bims-covirf Biomed News
on COVID19 risk factors
Issue of 2020‒09‒13
nine papers selected by
Catherine Rycroft
BresMed


  1. SN Compr Clin Med. 2020 Aug 29. 1-10
    Patel U, Malik P, Usman MS, Mehta D, Sharma A, Malik FA, Khan N, Siddiqi TJ, Ahmed J, Patel A, Sacks H.
      The increasing COVID-19 cases in the USA have led to overburdening of healthcare in regard to invasive mechanical ventilation (IMV) utilization as well as mortality. We aim to identify risk factors associated with poor outcomes (IMV and mortality) of COVID-19 hospitalized patients. A meta-analysis of observational studies with epidemiological characteristics of COVID-19 in PubMed, Web of Science, Scopus, and medRxiv from December 1, 2019 to May 31, 2020 following MOOSE guidelines was conducted. Twenty-nine full-text studies detailing epidemiological characteristics, symptoms, comorbidities, complications, and outcomes were included. Meta-regression was performed to evaluate effects of comorbidities, and complications on outcomes using a random-effects model. The pooled correlation coefficient (r), 95% CI, and OR were calculated. Of 29 studies (12,258 confirmed cases), 17 reported IMV and 21 reported deaths. The pooled prevalence of IMV was 23.3% (95% CI: 17.1-30.9%), and mortality was 13% (9.3-18%). The age-adjusted meta-regression models showed significant association of mortality with male (r: 0.14; OR: 1.15; 95% CI: 1.07-1.23; I 2: 95.2%), comorbidities including pre-existing cerebrovascular disease (r: 0.35; 1.42 (1.14-1.77); I 2: 96.1%), and chronic liver disease (r: 0.08; 1.08 (1.01-1.17); I 2: 96.23%), complications like septic shock (r: 0.099; 1.10 (1.02-1.2); I 2: 78.12%) and ARDS (r: 0.04; 1.04 (1.02-1.06); I 2: 90.3%), ICU admissions (r: 0.03; 1.03 (1.03-1.05); I 2: 95.21%), and IMV utilization (r: 0.05; 1.05 (1.03-1.07); I 2: 89.80%). Similarly, male (r: 0.08; 1.08 (1.02-1.15); I 2: 95%), comorbidities like pre-existing cerebrovascular disease (r: 0.29; 1.34 (1.09-1.63); I 2:93.4%), and cardiovascular disease (r: 0.28; 1.32 (1.1-1.58); I 2: 89.7%) had higher odds of IMV utilization. COVID-19 patients with comorbidities including cardiovascular disease, cerebrovascular disease, and chronic liver disease had poor outcomes. Diabetes and hypertension had higher prevalence but no association with mortality and IMV. Our study results will be helpful in right allocation of resources towards patients who need them the most.
    Keywords:  2019-nCoV; COVID risk factors; COVID-19; COVID-related complications; Coronavirus disease; Mechanical ventilation; Mortality; SARS-CoV-2; Severe acute respiratory syndrome
    DOI:  https://doi.org/10.1007/s42399-020-00476-w
  2. J Community Health. 2020 Sep 12.
    Noor FM, Islam MM.
      OBJECTIVES: The main aim of this study was to find the prevalence of mortality among hospitalized COVID-19 infected patients and associated risk factors for death.METHODS: Three electronic databases including PubMed, Science Direct and Google Scholar were searched to identify relevant cohort studies of COVID-19 disease from January 1, 2020, to August 11, 2020. A random-effects model was used to calculate pooled prevalence rate (PR), risk ratio (RR) and 95% confidence interval (CI) for both effect measures. Cochrane chi-square test statistic Q, [Formula: see text], and [Formula: see text] tests were used to measure the presence of heterogeneity. Publication bias and sensitivity of the included studies were also tested.
    RESULTS: In this meta-analysis, a total of 58 studies with 122,191 patients were analyzed. The pooled prevalence rate of mortality among the hospitalized COVID-19 patients was 18.88%, 95% CI (16.46-21.30), p < 0.001. Highest mortality was found in Europe [PR 26.85%, 95% CI (19.41-34.29), p < 0.001] followed by North America [PR 21.47%, 95% CI (16.27-26.68), p < 0.001] and Asia [PR 14.83%, 95% CI (12.46- 17.21), p < 0.001]. An significant association were found between mortality among COVID-19 infected patients and older age (> 65 years vs. < 65 years) [RR 3.59, 95% CI (1.87-6.90), p < 0.001], gender (male vs. female) [RR 1.63, 95% CI (1.43-1.87), p < 0.001], ICU admitted patients [RR 3.72, 95% CI (2.70-5.13), p < 0.001], obesity [RR 2.18, 95% CI (1.10-4.34), p < 0.05], hypertension [RR 2.08,95% CI (1.79-2.43) p < 0.001], diabetes [RR 1.87, 95% CI (1.23-2.84), p < 0.001], cardiovascular disease [RR 2.51, 95% CI (1.20-5.26), p < 0.05], and cancer [RR 2.31, 95% CI (1.80-2.97), p < 0.001]. In addition, significant association for high risk of mortality were also found for cerebrovascular disease, COPD, coronary heart disease, chronic renal disease, chronic liver disease, chronic lung disease and chronic kidney disease.
    CONCLUSION: This meta-analysis revealed that the mortality rate among COVID-19 patients was highest in the European region and older age, gender, ICU patients, patients with comorbidity had a high risk for case fatality. Those findings would help the health care providers to reduce the mortality rate and combat this pandemic to save lives using limited resources.
    Keywords:  COVID-19; Comorbidity; Meta-analysis; Mortality; Risk factors
    DOI:  https://doi.org/10.1007/s10900-020-00920-x
  3. PLoS Med. 2020 Sep;17(9): e1003321
    Harrison SL, Fazio-Eynullayeva E, Lane DA, Underhill P, Lip GYH.
      BACKGROUND: At the beginning of June 2020, there were nearly 7 million reported cases of coronavirus disease 2019 (COVID-19) worldwide and over 400,000 deaths in people with COVID-19. The objective of this study was to determine associations between comorbidities listed in the Charlson comorbidity index and mortality among patients in the United States with COVID-19.METHODS AND FINDINGS: A retrospective cohort study of adults with COVID-19 from 24 healthcare organizations in the US was conducted. The study included adults aged 18-90 years with COVID-19 coded in their electronic medical records between January 20, 2020, and May 26, 2020. Results were also stratified by age groups (<50 years, 50-69 years, or 70-90 years). A total of 31,461 patients were included. Median age was 50 years (interquartile range [IQR], 35-63) and 54.5% (n = 17,155) were female. The most common comorbidities listed in the Charlson comorbidity index were chronic pulmonary disease (17.5%, n = 5,513) and diabetes mellitus (15.0%, n = 4,710). Multivariate logistic regression analyses showed older age (odds ratio [OR] per year 1.06; 95% confidence interval [CI] 1.06-1.07; p < 0.001), male sex (OR 1.75; 95% CI 1.55-1.98; p < 0.001), being black or African American compared to white (OR 1.50; 95% CI 1.31-1.71; p < 0.001), myocardial infarction (OR 1.97; 95% CI 1.64-2.35; p < 0.001), congestive heart failure (OR 1.42; 95% CI 1.21-1.67; p < 0.001), dementia (OR 1.29; 95% CI 1.07-1.56; p = 0.008), chronic pulmonary disease (OR 1.24; 95% CI 1.08-1.43; p = 0.003), mild liver disease (OR 1.26; 95% CI 1.00-1.59; p = 0.046), moderate/severe liver disease (OR 2.62; 95% CI 1.53-4.47; p < 0.001), renal disease (OR 2.13; 95% CI 1.84-2.46; p < 0.001), and metastatic solid tumor (OR 1.70; 95% CI 1.19-2.43; p = 0.004) were associated with higher odds of mortality with COVID-19. Older age, male sex, and being black or African American (compared to being white) remained significantly associated with higher odds of death in age-stratified analyses. There were differences in which comorbidities were significantly associated with mortality between age groups. Limitations include that the data were collected from the healthcare organization electronic medical record databases and some comorbidities may be underreported and ethnicity was unknown for 24% of participants. Deaths during an inpatient or outpatient visit at the participating healthcare organizations were recorded; however, deaths occurring outside of the hospital setting are not well captured.
    CONCLUSIONS: Identifying patient characteristics and conditions associated with mortality with COVID-19 is important for hypothesis generating for clinical trials and to develop targeted intervention strategies.
    DOI:  https://doi.org/10.1371/journal.pmed.1003321
  4. medRxiv. 2020 Sep 01. pii: 2020.08.26.20182709. [Epub ahead of print]
    Leong A, Cole J, Brenner LN, Meigs JB, Florez JC, Mercader JM.
      IMPORTANCE: Early epidemiological studies report associations of diverse cardiometabolic conditions especially body mass index (BMI), with COVID-19 susceptibility and severity, but causality has not been established. Identifying causal risk factors is critical to inform preventive strategies aimed at modifying disease risk.OBJECTIVE: We sought to evaluate the causal associations of cardiometabolic conditions with COVID-19 susceptibility and severity.
    DESIGN: Two-sample Mendelian Randomization (MR) Study.
    SETTING: Population-based cohorts that contributed to the genome-wide association study (GWAS) meta-analysis by the COVID-19 Host Genetics Initiative.
    PARTICIPANTS: Patients hospitalized with COVID-19 diagnosed by RNA PCR, serologic testing, or clinician diagnosis. Population controls defined as anyone who was not a case in the cohorts. Exposures: Selected genetic variants associated with 17 cardiometabolic diseases, including diabetes, coronary artery disease, stroke, chronic kidney disease, and BMI, at p<5 x 10-8 from published largescale GWAS.
    MAIN OUTCOMES: We performed an inverse-variance weighted averages of variant-specific causal estimates for susceptibility, defined as people who tested positive for COVID-19 vs. population controls, and severity, defined as patients hospitalized with COVID-19 vs. population controls, and repeated the analysis for BMI using effect estimates from UKBB. To estimate direct and indirect causal effects of BMI through obesity-related cardiometabolic diseases, we performed pairwise multivariable MR. We used p<0.05/17 exposure/2 outcomes=0.0015 to declare statistical significance.
    RESULTS: Genetically increased BMI was causally associated with testing positive for COVID-19 [6,696 cases / 1,073,072 controls; p=6.7 x 10-4, odds ratio and 95% confidence interval 1.08 (1.03, 1.13) per kg/m2] and a higher risk of COVID-19 hospitalization [3,199 cases/897,488 controls; p=8.7 x 10-4, 1.12 (1.04, 1.21) per kg/m2]. In the multivariable MR, the direct effect of BMI was abolished upon conditioning on the effect on type 2 diabetes but persisted when conditioning on the effects on coronary artery disease, stroke, chronic kidney disease, and c-reactive protein. No other cardiometabolic exposures tested were associated with a higher risk of poorer COVID-19 outcomes.
    CONCLUSIONS AND RELEVANCE: Genetic evidence supports BMI as a causal risk factor for COVID-19 susceptibility and severity. This relationship may be mediated via type 2 diabetes. Obesity may have amplified the disease burden of the COVID-19 pandemic either single-handedly or through its metabolic consequences.
    DOI:  https://doi.org/10.1101/2020.08.26.20182709
  5. PLoS One. 2020 ;15(9): e0238905
    Carrillo-Vega MF, Salinas-Escudero G, García-Peña C, Gutiérrez-Robledo LM, Parra-Rodríguez L.
      BACKGROUND: Due to a high prevalence of chronic non-degenerative diseases, it is suspected that COVID 19 poses a high risk of fatal complications for the Mexican population. The present study aims to estimate the risk factors for hospitalization and death in the Mexican population infected by SARS-CoV-2.METHODS AND FINDINGS: We used the publicly available data released by the Epidemiological Surveillance System for Viral Respiratory Diseases of the Mexican Ministry of Health (Secretaría de Salud, SSA). All records of positive SARS-CoV-2 cases were included. Two multiple logistic regression models were fitted to estimate the association between hospitalization and mortality, with other covariables. Data on 10,544 individuals (57.68% men), with mean age 46.47±15.62, were analyzed. Men were about 1.54 times more likely to be hospitalized than women (p<0.001, 95% C.I. 1.37-1.74); individuals aged 50-74 and ≥74 were more likely to be hospitalized than people aged 25-49 (OR 2.05, p<0.001, 95% C.I. 1.81-2.32, and OR 3.84, p<0.001, 95% C.I. 2.90-5.15, respectively). People with hypertension, obesity, and diabetes were more likely to be hospitalized than people without these comorbidities (p<0.01). Men had more risk of death in comparison to women (OR = 1.53, p<0.001, 95% C.I. 1.30-1.81) and individuals aged 50-74 and ≥75 were more likely to die than people aged 25-49 (OR 1.96, p<0.001, 95% C.I. 1.63-2.34, and OR 3.74, p<0.001, 95% C.I. 2.80-4.98, respectively). Hypertension, obesity, and diabetes presented in combination conveyed a higher risk of dying in comparison to not having these diseases (OR = 2.10; p<0.001, 95% C.I. 1.50-2.93). Hospitalization, intubation and pneumonia entail a higher risk of dying (OR 5.02, p<0.001, 95% C.I. 3.88-6.50; OR 4.27, p<0.001, 95% C.I. 3.26-5.59, and OR = 2.57; p<0.001, 95% C.I. 2.11-3.13, respectively). Our study's main limitation is the lack of information on mild (asymptomatic) or moderate cases of COVID-19.
    CONCLUSIONS: The present study points out that in Mexico, where an important proportion of the population has two or more chronic conditions simultaneously, a high mortality rate is a serious risk for those infected by SARS-CoV-2.
    DOI:  https://doi.org/10.1371/journal.pone.0238905
  6. Nutr Metab Cardiovasc Dis. 2020 Jul 31. pii: S0939-4753(20)30306-9. [Epub ahead of print]
    Di Castelnuovo A, Bonaccio M, Costanzo S, Gialluisi A, Antinori A, Berselli N, Blandi L, Bruno R, Cauda R, Guaraldi G, My I, Menicanti L, Parruti G, Patti G, Perlini S, Santilli F, Signorelli C, Stefanini GG, Vergori A, Abdeddaim A, Ageno W, Agodi A, Agostoni P, Aiello L, Al Moghazi S, Aucella F, Barbieri G, Bartoloni A, Bologna C, Bonfanti P, Brancati S, Cacciatore F, Caiano L, Cannata F, Carrozzi L, Cascio A, Cingolani A, Cipollone F, Colomba C, Crisetti A, Crosta F, Danzi GB, D'Ardes D, de Gaetano Donati K, Di Gennaro F, Di Palma G, Di Tano G, Fantoni M, Filippini T, Fioretto P, Fusco FM, Gentile I, Grisafi L, Guarnieri G, Landi F, Larizza G, Leone A, Maccagni G, Maccarella S, Mapelli M, Maragna R, Marcucci R, Maresca G, Marotta C, Marra L, Mastroianni F, Mengozzi A, Menichetti F, Milic J, Murri R, Montineri A, Mussinelli R, Mussini C, Musso M, Odone A, Olivieri M, Pasi E, Petri F, Pinchera B, Pivato CA, Pizzi R, Poletti V, Raffaelli F, Ravaglia C, Righetti G, Rognoni A, Rossato M, Rossi M, Sabena A, Salinaro F, Sangiovanni V, Sanrocco C, Scarafino A, Scorzolini L, Sgariglia R, Simeone PG, Spinoni E, Torti C, Trecarichi EM, Vezzani F, Veronesi G, Vettor R, Vianello A, Vinceti M, De Caterina R, Iacoviello L, .
      BACKGROUND AND AIMS: There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death.METHODS AND RESULTS: Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6-14.7 for age ≥85 vs 18-44 y); HR = 4.7; 2.9-7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m2; HR = 2.3; 1.5-3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses.
    CONCLUSIONS: Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.
    Keywords:  COVID-19; Epidemiology; In-hospital mortality; Risk factors
    DOI:  https://doi.org/10.1016/j.numecd.2020.07.031
  7. Endocrinol Diabetes Metab. 2020 Aug 14. e00176
    Seidu S, Gillies C, Zaccardi F, Kunutsor SK, Hartmann-Boyce J, Yates T, Singh AK, Davies MJ, Khunti K.
      Background: Obesity accompanied by excess ectopic fat storage has been postulated as a risk factor for severe disease in people with SARS-CoV-2 through the stimulation of inflammation, functional immunologic deficit and a pro-thrombotic disseminated intravascular coagulation with associated high rates of venous thromboembolism.Methods: Observational studies in COVID-19 patients reporting data on raised body mass index at admission and associated clinical outcomes were identified from MEDLINE, Embase, Web of Science and the Cochrane Library up to 16 May 2020. Mean differences and relative risks (RR) with 95% confidence intervals (CIs) were aggregated using random effects models.
    Results: Eight retrospective cohort studies and one cohort prospective cohort study with data on of 4,920 patients with COVID-19 were eligible. Comparing BMI ≥ 25 vs <25 kg/m2, the RRs (95% CIs) of severe illness and mortality were 2.35 (1.43-3.86) and 3.52 (1.32-9.42), respectively. In a pooled analysis of three studies, the RR (95% CI) of severe illness comparing BMI > 35 vs <25 kg/m2 was 7.04 (2.72-18.20). High levels of statistical heterogeneity were partly explained by age; BMI ≥ 25 kg/m2 was associated with an increased risk of severe illness in older age groups (≥60 years), whereas the association was weaker in younger age groups (<60 years).
    Conclusions: Excess adiposity is a risk factor for severe disease and mortality in people with SARS-CoV-2 infection. This was particularly pronounced in people 60 and older. The increased risk of worse outcomes from SARS-CoV-2 infection in people with excess adiposity should be taken into account when considering individual and population risks and when deciding on which groups to target for public health messaging on prevention and detection measures. Systematic review registration: PROSPERO 2020: CRD42020179783.
    Keywords:  SARS‐CoV‐2; mortality; obesity; severe disease
    DOI:  https://doi.org/10.1002/edm2.176
  8. medRxiv. 2020 Sep 03. pii: 2020.09.02.20185983. [Epub ahead of print]
    Ingraham NE, Purcell LN, Karam BS, Dudley RA, Usher MG, Warlick CA, Allen ML, Melton GB, Charles A, Tignanelli CJ.
      Importance Despite past and ongoing efforts to achieve health equity in the United States, persistent disparities in socioeconomic status along with multilevel racism maintain disparate outcomes and appear to be amplified by COVID-19. Objective Measure socioeconomic factors and primary language effects on the risk of COVID-19 severity across and within racial/ethnic groups. Design Retrospective cohort study. Setting Health records of 12 Midwest hospitals and 60 clinics in the U.S. between March 4, 2020 to August 19, 2020. Participants PCR+ COVID-19 patients. Patients missing race or ethnicity data or those diagnosed with COVID-19 during a hospitalization were excluded. Exposures Main exposures included race/ethnicity, area deprivation index (ADI), and primary language. Main Outcomes and Measures The primary outcome was COVID-19 severity using hospitalization within 45 days of diagnosis. Logistic and competing-risk regression models (censored at 45 days and accounting for the competing risk of death prior to hospitalization) assessed the effects of neighborhood-level deprivation (using the ADI) and primary language. Within race effects of ADI and primary language were measured using logistic regression. Results 5,577 COVID-19 patients were included, 866 (n=15.5%) were hospitalized within 45 days of diagnosis. Hospitalized patients were older (60.9 years, IQR: 45.7-75.9 vs. 40.4 years, IQR: 25.6-58.3, p<0.001) and more likely to be male (n=425 [49.1%] vs. 2,049 [43.5%], p=0.002). Of those requiring hospitalization, 43.9% (n=381), 19.9% (n=172), 18.6% (n=161), and 11.8% (n=102) were White, Black, Asian, and Hispanic, respectively. Independent of ADI, minority race/ethnicity was associated with COVID-19 severity; Hispanic patients (OR 3.8, 95% CI 2.72-5.30), Asians (OR 2.39, 95% CI 1.74-3.29), and Blacks (OR 1.50, 95% CI 1.15-1.94). Surprisingly ADI was not associated with hospitalization; however, consistent trends within racial/ethnic groups were observed. Furthermore, non-English speaking (OR 1.91, 95% CI 1.51-2.43) significantly increased odds of hospital admission across and within minority groups. Conclusions Minority populations have increased odds of severe COVID-19 independent of neighborhood deprivation, a commonly suspected driver of disparate outcomes during the pandemic. Non-English speaking also accounts for between and within minority populations. These results support continued concern that racism contributes to disparities during COVID-19 while also highlighting the underappreciated role primary language plays in COVID-19 severity across and within minority groups.
    DOI:  https://doi.org/10.1101/2020.09.02.20185983
  9. Eur J Pediatr. 2020 Sep 10.
    Williams N, Radia T, Harman K, Agrawal P, Cook J, Gupta A.
      Data show that children are less severely affected with SARS-Covid-19 than adults; however, there have been a small proportion of children who have been critically unwell. In this systematic review, we aimed to identify and describe which underlying comorbidities may be associated with severe SARS-CoV-2 disease and death. The study protocol was in keeping with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A total of 1726 articles were identified of which 28 studies fulfilled the inclusion criteria. The 28 studies included 5686 participants with confirmed SARS-CoV-2 infection ranging from mild to severe disease. We focused on the 108 patients who suffered from severe/critical illness requiring ventilation, which included 17 deaths. Of the 108 children who were ventilated, the medical history was available for 48 patients. Thirty-six of the 48 patients (75%) had documented comorbidities of which 11/48 (23%) had pre-existing cardiac disease. Of the 17 patients who died, the past medical history was reported in 12 cases. Of those, 8/12 (75%) had comorbidities.Conclusion: Whilst only a small number of children suffer from COVID-19 disease compared to adults, children with comorbidities, particularly pre-existing cardiac conditions, represent a large proportion of those that became critically unwell. What is Known: • Children are less severely affected by SARS-CoV-2 than adults. • There are reports of children becoming critically unwell with SARS-CoV-2 and requiring intensive care. What is New: • The majority of children who required ventilation for SARS-CoV-2 infection had underlying comorbidities. • The commonest category of comorbidity in these patients was underlying cardiac disease.
    Keywords:  Adolescent; COVID-19; Comorbidities; Critically unwell; Paediatric; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
    DOI:  https://doi.org/10.1007/s00431-020-03801-6