Efficacy of early treatment with hydroxychloroquine in people with mild to moderate COVID-19: a systematic review and meta-analysis

IntroductionNo early treatment intervention for COVID-19 has proven effective to date. We systematically reviewed the efficacy of hydroxychloroquine as early treatment for COVID-19.Material and methodsRandomized controlled trials (RCTs) evaluating hydroxychloroquine for early treatment of COVID-19 were searched in five engines and preprint websites until September 14, 2021. Primary outcomes were hospitalization and all-cause mortality. Secondary outcomes included COVID-19 symptom resolution, viral clearance, and adverse events. Inverse variance random-effects meta-analyses were performed and quality of evidence (QoE) per outcome was assessed with GRADE methods.ResultsFive RCTs (n = 1848) were included. The comparator was placebo in four RCTs and usual care in one RCT. The RCTs used hydroxychloroquine total doses between 1,600 and 4,400 mg and had follow-up times between 14 and 90 days. Compared to the controls, early treatment with hydroxychloroquine did not reduce hospitalizations (RR = 0.80, 95% CI: 0.47–1.36, I² = 2%, 5 RCTs, low QoE), all-cause mortality (RR = 0.77, 95% CI: 0.16–3.68, I² = 0%, 5 RCTs, very low QoE), symptom resolution (RR = 0.94, 95% CI: 0.77–1.16, I² = 71%, 3 RCTs, low QoE) or viral clearance at 14 days (RR = 1.02, 95% CI: 0.82–1.27, I² = 65%, 2 RCTs, low QoE). There was a larger non-significant increase of adverse events with hydroxychloroquine vs. controls (RR = 2.17, 95% CI: 0.86–5.45, I² = 92%, 5 RCTs, very low QoE).ConclusionsHydroxychloroquine was not efficacious as early treatment for COVID-19 infections in RCTs with low to very low quality of evidence for all outcomes. More RCTs are needed to elucidate the efficacy of hydroxychloroquine as early treatment intervention.     

Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis

ObjectivesCytokine release syndrome with elevated interleukin-6 (IL-6) levels is associated with multiorgan damage and death in severe coronavirus disease 2019 (COVID-19). Our objective was to perform a living systematic review of the literature concerning the efficacy and toxicity of the IL-6 receptor antagonist tocilizumab in COVID-19 patients.MethodsData sources were Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus up, preprint servers and Google up to October 8, 2020. Study eligibility criteria were randomized controlled trials (RCTs) and observational studies at low or moderate risk of bias. Participants were hospitalized COVID-19 patients. Interventions included tocilizumab versus placebo or standard of care. We pooled crude risk ratios (RRs) of RCTs and adjusted RRs from cohorts, separately. We evaluated inconsistency between studies with I². We assessed the certainty of evidence using the GRADE approach.ResultsOf 1156 citations, 24 studies were eligible (five RCTs and 19 cohorts). Five RCTs at low risk of bias, with 1325 patients, examined the effect of tocilizumab on short-term mortality; pooled RR was 1.09 (95%CI 0.80–1.49, I² = 0%). Four RCTs with 771 patients examined the effect of tocilizumab on risk of mechanical ventilation; pooled RR was 0.71 (95%CI 0.52–0.96, I² = 0%), with a corresponding number needed to treat of 17 (95%CI 9–100). Among 18 cohorts at moderate risk of bias with 9850 patients, the pooled adjusted RR for mortality was 0.58 (95%CI 0.51–0.66, I² = 2.5%). This association was observed over all degrees of COVID-19 severity. Data from the RCTs did not show a higher risk of infections or adverse events with tocilizumab: pooled RR 0.63 (95%CI 0.38–1.06, five RCTs) and 0.83 (95%CI 0.55–1.24, five RCTs), respectively.ConclusionsCumulative moderate-certainty evidence shows that tocilizumab reduces the risk of mechanical ventilation in hospitalized COVID-19 patients. While RCTs showed that tocilizumab did not reduce short-term mortality, low-certainty evidence from cohort studies suggests an association between tocilizumab and lower mortality. We did not observe a higher risk of infections or adverse events with tocilizumab use. This review will continuously evaluate the role of tocilizumab in COVID-19 treatment.     

Risk Factors for Severe COVID-19 in Children: A Systematic Review and Meta-Analysis

BackgroundCoronavirus disease 2019 (COVID-19) has been the most important global issue since December 2019. Although the clinical course of COVID-19 is known to be milder in children than in adults, associated hospitalizations among children have increased since the emergence of contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the achievement of a high vaccination rate in adults. Considering these global and domestic situations, we believe that risk stratification in children with COVID-19 is urgently needed for decision making regarding hospitalization priority in children infected with SARS-CoV-2 and vaccination priority against COVID-19.MethodsThis systematic review and meta-analysis was performed by comprehensively searching the PubMed, EMBASE, Scopus and KoreaMed databases through August 25, 2021. The criteria for enrollment were “severe COVID-19” as poor outcomes (intensive care unit admission, invasive mechanical ventilation, and/or death) and underlying comorbidities before SARS-CoV-2 infection.ResultsAmong 872 screened studies, 17 articles were included in the systematic review, and 10 articles were included in the meta-analysis. Neonate (risk ratio [RR], 2.69; 95% confidence interval [CI], 1.83–3.97), prematurity in young infants (RR, 2.00; 95% CI, 1.63–2.46), obesity (RR, 1.43; 95% CI, 1.24–1.64), diabetes (RR, 2.26; 95% CI, 1.95–2.62), chronic lung disease (RR, 2.62; 95% CI, 1.71–4.00), heart disease (RR, 1.82; 95% CI, 1.58–2.09), neurologic disease (RR, 1.18; 95% CI, 1.05–1.33), and immunocompromised status (RR, 1.44; 95% CI, 1.01–2.04) were significant risk factors for severe COVID-19 in children. In the subgroup analysis, age younger than 3 months (RR, 0.26; 95% CI, 0.11–0.66), asthma (RR, 1.08; 95% CI, 0.98–1.20), and neurodevelopmental disorders (RR, 0.88; 95% CI, 0.75–1.04) were not risk factors for severe COVID-19.ConclusionChildren with comorbidities such as obesity, diabetes, heart disease, chronic lung diseases other than asthma, seizure disorders, and an immunocompromised status had a high prevalence of severe COVID-19. Neonate and premature infants had a high risk of severe COVID-19. Defining the high-risk group for severe COVID-19 could help to guide hospital admission and priority for vaccination against SARS-CoV-2.     

Long-term proton pump inhibitor use is a risk factor for mortality in patients hospitalized for COVID-19

Background and aimThe aim of this study is to evaluate whether the long-term (≥4 weeks) use of proton pump inhibitors (PPIs) is a risk factor for intubation requirement and mortality in patients hospitalized for COVID-19.Materials and methods In this multicentric retrospective study, a total of 382 adult patients (≥18 years of age) with confirmed COVID-19 who were hospitalized for treatment were enrolled. The patients were divided into two groups according to the periods during which they used PPIs: the first group included patients who were not on PPI treatment, and the second group included those who have used PPIs for more than 4 weeksResultsThe study participants were grouped according to their PPI usage history over the last 6 months. In total, 291 patients did not use any type of PPI over the last 6 months, and 91 patients used PPIs for more than 4 weeks. Older age (HR: 1.047, 95% CI: 1.026–1.068), current smoking (HR: 2.590, 95% CI: 1.334–5.025), and PPI therapy for more than 4 weeks (HR: 1.83, 95% CI: 1.06–2.41) were found to be independent risk factors for mortalityConclusionThe results obtained in this study show that using PPIs for more than 4 weeks is associated with negative outcomes for patients with COVID-19. Patients receiving PPI therapy should be evaluated more carefully if they are hospitalized for COVID-19 treatment.     

Prediction of Respiratory Failure and Mortality in COVID-19 Patients Using Long Pentraxin PTX3

The course of COVID-19 is unpredictable, ranging from asymptomatic to respiratory failure and death. Prognostic biomarkers are urgently needed. We hypothesized that long pentraxin PTX3 could be a valuable plasma biomarker due to its essential role in inflammatory processes. In a prospective hospitalized COVID-19 derivation cohort (n = 126) during the spring of 2020, we measured PTX3 within 4 days of admission. The predictive value of mechanical ventilation (MV) and 30-day mortality compared with clinical parameters and other markers of inflammation were assessed by logistic regression analysis and expressed as odds ratio (OR) with 95% confidence interval (CI). Analyses were repeated in a prospective validation cohort (n = 112) of hospitalized patients with COVID-19 treated with remdesivir and dexamethasone. Thirty-day mortality in the derivation cohort was 26.2%. In patients who died, the median PTX3 concentration upon admission was 19.5 ng/mL (IQR: 12.5–33.3) versus 6.6 ng/mL (IQR 2.9–12.3) (p < 0.0001) for survivors. After adjustment for covariates, the odds of 30-day mortality increased two-fold for each doubling of PTX3 (OR 2.03 [95% CI: 1.23–3.34], p = 0.006), which was also observed in the validation cohort (OR 1.70 [95% CI: 1.09–2.67], p = 0.02). Similarly, PTX3 levels were associated with MV. After adjustment for covariates, OR of MV was 2.34 (95% CI: 1.33–4.12, p = 0.003) in the derivation cohort and 1.64 (95% CI: 1.03–2.62, p = 0.04) in the validation cohort. PTX3 appears to be a useful clinical biomarker to predict 30-day respiratory failure and mortality risk in COVID-19 patients treated with and without remdesivir and dexamethasone.     

Length of stay and readmission in older adults hospitalized for heart failure

IntroductionHospital length of stay (LoS) and hospital readmissions are metrics of healthcare performance. We examined the association between these two metrics in older patients hospitalized with decompensated heart failure (HF).Material and methodsEight thousand and forty-nine patients hospitalized for HF in 106 U.S. hospitals had a median LoS of 5 days; among them, 3777 had a LoS > 5 days. Using propensity scores for LoS > 5 days, we assembled 2723 pairs of patients with LoS 1–5 vs. > 5 days. The matched cohort of 5446 patients was balanced on 40 baseline characteristics. We repeated the above process in 7045 patients after excluding those with LoS > 10 days, thus assembling a second matched cohort of 2399 pairs of patients with LoS 1–5 vs. 6–10 days. Hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with longer LoS were estimated in matched cohorts.ResultsIn the primary matched cohort (n = 5446), LoS > 5 days was associated with a higher risk of all-cause readmission at 30 days (HR = 1.16; 95% CI: 1.04–1.31; p = 0.010), but not during longer follow-up. A longer LoS was also associated with a higher risk of mortality during 8.8 years of follow-up (HR = 1.13; 95% CI: 1.06–1.21; p < 0.001). LoS had no association with HF readmission. Similar associations were observed among the matched sensitivity cohort (n = 4798) that excluded patients with LoS > 10 days.ConclusionsIn propensity score-matched balanced cohorts of patients with HF, a longer LoS was independently associated with poor outcomes, which persisted when LoS > 10 days were excluded.     

Clinical characteristics and risk factors for 28-day mortality in critically ill patients with COVID-19: a retrospective cohort study

BackgroundTo date, the coronavirus disease 2019 (COVID-19) caused more than 2.6 million deaths all around the world. Risk factors for mortality remain unclear. The primary aim was to determine the independent risk factors for 28-day mortality.Materials and MethodsIn this retrospective cohort study, critically ill patients (≥ 18 years) who were admitted to the intensive care unit due to COVID-19 were included. Patient characteristics, laboratory data, radiologic findings, treatments, and complications were analyzed in the study.ResultsA total of 249 patients (median age 71, 69.1% male) were included in the study. 28-day mortality was 67.9% (n = 169). The median age of deceased patients was 75 (66–81). Of them, 68.6% were male. Cerebrovascular disease, dementia, chronic kidney disease, and malignancy were significantly higher in the deceased group. In the multivariate analysis, sepsis/septic shock (OR, 15.16, 95% CI, 3.96–58.11, p < 0.001), acute kidney injury (OR, 4.73, 95% CI, 1.55–14.46,p = 0.006), acute cardiac injury (OR, 9.76, 95% CI, 1.84–51.83, p = 0.007), and chest CT score higher than 15 (OR, 4.49, 95% CI, 1.51-13.38, p = 0.007) were independent risk factors for 28-day mortality.ConclusionEarly detection of the risk factors and the use of chest CT score might improve the outcomes in patients with COVID-19.     

Long-Term Aspirin Use and 5-Year Survival in Healthy Adults: A Population-Based Cohort Study in South Korea

PurposeWe investigated whether long-term aspirin use is associated with 5-year all-cause mortality.Materials and MethodsParticipants were individuals aged ≥40 years who were registered in the 2010 sample cohort database of the National Health Insurance Service in South Korea. Aspirin users were divided into three groups: continuous users (2006–2010), previous users (2006–2009), and new users (2010). Individuals with a history of coronary artery disease and cerebrovascular disease were excluded. Five-year all-cause mortality was defined as mortality due to any cause from January 1, 2011 to December 31, 2015. Data were analyzed by multivariable Cox regression.ResultsIn total, 424444 individuals were included. Five-year all-cause mortality was 9% lower in continuous aspirin users than in unexposed individuals [hazard ratio (HR): 0.91, 95% confidence interval (CI): 0.86–0.97; p=0.003]. Five-year all-cause mortality rates in the new aspirin users (HR: 1.00, 95% CI: 0.90–1.11; p=0.995) and previous aspirin users (HR: 1.01, 95% CI: 0.94–1.09; p=0.776) were not significantly different from that in unexposed individuals. In the 40–60-year age group, 5-year all-cause mortality in the continuous aspirin users was 24% lower (HR: 0.76, 95% CI: 0.64–0.90; p=0.002) than that in unexposed individuals. However, in the >60-year age group, there was no significant association between aspirin use and 5-year all-cause mortality (HR: 0.96, 95% CI: 0.90–1.02; p=0.199).ConclusionLong-term aspirin use is associated with reduced 5-year all-cause mortality in healthy adults, especially those aged <60 years.     

Clinical Features of Adult COVID-19 Patients without Risk Factors before and after the Nationwide SARS-CoV-2 B.1.617.2 (Delta)-variant Outbreak in Korea: Experience from Gyeongsangnam-do

BackgroundData on severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) delta variant virulence are insufficient. We retrospectively compared the clinical features of adult coronavirus disease 2019 (COVID-19) patients without risk factors for severe COVID-19 who entered residential treatment centers (RTCs) before and after the delta variant outbreak.MethodsWe collected medical information from two RTCs in South Korea. On the basis of nationwide delta variant surveillance, we divided the patients into two groups: 1) the delta-minor group (diagnosed from December 2020–June 2021, detection rate < 10%) and 2) the delta-dominant group (diagnosed during August 2021, detection rate > 90%). After propensity-score matching, the incidences of pneumonia, hospital transfer and need for supplemental oxygen were compared between the groups. In addition, risk factors for hospital transfer were analysed.ResultsA total of 1,915 patients were included. The incidence of pneumonia (14.6% vs. 9.2%, P = 0.009), all-cause hospital transfer (10.4% vs. 6.3%, P = 0.020) and COVID-19-related hospital transfer (7.5% vs. 4.8%, P = 0.081) were higher in the delta-dominant group than those in the delta-minor group. In the multivariate analysis, the delta-dominant group was an independent risk factor for all-cause (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.16–3.13; P = 0.011) and COVID-19-related hospital transfer (aOR, 1.86; 95% CI, 1.04–3.32; P = 0.036).ConclusionHospitalization rates were increased in the adult COVID-19 patients during the delta variant nationwide outbreak. Our results showed that the delta variant may be more virulent than previous lineages.     

Validation of Machine Learning Models to Predict Adverse Outcomes in Patients with COVID-19: A Prospective Pilot Study

PurposeWe previously developed learning models for predicting the need for intensive care and oxygen among patients with coronavirus disease (COVID-19). Here, we aimed to prospectively validate the accuracy of these models.Materials and MethodsProbabilities of the need for intensive care [intensive care unit (ICU) score] and oxygen (oxygen score) were calculated from information provided by hospitalized COVID-19 patients (n=44) via a web-based application. The performance of baseline scores to predict 30-day outcomes was assessed.ResultsAmong 44 patients, 5 and 15 patients needed intensive care and oxygen, respectively. The area under the curve of ICU score and oxygen score to predict 30-day outcomes were 0.774 [95% confidence interval (CI): 0.614–0.934] and 0.728 (95% CI: 0.559–0.898), respectively. The ICU scores of patients needing intensive care increased daily by 0.71 points (95% CI: 0.20–1.22) after hospitalization and by 0.85 points (95% CI: 0.36–1.35) after symptom onset, which were significantly different from those in individuals not needing intensive care (p=0.002 and <0.001, respectively). Trends in daily oxygen scores overall were not markedly different; however, when the scores were evaluated within <7 days after symptom onset, the patients needing oxygen showed a higher daily increase in oxygen scores [1.81 (95% CI: 0.48–3.14) vs. -0.28 (95% CI: 1.00–0.43), p=0.007].ConclusionOur machine learning models showed good performance for predicting the outcomes of COVID-19 patients and could thus be useful for patient triage and monitoring.     

Effects of n-3 polyunsaturated fatty acid supplementation on pregnancy outcomes: a systematic review and meta-analysis

IntroductionThere are limited studies exploring the effects of n-3 PUFA supplementation on pregnancy outcomes. The goal of this study was to review relevant studies in order to determine the effect of n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on pregnancy outcomes based on eligible randomized controlled trials (RCTs).Material and methodsQualified studies were searched by keywords in PubMed, the Cochrane library and Embase. Studies from other pertinent sources were also reviewed, and RCTs published before January 2021 were reviewed. For each study, we assessed and synthesized the outcomes by relative risk (RR) or weighted mean difference (WMD) combined with the 95% confidence interval (95% CI).ResultsWe included 13 studies with 9069 patients. Compared with the control group, n-3 PUFA significantly decreased the incidence of preterm delivery (RR = 0.898, 95% CI: 0.819–0.984) and low birthweight (RR = 0.797, 95% CI: 0.655–0.970), and increased the birth weight (WMD = 99.340, 95% CI: 10.503–188.177) and birth length (WMD = 0.449, 95% CI: 0.236–0.663). There was no significant difference in pregnancy-induced hypertension, preeclampsia, intrauterine growth retardation (IUIG), early preterm delivery, anti-hypertensive therapy, gestational diabetes or head circumference at birth between the two groups.ConclusionsThe available evidence shows that n-3 PUFA is not beneficial in reducing the incidence of maternal pregnancy outcomes such as gestational diabetes mellitus and hypertension; but it is beneficial to neonatal health such as decreasing the incidence of preterm delivery and low birthweight and increasing birth weight and birth length.     

Primary care organisational interventions for secondary prevention of ischaemic heart disease: a systematic review and meta-analysis

BackgroundIschaemic heart disease (IHD) is the most common cause of death worldwide.AimTo determine the long-term impact of organisational interventions for secondary prevention of IHD.MethodSearches were conducted for randomised controlled trials of patients with established IHD, with long-term follow-up, of cardiac secondary prevention programmes targeting organisational change in primary care or community settings. A random-effects model was used and risk ratios were calculated.ResultsFive studies were included with 4005 participants. Meta-analysis of four studies with mortality data at 4.7–6 years showed that organisational interventions were associated with approximately 20% reduced mortality, with a risk ratio (RR) for all-cause mortality of 0.79 (95% confidence interval [CI] = 0.66 to 0.93), and a RR for cardiac-related mortality of 0.74 (95% CI = 0.58 to 0.94). Two studies reported mortality data at 10 years. Analysis of these data showed no significant differences between groups. There were insufficient data to conduct a meta-analysis on the effect of interventions on hospital admissions. Additional analyses showed no significant association between organisational interventions and risk factor management or appropriate prescribing at 4.7–6 years.ConclusionCardiac secondary prevention programmes targeting organisational change are associated with a reduced risk of death for at least 4–6 years. There is insufficient evidence to conclude whether this beneficial effect is maintained indefinitely.     

Improved COVID-19 ICU admission and mortality outcomes following treatment with statins: a systematic review and meta-analysis

IntroductionApproximately 1% of the world population has now been infected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). With cases still rising and vaccines just beginning to rollout, we are still several months away from seeing reductions in daily case numbers, hospitalisations, and mortality. Therefore, there is a still an urgent need to control the disease spread by repurposing existing therapeutics. Owing to antiviral, anti-inflammatory, immunomodulatory, and cardioprotective actions, statin therapy has been considered as a plausible approach to improve COVID-19 outcomes.Material and methodsWe carried out a meta-analysis to investigate the effect of statins on 3 COVID-19 outcomes: intensive care unit (ICU) admission, tracheal intubation, and death. We systematically searched the PubMed, Web of Science, Scopus, and ProQuest databases using keywords related to our aims up to November 2, 2020. All published observational studies and randomised clinical trials on COVID-19 and statins were retrieved. Statistical analysis with random effects modelling was performed using STATA16 software.ResultsThe final selected studies (n = 24 studies; 32,715 patients) showed significant reductions in ICU admission (OR = 0.78, 95% CI: 0.58–1.06; n = 10; I² = 58.5%) and death (OR = 0.70, 95% CI: 0.55–0.88; n = 21; I² = 82.5%) outcomes, with no significant effect on tracheal intubation (OR = 0.79; 95% CI: 0.57–1.11; n = 7; I²= 89.0%). Furthermore, subgroup analysis suggested that death was reduced further by in-hospital application of stains (OR = 0.40, 95% CI: 0.22–0.73, n = 3; I² = 82.5%), compared with pre-hospital use (OR = 0.77, 95% CI: 0.60–0.98, n = 18; I² = 81.8%).ConclusionsThese findings call attention to the need for systematic clinical studies to assess both pre- and in-hospital use of statins as a potential means of reducing COVID-19 disease severity, particularly in terms of reduction of ICU admission and total mortality reduction.     

Effect of tocilizumab,sarilumab, and baricitinib on mortality among patients hospitalized for COVID-19 treated with corticosteroids: a systematic review and meta-analysis

BackgroundRandomized controlled trials (RCT) established the mortality reduction by tocilizumab (Actemra), baricitinib (Olumiant), and sarilumab (Kevzara) in hospitalized COVID-19 patients. However, uncertainty remains about which treatment performs best in patients receiving corticosteroids.ObjectivesTo estimate probabilities of noninferiority between baricitinib and sarilumab compared to tocilizumab in patients treated with corticosteroids.Data sourcesPubMed, Embase, Cochrane Library, and MedRxiv.Study eligibility criteriaEligible RCTs assigning hospitalized adults with COVID-19 treated with corticosteroids to tocilizumab or baricitinib or sarilumab versus standard of care or placebo (control).MethodsReviewers independently abstracted published data and assessed study quality with the Risk of Bias 2 tool. Unpublished data, if required, were requested from authors of included studies. The outcome of interest was all-cause mortality at 28 days.ParticipantsTwenty-seven RCTs with 13 549 patients were included. Overall, the risk of bias was low. Bayesian pairwise meta-analyses were used to aggregate results of each treatment versus control. The average odds ratio for mortality was 0.78 (95% credible interval [CrI]: 0.65, 0.94) for tocilizumab; 0.78 (95% CrI: 0.56, 1.03) for baricitinib; and 0.91 (95% CrI: 0.60, 1.40) for sarilumab. The certainty of evidence (GRADE) ranged from moderate to low. Bayesian meta-regressions with multiple priors were used to estimate probabilities of noninferiority (margin of 13% greater effect by tocilizumab). Compared to tocilizumab, there were ≤94% and 90% probabilities of noninferiority with baricitinib and sarilumab, respectively.ResultsAll but two studies included data with only indirect evidence for the comparison of interest.ConclusionsAmong hospitalized COVID-19 treated with corticosteroids, there are high probabilities that both baricitinib and sarilumab are associated with similar mortality reductions in comparison to tocilizumab.     

Clinical characteristics,management and in-hospital mortality of patients with coronavirus disease 2019 in Genoa,Italy

ObjectivesTo describe clinical characteristics, management and outcome of individuals with coronavirus disease 2019 (COVID-19); and to evaluate risk factors for all-cause in-hospital mortality.MethodsThis retrospective study from a University tertiary care hospital in northern Italy, included hospitalized adult patients with a diagnosis of COVID-19 between 25 February 2020 and 25 March 2020.ResultsOverall, 317 individuals were enrolled. Their median age was 71 years and 67.2% were male (213/317). The most common underlying diseases were hypertension (149/317; 47.0%), cardiovascular disease (63/317; 19.9%) and diabetes (49/317; 15.5%). Common symptoms at the time of COVID-19 diagnosis included fever (285/317; 89.9%), shortness of breath (167/317; 52.7%) and dry cough (156/317; 49.2%). An ‘atypical’ presentation including at least one among mental confusion, diarrhoea or nausea and vomiting was observed in 53/317 patients (16.7%). Hypokalaemia occurred in 25.8% (78/302) and 18.5% (56/303) had acute kidney injury. During hospitalization, 111/317 patients (35.0%) received non-invasive respiratory support, 65/317 (20.5%) were admitted to the intensive care unit (ICU) and 60/317 (18.5%) required invasive mechanical ventilation. All-cause in-hospital mortality, assessed in 275 patients, was 43.6% (120/275). On multivariable analysis, age (per-year increase OR 1.07; 95% CI 1.04–1.10; p < 0.001), cardiovascular disease (OR 2.58; 95% CI 1.07–6.25; p 0.03), and C-reactive protein levels (per-point increase OR 1.009; 95% CI 1.004–1.014; p 0.001) were independent risk factors for all-cause in-hospital mortality.ConclusionsCOVID-19 mainly affected elderly patients with predisposing conditions and caused severe illness, frequently requiring non-invasive respiratory support or ICU admission. Despite supportive care, COVID-19 remains associated with a substantial risk of all-cause in-hospital mortality.     

Non-alcoholic Fatty Liver Disease and COVID-19 Susceptibility and Outcomes: a Korean Nationwide Cohort

BackgroundEvidence for the association between underlying non-alcoholic fatty liver disease (NAFLD), the risk of testing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive, and the clinical consequences of coronavirus disease 2019 (COVID-19) is controversial and scarce. We aimed to investigate the association between the presence of NAFLD and the risk of SARS-CoV-2 infectivity and COVID-19-related outcomes.MethodsWe used the population-based, nationwide cohort in South Korea linked with the general health examination records between January 1, 2018 and July 30, 2020. Data for 212,768 adults older than 20 years who underwent SARS-CoV-2 testing from January 1 to May 30, 2020, were obtained. The presence of NAFLDs was defined using three definitions, namely hepatic steatosis index (HSI), fatty liver index (FLI), and claims-based definition. The outcomes were SARS-CoV-2 test positive, COVID-19 severe illness, and related death.ResultsAmong 74,244 adults who completed the general health examination, there were 2,251 (3.0%) who were SARS-CoV-2 positive, 438 (0.6%) with severe COVID-19 illness, and 45 (0.06%) COVID-19-related deaths. After exposure-driven propensity score matching, patients with pre-existing HSI-NAFLD, FLI-NAFLD, or claims-based NAFLD had an 11–23% increased risk of SARS-CoV-2 infection (HSI-NAFLD 95% confidence interval [CI], 1–28%; FLI-NAFLD 95% CI, 2–27%; and claims-based NAFLD 95% CI, 2–31%) and a 35–41% increased risk of severe COVID-19 illness (HSI-NAFLD 95% CI, 8–83%; FLI-NAFLD 95% CI, 5–71%; and claims-based NAFLD 95% CI, 1–92%). These associations are more evident as liver fibrosis advanced (based on the BARD scoring system). Similar patterns were observed in several sensitivity analyses including the full-unmatched cohort.ConclusionPatients with pre-existing NAFLDs have a higher likelihood of testing SARS-CoV-2 positive and severe COVID-19 illness; this association was more evident in patients with NAFLD with advanced fibrosis. Our results suggest that extra attention should be given to the management of patients with NAFLD during the COVID-19 pandemic.     

The impact of selenium administration on severe sepsis or septic shock: a meta-analysis of randomized controlled trials

IntroductionThe efficacy of selenium administration to treat severe sepsis or septic shock remains controversial. We conduct a systematic review and meta-analysis to explore the impact of selenium administration on severe sepsis or septic shock.MethodsWe search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through May 2020 for randomized controlled trials (RCTs) assessing the effect of selenium administration on severe sepsis or septic shock. Meta-analysis is performed using the random-effect model.ResultsFive RCTs involving 1482 patients are included in the meta-analysis. Overall, compared with control group in septic patients, selenium administration is not associated with reduced 28-day mortality (RR=0.93; 95% CI=0.73 to 1.19; P=0.58), but results in substantially decreased all-cause mortality (RR=0.78; 95% CI=0.63 to 0.98; P=0.03) and length of hospital stay (MD=-3.09; 95% CI=-5.68 to -0.50; P=0.02).ConclusionSelenium administration results in notable decrease in all-cause mortality and length of hospital stay, but shows no substantial influence on the 28-day mortality, length of ICU stay, duration of vasopressor therapy, the incidence of acute renal failure, adverse events, and serious adverse events for septic patients.     

Incidence and Mortality Associated with Cardiovascular Medication among Hypertensive COVID-19 Patients in South Korea

PurposeWe aimed to investigate whether the use of cardiovascular drugs in coronavirus disease 2019 (COVID-19) patients with hypertension as a comorbidity has a significant effect on the incidence and associated mortality rate of COVID-19.Materials and MethodsData covering the period between January 1, 2020 and June 4, 2020 were extracted from The National Health Insurance Service-COVID-19 (NHIS-COVID-19) database in South Korea and analyzed as a population-based cohort study.ResultsA total of 101657 hypertensive adults aged 20 years or older were included for final analysis. Among them, 1889 patients (1.9%) were diagnosed with COVID-19 between January 1, 2020 and June 4, 2020, and hospital mortality occurred in 193 patients (10.2%). In a multivariable model, the use of beta-blockers was associated with an 18% lower incidence of COVID-19 [odds ratio (OR): 0.82, 95% confidence interval (CI): 0.69–0.98; p=0.029]. Among 1889 hypertensive patients diagnosed with COVID-19, the use of a calcium channel blocker (CCB) was associated with a 42% lower hospital mortality rate (OR: 0.58, 95% CI: 0.38–0.89; p=0.012). The use of other cardiovascular drugs was not associated with the incidence of COVID-19 or hospital mortality rate among COVID-19 patients. Similar results were observed in all 328374 adults in the NHIS-COVID-19 database, irrespective of the presence of hypertension.ConclusionIn South Korea, beta-blockers exhibited potential benefits in lowering the incidence of COVID-19 among hypertensive patients. Furthermore, CCBs may lower the hospital mortality rate among hypertensive COVID-19 patients. These findings were also applied to the general adult population, regardless of hypertension.     

Clinical Characteristics and Risk Factors for Mortality in Critical Coronavirus Disease 2019 Patients 50 Years of Age or Younger During the Delta Wave: Comparison With Patients > 50 Years in Korea

BackgroundNumerous patients around the globe are dying from coronavirus disease 2019 (COVID-19). While age is a known risk factor, risk analysis in the young generation is lacking. The present study aimed to evaluate the clinical features and mortality risk factors in younger patients (≤ 50 years) with a critical case of COVID-19 in comparison with those among older patients (> 50 years) in Korea.MethodsWe analyzed the data of adult patients only in critical condition (requiring high flow nasal cannula oxygen therapy or higher respiratory support) hospitalized with PCR-confirmed COVID-19 at 11 hospitals in Korea from July 1, 2021 to November 30, 2021 when the delta variant was a dominant strain. Patients’ electronic medical records were reviewed to identify clinical characteristics.ResultsDuring the study period, 448 patients were enrolled. One hundred and forty-two were aged 50 years or younger (the younger group), while 306 were above 50 years of age (the older group). The most common pre-existing conditions in the younger group were diabetes mellitus and hypertension, and 69.7% of the patients had a body mass index (BMI) > 25 kg/m². Of 142 younger patients, 31 of 142 patients (21.8%, 19 women) did not have these pre-existing conditions. The overall case fatality rate among severity cases was 21.0%, and it differed according to age: 5.6% (n = 8/142) in the younger group, 28.1% in the older group, and 38% in the ≥ 65 years group. Age (odds ratio [OR], 7.902; 95% confidence interval [CI], 2.754–18.181), mechanical ventilation therapy (OR, 17.233; 95% CI, 8.439–35.192), highest creatinine > 1.5 mg/dL (OR, 17.631; 95% CI, 8.321–37.357), and combined blood stream infection (OR, 7.092; 95% CI, 1.061–18.181) were identified as independent predictors of mortality in total patients. Similar patterns were observed in age-specific analyses, but most results were statistically insignificant in multivariate analysis due to the low number of deaths in the younger group. The full vaccination rate was very low among study population (13.6%), and only three patients were fully vaccinated, with none of the patients who died having been fully vaccinated in the younger group. Seven of eight patients who died had a pre-existing condition or were obese (BMI > 25 kg/m²), and the one remaining patient died from a secondary infection.ConclusionAbout 22% of the patients in the young critical group did not have an underlying disease or obesity, but the rate of obesity (BMI > 25 kg/m²) was high, with a fatality rate of 5.6%. The full vaccination rate was extremely low compared to the general population of the same age group, showing that non-vaccination has a grave impact on the progression of COVID-19 to a critical condition. The findings of this study highlight the need for measures to prevent critical progression of COVID-19, such as vaccinations and targeting young adults especially having risk factors.     

Combined Effects of Depression and Chronic Disease on the Risk of Mortality: The Korean Longitudinal Study of Aging (2006-2016)

BackgroundThe prevalence of depression is much higher in people with chronic disease than in the general population. Depression exacerbates existing physical conditions, resulting in a higher-than-expected death rate from the physical condition itself. In our aging society, the prevalence of multimorbid patients is expected to increase; the resulting mental problems, especially depression, should be considered. Using a large-scale cohort from the Korean Longitudinal Study of Aging (KLoSA), we analyzed the combined effects of depression and chronic disease on all-cause mortality.MethodsWe analyzed 10-year (2006–2016) longitudinal data of 9,819 individuals who took part in the KLoSA, a nationwide survey of people aged 45–79 years. We examined the association between multimorbidity and depression using chi-square test and logistic regression. We used the Cox proportional hazard model to determine the combined effects of multimorbidity and depression on the all-cause mortality risk.ResultsDuring the 10-year follow up, 1,574 people (16.0%) died. The hazard ratio associated with mild depression increased from 1.35 (95% confidence interval [CI], 1.05–1.73) for no chronic disease to 1.25 (95% CI, 0.98–1.60) for 1 chronic disease, and to 2.00 (95% CI, 1.58–2.52) for multimorbidity. The hazard ratio associated with severe depression increased from 1.73 (95% CI, 1.33–2.24) for no chronic disease, to 2.03 (95% CI, 1.60–2.57) for 1 chronic disease, and to 2.94 (95% CI, 2.37–3.65) for multimorbidity.ConclusionPatients with coexisting multimorbidity and depression are at an increased risk of all-cause mortality than those with chronic disease or depression alone.