Efficacy and Safety of Fluvoxamine as Outpatient Treatment for Patients With Covid-19: A Systematic Review and Meta-analysis of Clinical Trials.

BACKGROUND: Fluvoxamine may be beneficial for the management of coronavirus disease 2019 (Covid-19) because of its effect on the sigma-1 receptor. Available evidence from randomized clinical trials (RCTs) has shown conflicting results. OBJECTIVE: This study sought to analyze the efficacy and safety of fluvoxamine as an outpatient treatment for Covid-19. METHODS: Using specific keywords, we comprehensively go through the potential articles on PubMed, Scopus, Europe PMC, and ClinicalTrials.gov sources until February 1, 2023. We collected all published clinical trials on fluvoxamine and Covid-19. We were using Review Manager 5.4 to conduct statistical analysis. RESULTS: We include a total of 6 trials. Our pooled analysis revealed that fluvoxamine did not offer any significant benefit when compared with placebo in reducing the risk of clinical deterioration (risk ratio [RR] = 0.83; 95% CI: 0.65-1.06, P = 0.14, I2 = 29%), and hospitalization (RR = 0.80; 95% CI: 0.62-1.04, P = 0.09, I2 = 0%) of Covid-19 outpatients. The serious adverse events did not differ significantly between the 2 groups. CONCLUSIONS AND RELEVANCE: This study indicates that although safe, fluvoxamine was not effective for outpatient treatment of Covid-19. Until more evidence can be obtained from larger RCTs, our study did not encourage the use of fluvoxamine as routine management for patients with Covid-19.

Efficacy and safety of tixagevimab-cilgavimab as pre-exposure prophylaxis for COVID-19: A systematic review and meta-analysis.

Some proportions of populations, such as immunocompromised patients and organ transplant recipients might have inadequate immune responses to the vaccine for coronavirus disease 2019 (COVID-19). For these groups of populations, administering monoclonal antibodies might offer some additional protection. This review sought to analyze the effectiveness and safety of tixagevimab-cilgavimab (Evusheld) as pre-exposure prophylaxis against COVID-19. We used specific keywords to comprehensively search for potential studies on PubMed, Scopus, Europe PMC, and ClinicalTrials.gov sources until 3 September 2022. We collected all published articles that analyzed tixagevimab-cilgavimab on the course of COVID-19. Review Manager 5.4 was utilized for statistical analysis. Six studies were included. Our pooled analysis revealed that tixagevimab-cilgavimab prophylaxis may decrease the rate of SARS-CoV-2 infection (OR: 0.24; 95% CI: 0.15-0.40, p < 0.00001, I2  = 75%), lower COVID-19 hospitalization rate (OR: 0.13; 95% CI: 0.07-0.24, p < 0.00001, I2  = 0%), decrease the severity risk (OR: 0.13; 95% CI: 0.07-0.24, p < 0.00001, I2  = 0%), and lower COVID-19 deaths (OR: 0.17; 95% CI: 0.03-0.99, p = 0.05, I2  = 72%). In the included studies, no major adverse events were reported. This study proposes that tixagevimab-cilgavimab was effective and safe for preventing COVID-19. Tixagevimab-cilgavimab may be offered to those who cannot be vaccinated or have inadequate immune response from the COVID-19 vaccine to give additional protection.

Immune-Mediated Adverse Drug Reactions (IM-ARDs) in the Form of Drug-Induced Immune Thrombocytopenia and Cutaneous Adverse Drug Reactions (CARD) Due to Clindamycin in an Human Immunodeficieny Virus (HIV) Patient.

BACKGROUND Many drugs have been reported to cause immune-mediated adverse drug reactions (IM-ADRs) in human immunodeficiency virus (HIV) patients; the most common is cutaneous adverse drug reaction (CADR). Immune thrombocytopenia purpura (ITP) is frequent in HIV patients, and it can be caused HIV, opportunistic infections, or drugs. Although drugs can cause immune thrombocytopenia, termed drug-induced immune thrombocytopenia (DIIT), there has been no study on DIIT in HIV patients. CASE REPORT A 33-year-old male patient was admitted to our hospital with pruritic skin lesion over the entire body, which started 7 days before. He was diagnosed with HIV infection, brain toxoplasmosis, and pulmonary tuberculosis 2 weeks before admission, and was given trimethoprim sulphamethoxazole, isoniazid, rifampicin, pyrazinamide, and ethambutol. Clindamycin was added 10 days before admission. Skin examination revealed generalized erythematous macules with palpable petechiae and purpura. The platelet count was 141 000/µL when he was diagnosed with HIV, and it was 2000/µL at the time of admission. Clindamycin was discontinued and he was given steroids and platelet transfusion. The skin lesions improved along with an increased platelet count. He was discharged on the 10th day of admission, with platelet count of 42 000/µL. When he returned to the outpatient clinic on the 15th day, his platelet was 54 000/µL. The skin lesions had resolved completely and become hyperpigmented, and no purpura or petechiae were seen. CONCLUSIONS We present a case of an HIV patient with IM-ADR in the form of DIIT in conjunction with CADR that might have been caused by clindamycin.

Non-alcoholic fatty liver disease (NAFLD) and COVID-19 outcomes: A systematic review, meta-analysis, and meta-regression.

It is important to identify risk factors for poor outcomes of coronavirus disease 2019 (COVID-19) patients. Currently, the correlation between non-alcoholic fatty liver disease (NAFLD) and COVID-19 outcomes has not been established. This study was conducted to determine the association between NAFLD and in-hospital outcomes of COVID-19 patients. The systematic searches were conducted by using PubMed and the Europe PMC databases and particular keywords were used as of December 10, 2020. Further searches were conducted up to 2022. All articles that include data about COVID-19 and fatty liver disease were collected. Statistical analysis was performed by using Review Manager 5.4 and Comprehensive Meta-Analysis version 3 software. A total of 7,210 COVID-19 patients from 18 studies were included in the final analysis. Meta-analysis revealed that NAFLD increased the risk of developing poor in-hospital outcome (pooled both severe disease and death) in COVID-19 patients (RR 1.42; 95%CI: 1.17-1.73, p<0.001, I2=84%, random-effect modeling). Subgroup analysis however found that having NAFLD only increased the chance of getting severe COVID-19 (RR 1.67; 95%CI: 1.32-2.13, p<0.001, I2=86%, random-effect modeling) and not mortality (RR 1.00; 95%CI: 0.68-1.47, p=0.98, I2=80%, random-effect modeling). Meta-regression suggested that age (p=0.001) and diabetes (p=0.029) were significantly influenced the relationship between NAFLD and in-hospital outcomes of COVID-19 (pooled both severe disease and mortality). The weaker association of NAFLD and in-hospital outcomes of COVID-19 was found for studies with median age ≥45 years old (RR 1.29) when compared to studies with median age <45 years old (RR 2.96). In addition, studies with the prevalence of diabetes ≥25% (RR 1.29) had a weaker association with in-hospital outcomes when compared to studies with diabetes prevalence <25% (RR 1.85). In conclusion, NAFLD increased the risk of chance of getting severe COVID-19 and therefore it should be evaluated closely to reduce the chance of getting severe COVID-19.

Association between viral hepatitis and increased risk of severe coronavirus disease 2019 (COVID-19) outcome: a systematic review and meta-analysis.

Aim: The purpose of the current study is to analyze the potential association between viral hepatitis and the severity of COVID-19. Background: Coronavirus disease 2019 (COVID-19) is a worldwide concern that has created major issues with many aspects. It is important to identify the risk factors for severe outcomes of this disease. To date, no association between viral hepatitis and severe COVID-19 has not been established. Methods: Through November 5th, 2020, the databases of PubMed, Google Scholar, and medRxiv were systematically searched using specific keywords related to the focus of the study. All articles published on COVID-19 and viral hepatitis were retrieved. The Mantel-Haenszel formula with random-effects models was used to obtain the risk ratio (RR) along with its 95% confidence intervals (CIs) for dichotomous variables. The two-tailed p-value was set with a value ≤0.05 considered statistically significant. Restricted-maximum likelihood meta-regression was done for several variables, such as age, gender, hypertension, diabetes, and other liver disease. Results: Analysis results included a total of 16 studies with a total of 14,682 patients. Meta-analysis showed that viral hepatitis increases the risk of developing severe COVID-19 (RR 1.68 (95% CI 1.26 - 2.22), p = 0.0003, I 2 = 21%, random-effect modeling). According to the meta-regression analysis, the association between viral hepatitis and severe COVID-19 was not influenced by age (p = 0.067), diabetes (p = 0.057), or other liver disease (p = 0.646). Conclusion: An increase of severe COVID-19 risk is associated with viral hepatitis. To reduce the risk of COVID-19, patients with viral hepatitis should be monitored carefully.

Pre-Admission Beta-Blocker Therapy and Outcomes of Coronavirus Disease 2019 (COVID-19): A Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: Hypertension and heart failure are known risk factors for coronavirus disease 2019 (COVID-19) severity and mortality outcomes. Beta-blocker is one of the drugs of choice to treat these conditions. The purpose of this study is to explore the relationship between preadmission beta-blocker use and COVID-19 outcomes. METHODS: PubMed and Europe PMC were used as the database for our search strategy by using combined keywords related to our aims until December 10th, 2020. All articles related to COVID- 19 and beta-blocker were retrieved. Review Manager 5.4 and Comprehensive Meta-Analysis 3 software were used to perform statistical analysis. RESULTS: A total of 43 studies consisting of 11,388,556 patients were included in our analysis. Our meta-analysis showed that the use of beta-blocker was associated with increased risk of COVID-19 [OR 1.32 (95% CI 1.02 - 1.70), p = 0.03, I2 = 99%, random-effect modelling], clinical progression [OR 1.37 (95% CI 1.01 - 1.88), p = 0.04, I2 = 89%, random-effect modelling], and mortality from COVID-19 [OR 1.64 (95% CI 1.22 - 2.19), p = 0.0009, I2 = 94%, random-effect modelling]. Metaregression showed that the association with mortality outcome were influenced by age (p = 0.018) and hypertension (p = 0.005). CONCLUSION: The risk and benefits of using beta-blocker as a drug of choice to treat hypertensive patients should be considered and reviewed individually, case by case, knowing their association with higher incidence and severity of COVID-19 infections. Other first-line antihypertensive drugs may be considered as an alternative therapy if the risk of administering beta blockers outweighs the benefits of COVID-19 infection. REGISTRATION DETAILS: PROSPERO (CRD42021260455).

Coronavirus disease 2019 (Covid-19) outcomes in patients with sarcopenia: A meta-analysis and meta-regression.

BACKGROUND: Sarcopenia has been associated with patients' poor quality of life, disability, and hospitalization. As of today, evidence that highlights the association between sarcopenia and Covid-19 outcomes remains unclear. This study sought to analyze whether patients with sarcopenia are at higher risk for developing poor Covid-19 outcomes. METHODS: Using specific keywords, we comprehensively go through the potential articles on medRxiv, Europe PMC, and PubMed sources until July 31st, 2021. All published studies on sarcopenia and coronavirus disease 2019 were collected. We were using Review Manager 5.4 and Comprehensive Meta-Analysis 3 software to conduct statistical analysis. RESULTS: There were 9 studies with 492,245 Covid-19 patients included in the analysis. Evaluation of the data gathered yielded an association between sarcopenia and increased severity of Covid-19 (OR 1.99; 95%CI: 1.37-2.90, p = 0.0003, I2 = 79%, random-effect modelling); and mortality from Covid-19 (OR 1.96; 95%CI: 1.11-3.46, p = 0.020, I2 = 49%, random-effect modelling). The increased risk of developing severe Covid-19 in a sarcopenic patient is also further influenced by cancer. CONCLUSIONS: This study proposes that patients with sarcopenia are at risk of developing poor Covid-19 outcomes. Patients with sarcopenia need special attention and should be prioritized to receive the SARS-CoV-2 vaccine. REGISTRATION DETAILS: PROSPERO (CRD42021270725).

Factors associated with side effects of COVID-19 vaccine in Indonesia.

PURPOSE: As coronavirus disease 2019 (COVID-19) continues to spread rapidly causing approximately 186 million confirmed cases around the world, the urgency to reach herd immunity through vaccination is increasing. However, vaccine safety is a top priority to limit the occurrence of adverse events. Henceforth, this study aims to recognize and perceive COVID-19 vaccine safety in Indonesia during the pandemic. MATERIALS AND METHODS: This is a cross-sectional study and was conducted in Indonesia during the COVID-19 pandemic using an online survey of demographic information and a qualitative questionnaire. Responses were recorded and the association between demographic characteristics from survey questions was tested using chi-square with a risk estimate and 95% confidence interval. RESULTS: A total of 311 participants from 33 out of 34 provinces in Indonesia participated in this study. Recorded responses showed multiple side effects of the COVID-19 vaccine both short- and long-term experienced by the participants. Significant associations were found between demographic factors and COVID-19 vaccine side effects such as female gender with short-term puncture site (odds ratio [OR], 0.463; 95% confidence interval [CI], 0.263-0.816) and short-term other reactions (OR, 0.463; 95% CI, 0.263-0.816), domicile outside Java island with long-term puncture site (OR, 4.219; 95% CI, 1.401-12.701) and immune reactions (OR, 3.375; 95% CI, 1.356-8.398), also between married marital status and long-term vagal reaction (OR, 4.655; 95% CI, 1.321-16.409). CONCLUSION: Gender, domicile and marital status factors were associated with COVID-19 vaccine side effects in Indonesian people.

Insulin Therapy and Outcome of Coronavirus Disease 2019 (COVID-19): A Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: Currently, the relationship between insulin therapy and COVID-19 outcome is not yet established. Our study aims to evaluate the possible association between insulin and the composite poor outcome of COVID-19. METHODS: We systematically searched the PubMed and Europe PMC database using specific keywords related to our aims until December 12th, 2020. All articles published on COVID-19 and insulin were retrieved. Statistical analysis was done using Review Manager 5.4 and Comprehensive Meta-Analysis version 3 software. RESULTS: Our pooled analysis showed that insulin use was associated with composite poor outcomes of COVID-19 [OR 2.06 (95% CI 1.70 - 2.48), p < 0.00001, I2 = 83%, random-effect modelling], and its subgroup which comprised of risk of COVID-19 [OR 1.70 (95% CI 1.40 - 2.08), p < 0.00001, I2 = 34%, random-effect modelling], severe COVID-19 [OR 2.30 (95% CI 1.60 - 3.30), p < 0.00001, I2 = 88%, random-effect modelling], and mortality [OR 2.14 (95% CI 1.47 - 3.10), p < 0.0001, I2 = 85%, random-effect modelling]. Meta-regression showed that the association was influenced by age (p = 0.008), but not by diabetes p = 0.423) and cardiovascular disease (p = 0.086). CONCLUSION: Physicians should be more aware and take extra precautions with diabetes patients who use insulin therapy.

Mental health problems in Indonesian internship doctors during the COVID-19 pandemic.

BACKGROUND: All new graduate medical doctors in Indonesia will work in government healthcare facilities for one year as internship doctors. Problems such as the shortage of PPE, no specific treatment guidelines, and inadequate support from authorities, contributed to mental health problems. This study aimed to determine mental health problems and associated demographics and concerns of Indonesian internship doctors in the COVID-19 pandemic era. METHODS: This cross-sectional study was performed from 1-31 Januari 2021 via Google Form questionnaire to collect data. Logistic regression analysis was used to identify the association between demographic data, concerns in internship doctors' working place, and mental health using Depression Anxiety Stress Scale 21. RESULTS: Depression, anxiety, and stress in internship doctors were 32.6, 44.1, and 19.5% consecutively. Multivariate analysis showed that the only demographic factor associated with depression was female sex. Concerns of internship doctors were the most factors associated with mental health. Working in triage was associated with depression and stress. Donning and doffing training of PPE, difficulty to practice physical distancing and hesitancy to attend patients were associated with depression and anxiety. Difficulty to practice physical distancing in hospital w associated with anxiety and stress. LIMITATION: Firstly, some difficulties in data collection. Secondly, the self-reported tools of mental health are not always aligned with the psychiatric assessment. Lastly, possibility of recall biases from each batch. CONCLUSIONS: To minimize mental health problems of internship doctors, their concerns must be tackled. Medical schools have an important role to manage concerns of these internship doctors.

Psychiatric sequelae in COVID-19 survivors: A narrative review.

In December 2019, a novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was initially reported in Wuhan, China. Previous epidemics including SARS and middle east respiratory syndrome raises concern that COVID-19 infection may pose a significant threat to the mental health of affected individuals. Studies and reviews have shown the acute psychiatric manifestations in COVID-19 patients, although long term psychiatric sequelae are predicted, there are only few review studies about the long term psychiatry outcome in COVID-19 survivors. Clinically significant post-traumatic stress disorder, anxiety, and/or depression among COVID-19 survivors during 14-90 d were observed following the diagnosis. Risk of anxiety or depression were higher in patients with more severe illness at 6 mo follow-up, early convalescence, and at 1 mo follow-up. Diagnosis of COVID-19 Led to more first diagnoses and relapses of psychiatric illness during the first 14-90 d after COVID-19 diagnosis. The possible underlying mechanisms of psychiatric sequelae in COVID-19 infection are neurotropism, immune response to SARS-CoV-2, hypothalamo-pituitary-adrenal axis hyperactivity, disrupted neuronal circuits in several brain regions, increased stress levels, neuroinflammation, and neuronal death. This study will review the psychiatric sequelae in previous coronavirus pandemics, current studies, risk factors, and thorough explanation on pathophysiology of the psychiatric sequalae in COVID-19 survivors.

Adolescents' mental health status and influential factors amid the Coronavirus Disease pandemic.

Background The preventive measure of Coronavirus Disease pandemic, such as nationwide lockdown, might lead to stress, depression, and anxiety, prominently in adolescents. Many factors were indicated to influence its severity. This study aimed to investigate the magnitude of COVID-19-related mental health problems in adolescents and the associated factors. Methods This cross-sectional study gathered 2018 adolescents throughout Indonesia from April 22nd-28th 2020. The questionnaire was spread through social media and included Kessler-10 Psychological Distress scale and closed-ended questions about the risk and protective factors. The results were analyzed using Mann-Whitney U test, Kruskal-Wallis test, and Logistic Regression. Results The participants were mostly males (91.8%) with a median age of 19. The results showed 54.1% experienced varying degrees of distress. All variables were significantly related with psychological distress during Mann-Whitney-U and Kruskal-Wallis test. The logistic regression analysis showed maintaining or improving dietary pattern and sleep quality was found to be protective against psychological distress (OR = 0.497,95%CI = 0.34-0.725 and OR = 0.515,95%CI = 0.372-0.714, respectively), while others were risk factors, i.e.: Not having a confidant (OR = 1.539,95%CI = 1.226-1.931), frequent argument with parents (OR = 1.735,95%CI = 1.343-2.24), feeling worried (OR = 2.364, 95%CI1.528-3.656), chronic diseases (OR = 2.601,95%CI = 1.468-4.606), and mental illnesses (OR = 9.866,95%CI = 3.855-25.249). Conclusion More than half of adolescents experienced distress. The findings called for initiatives by experts in providing psychosocial support for adolescents.

The role of COVID-19 survivor status and gender towards neutralizing antibody titers 1, 2, 3 months after Sinovac vaccine administration on clinical-year medical students in Indonesia.

BACKGROUND: Sinovac was the first vaccine used in Indonesia against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, data regarding the effects of certain variables such as clinical demographics on antibody levels in individuals vaccinated with Sinovac are scarce. This study aimed to investigate the impact of gender and previous SARS-CoV-2 infection status on neutralizing antibody titers 1, 2, and 3 months after administration of the Sinovac vaccine. METHOD: A cross-sectional study was conducted from February to May 2021. Data on neutralizing antibody levels, previous SARS-CoV-2 infection status, and gender were retrieved from the monthly quantitative serology evaluation database of Siloam Hospitals Lippo Village, Tangerang, Indonesia. The role of each variable was analyzed using the t-test or Mann-Whitney U test, depending on data distribution. RESULT: Data from 350 participants were collected for the study. Participants with a history of a positive SARS-CoV-2 RT-PCR test had significantly higher neutralizing antibody titers in the first (144 U/mL, p = 0.036) and second months (144 U/mL, p = 0.005) after vaccination compared with those without a history of positive RT-PCR test. Female participants also had significantly higher neutralizing antibody titers in the first, second, and third months (43 U/mL, 42 U/mL, and 39 U/mL, respectively; p = 0.001, p = 0.002, and p = 0.003, respectively) after vaccination compared to males. CONCLUSION: COVID-19 survivor status and the female gender were associated with higher neutralizing antibody titers after Sinovac vaccine administration.

Pre-admission glucagon-like peptide-1 receptor agonist (GLP-1RA) and mortality from coronavirus disease 2019 (Covid-19): A systematic review, meta-analysis, and meta-regression.

AIMS: GLP-1RA has many beneficial properties, including anti-inflammatory, anti-obesogenic, pulmonary protective effects as well as beneficial impact on gut microbiome. However, the evidence regarding the benefit of GLP-1RA in Covid-19 patients with diabetes is still unclear. This study sought to analyze the benefit of pre-admission use of GLP-1RA in altering the mortality outcomes of coronavirus disease 2019 (Covid-19) patients with diabetes mellitus. METHODS: Using specific keywords, we comprehensively searched the potential articles on PubMed, Europe PMC, and medRxiv database until June 12th, 2021. All published studies on Covid-19 and GLP-1RA were retrieved. Statistical analysis was conducted using Review Manager 5.4 and Comprehensive Meta-Analysis version 3 software. RESULTS: A total of 9 studies with 19,660 diabetes mellitus patients who were infected by SARS-CoV-2 were included in the meta-analysis. Our data suggested that pre-admission use of GLP-1RA was associated with reduction in mortality rate from Covid-19 in patients with diabetes mellitus (OR 0.53; 95 %CI: 0.43-0.66, p < 0.00001, I2 = 0%, random-effect modelling). Further analysis showed that the associations were not influenced by age (p = 0.213), gender (p = 0.421), hypertension (p = 0.131), cardiovascular disease (p = 0.293), nor the use of metformin (p = 0.189) and insulin (p = 0.117). CONCLUSIONS: Our study suggests that pre-admission use of GLP-1RA may offer beneficial effects on Covid-19 mortality in patients with diabetes mellitus. However, more randomized clinical trials are required to confirm this conclusion.

Delirium is a good predictor for poor outcomes from coronavirus disease 2019 (COVID-19) pneumonia: A systematic review, meta-analysis, and meta-regression.

AIM: Delirium is a common presenting symptom among older patients. Patients who presented with delirium may have a higher morbidity and mortality rate due to older age, other comorbidities, and atypical COVID-19 presentation. Currently, the evidence supporting delirium as one of the predictors of poor outcome of COVID-19 is still insufficient. This study aims to explore the potential association between delirium and poor outcomes from COVID-19. METHODS: We systematically searched the PubMed and Google Scholar databases using specific keywords related to our aims until January 30th, 2021. All articles published on COVID-19 and delirium were retrieved. The quality of the study was assessed using the Newcastle Ottawa Scale (NOS) tool for observational studies and Joanna Briggs Institute (JBI) Critical Appraisal Tools for case-series studies. Statistical analysis was done using Review Manager 5.4 software. RESULTS: Our meta-analysis of 20 studies showed that delirium symptoms on admission was associated with poor outcomes from COVID-19 [OR 2.36 (95% CI 1.80-3.09), p < 0.00001, I2 = 76%, random-effect models] and its subgroup which consist of severe COVID-19 [OR 3.89 (95% CI 1.72-8.75), p = 0.001, I2 = 91%, random-effect models], and mortality from COVID-19 [OR 1.90 (95% CI 1.55-2.33), p < 0.00001, I2 = 36%, random-effect models]. Meta-regression showed that the association was influenced by age (p = 0.005). CONCLUSIONS: Our study suggests delirium as an important marker to identify patients at higher risk for developing poor COVID-19 outcomes. The physicians should add delirium as one of the common presenting symptoms of COVID-19 in older populations.