bims-covirf Biomed News
on COVID19 risk factors
Issue of 2020–08–02
eight papers selected by
Catherine Rycroft, BresMed



  1. Eur J Clin Invest. 2020 Jul 29. e13362
       BACKGROUND: Identification of reliable outcome predictors in Corona virus disease-2019 (Covid-19) is of paramount importance for improving patient's management.
    METHODS: A systematic review of literature was conducted until April 24th , 2020. From 6,843 articles, 49 studies were selected for a pooled assessment; cumulative statistics for age and sex were retrieved in 587,790 and 602,234 cases. Two endpoints were defined: 1) a composite outcome including death, severe presentation, hospitalization in intensive care unit (ICU) and/or mechanical ventilation; 2) in-hospital mortality. We extracted numeric data on patients' characteristics and cases with adverse outcomes and employed inverse variance random effects models to derive pooled estimates.
    RESULTS: We identified 18 and 12 factors associated with the composite endpoint and death, respectively. Among those, a history of CVD (odds ratio (OR)=3.15, 95% confidence intervals (CI) 2.26-4.41), acute cardiac (OR=10.58, 5.00-22.40) or kidney (OR=5.13, 1.78-14.83) injury, increased procalcitonin (OR=4.8, 2.034-11.31) or D-dimer (OR=3.7, 1.74-7.89), and thrombocytopenia (OR=6.23, 1.031-37.67) conveyed the highest odds for the adverse composite endpoint. Advanced age, male sex, cardiovascular comorbidities, acute cardiac or kidney injury, lymphocytopenia and D-dimer conferred an increased risk of in-hospital death. With respect to the treatment of the acute phase, therapy with steroids was associated with the adverse composite endpoint (OR=3.61, 95% CI 1.934-6.73), but not with mortality.
    CONCLUSIONS: Advanced age, comorbidities, abnormal inflammatory and organ injury circulating biomarkers captured patients with an adverse clinical outcome. Clinical history and laboratory profile may then help identify patients with a higher risk of in-hospital mortality.
    Keywords:  Covid-19; meta-analysis; outcomes; predictors
    DOI:  https://doi.org/10.1111/eci.13362
  2. Aging Clin Exp Res. 2020 Jul 30.
       BACKGROUND: At present, novel coronavirus disease 2019 (COVID-19) has become a serious global public health problem. The current meta-analysis aimed to find risk factors for the COVID-19-related death, helping to enhance the efficacy and reduce the mortality of COVID-19.
    METHODS: We searched PubMed, Embase, medRxiv, and Cochrane Library for articles published between January 1, 2020, and April 13, 2020. We statistically analyzed the risk factors of the COVID-19 deceased with meta-analysis.
    RESULTS: A total of 2401 patients in 15 articles were included in this study. Meta-analysis showed that 66.6% of COVID-19 deceased were male, with a median age of 69.9 years. Common symptoms of deceased included fever (70.6-100%), dyspnea (38.89-85.7%), cough (22.4-78%), and fatigue (22-61.9%). The incidence of hypertension, chronic cardiovascular disease, diabetes, and chronic cerebrovascular disease among the COVID-19 deceased were 38.56% (95% confidence interval (CI) 25.84 ~ 52.12%), 17.54% (95% CI 13.38 ~ 21.69%), 22.2% (95% CI 19.30 ~ 25.10%), and 15.58% (95% CI 10.05 ~ 21.12%), respectively. Compared with the surviving COVID-19 patients, the deceased had lower platelet levels (mean difference (MD) = - 39.35, 95% CI - 55.78 ~ - 22.93) and higher C-reactive protein (CRP) (MD = 80.85, 95% CI 62.53 ~ 99.18) and lactate dehydrogenase (LDH) (MD = 246.65, 95% CI 157.43 ~ 335.88) at admission. The most common complications of the deceased were acute respiratory distress syndrome (ARDS) (OR = 100.36, 95% CI 64.44 ~ 156.32) and shock (OR = 96.60, 95% CI 23.80 ~ 392.14).
    CONCLUSION: Most of the COVID-19 deceased were elderly males. Fever, dyspnea, dry cough, fatigue, hypertension, chronic cardiovascular and cerebrovascular disease, diabetes, and laboratory examinations showed low levels of platelet content, increased CRP and LDH were associated with the risk of dying. ARDS and shock were risk factors for death in COVID-19 patients.
    Keywords:  COVID-19; Death; Meta-analysis; Severe acute respiratory syndrome coronavirus 2
    DOI:  https://doi.org/10.1007/s40520-020-01664-3
  3. Int J Infect Dis. 2020 Jul 25. pii: S1201-9712(20)30572-5. [Epub ahead of print]
       OBJECTIVES: Existing findings regarding the relationship between comorbidities and Covid-19 severity is inconsistent and insufficient. The present study aimed to evaluate the association between different comorbidities and the severity of Covid-19.
    METHODS: PubMed, EMBASE, and the Cochrane Library were searched to identify studies reporting on the rate of comorbidities in Covid-19 patients with severe/fatal outcomes. Subgroup analyses were conducted according to disease severity, and the country of residence. Odds ratio (OR) with 95% confidence intervals (CI) were pooled using random-effects models.
    RESULTS: A total of 34 eligible studies were identified. In patients with severe/fatal Covid-19, the most prevalent chronic comorbidity was obesity (42%, 95CI 34-49%) and hypertension (40%, 95%CI 35-45%), followed by diabetes (17%, 95%CI 15-20%), cardiovascular disease (13%, 95%CI 11-15%), respiratory disease (8%, 95%CI 6-10%), cerebrovascular disease (6%, 95%CI 4-8%), malignancy (4%, 95% CI 3-6%), kidney disease (3%, 95%CI 2-4%), and liver disease (2%, 95%CI 1-3%). In order of the prediction, the pooled ORs of the chronic respiratory disease, hypertension, cardiovascular disease, kidney disease, cerebrovascular disease, malignancy, diabetes, and obesity in patients with severe or fatal Covid-19 were (OR 3.56, 95%CI 2.87-4.41), (OR 3.17, 95%CI 2.46-4.08), (OR 3.13, 95%CI 2.65-3.70), (OR 3.02, 95%CI 2.23-4.08), (OR 2.74, 95%CI 1.59-4.74), (OR 2.73, 95%CI 1.73-4.21), (OR 2.63, 95%CI 2.08-3.33), and (OR 1.72, 95%CI 1.04-2.85), respectively, compared with patients with non-severe/fatal Covid-19. No correlation was observed between liver disease and Covid-19 aggravation (OR 1.54, 95%CI 0.95-2.49).
    CONCLUSIONS: Chronic comorbidities, including obesity, hypertension, diabetes, cardia-cerebrovascular disease, respiratory disease, kidney disease, and malignancy, are clinical risk factors of severe or fatal outcomes associated with Covid-19, with obesity being the most prevalent, and respiratory disease being the most strongly predictive. Knowledge of these risk factors can help clinicians better identify and guide the high-risk populations.
    Keywords:  COVID-19; Comorbidity; Fatality; ICU admission; Severe
    DOI:  https://doi.org/10.1016/j.ijid.2020.07.029
  4. SSRN. 2020 Apr 21. 3566166
       BACKGROUND: COVID-19 is a new disease which has become a global pandemic, and is caused by a novel coronavirus, SARS-CoV-2. The disease is still not very well characterized, and factors associated with severe clinical course are not well known.
    METHODS: The main objectives were to determine the demographic, clinical and laboratory manifestations of COVID-19 and to identify the factors associated with severe clinical course. We searched the PubMed for studies published between Jan 1, 2020 and Mar 17, 2020, and included them if they were in English language, published in full, were retrospective or prospective observational or case control study with data on clinical, laboratory and imaging features of adult patients with COVID-19 disease from single or multiple centers. Studies that included exclusively pediatric patients were excluded. The demographic, clinical and laboratory data was displayed as n (%) or mean (SD). The meta-analysis on factors associated with severe clinical course was performed using the random effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated as the effect sizes.
    FINDINGS: We included 58 studies (6892 patients) for the systematic review on clinical manifestations and 21 studies (3496 patients) for meta-analysis on factors associated with severe clinical course. The mean age of patients with COVID-19 is 49.7±16.3 years with a male to female ratio of 1.2:1. Common symptoms and their frequency are: fever (83.4%), cough (60.5%), fatigue (33.8%), sputum (28.9%), dyspnea (22.1%), myalgia (20.6%), chest tightness / pain (16.3%), sore throat (13.5%), headache (11.2%), diarhhea (7.5%), nasal congestion / rhinorrhea (6.7%), nausea / vomiting (5.6%), pain abdomen (4.6%), and hemoptysis (1.7%). The comorbidities associated with COVID-19 are: hypertension (18.4%), diabetes mellitus (9.8%), cardiovascular diseases (8.8%), endocrine diseases (5.8%), gastrointestinal diseases (5%), CLD (3%), and COPD (2.8%). Among the laboratory parameters WBC was low in 27%, high in 9%, platelets were low in 22.9%, creatinine was high in 6.5%, AST was high in 25.3%, ALT was high in 22.7%, bilirubin was high in 8.8%, albumin was low 60.1%, CT chest was abnormal in 89%, CRP was high in 67.5%, LDH was high in 52%, D-dimer was high in 34.8%, CK was high in 14.4%, and procalcitonin was high in 15.4%. Factors significantly associated severe clinical course (with their ORs) are as follows: High CRP (5.78), high procalcitonin (5.45), age >60 (4.82), dyspnea (4.66), high LDH (4.59), COPD (4.37), low albumin (4.34), high D-dimer (4.03), cardiac disease (3.88), low lymphocyte count (3.22), any associated comorbidity (3.16), diabetes mellitus (3.11), high WBC count (2.67), high bilirubin level (2.55), high creatinine (2.34), high AST (2.31), hypertension (2.30), low platelets (1.78), High ALT (1.69), high CK (1.66), fever spikes ≥39°C (1.59), diarrhea (1.55), male gender (1.47), and sputum (1.35).
    INTERPRETATION: Identification of these factors associated with severe COVID-19 will help the physicians working at all levels of healthcare (primary, secondary, tertiary and ICU) in determining which patients need home care, hospital care, HDU care, and ICU admission; and thus, prioritize the scarce healthcare resource use more judiciously. Many of these identified factors can also help the public at large in the current COVID-19 epidemic setting, to judge when they should seek immediate medical care. Funding Statement: None. Declaration of Interests: The authors declare no competing interests.
    Keywords:  2019-nCoV; COVID-19; Novel coronavirus; SARS-CoV-2; coronavirus; nCoV-2019
    DOI:  https://doi.org/10.2139/ssrn.3566166
  5. Arch Bone Jt Surg. 2020 Apr;8(Suppl 1): 247-255
       Background: In this study, we aimed to assess the prevalence of comorbidities in the confirmed COVID-19 patients. This might help showing which comorbidity might pose the patients at risk of more severe symptoms.
    Methods: We searched all relevant databases on April 7th, 2020 using the keywords ("novel coronavirus" OR COVID-19 OR SARS-CoV-2 OR Coronavirus) AND (comorbidities OR clinical characteristics OR epidemiologic*). We reviewed 33 papers' full text out of 1053 papers. There were 32 papers from China and 1 from Taiwan. There was no language or study level limit. Prevalence of comorbidities including hypertension, diabetes mellitus, cardiovascular disease, chronic lung disease, chronic kidney disease, malignancies, cerebrovascular diseases, chronic liver disease and smoking were extracted to measure the pooled estimates. We used OpenMeta and used random-effect model to do a single arm meta-analysis.
    Results: The mean age of the diagnosed patients was 51 years. The male to female ratio was 55 to 45. The most prevalent finding in the confirmed COVID-19 patients was hypertension, which was found in 1/5 of the patients (21%). Other most prevalent finding was diabetes mellitus (DM) in 11%, cerebrovascular disease in 2.4%, cardiovascular disease in 5.8%, chronic kidney disease in 3.6%, chronic liver disease in 2.9%, chronic pulmonary disease in 2.0%, malignancy in 2.7%, and smoking in 8.7% of the patients.
    Conclusion: COVID-19 infection seems to be affecting every race, sex, age, irrespective of health status. The risk of symptomatic and severe disease might be higher due to the higher age which is usually accompanied with comorbidities. However, comorbidities do not seem to be the prerequisite for symptomatic and severe COVID-19 infection, except hypertension.
    Keywords:  COVID-19; Comorbidities; Coronavirus; Systematic review
    DOI:  https://doi.org/10.22038/abjs.2020.47754.2346
  6. Eur Respir J. 2020 Jul 30. pii: 2002144. [Epub ahead of print]
       BACKGROUND: There is insufficient information about risk factors for COVID-19 diagnosis and adverse outcomes from low and middle-income countries (LMICs).
    OBJECTIVES: We estimated the association between patients' characteristics and COVID-19 diagnosis, hospitalisation and adverse outcome in Mexico.
    METHODS: This retrospective case series used a publicly available nation-level dataset released on May 31, 2020 by the Mexican Ministry of Health, with patients classified as suspected cases of viral respiratory disease. Patients with COVID-19 were laboratory-confirmed. Their profile was stratified by COVID-19 diagnosis or not. Differences among COVID-19 patients based on two separate clinical endpoints, hospitalisation and adverse outcome, were examined. Multivariate logistic regressions examined the associations between patient characteristics and hospitalisation and adverse outcome.
    RESULTS: Overall, 236 439 patients were included, with 89 756 (38.0%) being diagnosed with COVID-19. COVID-19 patients were disproportionately older, males and with increased prevalence of one or more comorbidities, particularly diabetes, obesity, and hypertension. Age, male gender, diabetes, obesity and having one or more comorbidities were independently associated with laboratory-confirmed COVID-19. Current smokers were 23% less likely to be diagnosed with COVID-19 compared to non-smokers. Of all COVID-19 patients, 34.8% were hospitalised and 13.0% experienced an adverse outcome. Male gender, older age, having one or more comorbidities, and chronic renal disease, diabetes, obesity, COPD, immunosuppression and hypertension were associated with hospitalisation and adverse outcome. Current smoking was not associated with adverse outcome.
    CONCLUSION: This largest ever case series of COVID-19 patients identified risk factors for COVID-19 diagnosis, hospitalisation and adverse outcome. The findings could provide insight for the priorities the need to be set, especially by LMICs, to tackle the pandemic.
    DOI:  https://doi.org/10.1183/13993003.02144-2020
  7. Diabetes Res Clin Pract. 2020 Jul 22. pii: S0168-8227(20)30599-4. [Epub ahead of print] 108347
       BACKGROUND: COVID-19 pneumonia is a newly recognized illness that is spreading rapidly around the world and causes many disability and deaths. Some diseases, for instance diabetes, is continuously suggested as a risk factor which contributes to the severity and mortality of COVID-19. However, to date, there are no comprehensive studies aiming to explain the exact relationship between diabetes and COVID-19. Thus, this study aims to summarize the evidence about diabetes and COVID-19 outbreak through a systematic review and meta-analysis approach.
    METHOD: A literature review was implemented within databases of Scopus, PubMed, Science direct, and Web of science. Observational reviews, case-report, and case-series studies that assessed the diabetes in COVID-19 patients, were included. Data extraction and assessment were guided by PRISMA checklist.
    FINDINGS: Some studies suggest that there were no significant differences in symptoms between patients who suffered from both diabetes and COVID-19 and those who only suffered COVID-19. In the subsequent meta-analysis 14.5 % of the subjects were diabetic patient. These clients have poor ARDS prognosis, severe symptoms, and the death rate is higher among COVID-19 patients. In addition, it is suggested the diabetic patients will be treated with antibiotics, antivirals, and HCQ.
    CONCLUSION: The results of this study show that diabetes is a risk factor - and contributes to the severity and mortality of patients with COVID-19. This paper also provides recommendations and guidelines for which could be useful for prevention and treatment of diabetic patients affected by COVID-19.
    Keywords:  COVID-19; Complication; Diabetes; SARS-CoV-2; Treatment; prevalence
    DOI:  https://doi.org/10.1016/j.diabres.2020.108347
  8. Heart. 2020 Jul 31. pii: heartjnl-2020-317393. [Epub ahead of print]
       BACKGROUND: There is uncertainty about the associations of angiotensive enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) drugs with COVID-19 disease. We studied whether patients prescribed these drugs had altered risks of contracting severe COVID-19 disease and receiving associated intensive care unit (ICU) admission.
    METHODS: This was a prospective cohort study using routinely collected data from 1205 general practices in England with 8.28 million participants aged 20-99 years. We used Cox proportional hazards models to derive adjusted HRs for exposure to ACE inhibitor and ARB drugs adjusted for sociodemographic factors, concurrent medications and geographical region. The primary outcomes were: (a) COVID-19 RT-PCR diagnosed disease and (b) COVID-19 disease resulting in ICU care.
    FINDINGS: Of 19 486 patients who had COVID-19 disease, 1286 received ICU care. ACE inhibitors were associated with a significantly reduced risk of COVID-19 disease (adjusted HR 0.71, 95% CI 0.67 to 0.74) but no increased risk of ICU care (adjusted HR 0.89, 95% CI 0.75 to 1.06) after adjusting for a wide range of confounders. Adjusted HRs for ARBs were 0.63 (95% CI 0.59 to 0.67) for COVID-19 disease and 1.02 (95% CI 0.83 to 1.25) for ICU care.There were significant interactions between ethnicity and ACE inhibitors and ARBs for COVID-19 disease. The risk of COVID-19 disease associated with ACE inhibitors was higher in Caribbean (adjusted HR 1.05, 95% CI 0.87 to 1.28) and Black African (adjusted HR 1.31, 95% CI 1.08 to 1.59) groups than the white group (adjusted HR 0.66, 95% CI 0.63 to 0.70). A higher risk of COVID-19 with ARBs was seen for Black African (adjusted HR 1.24, 95% CI 0.99 to 1.58) than the white (adjusted HR 0.56, 95% CI 0.52 to 0.62) group.
    INTERPRETATION: ACE inhibitors and ARBs are associated with reduced risks of COVID-19 disease after adjusting for a wide range of variables. Neither ACE inhibitors nor ARBs are associated with significantly increased risks of receiving ICU care. Variations between different ethnic groups raise the possibility of ethnic-specific effects of ACE inhibitors/ARBs on COVID-19 disease susceptibility and severity which deserves further study.
    Keywords:  cardiac risk factors and prevention; diabetes; epidemiology; hypertension; primary care
    DOI:  https://doi.org/10.1136/heartjnl-2020-317393