Howell-Jolly Body-Like Inclusions in Coronavirus Disease 2019 (COVID-19): Possible Novel Findings.

Background: During COVID-19 pandemic, it is difficult to distinguish febrile patient infected by SARS-CoV-2 or bacterial causes. Howell-Jolly bodies are a well-known entity found in red blood cells. They are nuclear fragments, composed of deoxyribonucleic acid, commonly observed in the peripheral blood smears of hyposplenic or asplenic patients. Recently, similar inclusions often referred to as Howell-Jolly body-like inclusions (HJBLIs) have been reported in the neutrophils of patients with acquired immune deficiency syndrome (AIDS) and COVID-19 patient. Aim: To explore whether HJBLIs in peripheral blood smear could differentiate between patients with confirmed SARS-CoV-2 and bacterial pneumonia. Methods: We performed cross-sectional study using secondary data from COVID-19 database and re-evaluated peripheral blood smears to identify HJBLIs. We included confirmed COVID-19 adults age >18 years who were hospitalized in Dr. Hasan Sadikin General Hospital, Bandung, Indonesia from March 1st 2020-May 31st 2020. We also examined peripheral blood smears in patients with confirmed bacterial pneumonia as a control group. Clinical characteristics including disease severity, CURB-65 score, comorbidity, and the present of HJBLIs in peripheral blood smears were evaluated. Results: Overall, 33 patients were included: 22 were confirmed COVID-19 and 11 were confirmed bacterial pneumonia. The median (interquartile range) age in COVID-19 and patients with bacterial pneumonia were 53 years (40-64) vs 57 years (53-71), respectively. Compared with patients with bacterial pneumonia, HJBLIs were significantly higher in COVID-19 patients [21/22 (80.8%) vs 5/11 (45.5%), p 0.001]. Conclusion: Howell-Jolly body-like inclusions could be a potential feature to help differentiate between COVID-19 and bacterial pneumonia.

Composition and Bioactivity of a Modified Huang-Lian-Jie-Du Decoction.

Background: Epidermal growth factor receptor inhibitors (EGFRIs) and tyrosine kinase inhibitors (TKIs) are key drugs in targeted cancer therapy. However, they may cause skin toxicity. We previously prepared a modified Huang-Lian-Jie-Du (mHLJD) decoction cream using 10 herbs, which effectively alleviated EGFRI/TKI-induced skin toxicity. In the present study, we identified the reference markers of the mHLJD decoction and investigated the anti-inflammatory and antibacterial effects of the mHLJD decoction extract. Methods: We performed high-performance liquid chromatography (HPLC) to determine the composition of the mHLJD decoction. Human epidermoid A431 cells were treated with tumor necrosis factor (TNF)-α to induce inflammation; then, the effects of the mHLJD decoction extract on the cytokine expression were determined using a cytokine array and by performing real-time quantitative polymerase chain reaction (qPCR). The antibacterial effects of the extract were examined using disk diffusion and microdilution assays. Results: HPLC results revealed that the mHLJD decoction primarily consisted of geniposide, berberine chloride, baicalin, coptisine, and palmatine. TNF-α treatment increased the expression of certain cytokines, including IL-1ß, IL-8, M-CSF, and TGF-ß2; however, pretreatment with the mHLJD decoction extract reduced their expression. The qPCR results demonstrated a decreased mRNA expression of IL-8, M-CSF, and TGF-ß2. The antibacterial assay revealed that the extract exerted inhibitory effects on Staphylococcus aureus, forming an inhibition zone at the minimum inhibitory concentrations of 3.125 and 6.25 mg/mL; however, the extract exerted no effects on Escherichia coli and Pseudomonas aeruginosa. Conclusions. We developed an HPLC method to quantify the reference markers of the mHLJD decoction. The bioactivity analysis provided the potential mechanisms underlying the effects of the mHLJD decoction on EGFRI/TKI-induced skin toxicity.

Long-Term Post-Stroke Functional Outcomes: A Comparison of Diabetics and Nondiabetics.

INTRODUCTION: Diabetes mellitus (DM) is known to influence outcomes in the short term following stroke. However, the impact of DM on long-term functional outcomes after stroke is unclear. We compared functional outcomes periodically over 7 years between diabetic and nondiabetic ischemic stroke patients, and investigated the impact of DM on the long-term trajectory of post-stroke functional outcomes. We also studied the influence of age on the diabetes-functional outcome association. METHODS: This is a longitudinal observational cohort study of 802 acute ischemic stroke patients admitted to the Singapore General Hospital from 2005 to 2007. Functional outcomes were assessed using the modified Rankin Scale (mRS) with poor functional outcome defined as mRS ≥3. Follow-up data were determined at 6 months and at median follow-up durations of 29 and 86 months. RESULTS: Among the 802 ischemic stroke patients studied (mean age 64 ± 12 years, male 63%), 42% had DM. In regression analyses adjusting for covariates, diabetic patients were more likely to have poor functional outcomes at 6 months (OR = 2.12, 95% CI: 1.23-3.67) and at median follow-up durations of 29 months (OR = 1.96, 95% CI: 1.37-2.81) and 86 months (OR = 2.27, 95% CI: 1.58-3.25). In addition, age modulated the effect of DM, with younger stroke patients (≤65 years) more likely to have long-term poor functional outcome at the 29-month (p = 0.0179) and 86-month (p = 0.0144) time points. CONCLUSIONS: DM was associated with poor functional outcomes following ischemic stroke in the long term, with the effect remaining consistent throughout the 7-year follow-up period. Age modified the effect of DM in the long term, with an observed increase in risk in the ≤65 age-group but not in the >65 age-group.

The effects of aspirin on the outcome of COVID-19: A systematic review and meta-analysis.

BACKGROUND: Repurposing the use of aspirin to treat hospitalized patients with COVID-19 is a sensible approach. However, several previous studies showed conflicting results. This meta-analysis was aimed to assess the effect of aspirin on the outcome in patients with COVID-19. METHODS: Systematic search using relevant keywords was carried out via several electronic databases until February 21, 2021. Research studies on adults COVID-19 patients with documentation on the use of aspirin and reported our outcomes of interest were included in the analysis. Our main outcome of interest was all types of mortality, while the incidence of thrombosis and bleeding were considered as secondary outcomes. Estimated risk estimates of the included studies were then pooled using DerSimonian-Laird random-effect models regardless heterogeneity. RESULTS: Seven studies with a total of 34,415 patients were included in this systematic review and meta-analysis. The use of aspirin was associated with a reduced risk of mortality (RR 0.56, 95% CI 0.38-0.81, P = 0.002; I2: 68%, P = 0.005). Sensitivity analysis by differentiating in-hospital (active aspirin prescription) and pre-hospital use of aspirin could significantly reduce the heterogeneity (I2: 1%, P = 0.4). Only one study reported the incidence of major bleeding between aspirin and non-aspirin users (6.1% vs. 7.6%, P = 0.61). The association between the use of aspirin and the incidence of thrombosis were contradictory in two studies. CONCLUSION: The use of aspirin was significantly associated with a reduced risk of mortality among patients with COVID-19. Due to limited studies, the effect of aspirin on the incidence of thrombosis and bleeding in patients with COVID-19 could not be drawn definitively.

In-depth review of cardiopulmonary support in COVID-19 patients with heart failure.

Coronavirus disease 2019 infection has spread worldwide and causing massive burden to our healthcare system. Recent studies show multiorgan involvement during infection, with direct insult to the heart. Worsening of the heart function serves as a predictor of an adverse outcome. This finding raises a particular concern in high risk population, such as those with history of preexisting heart failure with or without implantable device. Lower baseline and different clinical characteristic might raise some challenge in managing either exacerbation or new onset heart failure that might occur as a consequence of the infection. A close look of the inflammatory markers gives an invaluable clue in managing this condition. Rapid deterioration might occur anytime in this setting and the need of cardiopulmonary support seems inevitable. However, the use of cardiopulmonary support in this patient is not without risk. Severe inflammatory response triggered by the infection in combination with the preexisting condition of the worsening heart and implantable device might cause a hypercoagulability state that should not be overlooked. Moreover, careful selection and consideration have to be met before selecting cardiopulmonary support as a last resort due to limited resource and personnel. By knowing the nature of the disease, the interaction between the inflammatory response and different baseline profile in heart failure patient might help clinician to salvage and preserve the remaining function of the heart.

Diabetes and COVID-19: The past, the present, and the future.

Diabetes, one of the most prevalent chronic diseases in the world, is strongly associated with a poor prognosis in COVID-19. Scrupulous blood sugar management is crucial, since the worse outcomes are closely associated with higher blood sugar levels in COVID-19 infection. Although recent observational studies showed that insulin was associated with mortality, it should not deter insulin use in hospitalized patients requiring tight glucose control. Back and forth dilemma in the past with regards to continue/discontinue certain medications used in diabetes have been mostly resolved. The initial fears of consequences related to continuing certain medications have been largely dispelled. COVID-19 also necessitates the transformation in diabetes care through the integration of technologies. Recent advances in health-related technologies, notably telemedicine and remote continuous glucose monitoring, have become essential in the management of diabetes during the pandemic. Today, these technologies have changed the landscape of medicine and become more important than ever. Being a high-risk population, patients with type 1 or type 2 diabetes, should be prioritized for vaccination. In the future, as the pandemic fades, the prevalence of non-communicable diseases is expected to rise due to lifestyle changes and medical issues/dilemma encountered during the pandemic.

The association between triglyceride-glucose index and the incidence of type 2 diabetes mellitus-a systematic review and dose-response meta-analysis of cohort studies.

ABSTARCT: AIMS: We aimed to assess the dose-response relationship between triglyceride-glucose (TyG) index and the incidence of type 2 diabetes mellitus (T2DM). METHODS: We performed a comprehensive systematic literature search using PubMed, Scopus, and Embase for records published from inception until 9 February 2021. The effect estimates were reported as relative risks (RRs). RESULTS: 270,229 subjects from 14 studies were included in this systematic review and meta-analysis. The pooled incidence of T2DM was 9%. Meta-regression analysis indicates that baseline age (coefficient: 0.67, p = 0.026), drinking (coefficient: 0.03, p = 0.035), and HDL (coefficient: -0.89, p = 0.035) affected the incidence of T2DM in future. High TyG index was associated with increased incidence of T2DM in pooled unadjusted (RR 4.68 [3.01, 7.29], p < 0.001; I2: 96.6%) and adjusted model (adjusted RR 3.54 [2.75, 4.54], p < 0.001; I2: 83.7%). Dose-response meta-analysis for the adjusted RR showed that the linear association analysis was not significant per 0.1 increase in TyG index (RR 1.01 [0.99, 1.03], p = 0.223). There is a non-linear trend (p < 0.001) for the association between TyG index and incidence of T2DM. The dose-response curve became increasingly steeper at TyG index above 8.6. CONCLUSIONS: TyG index was associated with the incidence of T2DM in a non-linear fashion.

Visceral adiposity, subcutaneous adiposity, and severe coronavirus disease-2019 (COVID-19): Systematic review and meta-analysis.

BACKGROUND AND AIMS: Body mass index (BMI) has previously been shown to increase mortality and disease severity in patients with COVID-19, but the pooled effect estimate was heterogeneous. Although BMI is widely used as an indicator, it cannot distinguish visceral from subcutaneous fat. This systematic review and meta-analysis aimed to investigate the association between visceral adiposity, subcutaneous fat, and severe COVID-19. METHODS: We performed a systematic literature search using the databases: PubMed, Embase, and EuropePMC. Data on visceral fat area (VTA), subcutaneous fat area (SFA), and total fat area (TFA) were collected. The outcome of interest was severe COVID-19. We used a REML random-effects model to pool the mean differences and odds ratio (OR). RESULTS: There were 5 studies comprising of 539 patients. Patients with severe COVID-19 have a higher VTA (mean difference 41.7 cm2 [27.0, 56.4], p < 0.001; I2: 0%) and TFA (mean difference 64.6 cm2 [26.2, 103.1], p = 0.001; I2: 0%). There was no significant difference in terms of SFA between patients with severe and non-severe COVID-19 (mean difference 9.3 cm2 [-4.9, 23.4], p = 0.199; I2: 1.2%). Pooled ORs showed that VTA was associated with severe COVID-19 (OR 1.9 [1.1, 2.2], p = 0.002; I2: 49.3%). CONCLUSION: Visceral adiposity was associated with increased COVID-19 severity, while subcutaneous adiposity was not. PROSPERO ID: CRD42020215876.

The use of Janus Kinase inhibitors in hospitalized patients with COVID-19: Systematic review and meta-analysis.

BACKGROUND: The evidence of using JAK inhibitors among hospitalized patients with COVID-19 is conflicting. The systematic review and meta-analysis aimed to address the efficacy of Janus Kinase (JAK) Inhibitors in reducing risk of mortality among hospitalized patients with COVID-19. METHODS: Several electronic databases, including PubMed, EuropePMC, and the Cochrane Central Register of Controlled Trials, with relevant keywords "COVID-19″ AND ("JAK inhibitor" OR "Ruxolitinib" OR "Tofacitinib" OR "Fedratinib" OR "Baricitinib") AND ("Severe" OR "Mortality"), were used to perform a systematic literature search up to December 11, 2020. All studies pertinent to the predetermined eligibility criteria were included in the analysis. Our outcome of interest was all types of mortality, clinical improvement, and clinical deterioration. Dichotomous variables of our outcomes of interest were analyzed using Maentel-Haenszel formula to obtain odds ratios (ORs) and 95% confidence intervals (CI) with random-effects modeling regardless of heterogeneity. RESULTS: Five studies with a total of 1190 patients and were included in this systematic review and meta-analysis. The use of JAK inhibitors was associated with a reduced risk of mortality (OR 0.51, 95% CI 0.28-0.93, P = 0.02; I2: 7.8%, P = 0.354) and clinical improvement (OR 1.76, 95% CI 1.05-2.95, P = 0.032; I2: 26.4%, P = 0.253). The use of JAK inhibitors was not associated with a reduced risk of clinical deterioration (OR 0.58, 95% CI 0.28-1.19, P = 0.136; I2: 24.1%, P = 0.267). CONCLUSION: The use of JAK inhibitors was significantly associated with a reduced risk of mortality, and clinical improvement in hospitalized patients with COVID-19.

Proton pump inhibitor on susceptibility to COVID-19 and its severity: a systematic review and meta-analysis.

BACKGROUND: The negative impacts of proton pump inhibitor (PPI), including the risk of pneumonia and mortality, have been reported previously. This meta-analysis aimed to address the current interest of whether the administration of PPI could increase the susceptibility and risk of poor outcome in COVID-19. METHODS: We performed a systematic literature search from PubMed, Embase, EBSCOhost, and EuropePMC databases up until 3 December 2020. The main outcome was composite poor outcome which comprised of mortality and severe COVID-19. Severe COVID-19 in this study was defined as patients with COVID-19 that fulfill the criteria for severe CAP, including the need for intensive unit care or mechanical ventilation. The secondary outcome was susceptibility, based on cohort comparing COVID-19 positive and COVID-19 negative participants. RESULTS: There were a total of 290,455 patients from 12 studies in this meta-analysis. PPI use was associated with increased composite poor outcome (OR 1.85 [1.13, 3.03], p = 0.014; I2 90.26%). Meta-regression analysis indicate that the association does not vary by age (OR 0.97 [0.92, 1.02], p = 0.244), male (OR 1.05 [0.99, 1.11], p = 0.091), hypertension (OR 9.98 [0.95, 1.02], p = 0.317), diabetes (OR 0.99 [0.93, 1.05], p = 0.699), chronic kidney disease (OR 1.01 [0.93, 1.10], p = 0.756), non-steroidal anti-inflammatory drug use (OR 1.02 [0.96, 1.09], p = 0.499), and pre-admission/in-hospital PPI use (OR 0.77 [0.26, 2.31], p = 0.644). PPI use was not associated with the susceptibility to COVID-19 (OR 1.56 [0.48, 5.05], p = 0.46; I2 99.7%). CONCLUSION: This meta-analysis showed a potential association between PPI use and composite poor outcome, but not susceptibility. PROSPERO ID: CRD42020224286.

Delirium and Mortality in Coronavirus Disease 2019 (COVID-19) - A Systematic Review and Meta-analysis.

INTRODUCTION: Older adults are indisputably struck hard by the coronavirus disease 2019 (COVID-19) pandemic. The main objective of this meta-analysis is to establish the association between delirium and mortality in older adults with COVID-19. METHODS: Systematic literature searches of PubMed, Embase, and Scopus databases were performed up until 28 November 2020. The exposure in this study was the diagnosis of delirium using clinically validated criteria. Delirium might be in-hospital, at admission, or both. The main outcome was mortality defined as clinically validated non-survivor/death. The effect estimates were reported as odds ratios (ORs) and adjusted odds ratios (aORs). RESULTS: A total of 3,868 patients from 9 studies were included in this systematic review and meta-analysis. The percentage of patients with delirium was 27% [20%, 34%]. Every 1 mg/L increase in CRP was significantly associated with 1% increased delirium risk (OR 1.01 [1.00. 1.02], p=0.033). Delirium was associated with mortality (OR 2.39 [1.64, 3.49], p<0.001; I2: 82.88%). Subgroup analysis on delirium assessed at admission indicate independent association (OR 2.12 [1.39, 3.25], p<0.001; I2: 82.67%). Pooled adjusted analysis indicated that delirium was independently associated with mortality (aOR 1.50 [1.16, 1.94], p=0.002; I2: 31.02%). Subgroup analysis on delirium assessed at admission indicate independent association (OR 1.40 [1.03, 1.90], p=0.030; I2: 35.19%). Meta-regression indicates that the association between delirium and mortality were not significantly influenced by study-level variations in age, sex [reference: male], hypertension, diabetes, and dementia. CONCLUSION: The presence of delirium is associated with increased risk of mortality in hospitalized older adults with COVID-19.

In-hospital use of statins is associated with a reduced risk of mortality in coronavirus-2019 (COVID-19): systematic review and meta-analysis.

BACKGROUND AND AIMS: The idea of treating COVID-19 with statins is biologically plausible, although it is still controversial. The systematic review and meta-analysis aimed to address the association between the use of statins and risk of mortality in patients with COVID-19. METHODS: Several electronic databases, including PubMed, SCOPUS, EuropePMC, and the Cochrane Central Register of Controlled Trials, with relevant keywords up to 11 November 2020, were used to perform a systematic literature search. This study included research papers containing samples of adult COVID-19 patients who had data on statin use and recorded mortality as their outcome of interest. Risk estimates of mortality in statin users versus non-statin users were pooled across studies using inverse-variance weighted DerSimonian-Laird random-effect models. RESULTS: Thirteen studies with a total of 52,122 patients were included in the final qualitative and quantitative analysis. Eight studies reported in-hospital use of statins; meanwhile, the remaining studies reported pre-admission use of statins. In-hospital use of statin was associated with a reduced risk of mortality (RR 0.54, 95% CI 0.50-0.58, p < 0.00001; I2: 0%, p = 0.87), while pre-admission use of statin was not associated with mortality (RR 1.18, 95% CI 0.79-1.77, p = 0.415; I2: 68.6%, p = 0.013). The funnel plot for the association between the use of statins and mortality were asymmetrical. CONCLUSION: This meta-analysis showed that in-hospital use of statins was associated with a reduced risk of mortality in patients with COVID-19.

Thrombocytopenia as a prognostic marker in COVID-19 patients: diagnostic test accuracy meta-analysis.

This systematic review and meta-analysis aimed to evaluate thrombocytopenia as a prognostic biomarker in patients with coronavirus disease 2019 (COVID-19). We performed a systematic literature search using PubMed, Embase and EuropePMC. The main outcome was composite poor outcome, a composite of mortality, severity, need for intensive care unit care and invasive mechanical ventilation. There were 8963 patients from 23 studies. Thrombocytopenia occurred in 18% of the patients. Male gender (P = 0.037) significantly reduce the incidence. Thrombocytopenia was associated with composite poor outcome (RR 1.90 (1.43-2.52), P < 0.001; I2: 92.3%). Subgroup analysis showed that thrombocytopenia was associated with mortality (RR 2.34 (1.23-4.45), P < 0.001; I2: 96.8%) and severity (RR 1.61 (1.33-1.96), P < 0.001; I2: 62.4%). Subgroup analysis for cut-off <100 × 109/l showed RR of 1.93 (1.37-2.72), P < 0.001; I2: 83.2%). Thrombocytopenia had a sensitivity of 0.26 (0.18-0.36), specificity of 0.89 (0.84-0.92), positive likelihood ratio of 2.3 (1.6-3.2), negative likelihood ratio of 0.83 (0.75-0.93), diagnostic odds ratio of 3 (2, 4) and area under curve of 0.70 (0.66-0.74) for composite poor outcome. Meta-regression analysis showed that the association between thrombocytopenia and poor outcome did not vary significantly with age, male, lymphocyte, d-dimer, hypertension, diabetes and CKD. Fagan's nomogram showed that the posterior probability of poor outcome was 50% in patients with thrombocytopenia, and 26% in those without thrombocytopenia. The Deek's funnel plot was relatively symmetrical and the quantitative asymmetry test was non-significant (P = 0.14). This study indicates that thrombocytopenia was associated with poor outcome in patients with COVID-19.PROSPERO ID: CRD42020213974.

Challenge in diagnosis of COVID-19 in hemodialysis patient: a case report and brief review of the literature.

Diagnosis of COVID-19 in end-stage kidney disease (ESKD) patients on hemodialysis is challenging,  as the symptoms are often atypical. Herein, we reported a confimed case of COVID-19 in a patient on maintenance hemodialysis. A 38-year-old man with ESKD on regular hemodialysis initially presented with progressive shortness of breath and dry cough, without fever. He had lymphopenia, and chest X-ray suggested pulmonary edema with cardiomegaly and suspected bilateral bronchopneumonia. The patient clinically improved after 7 days of hospitalization, and was subsequently discharged from hospital. Ten days after being discharged, the patient was re-admitted with progressive shortness of breath and dry cough, without fever. SARS-CoV-2 infection was later confirmed by a qualitative RT-PCR test and the diagnosis COVID-19 pneumonia was established. We presented a case of atypical presentation of COVID-19 in an ESKD patient on maintenance hemodialysis with a brief review of the current literature.

Successful Nucleoside Analog and Corticosteroid Therapy for Chronic Inflammatory Demyelinating Polyneuropathy in a Patient With Hepatitis B Virus Liver Cirrhosis.

Here, we describe the case of a 44-year-old man with chronic hepatitis B virus (HBV) infection, who was admitted with progressive muscle weakness and paresthesia in all extremities. He showed slight icterus. Positive HBV e-antigen test, significant HBV-deoxyribonucleic acid load, hypoalbuminemia, hyperbilirubinemia, mild ascites, and demyelinating peripheral axonal lesions in both sensory and motor nerves led to the diagnosis of Child-Pugh class B HBV cirrhosis with chronic inflammatory demyelinating polyneuropathy. Oral lamivudine, intravenous steroids, calcium, and vitamin D therapy led to a significant recovery of muscle strength within 6 weeks and a gradual return to normal after 24 weeks.

The prevalence of uninvestigated dyspepsia and the association of physical exercise with quality of life of uninvestigated dyspepsia patients in Indonesia: An internet-based survey.

BACKGROUND: Epidemiological data on the prevalence of uninvestigated dyspepsia (UD) and its impact on the health-related quality of life (HRQOL) in Indonesian population are still lacking. There is no study investigating the association between exercise and the HRQOL in UD patients. We aimed to investigate the prevalence of UD and its association with physical exercise, and its impact on HRQOL in Indonesian patients with UD. METHODS: This was a population-based, cross-sectional study, conducted using an internet-based questionnaire which was randomly distributed throughout Indonesia using the social media. The questionnaire contained socio-demographic details, exercise levels, Rome III criteria for dyspepsia, and SF-NDI (Short Form-Nepean Dyspepsia Index). The frequency, duration, the intensity of exercise, and the classification of exercise according to ACSM (American College of Sports Medicine) were included in the assessment. The screening for UD was conducted using the Rome III criteria and the SF-NDI score was calculated to assess the HRQOL in patients with UD. RESULTS: A total of 2725 valid responses were collected. The overall prevalence of UD in the study was 49.75%. Multiple logistic regression analysis showed that gender (female) and lack of exercise were independently associated with UD (OR 2.07, 95% CI 1.74-2.47, p < 0.001 and OR 1.72, 95% CI 1.42-2.07, p < 0.001). The median SF-NDI score among 1295 UD subjects in non-exercising and exercising groups was 21.00 and 18.00 (p < 0.001), respectively. CONCLUSION: This study demonstrated the prevalence of UD and the association between exercise and HRQOL among UD patients in Indonesia.

Clinical frailty scale and mortality in COVID-19: A systematic review and dose-response meta-analysis.

INTRODUCTION: National Institute for Health and Care Excellence (NICE) endorsed clinical frailty scale (CFS) to help with decision-making. However, this recommendation lacks an evidence basis and is controversial. This meta-analysis aims to quantify the dose-response relationship between CFS and mortality in COVID-19 patients, with a goal of supplementing the evidence of its use. METHODS: We performed a systematic literature search from several electronic databases up until 8 September 2020. We searched for studies investigating COVID-19 patients and reported both (1) CFS and its distribution (2) CFS and its association with mortality. The outcome of interest was mortality, defined as clinically validated death or non-survivor. The odds ratio (ORs) will be reported per 1% increase in CFS. The potential for a non-linear relationship based on ORs of each quantitative CFS was examined using restricted cubic splines with a three-knots model. RESULTS: There were a total of 3817 patients from seven studies. Mean age was 80.3 (SD 8.2), and 53% (48-58%) were males. The pooled prevalence for CFS 1-3 was 34% (32-36%), CFS 4-6 was 42% (40-45%), and CFS 7-9 was 23% (21-25%). Each 1-point increase in CFS was associated with 12% increase in mortality (OR 1.12 (1.04, 1.20), p = 0.003; I2: 77.3%). The dose-response relationship was linear (Pnon-linearity=0.116). The funnel-plot analysis was asymmetrical; Trim-and-fill analysis by the imputation of two studies on the left side resulted in OR of 1.10 [1.03, 1.19]. CONCLUSION: This meta-analysis showed that increase in CFS was associated with increase in mortality in a linear fashion.

Cardiac injury is associated with mortality and critically ill pneumonia in COVID-19: A meta-analysis.

Background: In this systematic review and meta-analysis, we aimed to explore the association between cardiac injury and mortality, the need for intensive care unit (ICU) care, acute respiratory distress syndrome (ARDS), and severe coronavirus disease 2019 (COVID-19) in patients with COVID-19 pneumonia. Methods: We performed a comprehensive literature search from several databases. Definition of cardiac injury follows that of the included studies, which includes highly sensitive cardiac troponin I (hs-cTnl) >99th percentile.The primary outcome was mortality, and the secondary outcomes were ARDS, the need for ICU care, and severe COVID-19. ARDS and severe COVID-19 were defined per the World Health Organization (WHO) interim guidance of severe acute respiratory infection (SARI) of COVID-19. Results: There were a total of 2389 patients from 13 studies. This meta-analysis showed that cardiac injury was associated with higher mortality (RR 7.95 [5.12, 12.34], p < 0.001; I2: 65%). Cardiac injury was associated with higher need for ICU care (RR 7.94 [1.51, 41.78], p = 0.01; I2: 79%), and severe COVID-19 (RR 13.81 [5.52, 34.52], p < 0.001; I2: 0%). The cardiac injury was not significant for increased risk of ARDS (RR 2.57 [0.96, 6.85], p = 0.06; I2: 84%). The level of hs-cTnI was higher in patients with primary + secondary outcome (mean difference 10.38 pg/mL [4.44, 16.32], p = 0.002; I2: 0%). Conclusion: Cardiac injury is associated with mortality, need for ICU care, and severity of disease in patients with COVID-19.

Elevated De Ritis Ratio Is Associated With Poor Prognosis in COVID-19: A Systematic Review and Meta-Analysis.

Objective: This meta-analysis aims to assess whether elevated De Ritis ratio is associated with poor prognosis in patients with coronavirus 2019 (COVID-19). Methods: A systematic literature search was performed using PubMed, Embase, and EuropePMC databases up until September 17, 2021. De Ritis ratio is also known as Aspartate aminotransferase/alanine transaminase (AST/ALT) ratio. The main outcome was poor prognosis, a composite of mortality, severity, the need for ICU care, and intubation. The effect measure was odds ratios (ORs) and mean differences. We generated sensitivity and specificity, negative and positive likelihood ratio (NLR and PLR), diagnostic odds ratio (DOR), and area under curve (AUC). Results: There were eight studies with 4,606 patients. De Ritis ratio was elevated in 44% of the patients. Patients with poor prognosis have higher De Ritis ratio [mean difference 0.41 (0.31, 0.50), p < 0.001; I 2: 81.0%] and subgroup analysis showed that non-survivors also have higher De Ritis Ratio [mean difference 0.47 (0.46, 0.48), p < 0.001; I 2: 0%]. Elevated De Ritis ratio was associated with poor prognosis [OR 3.28 (2.39, 4.52), p < 0.001; I 2: 35.8%]. It has a sensitivity of 55% (36-73), specificity of 71% (52-85), PLR 1.9, NLR.63, DOR of 3 (2-4), and AUC of.67 (0.63-0.71). The posterior probability of poor prognosis was 38% if De Ritis is elevated, while 17% if De Ritis is not elevated. Conclusion: Elevated De Ritis ratio is associated with poor prognosis in patients with COVID-19. Systematic Review Registration: PROSPERO ID: CRD42020216634.