Validation of the Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) questionnaire for adults.

BACKGROUND: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the internal validity of the co-primary outcome, a composite psychopathology "P-score". METHODS: The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r ≥ 0.5 with validated companion questionnaires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed. RESULTS: From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (ω = 0.95). Factor structure was consistent across age and sex. CONCLUSIONS: COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health.

Vickybot, a Chatbot for Anxiety-Depressive Symptoms and Work-Related Burnout in Primary Care and Health Care Professionals: Development, Feasibility, and Potential Effectiveness Studies.

BACKGROUND: Many people attending primary care (PC) have anxiety-depressive symptoms and work-related burnout compounded by a lack of resources to meet their needs. The COVID-19 pandemic has exacerbated this problem, and digital tools have been proposed as a solution. OBJECTIVE: We aimed to present the development, feasibility, and potential effectiveness of Vickybot, a chatbot aimed at screening, monitoring, and reducing anxiety-depressive symptoms and work-related burnout, and detecting suicide risk in patients from PC and health care workers. METHODS: Healthy controls (HCs) tested Vickybot for reliability. For the simulation study, HCs used Vickybot for 2 weeks to simulate different clinical situations. For feasibility and effectiveness study, people consulting PC or health care workers with mental health problems used Vickybot for 1 month. Self-assessments for anxiety (Generalized Anxiety Disorder 7-item) and depression (Patient Health Questionnaire-9) symptoms and work-related burnout (based on the Maslach Burnout Inventory) were administered at baseline and every 2 weeks. Feasibility was determined from both subjective and objective user-engagement indicators (UEIs). Potential effectiveness was measured using paired 2-tailed t tests or Wilcoxon signed-rank test for changes in self-assessment scores. RESULTS: Overall, 40 HCs tested Vickybot simultaneously, and the data were reliably transmitted and registered. For simulation, 17 HCs (n=13, 76% female; mean age 36.5, SD 9.7 years) received 98.8% of the expected modules. Suicidal alerts were received correctly. For the feasibility and potential effectiveness study, 34 patients (15 from PC and 19 health care workers; 76% [26/34] female; mean age 35.3, SD 10.1 years) completed the first self-assessments, with 100% (34/34) presenting anxiety symptoms, 94% (32/34) depressive symptoms, and 65% (22/34) work-related burnout. In addition, 27% (9/34) of patients completed the second self-assessment after 2 weeks of use. No significant differences were found between the first and second self-assessments for anxiety (t8=1.000; P=.34) or depressive (t8=0.40; P=.70) symptoms. However, work-related burnout scores were moderately reduced (z=-2.07, P=.04, r=0.32). There was a nonsignificant trend toward a greater reduction in anxiety-depressive symptoms and work-related burnout with greater use of the chatbot. Furthermore, 9% (3/34) of patients activated the suicide alert, and the research team promptly intervened with successful outcomes. Vickybot showed high subjective UEI (acceptability, usability, and satisfaction), but low objective UEI (completion, adherence, compliance, and engagement). Vickybot was moderately feasible. CONCLUSIONS: The chatbot was useful in screening for the presence and severity of anxiety and depressive symptoms, and for detecting suicidal risk. Potential effectiveness was shown to reduce work-related burnout but not anxiety or depressive symptoms. Subjective perceptions of use contrasted with low objective-use metrics. Our results are promising but suggest the need to adapt and enhance the smartphone-based solution to improve engagement. A consensus on how to report UEIs and validate digital solutions, particularly for chatbots, is required.

Clinical manifestations of COVID-19 breakthrough infections: A systematic review and meta-analysis.

To provide a comparative meta-analysis and systematic review of the risk and clinical outcomes of coronavirus 2019 (COVID-19) infection between fully vaccinated and unvaccinated groups. Eighteen studies of COVID-19 infections in fully vaccinated ("breakthrough infections") and unvaccinated individuals were reviewed from Medline/PubMed, Scopus, Embase, and Web of Science databases. The meta-analysis examined the summary effects and between-study heterogeneity regarding differences in the risk of infection, hospitalization, treatments, and mortality between vaccinated and unvaccinated individuals. he overall risk of infection was lower for the fully vaccinated compared to that of the unvaccinated (relative risk [RR] 0.20, 95% confidence interval [CI]: 0.19-0.21), especially for variants other than Delta (Delta: RR 0.29, 95% CI: 0.13-0.65; other variants: RR 0.06, 95% CI: 0.04-0.08). The risk of asymptomatic infection was not statistically significantly different between fully vaccinated and unvaccinated (RR 0.56, 95% CI: 0.27-1.19). There were neither statistically significant differences in risk of hospitalization (RR 1.06, 95% CI: 0.38-2.93), invasive mechanical ventilation (RR 1.65, 95% CI: 0.90-3.06), or mortality (RR 1.19, 95% CI: 0.79-1.78). Conversely, the risk of supplemental oxygen during hospitalization was significantly higher for the unvaccinated (RR 1.40, 95% CI: 1.08-1.82). Unvaccinated people were more vulnerable to COVID-19 infection than fully vaccinated for all variants. Once infected, there were no statistically significant differences in the risk of hospitalization, invasive mechanical ventilation, or mortality. Still, unvaccinated showed an increased need for oxygen supplementation. Further prospective analysis, including patients' risk factors, COVID-19 variants, and the utilized treatment strategies, would be warranted.

Immunogenicity of COVID-19 vaccines in patients with diverse health conditions: A comprehensive systematic review.

It remains unclear how effective COVID-19 vaccinations will be in patients with weakened immunity due to diseases, transplantation, and dialysis. We conducted a systematic review comparing the efficacy of COVID-19 vaccination in patients with solid tumor, hematologic malignancy, autoimmune disease, inflammatory bowel disease, and patients who received transplantation or dialysis. A literature search was conducted twice using the Medline/PubMed database. As a result, 21 papers were included in the review, and seropositivity rate was summarized by specific type of disease, transplantation, and dialysis. When different papers studied the same type of patient group, a study with a higher number of participants was selected. Most of the solid tumor patients showed a seropositivity rate of more than 80% after the second inoculation, but a low seropositivity was found in certain tumors such as breast cancer. Research in patients with certain types of hematological malignancy and autoimmune diseases has also reported low seropositivity, and this may have been affected by the immunosuppressive treatment these patients receive. Research in patients receiving dialysis or transplantation has reported lower seropositivity rates than the general population, while all patients with inflammatory bowel disease have converted to be seropositive. Meta-analysis validating these results will be needed, and studies will also be needed on methods to protect patients with reduced immunity from COVID-19.

The global case fatality rate of coronavirus disease 2019 by continents and national income: A meta-analysis.

The aim of this study is to provide a more accurate representation of COVID-19's case fatality rate (CFR) by performing meta-analyses by continents and income, and by comparing the result with pooled estimates. We used multiple worldwide data sources on COVID-19 for every country reporting COVID-19 cases. On the basis of data, we performed random and fixed meta-analyses for CFR of COVID-19 by continents and income according to each individual calendar date. CFR was estimated based on the different geographical regions and levels of income using three models: pooled estimates, fixed- and random-model. In Asia, all three types of CFR initially remained approximately between 2.0% and 3.0%. In the case of pooled estimates and the fixed model results, CFR increased to 4.0%, by then gradually decreasing, while in the case of random-model, CFR remained under 2.0%. Similarly, in Europe, initially, the two types of CFR peaked at 9.0% and 10.0%, respectively. The random-model results showed an increase near 5.0%. In high-income countries, pooled estimates and fixed-model showed gradually increasing trends with a final pooled estimates and random-model reached about 8.0% and 4.0%, respectively. In middle-income, the pooled estimates and fixed-model have gradually increased reaching up to 4.5%. in low-income countries, CFRs remained similar between 1.5% and 3.0%. Our study emphasizes that COVID-19 CFR is not a fixed or static value. Rather, it is a dynamic estimate that changes with time, population, socioeconomic factors, and the mitigatory efforts of individual countries.

Comparative effectiveness of N95, surgical or medical, and non-medical facemasks in protection against respiratory virus infection: A systematic review and network meta-analysis.

The aim of this systematic review and network meta-analysis is to evaluate the comparative effectiveness of N95, surgical/medical and non-medical facemasks as personal protective equipment against respiratory virus infection. The study incorporated 35 published and unpublished randomized controlled trials and observational studies investigating specific mask effectiveness against influenza virus, SARS-CoV, MERS-CoV and SARS-CoV-2. We searched PubMed, Google Scholar and medRxiv databases for studies published up to 5 February 2021 (PROSPERO registration: CRD42020214729). The primary outcome of interest was the rate of respiratory viral infection. The quality of evidence was estimated using the GRADE approach. High compliance to mask-wearing conferred a significantly better protection (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.23-0.82) than low compliance. N95 or equivalent masks were the most effective in providing protection against coronavirus infections (OR, 0.30; CI, 0.20-0.44) consistently across subgroup analyses of causative viruses and clinical settings. Evidence supporting the use of medical or surgical masks against influenza or coronavirus infections (SARS, MERS and COVID-19) was weak. Our study confirmed that the use of facemasks provides protection against respiratory viral infections in general; however, the effectiveness may vary according to the type of facemask used. Our findings encourage the use of N95 respirators or their equivalents (e.g., P2) for best personal protection in healthcare settings until more evidence on surgical and medical masks is accrued. This study highlights a substantial lack of evidence on the comparative effectiveness of mask types in community settings.

Physical and mental health impact of COVID-19 on children, adolescents, and their families: The Collaborative Outcomes study on Health and Functioning during Infection Times - Children and Adolescents (COH-FIT-C&A).

BACKGROUND: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. METHODS: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www.coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6-18 months plus 24-36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14-17 years), and children (age 6-13 years), recruited via non-probability/snowball and representative sampling and assessed via self-rating and parental rating. Non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co-primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life. RESULTS: Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COH-FIT project, with representative samples from eleven countries. LIMITATIONS: Cross-sectional and anonymous design. CONCLUSIONS: Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on children's, adolescents' and families', mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth.

No Effects of Meteorological Factors on the SARS-CoV-2 Infection Fatality Rate.

OBJECTIVE: Previous studies have shown that meteorological factors may increase COVID-19 mortality, likely due to the increased transmission of the virus. However, this could also be related to an increased infection fatality rate (IFR). We investigated the association between meteorological factors (temperature, humidity, solar irradiance, pressure, wind, precipitation, cloud coverage) and IFR across Spanish provinces ( n = 52) during the first wave of the pandemic (weeks 10-16 of 2020). METHODS: We estimated IFR as excess deaths (the gap between observed and expected deaths, considering COVID-19-unrelated deaths prevented by lockdown measures) divided by the number of infections (SARS-CoV-2 seropositive individuals plus excess deaths) and conducted Spearman correlations between meteorological factors and IFR across the provinces. RESULTS: We estimated 2,418,250 infections and 43,237 deaths. The IFR was 0.03% in < 50-year-old, 0.22% in 50-59-year-old, 0.9% in 60-69-year-old, 3.3% in 70-79-year-old, 12.6% in 80-89-year-old, and 26.5% in ≥ 90-year-old. We did not find statistically significant relationships between meteorological factors and adjusted IFR. However, we found strong relationships between low temperature and unadjusted IFR, likely due to Spain's colder provinces' aging population. CONCLUSION: The association between meteorological factors and adjusted COVID-19 IFR is unclear. Neglecting age differences or ignoring COVID-19-unrelated deaths may severely bias COVID-19 epidemiological analyses.

The collaborative outcomes study on health and functioning during infection times in adults (COH-FIT-Adults): Design and methods of an international online survey targeting physical and mental health effects of the COVID-19 pandemic.

BACKGROUND: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. METHODS: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative sampling. COH-FIT aims to identify non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to improve social/health outcomes in the general population/vulnerable subgrous during/after COVID-19. In adults, co-primary outcomes are change from pre-COVID-19 to intra-COVID-19 in well-being (WHO-5) and a composite psychopathology P-Score. Key secondary outcomes are a P-extended score, global mental and physical health. Secondary outcomes include health-service utilization/functioning, treatment adherence, functioning, symptoms/behaviors/emotions, substance use, violence, among others. RESULTS: . Starting 04/26/2020, up to 14/07/2021 >151,000 people from 155 countries/territories/regions and six continents have participated. Representative samples of ≥1,000 adults have been collected in 15 countries. Overall, 43.0% had prior physical disorders, 16.3% had prior mental disorders, 26.5% were health care workers, 8.2% were aged ≥65 years, 19.3% were exposed to someone infected with COVID-19, 76.1% had been in quarantine, and 2.1% had been COVID 19-positive. LIMITATIONS: . Cross-sectional survey, preponderance of non-representative participants. CONCLUSIONS: . Results from COH-FIT will comprehensively quantify the impact of COVID-19, seeking to identify high-risk groups in need for acute and long-term intervention, and inform evidence-based health policies/strategies during this/future pandemics.

Self-reported neurocognitive symptoms during COVID-19 lockdown and its associated factors in a sample of psychiatric patients. Results from the BRIS-MHC study.

Lockdown caused by COVID-19 pandemic has a negative impact on mental health. The aim was to assess self-reported neurocognitive symptoms during the lockdown and identify associated vulnerable and protective factors in a sample of psychiatric patients in a Spanish population. These results are part of the Barcelona ResIlience Survey for Mental Health COVID-19 (BRIS-MHC) project. Neurocognitive symptoms were assessed through an online survey considering the five items that represented self-reported neurocognitive complaints. We split the sample into two groups based on the severity of the self-reported neurocognitive complaints: intact cognitive function/mild cognitive impairment (CI-) and moderate/severe cognitive impairment (CI+). Univariate analyses were used to compare both groups in terms of sociodemographic and clinical variables. Multiple logistic regression models were carried out to identify clinical variables and coping strategies associated with neurocognitive symptoms. 198 patients with different psychiatric diagnoses were included in this study. One hundred seventeen patients were classified in the CI- group and 81 in the CI+ group. Depressive symptoms and negative psychotic-like symptoms were vulnerable factors for neurocognitive impairment. Coping strategies of performing physical activity, carrying out relaxing activities and maintaining a routine were protective factors against cognitive impairment. Lockdown situation negatively impact on neurocognitive function. Psychopathological symptoms and coping strategies were associated with neurocognitive symptoms during lockdown in subjects with psychiatric illness. The early treatment of psychopathological symptoms in psychiatric patients and promoting coping strategies during lockdown should be considered an intervention strategy against cognitive impairment.

Study Protocol-Coping With the Pandemics: What Works Best to Reduce Anxiety and Depressive Symptoms.

Background: The coronavirus disease 2019 (COVID-19) pandemic and lockdown might increase anxiety and depressive symptoms in most individuals. Health bodies recommend several coping behaviors to protect against such symptoms, but evidence on the relationship between these behaviors and symptoms mostly comes from cross-sectional studies in convenience samples. We will conduct a prospective longitudinal study of the associations between coping behaviors and subsequent anxiety and depressive symptoms during the COVID-19 pandemic in a representative sample of the Spanish general adult population. Methods: We will recruit 1,000 adult participants from all autonomous communities of Spain and with sex, age, and urbanicity distributions similar to those of their populations and assess anxiety and depressive symptoms and coping behaviors using fortnightly questionnaires and real-time methods (ecological momentary assessments) for 1 year. The fortnightly questionnaires will inquire about anxiety and depressive symptoms [General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9)] and the frequency of 10 potential coping behaviors (e.g., follow a routine) during the past 2 weeks. In addition, we will collect several variables that could confound or moderate these associations. These will include subjective well-being [International Positive and Negative Affect Schedule Short Form (I-PANAS-SF) and Satisfaction with Life Scale (SWLS)], obsessive-compulsive symptoms [Obsessive Compulsive Inventory-Revised (OCI-R)], personality and emotional intelligence [International Personality Item Pool (IPIP) and Trait Emotional Intelligence Questionnaire Short Form (TEIQue-SF)], sociodemographic factors (e.g., work status, housing-built environment), and COVID-19 pandemic-related variables (e.g., hospitalizations or limitations in social gatherings). Finally, to analyze the primary relationship between coping behaviors and subsequent anxiety and depressive symptoms, we will use autoregressive moving average (ARMA) models. Discussion: Based on the study results, we will develop evidence-based, clear, and specific recommendations on coping behaviors during the COVID-19 pandemic and lockdown. Such suggestions might eventually help health bodies or individuals to manage current or future pandemics.

Predicting pulmonary embolism in patients infected with COVID-19 based on D-dimer levels and days between diagnosis of the infection and D-dimer determination.

Ruling out pulmonary embolism (PE) can be challenging in a situation of elevated D-dimer values such as in a case of COVID-19 infection. Our objective was to evaluate the difference in D-dimer values of subjects infected with COVID-19 in those with PE and those without and to analyze the predictive value of D-dimer for PE in these subjects based on the day of D-dimer determination. This was an observational, retrospective study, conducted at a tertiary hospital. All subjects with PCR-confirmed COVID-19 infection requiring hospital admission at our institution between the months of March and April 2020 were included in the study. We compared D-dimer levels in subjects who went on to develop a PE and those who did not. We then created a model to predict the subsequent development of a PE with the current D-dimer levels of the subject. D-dimer levels changed over time from COVID-19 diagnosis, but were always higher in subjects who went on to develop a PE. Regarding the predictive model created, the area under the curve of the ROC analyses of the cross-validation predictions was 0.72. The risk of pulmonary embolism for the same D-dimer levels varied depending on the number of days elapsed since COVID-19 diagnosis and D-dimer determination. To conclude, D-dimer levels were elevated in subjects with a COVID-19 infection, especially in those with PE. D-dimer levels increased during the first 10 days after the diagnosis of the infection and can be used to predict the risk of PE in COVID-19 subjects.

Resilience and mental health during the COVID-19 pandemic.

BACKGROUND: Resilience is a process that allows recovery from or adaptation to adversities. The aim of this study was to evaluate state resilience during the COVID-19 pandemic in psychiatric patients (PP), unaffected relatives (UR) and community controls (CC). METHODS: This study is part of the Barcelona ResIlience Survey for Mental Health COVID-19 (BRIS-MHC) project. Logistic regression models were performed to identify mental health outcomes associated with bad state resilience and predictors of good state resilience. The association between state resilience and specific affective temperaments as well as their influence on the association between depressive symptoms and state resilience were verified. RESULTS: The study recruited 898 participants that took part in the survey. The presence of depressive symptoms was a predictor of bad state resilience in PP (ß=0.110, OR=1.117, p=0.028). No specific mental health outcome was associated with bad state resilience in UR and CC. Predictors of good state resilience in PP were having pursued hobbies/conducted home tasks (ß=1.261, OR=3.528, p=0.044) and level of organization in the family (ß=0.986, OR=2.682, p=0.008). Having a controlling family was inversely associated with good state resilience in CC (ß=-1.004, OR=0.367, p=0.012). The association between bad state resilience and depressive symptoms was partially mediated by affective temperaments. LIMITATIONS: Participants self-reported their psychiatric diagnoses, their relatives' diagnoses or the absence of a psychiatric disorder, as well as their psychiatric symptoms. CONCLUSIONS: Enhancing resilience and coping strategies in the face of the COVID-19 pandemic might have important implications in terms of mental health outcomes.

Impact of simulation-based teamwork training on COVID-19 distress in healthcare professionals.

CONTEXT: Non-technical skills such as leadership, communication, or situation awareness should lead to effective teamwork in a crisis. This study aimed to analyse the role of these skills in the emotional response of health professionals to the COVID-19 pandemic. METHODS: Before the COVID-19 outbreak, 48 doctors and 48 nurses participated in a simulation-based teamwork training program based on teaching non-technical skills through simulation. In May 2020, this group of professionals from a COVID-19 referral hospital was invited to participate in a survey exploring stress, anxiety, and depression, using the PSS-14 (Perceived Stress Scale) and the HADS (Hospital Anxiety and Depression Scale) measures. A control group that did not receive the training was included. We conducted a logistic regression to assess whether having attended a simulation-based teamwork training program modified the probability of presenting psychological distress (PSS-14 > 18 or HADS> 12). RESULTS: A total of 141 healthcare professionals were included, 77 in the intervention group and 64 in the control group. Based on the PSS-14, 70.1% of the intervention group and 75% of the control group (p = 0.342) had symptoms of stress. Having contact with COVID-19 patients [OR 4.16(1.64-10.52)]; having minors in charge [OR 2.75 (1.15-6.53)]; working as a doctor [0.39(0.16-0.95)], and being a woman [OR 2.94(1.09-7.91)] were related with PSS14 symptoms. Based on the HADS, 54.6% of the intervention group and 42.2% of the control group (p = 0.346) had symptoms of anxiety or depression. Having contact with COVID-19 patients [OR 2.17(1.05-4.48)] and having minors in charge [OR 2.14(1.06-4.32)] were related to HADS symptoms. Healthcare professionals who attended COVID-19 patients showed higher levels of anxiety and depression [OR 2.56(1.03-6.36) (p = 0.043)]. CONCLUSION: Healthcare professionals trained in non-technical skills through simulation tended towards higher levels of anxiety and depression and fewer levels of stress, during the COVID-19 pandemic.

Treatment of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19): a systematic review of in vitro, in vivo, and clinical trials.

Rationale: Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19. Methods: We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of in vitro, in vivo, and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020. Results: We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study. Through 12,200 title and 830 full-text screenings for COVID-19, eight in vitro studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated. There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19. Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461). Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), IFN-ß1b (n = 193), and convalescent plasma therapy (n = 126). Conclusions: This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence. Further RCTs are required.

Estimation of global case fatality rate of coronavirus disease 2019 (COVID-19) using meta-analyses: Comparison between calendar date and days since the outbreak of the first confirmed case.

OBJECTIVE: Since the outbreak of the coronavirus disease 2019 (COVID-19) in December of 2019 in China, estimating the pandemic's case fatality rate (CFR) has been the focus and interest of many stakeholders. In this manuscript, we prove that the method of using the cumulative CFR is static and does not reflect the trend according to the daily change per unit of time. METHODS: A proportion meta-analysis was carried out on the CFR in every country reporting COVID-19 cases. Based on these results, we performed a meta-analysis for a global COVID-19 CFR. Each analysis was performed using two different calculations of CFR: according to the calendar date and according to the days since the outbreak of the first confirmed case. We thus explored an innovative and original calculation of CFR, concurrently based on the date of the first confirmed case as well as on a daily basis. RESULTS: For the first time, we showed that using meta-analyses according to the calendar date and days since the outbreak of the first confirmed case, were different. CONCLUSION: We propose that a CFR according to days since the outbreak of the first confirmed case might be a better predictor of the current CFR of COVID-19 and its kinetics.

Efficacy of Corticosteroids in Patients with SARS, MERS and COVID-19: A Systematic Review and Meta-Analysis.

(1) Background: The use of corticosteroids in critical coronavirus infections, including severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome (MERS), or Coronavirus disease 2019 (COVID-19), has been controversial. However, a meta-analysis on the efficacy of steroids in treating these coronavirus infections is lacking. (2) Purpose: We assessed a methodological criticism on the quality of previous published meta-analyses and the risk of misleading conclusions with important therapeutic consequences. We also examined the evidence of the efficacy of corticosteroids in reducing mortality in SARS, MERS and COVID-19. (3) Methods: PubMed, MEDLINE, Embase, and Web of Science were used to identify studies published until 25 April 2020, that reported associations between steroid use and mortality in treating SARS/MERS/COVID-19. Two investigators screened and extracted data independently. Searches were restricted to studies on humans, and articles that did not report the exact number of patients in each group or data on mortality were excluded. We calculated odds ratios (ORs) or hazard ratios (HRs) under the fixed- and random-effect model. (4) Results: Eight articles (4051 patients) were eligible for inclusion. Among these selected studies, 3416 patients were diagnosed with SARS, 360 patients with MERS, and 275 with COVID-19; 60.3% patients were administered steroids. The meta-analyses including all studies showed no differences overall in terms of mortality (OR 1.152, 95% CI 0.631-2.101 in the random effects model, p = 0.645). However, this conclusion might be biased, because, in some studies, the patients in the steroid group had more severe symptoms than those in the control group. In contrast, when the meta-analysis was performed restricting only to studies that used appropriate adjustment (e.g., time, disease severity), there was a significant difference between the two groups (HR 0.378, 95% CI 0.221-0.646 in the random effects model, p < 0.0001). Although there was no difference in mortality when steroids were used in severe cases, there was a difference among the group with more underlying diseases (OR 3.133, 95% CI 1.670-5.877, p < 0.001). (5) Conclusions: To our knowledge, this study is the first comprehensive systematic review and meta-analysis providing the most accurate evidence on the effect of steroids in coronavirus infections. If not contraindicated, and in the absence of side effects, the use of steroids should be considered in coronavirus infection including COVID-19.