Association of Sex, Age, and Comorbidities with Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis

Mohitosh Biswas, Shawonur Rahaman, Tapash Kumar Biswas, Zahirul Haque, Baharudin Ibrahim, Mohitosh Biswas, Shawonur Rahaman, Tapash Kumar Biswas, Zahirul Haque, Baharudin Ibrahim

Abstract

Introduction: Although severe acute respiratory syndrome coronavirus-2 infection is causing mortality in considerable proportion of coronavirus disease-2019 (COVID-19) patients, however, evidence for the association of sex, age, and comorbidities on the risk of mortality is not well-aggregated yet. It was aimed to assess the association of sex, age, and comorbidities with mortality in COVID-2019 patients.

Methods: Literatures were searched using different keywords in various databases. Relative risks (RRs) were calculated by RevMan software where statistical significance was set as p < 0.05.

Results: COVID-19 male patients were associated with significantly increased risk of mortality compared to females (RR 1.86: 95% confidence interval [CI] 1.67-2.07; p < 0.00001). Patients with age ≥50 years were associated with 15.4-folds significantly increased risk of mortality compared to patients with age <50 years (RR 15.44: 95% CI 13.02-18.31; p < 0.00001). Comorbidities were also associated with significantly increased risk of mortality; kidney disease (RR 4.90: 95% CI 3.04-7.88; p < 0.00001), cereborovascular disease (RR 4.78; 95% CI 3.39-6.76; p < 0.00001), cardiovascular disease (RR 3.05: 95% CI 2.20-4.25; p < 0.00001), respiratory disease (RR 2.74: 95% CI 2.04-3.67; p < 0.00001), diabetes (RR 1.97: 95% CI 1.48-2.64; p < 0.00001), hypertension (RR 1.95: 95% CI 1.58-2.40; p < 0.00001), and cancer (RR 1.89; 95% CI 1.25-2.84; p = 0.002) but not liver disease (RR 1.64: 95% CI 0.82-3.28; p= 0.16).

Conclusion: Implementation of adequate protection and interventions for COVID-19 patients in general and in particular male patients with age ≥50 years having comorbidities may significantly reduce risk of mortality associated with COVID-19.

Keywords: Coronavirus disease-2019; Demographic characteristics; Risk of mortality; Severe acute respiratory syndrome coronavirus-2.

Conflict of interest statement

The authors declare no conflict of interest.

© 2020 S. Karger AG, Basel.

Figures

Fig. 1
Fig. 1
PRISMA flowchart for identifying studies for this systematic review and meta-analysis. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Fig. 2
Fig. 2
Forest plot of the pooled effects of COVID-19 male patients against female patients on the risk of mortality. M, male; F, female; CI, confidence interval; COVID-19, coronavirus disease-2019.
Fig. 3
Fig. 3
Forest plot of the pooled effects of COVID-19 patients with age ≥50 years against patients with age

Fig. 4

a Forest plot of the…

Fig. 4

a Forest plot of the pooled effects of comorbidities on the risk of…
Fig. 4
a Forest plot of the pooled effects of comorbidities on the risk of mortality associated with hypertension, diabetes or respiratory disease. b Forest plot of the pooled effects of comorbidities on the risk of mortality associated with cardiovascular or cereborovascular disease. c Forest plot of the pooled effects of comorbidities on the risk of mortality associated with kidney disease, liver disease, or cancer. Incre, increase; CI, confidence interval.

Fig. 5

Funnel plot for detection of…

Fig. 5

Funnel plot for detection of publication bias as determined by Egger's test. a…

Fig. 5
Funnel plot for detection of publication bias as determined by Egger's test. a Funnel plot for COVID-19 patients positive for SARS-CoV-2 test. b Funnel plot for COVID-19-hypertensive patients and risk for mortality. COVID-19, coronavirus disease-2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2.
Fig. 4
Fig. 4
a Forest plot of the pooled effects of comorbidities on the risk of mortality associated with hypertension, diabetes or respiratory disease. b Forest plot of the pooled effects of comorbidities on the risk of mortality associated with cardiovascular or cereborovascular disease. c Forest plot of the pooled effects of comorbidities on the risk of mortality associated with kidney disease, liver disease, or cancer. Incre, increase; CI, confidence interval.
Fig. 5
Fig. 5
Funnel plot for detection of publication bias as determined by Egger's test. a Funnel plot for COVID-19 patients positive for SARS-CoV-2 test. b Funnel plot for COVID-19-hypertensive patients and risk for mortality. COVID-19, coronavirus disease-2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2.

References

    1. WHO Coronavirus disease (COVID-2019) situation reports [Internet] 2020. [cited 2020 Jun 2]. Available from: .
    1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395((10223)):497–506.
    1. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8((5)):475–81.
    1. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395((10223)):507–13.
    1. Xu X, Yu C, Qu J, Zhang L, Jiang S, Huang D, et al. Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2. Eur J Nucl Med Mol Imaging. 2020 May;47((5)):1275–80.
    1. Qian G-Q, Yang N-B, Ding F, Ma AHY, Wang Z-Y, Shen Y-F, et al. Epidemiologic and clinical characteristics of 91 hospitalized patients with COVID-19 in Zhejiang, China: a retrospective, multi-centre case series. QJM. 2020 Jul 1;113((7)):474–81.
    1. Zhang J, Dong X, Cao Y, Yuan Y, Yang Y, Yan Y, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020 Jul;75((7)):1730–41.
    1. Xu YH, Dong JH, An WM, Lv XY, Yin XP, Zhang JZ, et al. Clinical and computed tomographic imaging features of novel coronavirus pneumonia caused by SARS-CoV-2. J Infect. 2020 Apr;80((4)):394–400.
    1. Wang Z, Yang B, Li Q, Wen L, Zhang R. OUP accepted manuscript. Clin Infect Dis. 2020
    1. Li B, Yang J, Zhao F, Zhi L, Wang X, Liu L, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. 2020 May;109((5)):531–8.
    1. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ WV. Handbook. 2019. Cochrane Handbook for Systematic Reviews of Interventions version 6.0 (updated July 2019). Cochrane, 2019. [Internet]
    1. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan: a web and mobile app for systematic reviews. Syst Rev. 2016;5((1)):210.
    1. Wells G, Shea B, O'Connell D, Peterson J. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses [Internet] Ottawa Hosp Res Inst. 2000
    1. Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. 1997;127((9)):820–6.
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327((7414)):557–60.
    1. Sutton AJ, Duval SJ, Tweedie RL, Abrams KR, Jones DR. Empirical assessment of effect of publication bias on meta-analyses. BMJ. 2000;320((7249)):1574–7.
    1. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315((7109)):629–34.
    1. Cao J, Tu WJ, Cheng W, Yu L, Liu YK, Hu X, et al. Clinical features and short-term outcomes of 102 patients with corona virus disease 2019 in Wuhan, China. Clin Infect Dis. 2020;71((15)):748–55.
    1. Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020 Mar 26;368
    1. Chen TL, Dai Z, Mo P, Li X, Ma Z, Song S, et al. Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study. J Gerontol A Biol Sci Med Sci. 2020 Sep 16;75((9)):1788–95.
    1. Deng Y, Liu W, Liu K, Fang YY, Shang J, Zhou L, et al. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 (COVID-19) in Wuhan, China: a retrospective study. Chin Med J. 2020 Jun 5;133((11)):1261–67.
    1. Du RH, Liang LR, Yang CQ, Wang W, Cao TZ, Li M, et al. Predictors of mortality for patients with COVID-19 pneumonia caused by SARSCoV-2: a prospective cohort study. Eur Respir J. 2020;55((5))
    1. Hu H, Yao N, Qiu Y. Comparing rapid scoring systems in mortality prediction of critical ill patients with novel coronavirus disease. Acad Emerg Med. 2020 Jun;27((6)):461–8.
    1. Zijian Feng QL, Zhang Y, Wu Z, Xiaoping Dong H, Ma, Yin D, et al. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19): China, 2020. CCDC Wkly. 2020;2((8)):113–22.
    1. Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020 Jul 1;5((7)):802–10.
    1. Sun H, Ning R, Tao Y, Yu C, Deng X, Zhao C, et al. Risk factors for mortality in 244 older adults with COVID-19 in Wuhan, China: a retrospective study. J Am Geriatr Soc. 2020 Jun;68((6)):E19–23.
    1. Wang L, He W, Yu X, Hu D, Bao M, Liu H, et al. Coronavirus disease 2019 in elderly patients: characteristics and prognostic factors based on 4-week follow-up. J Infect. 2020;80((6)):639–45.
    1. Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul 1;180((7)):934–43.
    1. Yan Y, Yang Y, Wang F, Ren H, Zhang S, Shi X, et al. Clinical characteristics and outcomes of patients with severe covid-19 with diabetes. BMJ Open Diabetes Res Care. 2020;8((1))
    1. Yao Q, Wang P, Wang X, Qie G, Meng M, Tong X, et al. Retrospective study of risk factors for severe SARS-Cov-2 infections in hospitalized adult patients. Polish Arch Intern Med. 2020 May 29;130((5)):390–9.
    1. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395((10229)):1054–62.
    1. Mehra MR, Desai SS, Kuy S, Henry TD, Patel AN. Cardiovascular disease, drug therapy, and mortality in Covid-19. N Engl J Med. 2020 Jun 18;382((25)):e102.
    1. Palaiodimos L, Kokkinidis DG, Li W, Karamanis D, Ognibene J, Arora S, et al. Severe obesity is associated with higher in-hospital mortality in a cohort of patients with COVID-19 in the Bronx. New York: Metabolism; 2020. p. p. 154262.
    1. Shi Q, Zhang X, Jiang F, Zhang X, Hu N, Bimu C, et al. Clinical characteristics and risk factors for mortality of COVID-19 patients with diabetes in Wuhan, China: a two-center, retrospective study. Diabetes Care. 2020;43((7)):1382.
    1. Tian S, Hu N, Lou J, Chen K, Kang X, Xiang Z, et al. Characteristics of COVID-19 infection in Beijing. J Infect. 2020 Apr;80((4)):401–6.
    1. Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L, Castelli A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the lombardy region. JAMA. 2020 Apr 28;323((16)):1574–81.
    1. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020 May 26;323((20)):2052–59.
    1. La Vignera S, Cannarella R, Condorelli RA, Torre F, Aversa A, Calogero AE. Sex-specific SARS-CoV2 mortality: among hormone-modulated ace2 expression, risk of venous thromboembolism and hypovitaminosis D. Int J Mol Sci. 2020;21((8))
    1. Gemmati D, Bramanti B, Serino ML, Secchiero P, Zauli G, Tisato V. COVID-19 and individual genetic susceptibility/receptivity: role of ACE1/ACE2 genes, immunity, inflammation and coagulation. Might the double X-chromosome in females be protective against SARS-CoV-2 compared to the single X-chromosome in males? Int J Mol Sci. 2020;21((10)):3474.
    1. Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-angiotensin-aldosterone system inhibitors in patients with Covid-19. N Engl J Med. 2020;382((17)):1653–9.
    1. Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020 Aug;81((5)):537–40.
    1. Leng J, Goldstein DR. Impact of aging on viral infections. Microbes Infect. 2010;12((14–15)):1120–4.
    1. Lavan AH, Gallagher P. Predicting risk of adverse drug reactions in older adults. Ther Adv Drug Saf. 2016;7((1)):11–22.
    1. Bunyavanich S, Do A, Vicencio A. Nasal gene expression of angiotensin-converting enzyme 2 in children and adults. JAMA. 2020 Jun 16;323((23)):2427–9.
    1. Berbudi A, Rahmadika N, Cahyadi AI, Ruslami R. Type 2 diabetes and its impact on the immune system. Curr Diabetes Rev. 2020;16((5)):442–9.
    1. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. 2020 Apr;8((4)):e21.
    1. Li XC, Zhang J, Zhuo JL. The vasoprotective axes of the renin-angiotensin system: physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases. Pharmacol Res. 2017;125((Pt A)):21–38.
    1. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS. J Virol. 2020 Mar 17;94((7)):e00127-20.
    1. Zhang X, Yu J, Pan LY, Jiang HY. ACEI/ARB use and risk of infection or severity or mortality of COVID-19: a systematic review and meta-analysis. Pharmacol Res. 2020;158:104927.
    1. Mehta N, Kalra A, Nowacki AS, Anjewierden S, Han Z, Bhat P, et al. Association of use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with testing positive for coronavirus disease 2019 (COVID-19) JAMA Cardiol. 2020 Sep 1;5((9)):1020–6.
    1. Oyelade T, Alqahtani J, Canciani G. Prognosis of COVID-19 in patients with liver and kidney diseases: an early systematic review and meta-analysis. Trop Med Infect Dis. 2020;5((2)):80.
    1. Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 2020;14((2)):185–92.
    1. Chen L, Li X, Chen M, Feng Y, Xiong C. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res. 2020;116((6)):1097–100.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner