Management of drug-resistant tuberculosis in Indonesia: a four-year cascade of care analysis.

Background: In Indonesia, drug resistance testing for TB largely relies on Xpert MTB/RIF, and it is unknown what proportion of drug-resistant (DR) TB is adequately diagnosed and treated. Methods: We conducted a cascade of care analysis on a cohort of presumptive rifampicin-resistant (RR) TB patients registered in 2015-2018 in a tertiary hospital in Indonesia. Estimated incidences of (presumptive) DR-TB cases were assumption-based using global reports. Data on diagnosis and consecutive cascades steps, including their timing were collected from national electronic registers, and medical records. We described a secondary cascade for patients receiving treatment not supported by phenotypic drug susceptibility testing (pDST). Factors associated with delay and loss between diagnosis and treatment were identified using logistic regression. Findings: Less than a third of estimated incident TB cases at risk of DR-TB were identified as presumptive DR-TB case and tested, and 9.8% (982/10,065) of estimated true DR-TB cases was diagnosed. Of those diagnosed, only 45.1% (443/982) had treatment regimens supported by pDST results, but this did not significantly influence treatment outcomes. Only 25.5% (250/982) of diagnosed patients completed all steps of the cascade including successful treatment. Delays between diagnosis and treatment were substantial, and more common among those referred from a primary healthcare facility, and among those who were employed, living outside of Bandung, and reporting engagement with the private sector. Interpretation: The DR-TB care cascade in this urban setting in Indonesia is characterized by substantial attrition and delays. Strategies to increase access to DR-TB diagnosis accompanied by optimisation of clinical care could substantially improve outcomes and reduce onward transmission. Funding: Radboud university medical center and University of Otago.

The efficacy of thymosin alpha-1 therapy in moderate to critical COVID-19 patients: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: Effort to search for the optimal COVID-19 treatment has continuously been attempted. Thymosin alpha-1 have immunomodulatory properties which may be beneficial in case of viral infection. This study's goal is to determine whether thymosin alpha-1 is effective in treating people with moderate-to-severe COVID-19. METHODS: We searched for literature in 4 database: Scopus, Europe PMC, Medline, ClinicalTrials.gov, and Cochrane Library until March 25th, 2023. If those articles have data on the efficacy of thymosin alpha-1 therapy on COVID-19, they would be included. Risk ratio (RR) and Mean Difference (MD) along with their 95% confidence intervals were used to pool the results of dichotomous and continuous variables, respectively. RESULTS: Pooled data from 8 studies indicated that moderate to critical Covid-19 patients who were receiving thymosin alpha-1 therapy had significantly lower mortality from COVID-19 (RR 0.59; 95% CI 0.37-0.93, p = 0.02, I2 = 84%), but without any difference in the needs for mechanical ventilation (RR 0.83; 95% CI 0.48-1.44, p = 0.51, I2 = 74%) and hospital length of stay (MD 2.32; 95% CI - 0.93, 5.58, p = 0.16, I2 = 94%) compared to placebo. The benefits of thymosin alpha-1 on the mortality rate were significantly affected only by sample size (p = 0.0000) and sex (p = 0.0117). CONCLUSION: Our study suggests that treatment with thymosin alpha-1 may reduce mortality rate in moderate to critical COVID-19 patients. Randomized clinical trials (RCTs) are still required to verify the findings of our study.

High Levels of Anti-SARS-CoV-2 Receptor-Binding Domain (RBD) Antibodies One Year Post Booster Vaccinations among Hospital Workers in Indonesia: Was the Second Booster Needed?

In August 2022, Indonesia prioritized healthcare workers to receive the second booster dose. We conducted a sequential serosurvey to understand the dynamics of the antibody titers. The first serosurvey, which was conducted in June 2021, 1-6 months after Sinovac vaccination, showed a median antibody level of 41.4 BAU/mL (interquartile range (IQR): 10-629.4 BAU/mL). The second serosurvey was conducted one month (August 2021) after the first Moderna booster vaccine and showed a median level of 4000 BAU/mL (IQR: 3081-4000 BAU/mL). The last serosurvey was conducted a year (August 2022) after the booster and showed a median level of 4000 BAU/mL (IQR: 4000-4000 BAU/mL). In this last survey, only 39 (11.9%) of healthcare workers had antibody levels below the maximum level of 4000 BAU/mL. Thus, one year after the first booster dose, we did not observe the waning of antibody levels. The average increase was perhaps because of natural infection. Based on these considerations, we believe that a second booster dose was not necessary for this category of subjects at that time. Because vaccine supply is often limited, priority could be given to the general population or other high-risk patient groups with low antibody titers based on serological tests.

Effectiveness and safety of normoxic allogenic umbilical cord mesenchymal stem cells administered as adjunctive treatment in patients with severe COVID-19.

Inflammatory response in COVID-19 contributes greatly to disease severity. Mesenchymal Stem Cells (MSCs) have the potential to alleviate inflammation and reduce mortality and length of stay in COVID-19 patients. We investigated the safety and effectiveness of normoxic-allogenic umbilical cord (NA-UC)-MSCs as an adjunctive treatment in severe COVID-19 patients. A double-blind, multicentric, randomized, placebo-controlled trial involving severe COVID-19 patients was performed from January to June 2021 in three major hospitals across Java, Indonesia. Eligible participants (n = 42) were randomly assigned to two groups (1:1), namely the intervention (n = 21) and control (n = 21) groups. UC-MSCs dose was 1 × 106 /kg body weight on day D0, D3, and D6. The primary outcome was the duration of hospitalization. Meanwhile, the secondary outcomes were radiographical progression (Brixia score), respiratory and oxygenation parameters, and inflammatory markers, in addition to the safety profile of NA-UC-MSCs. NA-UC-MSCs administration did not affect the length of hospital stay of severe COVID-19 patients, nor did it improve the Brixia score or mMRC dyspnoea scale better than placebo. Nevertheless, NA-UC-MSCs led to a better recuperation in oxygenation index (120.80 ± 72.70 baseline vs. 309.63 ± 319.30 D + 22, p = 0.038) and oxygen saturation (97.24 ± 4.10% vs. 96.19 ± 3.75% in placebo, p = 0.028). Additionally, compared to the placebo group, the treatment group had a significantly smaller increase in PCT level at D + 22 (1.43 vs. 12.76, p = 0.011). No adverse effects, including serious ones, were recorded until D + 91. NA-UC-MSCs therapy is a very safe adjunct for COVID-19 patients. It improves the oxygenation profile and carries potential to suppress inflammation.

The effect of diabetes mellitus on COVID-19 mortality among patients in a tertiary-level hospital in Bandung, Indonesia.

Immune system dysregulation in people with diabetes mellitus (DM) increases the risk of acquiring severe infection. We compared the clinical characteristics and laboratory parameters of coronavirus disease 2019 (COVID-19) patients with and without DM and estimated the effect of DM on mortality among COVID-19 patients. A retrospective cohort study collecting patients' demographic, clinical characteristics, laboratory parameters and treatment outcomes from medical records was conducted in a hospital in Bandung City from March to December 2020. Univariable and multivariable logistic regression was performed to determine the association between DM and death. A total of 664 COVID-19 patients with positive real-time reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 were included in this study, of whom 147 were with DM. Half of DM patients presented HbA1c ≥10%. DM patients were more likely to present with comorbidities and severe to critical conditions at admission (P <0.001). Laboratory parameters such as neutrophil-lymphocyte count ratio, C-reactive protein, D-dimer, ferritin, and lactate dehydrogenase were higher in the DM group. In the univariate analysis, variables associated with death were COVID-19 severity at baseline, neurologic disease, DM, age ≥60 years, hypertension, cardiovascular disease, and chronic kidney disease. DM remained associated with death (aOR 1.82; 95% CI 1.13-2.93) after adjustment with sex, age, hypertension, cardiovascular disease, and chronic kidney disease. In conclusion, COVID-19 patients with DM are more likely to present with a very high HbA1c, comorbidities, and severe-critical illness. Chronic inflammation in DM patients may be aggravated by the disruption of immune response caused by COVID-19, leading to worse laboratory results and poor outcomes.

Antibodies against Histoplasma capsulatum and Aspergillus fumigatus among chronic TB patients in Indonesia: a cross-sectional study.

Chronic pulmonary fungal infections may occur in patients with previous history of pulmonary tuberculosis (TB), and are often clinically misclassified as TB, especially when bacteriological confirmation for Mycobacterium tuberculosis is absent. In this study, we investigated the prevalence of antibody against Histoplasma capsulatum and Aspergillus fumigatus in patients with confirmed and clinically chronic TB. Antibodies against H. capsulatum and A. fumigatus were measured from serum samples using enzyme-linked immunosorbent assay (ELISA). The presence M. tuberculosis in sputum was confirmed using smear microscopy, GeneXpert MTB/RIF assay, or culture. Antibodies against H. capsulatum and A. fumigatus were elevated in 16.9% and 26.9% of bacteriologically confirmed chronic TB patients, and 12.1% and 18.2% in those without bacteriological confirmation, respectively. Approximately one-third of patients who had positive anti-Histoplasma antibody also had elevated levels of antibody against Aspergillus fumigatus (P < .001). Our study highlights the importance of chronic pulmonary fungal infection in post-TB patients with recurrent respiratory symptoms.

This study describes the presence of antibodies against Aspergillus fumigatus and Histoplasma capsulatum in patient with pulmonary TB patients. Our study highlights the importance of chronic pulmonary fungal infections in post-TB patients with recurrent respiratory symptoms.

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.

MDR Pathogens Organisms as Risk Factor of Mortality in Secondary Pulmonary Bacterial Infections Among COVID-19 Patients: Observational Studies in Two Referral Hospitals in West Java, Indonesia.

Purpose: The coronavirus disease (COVID-19) outbreak has created a global health crisis. Secondary pulmonary bacterial infection is a COVID-19 complication, increasing morbidity and mortality. This study aimed to determine the pathogens, antibiotic susceptibility patterns, and risk factors for mortality in hospitalized COVID-19 patients. Patients and Methods: This retrospective study used secondary data from patients' electronic medical records at Hasan Sadikin General Hospital and Santo Borromeus Hospital between March 2020 and March 2021. Overall, 2230 hospitalized COVID-19 patients were screened, and 182 of them who were hospitalized ≥48 hours with a procalcitonin level of ≥0.25 ng/mL were enrolled. Culture examination was performed on sputum samples to determine pathogen and antibiotic susceptibilities. Univariate and multivariate analyses were used to determine mortality-related risk factors in hospitalized COVID-19 patients. Results: The prevalence of secondary pulmonary bacterial infections in COVID-19 patients was 8.2%, with 161/182 pathogen growth from sputum samples. Mainly gram-negative bacteria (64.8%) were present, including Acinetobacter baumannii (31.9%), Klebsiella pneumoniae (19.8%), and Pseudomonas aeruginosa (8.8%). High rate of multidrug-resistant (MDR) pathogens was found among isolate (45.9%), ie carbapenem-resistance A. baumannii (CR-Ab) was 84.2%, extended-spectrum ß-lactamase (ESBL) among K. pneumoniae was 61.1%. Secondary infection of MDR pathogens was associated with a higher risk of mortality (AOR 5.63, p = 0.001). Other associated factors were age ≥60 years, ventilator use, and female gender. Conclusion: Gram-negative bacteria are the predominant pathogens causing secondary pulmonary bacterial infection in COVID-19 patients, implying nosocomial infection. High resistance to first-line antimicrobial drugs was observed in Gram-negative bacteria and Gram-positive bacteria. High rate of MDR pathogens was found among isolate and was associated with a significant risk of mortality.

The role of 99mTc-ethambutol scintigraphy to diagnose pulmonary tuberculosis.

Tuberculosis is a significant health problem in many parts of the world. According to the Global Tuberculosis Report 2020, 10 million new tuberculosis cases were reported worldwide in 2019, with only 57% of these cases being bacteriologically confirmed. Current tuberculosis diagnostic tests depend on the quality of the sputum, leaving many diagnostic uncertainties. Diagnostic delays result in ongoing transmission and more severe, progressive disease in the affected person. This shows that current diagnostic tests are not sufficient to establish all tuberculosis cases accurately, and there is a need for a new diagnostic technique. 99mTc-ethambutol scintigraphy was recently reported as a new diagnostic test for tuberculosis, with a sensitivity and specificity of 93.9% and 85.7%, respectively. Here, we report a case of the importance of this new technique for diagnosing tuberculosis when the existing bacteriological and molecular tests failed to confirm the diagnosis.

Factors associated with treatment outcome of MDR/RR-TB patients treated with shorter injectable based regimen in West Java Indonesia.

BACKGROUND AND AIMS: Multi drug or rifampicin resistant tuberculosis (MDR/RR-TB) is a major burden to TB prevention and eradication globally. Since 2016, WHO guidelines have included options for treating MDR/RR-TB with a standard regimen of 9 to 11 months duration (the 'shorter regimen') rather than an individual regimen of at least 20 months. This regimen has been introduced in Indonesia since September 2017. Therefore, we aimed to determine the success rate and factors associated with the treatment outcome of shorter injectable based regimen in West Java province, Indonesia. METHODS: This was a retrospective cohort study of MDR/RR-TB patients aged over 18 years old who received the shorter injectable based regimen between September 2017 and December 2020. We defined successful outcomes as the combined proportion of patients who were cured or had complete treatment. While, unsuccessful outcomes were defined as the combined proportion of patients who died from any causes, failure, and loss to follow-up (LTFU). RESULTS: A total of 315 patients were included in this study. The success rate was 64.5%. Multivariate analysis showed male gender (aRR = 1.18, 95% CI 1.04 to 1.34) increased the chance of successful outcome, while malnutrition (aRR = 0.78, 95% CI 0.68 to 0.89), history of previous TB treatment (aRR = 0.80%CI 0.68 to 0.94), and time of culture conversion >2 months (aRR = 0.72 (95% CI 0.59 to 0.87) decreased the chance of successful outcome. CONCLUSION: History of previous TB treatment, time of culture conversion >2 months, and malnutrition were independent factors that decrease the chance for success rate, while male gender increase the likelihood for success rate of patients treated by the shorter injectable based regimen.

Polymorphisms of SLCO1B1 Gene in Sundanese Ethnic Population of Tuberculosis Patients in Indonesia.

BACKGROUND: The blood level of rifampicin, one of the tuberculosis (TB) drugs, depends on the organic anion transporting polypeptide 1B1 (OATP1B1) in hepatocytes. This protein is encoded by the solute carrier organic anion 1B1 (SLCO1B1) gene. Its genetic variation has been reported to have an impact on clinical outcomes and drug efficacy. However, the polymorphism in the SLCO1B1 gene has not been examined in Indonesia yet. We aimed to identify the frequency of polymorphism in SLCO1B1 gene among pulmonary TB patients in Bandung, Indonesia. METHODS: Cross-sectional study was conducted in West Java. 145 pulmonary TB patients who were treated with first-line drugs treatment (including rifampicin 450 mg daily) were analyzed for polymorphism in SLCO1B1 gene. Patients aged between 18-64 years old and mainly came from Sundanese ethnic group (92.4%). Genetic variants were detected using Polymerase Chain Reaction (PCR) and Sanger sequencing. RESULTS: Polymorphism of c.463C>A(rs11045819) was not identified, while heterozygous and homozygous polymorphism of c.85-7793C>T(rs4149032) were identified in 74 (51.0%) and 56 (38.6%) patients, respectively. The minor allele frequency (MAF) of T (mutant) allele of c.85-7793C>T(rs4149032) was 64.13% (186/209), higher than in the general population, which the MAF of rs4149032 is 53.6% based on 1000 genome database. CONCLUSION: This study highlights the presence of different allele frequencies of polymorphisms within the population, which might affect treatment outcomes.

Association Between Vitamin D Levels and FEV1, Number of Exacerbations, and CAT Score in Stable COPD Patients in Indonesia.

PURPOSE: This study aimed to assess the association between vitamin D levels and forced expiratory volume in one second (FEV1), number of exacerbations, and symptoms based on COPD assessment test (CAT) scores in stable COPD patients in Indonesia. PATIENTS AND METHODS: An observational cross-sectional study was conducted. Subjects were stable COPD patients who were treated at a pulmonary clinic in a tertiary referral hospital in West Java from March to June 2018. RESULTS: Thirty subjects were recruited this study with an average age 62±8 years. The mean vitamin D level was 20.17±8.91 ng/mL. Half of the patients had low vitamin D level (<20ng/mL) (50%). The mean FEV1 (%) predicted value was 37.2±14. The median exacerbation per year was 1 (0-5) and symptoms based on CAT score was 14 (3-34). No correlation was found between vitamin D levels and FEV1 (%) predicted value (r=0.126, p=0.253). Vitamin D level was inversely correlated with number of exacerbations (r=-0.639, p<0.001) and CAT (r= -0.802, p<0.001). CONCLUSION: Low level of vitamin D was associated with more frequent exacerbation and higher CAT scores but was not associated with FEV1 (%) predicted.

Asthma does not increase COVID-19 mortality and poor outcomes: A systematic review and meta-analysis.

BACKGROUND: The Center for Disease Control and Prevention (CDC) has mentioned Coronavirus Disease 2019 (COVID-19) patients with moderate or severe asthma as a high risk group for severe illness. While WHO mentioned only chronic respiratory diseases, not specifically asthma as a risk factor for severe illness. There has been asthma prevalence discrepancy in studies of COVID-19 across the world. OBJECTIVE: This meta-analysis aims to investigate the association between asthma and composite poor outcome in patients with coronavirus disease (COVID-19). METHODS: We conducted a systematic literature search from PubMed and Embase database. We included all original research articles with adult COVID-19 patients > 18 years old and had information related to asthma as a risk factor. Studies with outcomes consisting of mortality, severe COVID-19, use of mechanical ventilation, ICU admission, and hospital admission were included in this study. The outcomes of interest were divided into severe COVID-19, mortality and other poor outcomes. RESULTS: Eleven studies were included in meta-analysis with a total of 6,046 patients. Asthma was not associated with composite poor outcomes with OR = 0.92 (95%CI 0.71-1.19, p = 0.61, and I2 = 8.49%). Furthermore, subgroup analysis showed that asthma was not associated with severe COVID (p = 0.76), mortality (p = 0.45), and other poor outcomes (p = 0.28). CONCLUSIONS: Our study showed that asthma was not associated with severe COVID-19, mortality, and other poor outcomes in patients with COVID-19.

Current views on the potentials of convalescent plasma therapy (CPT) as Coronavirus disease 2019 (COVID-19) treatment: A systematic review and meta-analysis based on recent studies and previous respiratory pandemics.

Convalescent plasma therapy (CPT) has been investigated as a treatment for COVID-19. This review evaluates CPT in COVID-19 and other viral respiratory diseases, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and influenza. PubMed and Google scholar databases were used to collect eligible publications until 8 December 2020. Meta-analysis used Mantel-Haenszel risk ratio (RR) with 95% confidence interval (CI) and pooled analysis for individual patient data with inverse variance weighted average. The study is registered at PROSPERO with the number of CRD4200270579. Forty-four studies with 36,716 participants were included in the pooled analysis and 20 studies in the meta-analysis. Meta-analysis showed reduction of mortality (RR 0.57, 95% CI [0.43, 0.76], z = 3.86 [p < 0.001], I2  = 44% [p = 0.03]) and higher number of discharged patients (RR 2.53, 95% CI [1.72, 3.72], z = 4.70 [p < 0.001], I2  = 3% [p = 0.39]) in patients receiving CPT compared to standard care alone. A possible mechanism of action is prompt reduction in viral titre. Serious transfusion-related adverse events were reported to be less than 1% of cases, suggesting the overall safety of CPT; nevertheless, the number of patients participating in the studies was still limited. It is also important to notice that in all the studies, the majority of patients were also given other medications, such as antivirals, antibiotics and corticosteroid; furthermore, randomized controlled studies involving more patients and in combination with other treatment modalities are urgently needed.

Factors affecting outcome of longer regimen multidrug-resistant tuberculosis treatment in West Java Indonesia: A retrospective cohort study.

BACKGROUND: Multidrug-resistant tuberculosis had high treatment failure and mortality. Success rate of treatment currently 56% at global level, 48% in Indonesia and 36% in West Java province, the most populated province and surround Jakarta, the capitol of Indonesia. OBJECTIVE: This study aimed to evaluate factors affecting success of multidrug-resistant tuberculosis treatment in patients using longer treatment regimen in West Java Indonesia. METHODS: This was a retrospective cohort study of multidrug-resistant tuberculosis patients treated with longer regimen at Hasan Sadikin General Hospital from January 2015 to December 2017. Potential risk factors associated with the treatment outcome were analyzed using multiple logistic regression. RESULTS: A total of 492 patients were enrolled during the study period. Fifty percents multidrug-resistant tuberculosis patients had successful treatment outcome. Age ≤45 years, male, normal body mass index, no previous tuberculosis treatment, culture conversion ≤2 months, acid fast bacilli sputum smear ≤+1 were independent factors associated with increased treatment success. Sputum culture conversion ≤2 months was the major factor affecting successful outcome (RR 2.79; 95% CI: 1.61-4.84; p-value<0.001). Human Immunodeficiency Virus infection, chronic kidney disease, and cavitary lesion were independent risk factors for unfavourable outcome. CONCLUSION: Age, gender, body mass index, tuberculosis treatment history, time of sputum conversion, acid fast bacilli sputum smear, HIV infection, chronic kidney disease, and cavitary lesion can be used as predictors for longer multidrug-resistant tuberculosis treatment regimen outcome.

Report of Two COVID-19 ARDS (CARDS) Cases Who Survived without Intubation and Mechanical Ventilation.

The most severe clinical feature of COVID-19 is Acute Respiratory Distress Syndrome (ARDS) which requires intubation and mechanical ventilation and it occurs in approximately 2.3% of cases. About 94% of of these cases end in death. This case series report two confirmed COVID-19 patients who had met criteria of intubation and mechanical ventilation, but not performed to them. Both patients experienced clinical improvement and recovery. Probably this is due to differences of COVID-19 ARDS (CARDS) with typical or classic ARDS.  CARDS is divided into two phenotypes of type L (Low Elastance) and type H (High Elastance). These different phenotypic also distinguish subsequent pathophysiology and clinical management. These phenotype can be differentiate by chest CT scan. This case series emphasizes the importance of understanding this phenotype so that clinicians can provide more appropriate treatment management and also availability of CT scans in health facilities that manage COVID -19.

Effect of increased BMI and obesity on the outcome of COVID-19 adult patients: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Corona virus diseases 2019 (COVID-19) pandemic spread rapidly. Growing evidences that overweight and obesity which extent nearly a third of the world population were associated with severe COVID-19. This study aimed to explore the association and risk of increased BMI and obesity with composite poor outcome in COVID-19 adult patients. METHODS: We conducted a systematic literature search from PubMed and Embase database. We included all original research articles in COVID-19 adult patients and obesity based on classification of Body Mass Index (BMI) and composite poor outcome which consist of ICU admission, ARDS, severe COVID-19, use of mechanical ventilation, hospital admission, and mortality. RESULTS: Sixteen studies were included in meta-analysis with 9 studies presented BMI as continuous outcome and 10 studies presented BMI as dichotomous outcome (cut-off ≥30 kg/m2). COVID-19 patients with composite poor outcome had higher BMI with mean difference 1.12 (95% CI, 0.67-1.57, P < 0.001). Meanwhile, obesity was associated with composite poor outcome with odds ratio (OR) = 1.78 (95% CI, 1.25-2.54, P < 0.001) Multivariate meta-regression showed the association between BMI and obesity on composite poor outcome were affected by age, gender, DM type 2, and hypertension. CONCLUSION: Obesity is a risk factor of composite poor outcome of COVID-19. On the other hand, COVID-19 patients with composite poor outcome have higher BMI. BMI is an important routine procedure that should always be assessed in the management of COVID-19 patients and special attention should be given to patients with obesity.

Multiorgan Failure With Emphasis on Acute Kidney Injury and Severity of COVID-19: Systematic Review and Meta-Analysis.

BACKGROUND: Abnormalities in hematologic, biochemical, and immunologic biomarkers have been shown to be associated with severity and mortality in Coronavirus Disease 2019 (COVID-19). Therefore, early evaluation and monitoring of both liver and kidney functions, as well as hematologic parameters, are pivotal to forecast the progression of COVID-19. OBJECTIVES: In this study, we performed a systematic review and meta-analysis to investigate the association between several complications, including acute kidney injury (AKI), acute liver injury (ALI), and coagulopathy, with poor outcomes in COVID-19. DESIGN: Systematic review and meta-analysis. SETTING: Observational studies reporting AKI, ALI, and coagulopathy along with the outcomes of clinically validated death, severe COVID-19, or intensive care unit (ICU) care were included in this study. The exclusion criteria were abstract-only publications, review articles, commentaries, letters, case reports, non-English language articles, and studies that did not report key exposures or outcomes of interest. PATIENTS: Adult patients diagnosed with COVID-19. MEASUREMENTS: Data extracted included author, year, study design, age, sex, cardiovascular diseases, hypertension, diabetes mellitus, respiratory comorbidities, chronic kidney disease, mortality, severe COVID-19, and need for ICU care. METHODS: We performed a systematic literature search from PubMed, SCOPUS, EuropePMC, and the Cochrane Central Database. AKI and ALI follow the definition of the included studies. Coagulopathy refers to the coagulopathy or disseminated intravascular coagulation defined in the included studies. The outcome of interest was a composite of mortality, need for ICU care, and severe COVID-19. We used random-effects models regardless of heterogeneity to calculate risk ratios (RRs) for dichotomous variables. Heterogeneity was assessed using I 2. Random effects meta-regression was conducted for comorbidities and the analysis was performed for one covariate at a time. RESULTS: There were 3615 patients from 15 studies. The mean Newcastle-Ottawa scale of the included studies was 7.3 ± 1.2. The AKI was associated with an increased the composite outcome (RR: 10.55 [7.68, 14.50], P < .001; I 2: 0%). Subgroup analysis showed that AKI was associated with increased mortality (RR: 13.38 [8.15, 21.95], P < .001; I 2: 24%), severe COVID-19 (RR: 8.12 [4.43, 14.86], P < .001; I 2: 0%), and the need for ICU care (RR: 5.90 [1.32, 26.35], P = .02; I 2: 0%). The ALI was associated with increased mortality (RR: 4.02 [1.51, 10.68], P = .005; I 2: 88%) in COVID-19. Mortality was higher in COVID-19 with coagulopathy (RR: 7.55 [3.24, 17.59], P < .001; I 2: 69%). The AKI was associated with the composite outcome and was not influenced by age (P = .182), sex (P = .104), hypertension (P = .788), cardiovascular diseases (P = .068), diabetes (P = .097), respiratory comorbidity (P = .762), and chronic kidney disease (P = .77). LIMITATIONS: There are several limitations of this study. Many of these studies did not define the extent of AKI (grade), which may affect the outcome. Acute liver injury and coagulopathy were not defined in most of the studies. The definition of severe COVID-19 differed across studies. Several articles included in the study were published at preprint servers and are not yet peer-reviewed. Most of the studies were from China; thus, some patients might overlap across the reports. Most of the included studies were retrospective in design. CONCLUSIONS: This meta-analysis showed that the presence of AKI, ALI, and coagulopathy was associated with poor outcomes in patients with COVID-19.

The use of renin angiotensin system inhibitor on mortality in patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

BACKGROUND: and Aims; To investigate the association between use of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB) and outcomes of hypertensive COVID-19 patients, a systematic review and meta-analysis were performed. METHODS: We systematically searched PubMed, EuropePMC, ProQuest, and Cochrane Central Databases using the terms "(COVID-19 OR SARS-CoV-2) AND (angiotensin converting enzyme OR angiotensin receptor blocker)". The primary and second outcomes were mortality (non-survivor) and severe COVID-19, respectively. RESULTS: Totally, 7410 patients were included from 15 studies. Pooled analysis showed that the use of ACEI/ARB was not associated with mortality (OR 0.73 [0.38, 1.40], p = 0.34; I2: 81%) and severity (OR 1.03 [0.73, 1.45], p = 0.87; I2: 65%). Pooled adjusted OR showed no risk/benefit associated with ACEI/ARB use in terms of mortality (OR 0.83 [0.54, 1.27], p = 0.38; I2: 0%). Subgroup analysis showed that the use of ARB was associated with reduced mortality (OR 0.51 [0.29, 0.90], p = 0.02; I2: 22%) but not ACEI subgroup (OR 0.68 [0.39, 1.17], p = 0.16; I2: 0%). Meta-regression showed that the association between ACEI/ARB use and mortality in patients with COVID-19 do not varies by gender (p = 0.104). GRADE showed a very low certainty of evidence for effect of ACEI/ARB on mortality and severity. The certainty of evidence was very low for both ACEI and ARB subgroups. CONCLUSION: Administration of a renin angiotensin system (RAS) inhibitor, was not associated with increased mortality or severity of COVID-19 in patients with hypertension. Specifically, ARB and not ACEI use, was associated with lower mortality.