Research Note: COVID-19 Is Not an Independent Cause of Death.

The COVID-19 pandemic has had overwhelming global impacts with deleterious social, economic, and health consequences. To assess the COVID-19 death toll, researchers have estimated declines in 2020 life expectancy at birth (e0). When data are available only for COVID-19 deaths, but not for deaths from other causes, the risks of dying from COVID-19 are typically assumed to be independent of those from other causes. In this research note, we explore the soundness of this assumption using data from the United States and Brazil, the countries with the largest number of reported COVID-19 deaths. We use three methods: one estimates the difference between 2019 and 2020 life tables and therefore does not require the assumption of independence, and the other two assume independence to simulate scenarios in which COVID-19 mortality is added to 2019 death rates or is eliminated from 2020 rates. Our results reveal that COVID-19 is not independent of other causes of death. The assumption of independence can lead to either an overestimate (Brazil) or an underestimate (United States) of the decline in e0, depending on how the number of other reported causes of death changed in 2020.

Prevalence and impact of diabetes in hospitalized COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND: Diabetes is a cardiometabolic comorbidity that may predispose COVID-19 patients to worse clinical outcomes. This study sought to determine the prevalence of diabetes in hospitalized COVID-19 patients and investigate the association of diabetes severe COVID-19, rate of acute respiratory distress syndrome (ARDS), mortality, and need for mechanical ventilation by performing a systematic review and meta-analysis. METHODS: Individual studies were selected using a defined search strategy, including results up until July 2021 from PubMed, Embase, and Cochrane Central Register of Controlled Trials. A random-effects meta-analysis was performed to estimate the proportions and level of association of diabetes with clinical outcomes in hospitalized COVID-19 patients. Forest plots were generated to retrieve the odds ratios (OR), and the quality and risk assessment was performed for all studies included in the meta-analysis. RESULTS: The total number of patients included in this study was 10 648, of whom 3112 had diabetes (29.23%). The overall pooled estimate of prevalence of diabetes in the meta-analysis cohort was 31% (95% CI, 0.25-0.38; z = 16.09, P < .0001). Diabetes significantly increased the odds of severe COVID-19 (OR 3.39; 95% CI, 2.14-5.37; P < .0001), ARDS (OR 2.55; 95% CI, 1.74-3.75; P = <.0001), in-hospital mortality (OR 2.44; 95% CI, 1.93-3.09; P < .0001), and mechanical ventilation (OR 3.03; 95% CI, 2.17-4.22; P < .0001). CONCLUSIONS: Our meta-analysis demonstrates that diabetes is significantly associated with increased odds of severe COVID-19, increased ARDS rate, mortality, and need for mechanical ventilation in hospitalized patients. We also estimated an overall pooled prevalence of diabetes of 31% in hospitalized COVID-19 patients.

COVID-19 associated mucormycosis: A Descriptive Multisite Study from India.

BACKGROUND AND AIMS: Mucormycosis is an invasive fungal infection and carries a significant morbidity and mortality. A number of cases of mucormycosis have been reported in association with COVID-19. In this study, a consortium of clinicians from various parts of India studied clinical profile of COVID-19 associated mucormycosis (CAM) and this analysis is presented here. METHODS: Investigators from multiple sites in India were involved in this study. Clinical details included the treatment and severity of COVID-19, associated morbidities, as well as the diagnosis, treatment and prognosis of mucormycosis. These data were collected using google spreadsheet at one centre. Descriptive analysis was done. RESULTS: There were 115 patients with CAM. Importantly, all patients had received corticosteroids. Diabetes was present in 85.2% of patients and 13.9% of patients had newly detected diabetes. The most common site of involvement was rhino-orbital. Mortality occurred in 25 (21.7%) patients. On logistic regression analysis, CT scan-based score for severity of lung involvement was associated with mortality. CONCLUSION: Universal administration of corticosteroids in our patients is notable. A large majority of patients had diabetes, while mortality was seen in ∼1/5th of patients, lower as compared to recently published data.

Does diabetes mellitus mitigate the gender gap in COVID-19 mortality?

In this SARS-COV2-pandemic, diabetes mellitus (DM) soon emerged as one of the most prominent risk factors for a severe course of corona virus disease-2019 (COVID-19) and increased mortality due to hyperglycemia/insulin resistance, obesity, inflammation, altered immune status, and cardiovascular complications. In general, men are at a higher risk of severe or fatal COVID-19 disease irrespective of age, region and despite comparable infection rates in both sexes. In COVID-19, there is also a male predominance among hospitalized patients with diabetes, however, overall, data among patients with diabetes are ambiguous so far. Of note, similar to cardiovascular complications, women with type 2 diabetes (DM2) appear to lose their biological female advantage resulting in comparable death rates to those of men. The complex interplay of biological and behavioral factors, which may put men at greater risk of a severe or fatal course of COVID-19, and gender-related psychosocial factors, which may cause disadvantage to women concerning the infection rates, might explain why sex-disaggregated data among infected patients with diabetes are conflicting. Better knowledge on biological factors leading to functionally different immune responses and of gender-sensitive sociocultural determinants of COVID-19 infection rates may help to optimize prevention and management in the high-risk groups of men and women with diabetes.

Mucormycosis in patients with COVID-19: A cross-sectional descriptive multicentre study from Iran.

PURPOSE: The aim of the study was to report clinical features, contributing factors and outcome of patients with coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM). METHODS: A cross-sectional descriptive multicentre study was conducted on patients with biopsy-proven mucormycosis with RT-PCR-confirmed COVID-19 from April to September 2020. Demographics, the time interval between COVID-19 and mucormycosis, underlying systemic diseases, clinical features, course of disease and outcomes were collected and analysed. RESULTS: Fifteen patients with COVID-19 and rhino-orbital mucormycosis were observed. The median age of patients was 52 years (range 14-71), and 66% were male. The median interval time between COVID-19 disease and diagnosis of mucormycosis was seven (range: 1-37) days. Among all, 13 patients (86%) had diabetes mellitus, while 7 (46.6%) previously received intravenous corticosteroid therapy. Five patients (33%) underwent orbital exenteration, while seven (47%) patients died from mucormycosis. Six patients (40%) received combined antifungal therapy and none that received combined antifungal therapy died. CONCLUSION: Clinicians should be aware that mucormycosis may be complication of COVID-19 in high-risk patients. Poor control of diabetes mellitus is an important predisposing factor for CAM. Systematic surveillance for control of diabetes mellitus and educating physician about the early diagnosis of CAM are suggested.

Could Exogenous Insulin Ameliorate the Metabolic Dysfunction Induced by Glucocorticoids and COVID-19?

The finding that high-dose dexamethasone improves survival in those requiring critical care due to COVID-19 will mean much greater usage of glucocorticoids in the subsequent waves of coronavirus infection. Furthermore, the consistent finding of adverse outcomes from COVID-19 in individuals with obesity, hypertension and diabetes has focussed attention on the metabolic dysfunction that may arise with critical illness. The SARS coronavirus itself may promote relative insulin deficiency, ketogenesis and hyperglycaemia in susceptible individuals. In conjunction with prolonged critical care, these components will promote a catabolic state. Insulin infusion is the mainstay of therapy for treatment of hyperglycaemia in acute illness but what is the effect of insulin on the admixture of glucocorticoids and COVID-19? This article reviews the evidence for the effect of insulin on clinical outcomes and intermediary metabolism in critical illness.

Risk phenotypes of diabetes and association with COVID-19 severity and death: a living systematic review and meta-analysis.

AIMS/HYPOTHESIS: Diabetes has been identified as a risk factor for poor prognosis of coronavirus disease-2019 (COVID-19). The aim of this study is to identify high-risk phenotypes of diabetes associated with COVID-19 severity and death. METHODS: This is the first edition of a living systematic review and meta-analysis on observational studies investigating phenotypes in individuals with diabetes and COVID-19-related death and severity. Four different databases were searched up to 10 October 2020. We used a random effects meta-analysis to calculate summary relative risks (SRR) with 95% CI. The certainty of evidence was evaluated by the GRADE tool. RESULTS: A total of 22 articles, including 17,687 individuals, met our inclusion criteria. For COVID-19-related death among individuals with diabetes and COVID-19, there was high to moderate certainty of evidence for associations (SRR [95% CI]) between male sex (1.28 [1.02, 1.61], n = 10 studies), older age (>65 years: 3.49 [1.82, 6.69], n = 6 studies), pre-existing comorbidities (cardiovascular disease: 1.56 [1.09, 2.24], n = 8 studies; chronic kidney disease: 1.93 [1.28, 2.90], n = 6 studies; chronic obstructive pulmonary disease: 1.40 [1.21, 1.62], n = 5 studies), diabetes treatment (insulin use: 1.75 [1.01, 3.03], n = 5 studies; metformin use: 0.50 [0.28, 0.90], n = 4 studies) and blood glucose at admission (≥11 mmol/l: 8.60 [2.25, 32.83], n = 2 studies). Similar, but generally weaker and less precise associations were observed between risk phenotypes of diabetes and severity of COVID-19. CONCLUSIONS/INTERPRETATION: Individuals with a more severe course of diabetes have a poorer prognosis of COVID-19 compared with individuals with a milder course of disease. To further strengthen the evidence, more studies on this topic that account for potential confounders are warranted. REGISTRATION: PROSPERO registration ID CRD42020193692.

Colchicine and mortality in patients with coronavirus disease 2019 (COVID-19) pneumonia: A systematic review, meta-analysis, and meta-regression.

OBJECTIVE: This systematic review, with meta-analysis and meta-regression aims to evaluate the effect of colchicine administration on mortality in patients with coronavirus disease 2019 (COVID-19) and factors affecting the association. METHODS: A systematic literature search using the PubMed, Scopus, and Embase databases were performed from inception of databases up until 3 March 2021. We included studies that fulfill all of the following criteria: 1) observational studies or randomized controlled trials (RCTs) that report COVID-19 patients, 2) reporting colchicine use, and 3) mortality within 30 days. There was no restriction on the age, inpatients or outpatients setting, and severity of diseases. The intervention was colchicine administration during treatment for COVID-19. The control was receiving placebo or standard of care. The outcome was mortality and the pooled effect estimate was reported as odds ratio (OR). Random-effects restricted maximum likelihood meta-regression was performed to evaluate factors affecting the pooled effect estimate. RESULTS: Eight studies comprising of 5530 patients were included in this systematic review and meta-analysis. There were three RCTs and five observational studies. Pooled analysis showed that colchicine was associated with lower mortality in patients with COVID-19 (OR 0.47 [0.31, 0.72], p = 0.001; I2: 30.9, p = 0.181). Meta-regression analysis showed that the association between colchicine and mortality was reduced by increasing age (OR 0.92 [0.85, 1.00], p = 0.05), but not gender (reference: male, p = 0.999), diabetes (p = 0.376), hypertension (p = 0.133), and CAD (p = 0.354). CONCLUSION: This meta-analysis indicates that colchicine may reduce mortality in patients with COVID-19. Meta-regression analysis showed that the benefit was reduced as age increases. PROSPERO: CRD42021240609.

Beneficial Effect of Statins in COVID-19-Related Outcomes-Brief Report: A National Population-Based Cohort Study.

OBJECTIVE: Although statins are widely prescribed lipid-lowering drugs, there are concerns about the safety of their use in the context of coronavirus disease 2019 (COVID-19), since statins increase the expression of ACE2 (angiotensin-converting enzyme 2). This study aimed to disclose the association between statins and 60-day COVID-19 mortality. Approach and Results: All patients hospitalized with laboratory-confirmed COVID-19 were enrolled in this study from January 19 to April 16, 2020, in Korea. We evaluated the association between the use of statins and COVID-19-related mortality in the overall and the nested 1:2 propensity score-matched study. Furthermore, a comparison of the hazard ratio for death was performed between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia between January and June 2019 in Korea. The median age of the 10 448 COVID-19 patients was 45 years. Statins were prescribed in 533 (5.1%) patients. After adjusting for age, sex, and comorbidities, Cox regression showed a significant decrease in hazard ratio associated with the use of statins (hazard ratio, 0.637 [95% CI, 0.425-0.953]; P=0.0283). Moreover, on comparing the hazard ratio between COVID-19 patients and the retrospective cohort of hospitalized pneumonia patients, the use of statins showed similar benefits. CONCLUSIONS: The use of statins correlates significantly with lower mortality in patients with COVID-19, consistent with the findings in patients with pneumonia. Graphic Abstract: A graphic abstract is available for this article.

Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study.

AIMS/HYPOTHESIS: This is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19). METHODS: The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalised for COVID-19 with a 28-day follow-up. The patients were screened after hospital admission from 10 March to 10 April 2020. We mainly focused on hospital discharge and death within 28 days. RESULTS: We included 2796 participants: 63.7% men, mean age 69.7 ± 13.2 years, median BMI (25th-75th percentile) 28.4 (25.0-32.4) kg/m2. Microvascular and macrovascular diabetic complications were found in 44.2% and 38.6% of participants, respectively. Within 28 days, 1404 (50.2%; 95% CI 48.3%, 52.1%) were discharged from hospital with a median duration of hospital stay of 9 (5-14) days, while 577 participants died (20.6%; 95% CI 19.2%, 22.2%). In multivariable models, younger age, routine metformin therapy and longer symptom duration on admission were positively associated with discharge. History of microvascular complications, anticoagulant routine therapy, dyspnoea on admission, and higher aspartate aminotransferase, white cell count and C-reactive protein levels were associated with a reduced chance of discharge. Factors associated with death within 28 days mirrored those associated with discharge, and also included routine treatment by insulin and statin as deleterious factors. CONCLUSIONS/INTERPRETATION: In patients with diabetes hospitalised for COVID-19, we established prognostic factors for hospital discharge and death that could help clinicians in this pandemic period. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04324736.

The triumvirate: why hypertension, obesity, and diabetes are risk factors for adverse effects in patients with COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a pandemic. The cellular receptor for SARS-CoV-2 entry is the angiotensin-converting enzyme 2, a membrane-bound homolog of angiotensin-converting enzyme. Henceforth, this has brought the attention of the scientific community to study the interaction between COVID-19 and the renin-angiotensin system (RAS), as well as RAS inhibitors. However, these inhibitors are commonly used to treat hypertension, chronic kidney disorder, and diabetes. Obesity is a known risk factor for heart disease, diabetes, and hypertension, whereas diabetes and hypertension may be indirectly related to each other through the effects of obesity. Furthermore, people with hypertension, obesity, diabetes, and other related complications like cardiovascular and kidney diseases have a higher risk of severe COVID-19 infection than the general population and usually exhibit poor prognosis. This severity could be due to systemic inflammation and compromised immune response and RAS associated with these comorbid conditions. Therefore, there is an urgent need to develop evidence-based treatment methods that do not affect the severity of COVID-19 infection and effectively manage these chronic diseases in people with COVID-19.

Estimation of case-fatality rate in COVID-19 patients with hypertension and diabetes mellitus in the New York state: a preliminary report.

Pre-existing health conditions may exacerbate the severity of coronavirus disease 2019 (COVID-19). We aimed to estimate the case-fatality rate (CFR) and rate ratios (RR) for patients with hypertension (HBP) and diabetes mellitus (DM) in the New York state. We obtained the age-specific number of COVID-19 confirmed cases and deaths from public reports provided by the New York State Department of Health, and age-specific prevalence of HBP and DM from the Behavioral Risk Factor Surveillance System 2017. We calculated CFR and RR for COVID-19 patients with HBP and DM based on the reported number of deaths with the comorbidity divided by the expected number of COVID-19 cases with the comorbidity. We performed subgroup analysis by age and calculated the CFR and RR for ages of 18-44, 45-64 and 65+ years, respectively. We found that the older population had a higher CFR, but the elevated RRs associated with comorbidities are more pronounced among the younger population. Our findings suggest that besides the elderly, the young population with comorbidity should also be considered as a vulnerable group.

Impact of Diabetes in Patients Diagnosed With COVID-19.

COVID-19 is a disease caused by the coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2), known as a highly contagious disease, currently affecting more than 200 countries worldwide. The main feature of SARS-CoV-2 that distinguishes it from other viruses is the speed of transmission combined with higher risk of mortality from acute respiratory distress syndrome (ARDS). People with diabetes mellitus (DM), severe obesity, cardiovascular disease, and hypertension are more likely to get infected and are at a higher risk of mortality from COVID-19. Among elderly patients who are at higher risk of death from COVID-19, 26.8% have DM. Although the reasons for this increased risk are yet to be determined, several factors may contribute to type-2 DM patients' increased susceptibility to infections. A possible factor that may play a role in increasing the risk in people affected by diabetes and/or obesity is the impaired innate and adaptive immune response, characterized by a state of chronic and low-grade inflammation that can lead to abrupt systemic metabolic alteration. SARS patients previously diagnosed with diabetes or hyperglycemia had higher mortality and morbidity rates when compared with patients who were under metabolic control. Similarly, obese individuals are at higher risk of developing complications from SARS-CoV-2. In this review, we will explore the current and evolving insights pertinent to the metabolic impact of coronavirus infections with special attention to the main pathways and mechanisms that are linked to the pathophysiology and treatment of diabetes.

Characteristics, comorbidities and survival analysis of young adults hospitalized with COVID-19 in New York City.

This study reviewed 395 young adults, 18-35 year-old, admitted for COVID-19 to one of the eleven hospitals in New York City public health system. Demographics, comorbidities, clinical course, outcomes and characteristics linked to hospitalization were analyzed including temporal survival analysis. Fifty-seven percent of patients had a least one major comorbidity. Mortality without comorbidity was in 3.8% patients. Further investigation of admission features and medical history was conducted. Comorbidities associated with mortality were diabetes (n = 54 deceased/73 diagnosed,74% tested POS;98.2% with diabetic history deceased; Wilcoxon p (Wp) = .044), hypertension (14/44,32% POS, 25.5%; Wp = 0.030), renal (6/16, 37.5% POS,11%; Wp = 0.000), and cardiac (6/21, 28.6% POS,11%; Wp = 0.015). Kaplan survival plots were statistically significant for these four indicators. Data suggested glucose >215 or hemoglobin A1c >9.5 for young adults on admission was associated with increased mortality. Clinically documented respiratory distress on admission was statistically significant outcome related to mortality (X2 = 236.6842, df = 1, p < .0001). Overall, 28.9% required supportive oxygen beyond nasal cannula. Nasal cannula oxygen alone was required for 71.1%, who all lived. Non-invasive ventilation was required for 7.8%, and invasive mechanical ventilation 21.0% (in which 7.3% lived, 13.7% died). Temporal survival analysis demonstrated statistically significant response for Time to Death <10 days (X2 = 18.508, df = 1, p = .000); risk lessened considerably for 21 day cut off (X2 = 3.464, df = 1, p = .063), followed by 31 or more days of hospitalization (X2 = 2.212, df = 1, p = .137).

Diabetes mellitus increases the risk of hospital mortality in patients with Covid-19: Systematic review with meta-analysis.

BACKGROUND: The mortality rate associated with Covid-19 varies considerably among studies and determinants of this variability are not well characterized. METHODS: A systematic review of peer-reviewed literature published through March 31, 2020 was performed to estimate the mortality rate among hospitalized patients in China with a confirmed diagnosis of Covid-19. Hospital mortality rates were estimated using an inverse variance-weighted random-effects meta-analysis model. Funnel plot symmetry was evaluated for small-study effects, a one-study removed sensitivity analysis assessed the influence of individual studies on the pooled mortality rate, and metaregression assessed the association of potential confounding variables with mortality rates. RESULTS: The review included 16 observational studies involving 1832 hospitalized patients with a diagnosis of Covid-19. The surveillance period among studies ranged from December 16, 2019 to February 23, 2020. The median patient age was 53 years and 53% were males. A total of 38.5% of patients presented with at least 1 comorbidity, most commonly hypertension (24.0%), cardiac disease (15.1%), and diabetes mellitus (14.4%). Fever and cough, reported in 84.8% and 61.7% of patients respectively, were the most common patient symptoms. The pooled mortality rate was 9.9% (95% confidence interval 6.1% to 14.5%). Funnel plot asymmetry was not observed and the meta-analysis results were not substantially influenced by any single study since the pooled mortality rate ranged from 8.9% to 11.1% following iterative removal of one study at a time. Substantial heterogeneity in the mortality rate was identified among studies (I = 87%; P < .001). In a metaregression that included demographics, patient risk factors, and presenting symptoms, only a higher prevalence of diabetes mellitus was associated with a higher mortality rate (P = .03). CONCLUSIONS: In a meta-analysis of hospitalized patients in China with a diagnosis of Covid-19, the mortality rate was 9.9% and a higher diabetes mellitus prevalence was independently associated with a worse prognosis. The independent influence of diabetes mellitus with Covid-19 mortality should be viewed as hypothesis-generating and warrants further study.

COVID-19-related strokes are associated with increased mortality and morbidity: A multicenter comparative study from Bengaluru, South India.

BACKGROUND: COVID-19-related strokes are increasingly being diagnosed across the world. Knowledge about the clinical profile, imaging findings, and outcomes is still evolving. Here we describe the characteristics of a cohort of 62 COVID-19-related stroke patients from 13 hospitals, from Bangalore city, south India. OBJECTIVE: To describe the clinical profile, neuroimaging findings, interventions, and outcomes in COVID-19-related stroke patients. METHODS: This is a multicenter retrospective study of all COVID-19-related stroke patients from 13 hospitals from south India; 1st June 2020-31st August 2020. The demographic, clinical, laboratory, and neuroimaging data were collected along with treatment administered and outcomes. SARS-CoV-2 infection was confirmed in all cases by RT-PCR testing. The data obtained from the case records were entered in SPSS 25 for statistical analysis. RESULTS: During the three-month period, we had 62 COVID-19-related stroke patients, across 13 centers; 60 (97%) had ischemic strokes, while 2 (3%) had hemorrhagic strokes. The mean age of patients was 55.66 ± 13.20 years, with 34 (77.4%) males. Twenty-six percent (16/62) of patients did not have any conventional risk factors for stroke. Diabetes mellitus was seen in 54.8%, hypertension was present in 61.3%, coronary artery disease in 8%, and atrial fibrillation in 4.8%. Baseline National Institutes of Health Stroke Scale score was 12.7 ± 6.44. Stroke severity was moderate (National Institutes of Health Stroke Scale 5-15) in 27 (61.3%) patients, moderate to severe (National Institutes of Health Stroke Scale 16-20) in 13 (20.9%) patients and severe (National Institutes of Health Stroke Scale 21-42) in 11 (17.7%) patients. According to TOAST classification, 48.3% was stroke of undetermined etiology, 36.6% had large artery atherosclerosis, 10% had small vessel occlusion, and 5% had cardioembolic strokes. Three (5%) received intravenous thrombolysis with tenecteplase 0.2 mg/kg and 3 (5%) underwent mechanical thrombectomy, two endovascular and one surgical. Duration of hospital stay was 16.16 ± 6.39 days; 21% (13/62) died in hospital, while 37 (59.7%) had a modified Rankin score of 3-5 at discharge. Hypertension, atrial fibrillation, and higher baseline National Institutes of Health Stroke Scale scores were associated with increased mortality. A comparison to 111 historical controls during the non-COVID period showed a higher proportion of strokes of undetermined etiology, higher mortality, and higher morbidity in COVID-19-related stroke patients. CONCLUSION: COVID-19-related strokes are increasingly being recognized in developing countries, like India. Stroke of undetermined etiology appears to be the most common TOAST subtype of COVID-19-related strokes. COVID-19-related strokes were more severe in nature and resulted in higher mortality and morbidity. Hypertension, atrial fibrillation, and higher baseline National Institutes of Health Stroke Scale scores were associated with increased mortality.