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.

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.

Tocilizumab administration is associated with the reduction in biomarkers of coronavirus disease 2019 infection.

Coronavirus disease 2019 (COVID-19) has caused a significant impact on all aspects of life, with the number of death cases still increasing. Therefore, identification of potential treatment for reducing the severity of the disease is important. Currently, the data regarding the effectiveness of tocilizumab as treatment agents for COVID-19 infection is still conflicting. This study aims to give clear evidence regarding the potential benefit of tocilizumab in reducing the biomarkers of COVID-19 infection. We systematically searched the PubMed Central database using specific keywords related to our aims until July 24th, 2020. All articles published on COVID-19 and tocilizumab were retrieved. A total of 9 studies with a total of 577 patients were included in our analysis. Our meta-analysis showed that tocilizumab treatment is associated with reduction of C-reactive protein (mean difference [MD]: -106.69 mg/L [95% confidence interval [CI]: -146.90, -66.49 mg/L], p < .00001; I2 = 98%, random-effect modeling), d-dimer (MD: -3.06 mg/L [95% CI: -5.81, -0.31 mg/L], p = .03; I2 = 98%, random-effect modeling), Ferritin (MD: -532.80 ng/ml [95% CI: -810.93, -254.67 ng/ml], p = .0002; I2 = 25%, random-effect modeling), procalcitonin (MD: -0.67 ng/ml [95% CI: -1.13, -0.22 ng/ml], p = .004; I2 = 92%, random-effect modeling], and increment in the levels of lymphocyte count (MD: 0.36 × 103 /µl [95% CI: 0.18, 0.54 × 103 /µl], p < .0001; I2 = 88%, random-effect modeling). Administration of tocilizumab is effective in reducing the biomarkers of the COVID-19 infection.

Experience of using tocilizumab for treatment in Indonesian patients with severe COVID-19.

COVID-19 is a public health emergency of international concern with millions confirmed cases globally including in Indonesia with more than two hundred thousand confirmed cases to date COVID-19. (1) COVID-19 has wide clinical manifestation ranging from asymptomatic, acute respiratory illness, respiratory failure that necessitates mechanical ventilation and support in an ICU, to MODS. (2) Several comorbidities have been demonstrated to be associated with the development of severe outcomes from COVID-19 infection, such as hypertension, diabetes, cardiovascular disease, dyslipidemia, thyroid disease, and pulmonary disease. (3)-(5) Severe COVID-19 is associated with increased plasma concentrations of IL-6, resulting in cytokine storm. (6) Tocilizumab, an interleukin-6 inhibitor, might alleviates the cytokine storm, prevents significant lungs and organs damage, thus improving clinical outcomes. (7) Therefore, tocilizumab, might be one of the promising therapies for severe COVID-19. (8) However there were limited studies regarding the efficacy in COVID-19 patients, especially with control group. We would like to report our experience in using tocilizumab as treatment in severe COVID-19 patients in Indonesia, which is the first in Indonesia to the best of our knowledge.

Statin and outcomes of coronavirus disease 2019 (COVID-19): A systematic review, meta-analysis, and meta-regression.

AIMS: One of the comorbidities associated with severe outcome and mortality of COVID-19 is dyslipidemia. Statin is one of the drugs which is most commonly used for the treatment of dyslipidemic patients. This study aims to analyze the association between statin use and composite poor outcomes of COVID-19. DATA SYNTHESIS: We systematically searched the PubMed and Europe PMC database using specific keywords related to our aims until November 25th, 2020. All articles published on COVID-19 and statin were retrieved. Statistical analysis was done using Review Manager 5.4 and Comprehensive Meta-Analysis 3 software. RESULTS: A total of 35 studies with a total of 11, 930, 583 patients were included in our analysis. Our meta-analysis showed that statin use did not improve the composite poor outcomes of COVID-19 [OR 1.08 (95% CI 0.86-1.35), p = 0.50, I2 = 98%, random-effect modelling]. Meta-regression showed that the association with composite poor outcomes of COVID-19 was influenced by age (p = 0.010), gender (p = 0.045), and cardiovascular disease (p = 0.012). Subgroup analysis showed that the association was weaker in studies with median age ≥60 years-old (OR 0.94) compared to <60 years-old (OR 1.43), and in the prevalence of cardiovascular disease ≥25% (RR 0.94) compared to <25% (RR 1.24). CONCLUSION: Statin use did not improve the composite poor outcomes of COVID-19. Patients with dyslipidemia should continue taking statin drugs despite COVID-19 infection status, given its beneficial effects on cardiovascular outcomes.

Colchicine treatment can improve outcomes of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

Currently, there is no widely acceptable and proven effective treatment for coronavirus disease 2019 (COVID-19). Colchicine has been shown to offer a benefit in reducing the inflammation in several inflammatory diseases. This study aims to analyze the efficacy of colchicine administration and outcomes of COVID-19. We systematically searched the PubMed and Europe PMC database using specific keywords related to our aims until January 29, 2021. All articles published on COVID-19 and colchicine treatment were retrieved. The quality of the study was assessed using the Newcastle-Ottawa Scale (NOS) tool for observational studies and Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) for clinical trial studies. Statistical analysis was done using Review Manager 5.4 software. A total of eight studies with 5778 COVID-19 patients were included in this meta-analysis. This meta-analysis showed that the administration of colchicine was associated with improvement of outcomes of COVID-19 [OR 0.43 (95% CI 0.34-0.55), p < 0.00001, I2  = 0%, fixed-effect modelling] and its subgroup which comprised of reduction from severe COVID-19 [OR 0.44 (95% CI 0.31-0.63), p < 0.00001, I2  = 0%, fixed-effect modelling] and reduction of mortality rate from COVID-19 [OR 0.43 (95% CI 0.32-0.58), p < 0.00001, I2  = 0%, fixed-effect modelling]. Our study suggests the routine use of colchicine for treatment modalities of COVID-19 patients. More randomized clinical trial studies are still needed to confirm the results from this study.

Inflammatory and hematologic markers as predictors of severe outcomes in COVID-19 infection: A systematic review and meta-analysis.

BACKGROUND: Laboratory testing is commonly performed in patients with COVID-19. Each of the laboratory parameters has potential value for risk stratification and prediction of COVID-19 outcomes. This systematic review and meta-analysis aimed to evaluate the difference between these parameters in severe and nonsevere disease and to provide the optimal cutoff value for predicting severe disease. METHOD: We performed a systematic literature search through electronic databases. The variables of interest were serum procalcitonin, albumin, C-reactive protein (CRP), D-dimer, and lactate dehydrogenase (LDH) levels in each group of severity outcomes from COVID-19. RESULTS: There were a total of 4848 patients from 23 studies. Our meta-analysis suggest that patients with severe COVID-19 infections have higher procalcitonin, (mean difference 0.07; 95% CI 0.05-0.10; p < 0.00001), CRP (mean difference 36.88; 95% CI 29.10-44.65; p < 0.00001), D-Dimer (mean difference 0.43; 95% CI 0.31-0.56; p < 0.00001), and LDH (mean difference 102.79; 95% CI 79.10-126.49; p < 0.00001) but lower levels of albumin (mean difference -4.58; 95% CI -5.76 to -3.39; p < 0.00001) than those with nonsevere COVID-19 infections. The cutoff values for the parameters were 0.065 ng/mL for procalcitonin, 38.85 g/L for albumin, 33.55 mg/L for CRP, 0.635 µ/L for D-dimer, and 263.5 U/L for LDH, each with high sensitivity and specificity. CONCLUSION: This meta-analysis suggests elevated procalcitonin, CRP, D-dimer, and LDH and decreased albumin can be used for predicting severe outcomes in COVID-19.

Correction: Potential Correlates of Internet Gaming Disorder Among Indonesian Medical Students: Cross-sectional Study.

[This corrects the article DOI: 10.2196/25468.].

Potential Correlates of Internet Gaming Disorder Among Indonesian Medical Students: Cross-sectional Study.

BACKGROUND: Internet gaming disorder has been a controversial topic for nearly a decade. Although internet addiction has been studied in medical students, there is a paucity of evidence regarding internet gaming disorder. Previous studies in Indonesia explored only the prevalence rate and characteristics. OBJECTIVE: This study aimed to determine the prevalence rate of internet gaming disorder and correlations between internet gaming disorder, temperament, and psychopathology among Indonesian medical students. METHODS: A cross-sectional study was performed from August 2019 to September 2019 using total and convenience sampling at a private university and a public university, respectively. The study variables were measured using the Indonesian version of the 10-item Internet Gaming Disorder Test, the Temperament and Character Inventory, and the Symptoms Checklist 90. Chi-square and logistic regression analyses were conducted to examine the relationships between demographic factors, temperament, psychopathology, and the presence of internet gaming disorder. RESULTS: Among the 639 respondents, the prevalence rate of internet gaming disorder was 2.03% (n=13), with a mean age of 20.23 (SD 0.13) years and an average gaming duration of 19.0 (SD 0.96) hours/week. Up to 71.2% respondents played using their mobile phones, and respondents with internet gaming disorder reported experiencing all psychopathologies assessed, except phobic anxiety. Bivariate analysis demonstrated that internet gaming disorder was associated with gender, gaming duration, gaming community affiliation, and 9 out of 10 domains of psychopathology. In a logistic regression model, internet gaming disorder was correlated with weekly gaming hours ≥20 hours (odds ratio [OR] 4.21, 95% CI 1.08-16.38, P=.04). CONCLUSIONS: These findings suggest that the prevalence of internet gaming disorder among medical students in Jakarta, Indonesia is similar to that in other populations of Asian countries. The predisposing factor for internet gaming disorder was weekly gaming duration, while other demographic, temperament, and psychopathology variables acted as probable moderators. Strategies should, therefore, be developed and integrated into medical curriculum to screen and aid individuals with these predisposing factors.

Immunoglobulin G (IgG) to IgM ratio in secondary adult dengue infection using samples from early days of symptoms onset.

BACKGROUND: Dengue virus (DENV) infection is an emerging arboviral infection in tropical and sub-tropical countries in South-East Asia, the Western Pacific and South and Central America. Secondary DENV infection is the most widely accepted risk factor for the development of severe forms. Methods to discriminate primary and secondary DENV infection may be of great prognostic value. ELISA based detection of specific antibodies (IgG and IgM) to the four DENV serotypes is valuable for determination of primary or secondary infection. Several studies had been performed to discriminate primary and secondary DENV infection using the ratio of IgG and IgM at the various days of symptoms onset. The aim of this study is to determine the best cut-off point of IgG to IgM ratio is able to discriminating secondary from primary DENV infection in adult using samples from early days of symptoms onset. METHODS: This prospective cohort study on 48 adult patients with DENV infected patients on the period of August 2011-January 2012 in 5 out-patient settings health facilities in Tangerang district, Banten province, Indonesia with chief complaint of fever less than 3 days. Datas were collected on the day the patients attended health facilities, consisted of demographic, clinical, laboratory, and serological data. Serological data from 48 serum sample from adult patients were evaluated using Focus Diagnostics Dengue Virus IgM and IgG Capture DxSelect™ ELISA Kits to determine IgG, IgM index values and SD Bioline Dengue Duo™ Rapid Tests to determine NS1, IgG, and IgM result. RESULTS: According to NS1, IgG and IgM results, 36 patients were classified as secondary infection, 12 were primary Infection. The mean (SD) of IgG/IgM ratios for secondary and primary infection were 3.28 (0.54) and 0.18 (0.11) consecutively. The IgG/IgM ratio of ≥ 1.14 confirmed secondary infection with sensitivity of 80.56 %, specificity 91.67 %, accuracy level 83.33 %, and likely hood ratio of (LR) 9.67. CONCLUSION: The IgG/IgM ratio of ≥ 1.14 as the best cut off point to determine secondary DENV infection in early days of symptoms onset.

Hemoperitoneum caused by spontaneous rupture of hepatocellular carcinoma.

We are reporting a male, 46 years old came to emergency unit with a chief complaint of abdominal tenderness since 1 day prior to admission. No history of abdominal trauma. He often felt abdominal discomfort for the last 5 years. Physical examination revealed decreased consciousness, shock, pale conjungtiva, distended abdomen, with tenderness of the whole abdomen on palpation, and no bowel movement. Laboratory examination found anemia, leucocytosis, normal amilase and lipase. FAST (focus assissted Sonography on trauma) found massive ascites. Patient underwent cito laparotomic exploration that found blood on abdominal cavity, nodular liver, and actively bleeding tumour of liver. During hospitalization, patient recovered and discharged. In the case of acute abdomen, spontaneous ruptured hepatocellular carcinoma (HCC) is one of differential diagnosis, considering high incidence of HCC in South East Asia, especially Indonesia. Confirming diagnosis of generalized peritonitis requires abdominal CT scan and ultrasonography, to rule out ruptured HCC.

Pulmonary papillomatosis: a rare case of recurrent respiratory papillomatosis presenting with multiple nodular and cavitary lesions.

Pulmonary papillomatosis is an extremely rare variant of recurrent respiratory papillomatosis which is hard to treat, causes prolonged morbidity, and may transform into malignant disorder in several cases. Since the symptoms and radiologic findings are not specific, pulmonary papillomatosis is often being misdiagnosed. Although considered benign, pulmonary papillomatosis carries the most significant mortality. This is a case report of a 26 year old man who complained recurrent chronic cough, slight hemoptoe, occasional pleuritic pain, and several episodes of fever. He also had laryngeal papillomatosis and undergone serial endoscopic resection since his childhood. Multiple nodular and cavitary lesions, some with air fluid level, were found in both lung fields at chest radiography and scintigraphy. Diagnosis of pulmonary papillomatosis complicated with secondary infection was made after endoscopic and histologic study.

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.

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.

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).