congenital heart disease, chronic pulmonary disease, neurological diseases, obesity, and gastrointestinal symptoms, in need for intensive care, elevated CRP and D-dimer are risk factors for poor prognosis in children and adolescents with COVID-19.Funding: None.Declaration of Interests: The authors declare that they have no competing interests.

Did Patients With COVID-19 Receive Timely Treatment in the Early Epidemic? A Systematic Review and Meta-analysis (preprint)

Background: COVID-19 showed a significant difference in case fatality rate between different regions at the early stage of the epidemic. In addition to the well-known factors such as age structure, detection efficiency, and race, there was also a possibility that medical resource shortage caused the increase of the case fatality rate in some regions. Methods: Medline, Cochrane Library, Embase, Web of Science, CBM, CNKI, and Wan fang of identified articles were searched through 29 June 2020. Cohort studies and case series with duration information on COVID-19 patients were included. Two independent reviewers extracted the data using a standardized data collection form and assessed the risk of bias. Data were synthesized through description and analysis methods including a meta-analysis.Results: A total of 109 articles were retrieved. The time interval from onset to the first medical visit of COVID-19 patients in China was 3.38±1.55 days (corresponding intervals in Hubei province, non-Hubei provinces, Wuhan, Hubei provinces without Wuhan were 4.22±1.13 days, 3.10±1.57 days, 4.20±0.97 days, and 4.34±1.72 days, respectively). The time interval from onset to the hospitalization of COVID-19 patients in China was 8.35±6.83 days (same corresponding intervals were 12.94±7.43 days, 4.17±1.45 days, 14.86±7.12 days, and 5.36±1.19 days, respectively), and when it was outside China, this interval was 5.27±1.19 days. Conclusion: In the early stage of the COVID-19 epidemic, patients with COVID-19 did not receive timely treatment, resulting in a higher case fatality rate in Hubei province, partly due to the relatively insufficient and unequal medical resources. This research suggested that additional deaths caused by the out-of-control epidemic can be avoided if prevention and control work is carried out at the early stage of the epidemic.PROSPERO registration number CRD42020195606.

Projecting the second outbreaks for global COVID-19 pandemic (preprint)

COVID-19 is now in an epidemic phase, with a second outbreak likely to appear at any time. The intensity and timing of a second outbreak is a common concern worldwide. In this study, we made scenario projections of the potential second outbreak of COVID-19 using a statistical-epidemiology model, which considers both the impact of seasonal changes in meteorological elements and human social behaviors such as protests and city unblocking. Recent street protests in the United States and other countries are identified as a hidden trigger and amplifier of the second outbreak. The scale and intensity of subsequent COVID-19 outbreaks in the U.S. cities where the epidemic is under initial control are projected to be much greater than those of the first outbreak. For countries without reported protests, lifting the COVID-19 related restrictions prematurely would accelerate the spread of the disease and place mounting pressure on the local medical system that is already overloaded. We anticipate these projections will support public health planning and policymaking by governments and international organizations.

Effectiveness and Safety of Glucocorticoids to Treat COVID-19: A Rapid Review and Meta-Analysis (preprint)

Background: Glucocorticoids are widely used in the treatment of various pulmonary inflammatory diseases, but they are also often accompanied by significant adverse reactions. Published guidelines point out that low dose and short duration systemic glucocorticoid therapy may be considered for patients with rapidly progressing COVID-19 while the evidence is still limited. Methods: We comprehensively searched electronic databases and supplemented the screening by conducting a manual search. We included RCTs and cohort studies evaluating the effectiveness and safety of glucocorticoids in children and adults with COVID-19, SARS and MERS, and conducted meta-analyses of the main indicators that were identified in the studies. Results: Our search retrieved 23 studies, including one RCT and 22 cohort studies, with a total of 13,815 patients. In adults with COVID-19, the use of systemic glucocorticoid did not reduce mortality (RR=2.00, 95% CI: 0.69 to 5.75, I 2=90.9%) or the duration of lung inflammation (WMD=-1 days, 95% CI: -2.91 to 0.91), while a significant reduction was found in the duration of fever (WMD=-3.23 days, 95% CI: -3.56 to -2.90). In patients with SARS, glucocorticoids also did not reduce the mortality (RR=1.52, 95% CI: 0.89 to 2.60, I2=84.6%), duration of fever (WMD=0.82 days, 95% CI: -2.88 to 4.52, I2=97.9%) or duration of lung inflammation absorption (WMD=0.95 days, 95% CI: -7.57 to 9.48, I2=94.6%). The use of systemic glucocorticoid therapy prolonged the duration of hospital stay in all patients (COVID-19, SARS and MERS). Conclusions: Glucocorticoid therapy was found to reduce the duration of fever, but not mortality, duration of hospitalization or lung inflammation absorption. Long-term use of high-dose glucocorticoids increased the risk of adverse reactions such as coinfections, so routine use of systemic glucocorticoids for patients with COVID-19 cannot be recommend. Keywords: COVID-19; glucocorticoids; meta-analysis; rapid review

Effectiveness of Intravenous Immunoglobulin for Children with Severe COVID-19: A Rapid Review (preprint)

Background: Intravenous immunoglobulin (IVIG) is usually used as supportive therapy, but the treatment of COVID-19 by IVIG is controversial. This rapid review aims to explore the clinical effectiveness and safety of IVIG in the treatment of children with severe COVID-19. Methods: We systematically searched the literature on the use of IVIG in patients with COVID-19, Severe Acute Respiratory Syndrome (SARS) or Middle East Respiratory Syndrome (MERS), including both adults and children. We assessed the risk of bias and quality of evidence and reported the main findings descriptively. Results: A total of 1519 articles were identified by initial literature search, and finally six studies, included one randomized controlled trial (RCT), four case series and one case report involving 198 patients. One case series showed the survival of COVID-19 patients with acute respiratory distress syndrome (ARDS) was not improved by IVIG. One case report showed high-dose IVIG could improve the outcome of COVID-19 adults. Three observational studies showed inconsistent results of the effect of IVIG on SARS patients. One RCT showed that IVIG did not reduce mortality or the incidence of nosocomial infection in adults with severe SARS. The quality of evidence was between low and very low. Conclusions: The existing evidence is insufficient to support the efficacy or safety of IVIG in the treatment of COVID-19. Keywords: COVID-19; children; intravenous immunoglobulin; rapid review.

Breastfeeding of Infants Born to Mothers with COVID-19: A Rapid Review (preprint)

Abstract Background: Existing recommendations on whether mothers with COVID-19 should continue breastfeeding are still conflicting. We aimed to conduct a rapid review of mother-to-child transmission of COVID-19 during breastfeeding. Methods: We systematically searched Medline, Embase, Web of Science, Cochrane library, China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang, and preprint articles up to March 2020. We included studies relevant to transmission through milk and respiratory droplets during breastfeeding of mothers with COVID-19, SARS, MERS and influenza. Two reviewers independently screened studies for eligibility, extracted data, assessed risk of bias and used GRADE to assess certainty of evidence. Results: A total of 4481 records were identified in our literature search. Six studies (five case reports and one case series) involving 58 mothers (16 mothers with COVID-19, 42 mothers with influenza) and their infants proved eligible. Five case reports showed that the viral nucleic acid tests for all thirteen collected samples of breast milk from mothers with COVID-19 were negative. A case series of 42 influenza infected postpartum mothers taking precautions (hand hygiene and wearing masks) before breastfeeding showed that no neonates were infected with influenza during one-month of follow-up. Conclusions: The current evidence indicates that SARS-CoV-2 viral nucleic acid has not been detected in breast milk. The benefits of breastfeeding may outweigh the risk of SARS-CoV-2 infection in infants. Mothers with COVID-19 should take appropriate precautions to reduce the risk of transmission via droplets and close contact during breastfeeding. Keywords: Breastfeeding; COVID-19; infant; mother-to-child transmission; rapid Review.

Health Education for Parents During the COVID-19 OutbreakPublic Health Education for Parents During the Outbreak of COVID-19: A Rapid Review (preprint)

Background: It is well-known that public health education plays a crucial role in the prevention and control of emerging infectious diseases, but how health providers should advise families and parents to obtain health education information is a challenging question. With COVID-19 (Coronavirus disease 2019) spreading around the world, this rapid review aims to answer that question and thus to promote evidence-based decision making in health education policy and practice. Methods: We systematically searched the literature on health education during COVID-19, SARS (severe acute respiratory syndrome) and MERS (middle east respiratory syndrome) epidemics in Medline (via PubMed), Cochrane Library, EMBASE, Web of Science, CBM (China Biology Medicine disc), CNKI (China National Knowledge Infrastructure), and Wanfang Data from their inception until March 31, 2020. The potential bias of the studies was assessed by Joanna Briggs Institute Prevalence Critical Appraisal Tool. Results: Of 1067 papers found, 24 cross-sectional studies with a total of 35,967 participants were included in this review. The general public lacked good knowledge of SARS and MERS at the early stage of epidemics. Some people's knowledge, attitude and practice (KAP) of COVID-19 had been improved, but the health behaviors of some special groups including children and their parents need to be strengthened. Negative emotions including fear and stigmatization occurred during the outbreaks. Reliable health information was needed to improve public awareness and mental health for infectious diseases. Health information from nonprofit, government and academic websites was more accurate than privately owned commercial websites and media websites. Conclusions: For educating and cultivating children, parents should obtain information from the official websites of authorities such as the World Health Organization (WHO) and national Centers for Disease Control, or from other sources endorsed by these authorities, rather than from a general search of the internet or social media.

Chest Computed Tomography for the Diagnosis of Patients with Coronavirus Disease 2019 (COVID-19): A Rapid Review and Meta-Analysis (preprint)

Background: The outbreak of the coronavirus disease 2019 (COVID-19) has had a massive impact on the whole world. Computed tomography (CT) has been widely used in the diagnosis of this novel pneumonia. This study aims to understand the role of CT for the diagnosis and the main imaging manifestations of patients with COVID-19. Methods: We conducted a rapid review and meta-analysis on studies about the use of chest CT for the diagnosis of COVID-19. We comprehensively searched databases and preprint servers on chest CT for patients with COVID-19 between 1 January 2020 and 31 March 2020. The primary outcome was the sensitivity of chest CT imaging. We also conducted subgroup analyses and evaluated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: A total of 104 studies with 5694 patients were included. Using RT-PCR results as reference, a meta-analysis based on 64 studies estimated the sensitivity of chest CT imaging in COVID-19 was 99% (95% CI, 0.97-1.00). If case reports were excluded, the sensitivity in case series was 96% (95% CI, 0.93-0.99). The sensitivity of CT scan in confirmed patients under 18 years old was only 66% (95% CI, 0.11-1.00). The most common imaging manifestation was ground-glass opacities (GGO) which was found in 75% (95% CI, 0.68-0.82) of the patients. The pooled probability of bilateral involvement was 84% (95% CI, 0.81-0.88). The most commonly involved lobes were the right lower lobe (84%, 95% CI, 0.78-0.90) and left lower lobe (81%, 95% CI, 0.74-0.87). The quality of evidence was low across all outcomes. Conclusions: In conclusion, this meta-analysis indicated that chest CT scan had a high sensitivity in diagnosis of patients with COVID-19. Therefore, CT can potentially be used to assist in the diagnosis of COVID-19.

Application of Telemedicine During the Coronavirus Disease Epidemics: A Rapid Review and Meta-Analysis (preprint)

Background: As COVID-19 has become a global pandemic, early prevention and control of the epidemic is extremely important. Telemedicine, which includes medical advice given over telephone, Internet, mobile phone applications or other similar ways, may be an efficient way to reduce transmission and pressure on medical institutions. Methods: We searched MEDLINE, Web of science, Embase, Cochrane, CBM, CNKI and Wanfang databases for literature on the use of telemedicine for COVID-19, SARS and MERS. from their inception to March 31st, 2020. We included studies about the content of the consultation (such as symptoms, therapy and prevention, policy, public service), screening of suspected cases, the provision of advice given to those people who may have symptoms or contact history. We conducted meta-analyses on the main outcomes of the studies. Results: A total of 2041 articles were identified after removing duplicates. After reading the full texts, we finally included nine studies. People were most concerned about symptoms (64.2%), epidemic situation and public problems (14.5%), and psychological problems (10.3%) during COVID-19 epidemic. During the SARS epidemic, the proportions of people asking for consultation for symptoms, prevention and therapy, and psychological problems were 35.0%, 22.0%, and 23.0%, respectively. Two studies demonstrated that telemedicine can be used to screen the suspected patients and give advice. One study emphasized the limited possibilities to follow up people calling hotlines and difficulties in identifying all suspect cases. Conclusions: Telemedicine services should focus on the issues that the public is most concerned about, such as then symptoms, prevention and treatment of the disease, and provide reasonable advice to patients with symptoms or people with epidemic history. KeywordsCOVID-19; SARS; MERS; telemedicine; rapid review

Efficacy and Safety of Antibiotic Agents in Children with COVID-19: A Rapid Review (preprint)

Background: The aim of this review was to evaluate the efficacy and safety of antibiotic agents in children with COVID-19, as well as to introduce the present situation of antibiotics use and bacterial coinfections in COVID-19 patients. Methods: We searched Cochrane library, Medline, Embase, Web of Science, CBM, Wanfang Data and CNKI from their inception to March 31, 2020. In addition, we searched related studies on COVID-19 published before March 31, 2020 through Google Scholar. We evaluated the risk of bias of included studies, and synthesized the results using a qualitative synthesis. Results: Six studies met our inclusion criteria. Five studies on SARS showed an overall risk of death of 7.2% to 20.0%. One study of SARS patients who used macrolides, quinolones or beta lactamases showed that the mean duration of hospital stay was 14.2, 13.8 and 16.2 days, respectively, and their average duration of fever was 14.3, 14.0 and 16.2 days, respectively. One cohort study on MERS indicated that macrolide therapy was not associated with a significant reduction in 90-day mortality (adjusted odds ratio [OR] 0.84, 95% confidence interval [CI] 0.47-1.51, P = 0.56) and improvement in MERS-CoV RNA clearance (adjusted hazard ratio [HR] 0.88, 95% CI 0.47, -1.64], P = 0.68). According to the findings of 33 studies, the proportion of antibiotics use ranged from 19.4% to 100.0% in children and 13.2% to 100.0% in adults, despite the lack of etiological evidence. The most commonly used antibiotics in adults were quinolones, cephalosporins and macrolides and in children meropenem and linezolid. Conclusions: The benefits of antibiotic agents for adults with SARS or MERS were questionable in the absence of bacterial coinfections. There is no evidence to support the use of antibiotic agents for children with COVID-19 in the absence of bacterial coinfection.

Supportive Care for Patient with Respiratory Diseases: An Umbrella Review (preprint)

Abstract Background: Supportive treatment is an important and effective part of the management for patients with life-threatening diseases. This study aims to identify and evaluate the forms of supportive care for patients with respiratory diseases. Methods: An umbrella review of supportive care for patient respiratory diseases was undertaken. We comprehensively searched the following databases: Medline, EMBASE, Web of Science, CNKI (China National Knowledge Infrastructure), Wanfang Data and CBM (SinoMed) from their inception to 31 March 2020, and other sources to identify systematic reviews and meta-analyses related to supportive treatments for patient with respiratory diseases including COVID-19, SARS, MERS and influenza. We assessed the methodological quality using the AMSTAR score and the quality of the evidence for the primary outcomes of each included systematic review and meta-analysis. Results: We included 18 systematic reviews and meta-analyses in this study. Most studies focused on the respiratory and circulatory support. Ten studies were of high methodological quality, five studies of medium quality, and three studies of low quality. According to four studies extracorporeal membrane oxygenation did not reduce mortality in adults (OR/RR ranging from 0.71 to 1.28), but two studies reported significantly lower mortality in patients receiving venovenous extracorporeal membrane oxygenation than in the control group (OR/RR ranging from 0.38 to 0.73). Besides, monitoring of vital signs and increasing the number of medical staff may also reduce the mortality in patients with respiratory diseases. Conclusions: Our overview suggests that supportive care may reduce the mortality of patients with respiratory diseases to some extent. However, the quality of evidence for the primary outcomes in the included studies was low to moderate. Further systematic reviews and meta-analyses are needed to address the evidence gap regarding the supportive care for SARS, MERS and COVID-19.

Nosocomial Infections Among Patients with COVID-19, SARS and MERS: A Rapid Review and Meta-Analysis (preprint)

Background: COVID-19, a disease caused by SARS-CoV-2 coronavirus, has now spread to most countries and regions of the world. As patients potentially infected by SARS-CoV-2 need to visit hospitals, the incidence of nosocomial infection can be expected to be high. Therefore, a comprehensive and objective understanding of nosocomial infection is needed to guide the prevention and control of the epidemic. Methods: We searched major international and Chinese databases Medicine, Web of science, Embase, Cochrane, CBM(China Biology Medicine disc), CNKI (China National Knowledge Infrastructure) and Wanfang database)) for case series or case reports on nosocomial infections of COVID-19, SARS(Severe Acute Respiratory Syndromes) and MERS(Middle East Respiratory Syndrome) from their inception to March 31st, 2020. We conducted a meta-analysis of the proportion of nosocomial infection patients in the diagnosed patients, occupational distribution of nosocomial infection medical staff and other indicators. Results: We included 40 studies. Among the confirmed patients, the proportions of nosocomial infections were 44.0%, 36.0% and 56.0% for COVID-19, SARS and MERS, respectively. Of the confirmed patients, the medical staff and other hospital-acquired infections accounted for 33.0% and 2.0% of COVID-19 cases, 37.0% and 24.0% of SARS cases, and 19.0% and 36.0% of MERS cases, respectively. Nurses and doctors were the most affected among the infected medical staff. The mean numbers of secondary cases caused by one index patient were 29.3 and 6.3 for SARS and MERS, respectively. Conclusions: The proportion of nosocomial infection in patients with COVID-19 was 44%. Patients attending hospitals should take personal protection. Medical staff should be awareness of the disease to protect themselves and the patients. Keywords: COVID-19; meta-analysis; nosocomial infection; rapid review.