Introduction
Since December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global outbreak of coronavirus disease 2019 (COVID-19). Currently, the pandemic has affected more than 127,319,002 people in more than 200 countries and killed more than 2,785,838 people (https://www.who.int/emergencies/diseases/novel-coronavirus-2019). Previous studies have reported that several pre-existing medical conditions, such as hypertension, diabetes and so on, might accelerate disease progression of COVID-19 [1‐3]. Cardiovascular disease (CVD), one of the most common comorbidities of COVID-19, has been observed to be associated with adverse outcomes among COVID-19 patients by Li et al. in a meta-analysis study [4]. Nevertheless, it is worth noting that the results of Li et al.’s study were based on the unadjusted effect estimates [4]. It is reported that age, sex, and co-existing diseases are known to affect the outcomes of COVID-19 patients [5‐7], which may modulate the association between CVD and adverse outcomes in COVID-19 patients. Moreover, Zhou et al. observed that coronary heart disease (CHD), one of CVD, was strongly correlated with an increased risk of in-hospital mortality among COVID-19 patients in univariable analysis (odds ratio (OR) = 21.4, 95% confidence interval (CI): 4.64-98.76), but no significant correlation was observed in multivariable analysis (OR = 2.14, 95% CI: 0.26-17.79) [8]. The similar results were also observed by Robilotti et al. [9] and Louapre et al. [10]. Therefore, it is necessary to clarify whether pre-existing CVD was an independent risk factor associated with adverse outcomes in COVID-19 patients. In this study, we performed a quantitative meta-analysis on the basis of adjusted effect estimates.
Methods
This is a quantitative meta-analysis on the basis of adjusted effect estimates. Admittedly, our study was not registered, but our meta-analysis was made in strict accordance with the process of systematic evaluation (Fig. 1). Moreover, our study is less likely to be biased by artificial bias because this study was carried out rigorously in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines (Online supplemental Table A1) [11].
Fig. 1
Flow diagram of selection process
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Literature search strategy
The databases of PubMed, Web of Science, MedRxiv, Scopus, Elsevier ScienceDirect, Cochrane Library and Embase were searched to obtain a complete data source up to January 7, 2021. The search strategies were as follows: (“COVID-19” OR “coronavirus disease 2019” OR “SARS-CoV-2” OR “2019-nCoV”) AND (“cardiovascular disease” OR “coronary heart disease” OR “cardiac disease” OR “heart disease” OR “heart failure” OR “coronary artery disease”) AND (“outcome” OR “severe” OR “critical” OR “severity” OR “fatality” OR “mortality” OR “death” OR “adverse outcome” OR “poor outcome” OR “clinical characteristics”). All the terms matched the MesH browser. Beyond that, the relevant references of preceding studies were also taken into account.
Eligibility criteria
The criteria for including studies were: (1) Subjects should be laboratory-confirmed COVID-19 patients; (2) Studies should report the correlation between CVD and COVID-19 patients and the data are available; (3) Studies should be published in English; (4) Studies should include the multivariate analysis. The studies with the largest sample size were selected for inclusion when studies were conducted in the same hospital and the overlapping period. There was no restriction for region of study. The exclusion criteria included case reports, review papers, comments, errata, repeated studies, studies only reporting the characteristics of COVID-19 patients with CVD, and studies without available full text.
Data extraction and quality assessment
Data were extracted independently by two investigators (J.X. and W.X.), including the following information: the first author, source of data, country, date of data collection, number of patients, mean/median age, the percent of males, study design, the percent of COVID-19 patients with CVD, adjusted effect estimates (hazard ratio (HR) or OR) and adjusted risk factors. When both OR and HR existed in the same article, it was preferred to include HR because cox regression took time into account. Two researchers negotiated to resolve it in case of any issues not covered by the criteria and Y.W. acted as arbiter. The quality of the included studies was evaluated by investigators according to the Newcastle-Ottawa Scale [12]. High-quality studies referred to studies with a score above 7.
Data synthesis
The major information such as study design and effect estimates were directly extracted from original articles. The research type of some articles was not clear and some articles provided both OR and HR. Besides, the calculation methods of HR and OR are different. The calculation of HR takes into account the concept of time, and OR is the approximate value of risk ratio. Therefore, pooled HR, OR and 95% confidence intervals (CIs) were separately calculated to address the risk of adverse outcomes in COVID-19 patients with a history of CVD. Heterogeneity was assessed by Cochran’s Q-statistic and I2 test, if no significant heterogeneity was observed (I2 ≤ 50%, P > 0.1), a fixed-effects model was adopted; otherwise, a random-effects model was applied [13]. In addition, we also provided the prediction interval, which was helpful for assessing whether the variation across studies was clinically significant [14, 15]. The robustness of the results was evaluated by sensitivity analysis which omitted one study at a time. Publication bias was assessed by Begg’s test [16], Egger’s test [17] and trim-and-fill method [18]. Subgroup analysis and meta-regression were conducted to determine the source of heterogeneity. Data analyses were conducted using Stata, version 12.0 (meta-program) and R, version 3.6.1 (netmeta package). A two-tailed P-value < 0.05 was regarded as significant.
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Results
The flow chart of selection process is shown in Fig. 1. 5,025 records were retrieved after removing 23,826 duplicates, of which 245 studies were full-text assessed. Eventually, a total of 203 eligible studies with 24,032,712 patients were enrolled in our meta-analysis [2, 3, 8, 9, 19‐210, 212‐218]. 81 studies originated from Europe, 54 studies came from North America, 61 from Asia, 2 from Australia, and the remained 5 were not just from one country (Table 1). Among these studies, cardiac disease was mentioned in 63 studies, HF was involved in 35 studies, and CAD was involved in 35 studies (Table 2). Adjusted HR was reported in 65 studies and adjusted OR was reported in 138 studies (Table 2). The main characteristics of the selected studies are summarized in Table 1.
Table 1
Main characteristics of the included studies
Author (Year) | Country | Patients(n) | Mean/Median Age(years) | Male (%) | Study design | Kinds of diseases | CVD (%) | Adjusted effect estimate (95%CI) | Outcome | Confounders | NOS Score |
|---|---|---|---|---|---|---|---|---|---|---|---|
Zhou et al. (2020) [8] | China | 191 | 56·0 (46·0–67·0) | 119 (62) | Retrospective cohort study | Coronary heart disease | 18 (8) | OR 2.14 (0.26-17.79) | In-hospital death | Age, SOFA score | 7 |
Yu et al. (2020) [19] | China | 333 | 50(35-63) | 172 (51.7) | Descriptive study | Heart disease | 24 (7.2) | OR 4.2 (1.2-14.2) | Severity | Age, sex, diabetes, HTN, respiratory disease | 8 |
Cummings et al. (2020) [3] | USA | 257 | 62 (51–72) | 171 (67) | Prospective observational cohort study t | Chronic cardiac disease | 49 (19) | HR 1.76 (1.08-2.86) | In-hospital mortality | Age, gender, symptom duration before hospital, presentation, COPD or interstitial lung disease, diabetes, IL-6, D-dimer | 8 |
Zhao et al. (2020) [20] | China | 1000 | 61 (46-70) | 466 (46.6) | Retrospective study | Coronary heart disease | 60 (6) | HR 0.972 (0.547-1.726) | Death | Age | 8 |
Sabri et al. (2020) [21] | Iran | 60 | 54.1±15.5 | NR | Retrospective cohort study | Heart Disease | 10 (15.9) | OR 1.12 (1.08-1.14) | ICU admission | Pericardial effusion, blood oxygen saturation | 7 |
Lala et al. (2020) [22] | USA | 2736 | 66.4 | 1630 (59.6) | NR | Coronary Artery Disease | 453 (16.6) | OR 1.08 (0.85-1.37) | Mortality | age, sex, BMI, race, ethnicity, history of CAD, history of AF, history of HF, history of HTN, history of CKD, history of DM, statin use, angiotensin converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) use, and CURB-65 score at hospital admission | 7 |
Cen et al. (2020) [2] | China | 1007 | 61(49-68) | 493(49.0) | Multi-center observational study | Coronary artery disease | 65 (6.5) | HR 1.828 (1.256-2.660) | Disease progression was defined as progression to the severe or critical disease stage, or death | Age, sex, smoking history, HTN, diabetes, chronic obstructive lung disease, CAD, CRD, CVA, hepatitis B infection, anti-viral drug, aeration of anti-viral therapy | 7 |
Ciceri et al. (2020) [23] | Italy | 410 | 65 (56-75) | 299 (72.9) | NR | Coronary artery disease | 51 (12.6) | HR 2.93 (1.77-4.86) | Death | Age, gender, cancer, radiographic assessment of lung edema score, WBC count, lymphocyte count, hemoglobin, platelets. | 7 |
Barman et al. (2020) [24] | Turkey | 607 | 59.5±14.8 | 334 (55.02) | Multi-center retrospective study | Coronary artery disease | 116 (19.1) | OR 1.26 (1.06-1.50) | Mortality | Age, gender, HTN, diabetes, CAD, COPD, smoking, creatinine, uric acid, glucose | 7 |
Bravi et al. (2020) [25] | Italy | 1603 | 58.0±20.9 | 758 (47.36) | Case-control, retrospective study | Major cardiovascular diseases | 258 (16.1) | OR 1.88 (1.32-2.70) | Severe or very severe/lethal | Age, gender, HTN, diabetes, cancer, COPD, renal disease | 7 |
Deiana et al. (2020) [26] | Italy | 1223 | 80.4±10.6 | 499 (40.8) | Matched case-control study | CVD | 63 (64.9) | OR 4.0 (1.7-9.7) | Severity | Active tumors, diabetes, HIV, CLD, CRD, metabolic diseases, obesity, chronic neurological diseases, other pathologies | 7 |
Zhang et al. (2020) [27] | China | 80 | 51.16±17.476 | 33 (41.25) | Retrospective cohort | Cardiac disease | 9 (11.25) | HR 0.21 (0-22.09) | Severity | Age, respiratory diseases, HTN, more than 2 kinds of diseases, WBC, neutrophil, LYM%, NEU%, NLR, FIB, CRP, TBIL, ALB, GFR, CK-MB, myoglobin, troponin | 7 |
Nie et al. (2020) [28] | China | 671 | 43±15.09 | 377 (56.2) | NR | CVD | 70 (10.4) | OR 0.809 (0.306–2.142) | Severity | Age, gender, coexisting disorder (HTN, diabetes, respiratory diseases, diabetes, respiratory diseases), Animal/human transmission source contact, Contact with confirmed cases, Contact with confirmed cases, Contact with individuals who had been to Wuhan, Close to cluster outbreak, Visited hospital, Visited wet market, No contact, Days from illness onset to diagnosis, X-ray with pneumonia features, CT with pneumonia features, Blood routine test Leucocyte count, Lymphocyte count, Lymphocyte percentage, Neutrophil percentage | 7 |
Robilotti et al. (2020) [9] | USA | 423 | 60.2 | 212 (50) | NR | Cardiac disorder | 84 (20) | HR 1.44 (0.88-2.37) | Severe respiratory illness, | Age, gender, race, BMI, smoking, asthma/COPD, cancer, major surgery, diabetes, HTN/CKI, Systemic chemotherapy, Chronic lymphopenia or corticosteroids, ICI | 8 |
Hashemi et al. (2020) [29] | USA | 363 | 63.2±13.2 | 201 (55.37) | Multi-center retrospective study | Cardiac diseases | 39 (10.7) | OR 0.98 (0.46-2.09) | Death | CLD, age, obesity, gender, HTN, diabetes, hyperlipidemia, pulmonary disorders | 7 |
Lanza et al. (2020) [30] | Italy | 222 | 66.4 (53.8–75.8) | 163 (73) | Observational retrospective study, | Heart disease | 27 (12.16) | OR 1.19 (0.58-2.44) | In-hospital death | Age, gender, smoke habit, CRP, Lung disease, cancer, diabetes, CKD, CURB-65a 1, CURB-65a 2, diabetes, BMI | 8 |
Zeng et al. (2020) [31] | China | 461 | 45.00 (34.50-57.00) | 239 (51.84) | Multicenter retrospective study | CVD | 25 (5.42) | HR 2.30 (0.99-5.38) | Severity | Age, gender, HTN, diabetes, hematology, biochemistry, infection-related indices, coagulation function | 8 |
Petrilli et al. (2020) [32] | USA | 5279 | 54 (38-66) | 2615 (49.5) | Prospective cohort study | Coronary artery disease | 704 (13.3) | OR 1.08 (0.81-1.44) | Mortality | Age, gender, BMI, race, COPD and asthma, diabetes, HTN, cirrhosis, CKD, CAD, immunosuppression, cancer, tobacco smoking | 8 |
Arshad et al. (2020) [33] | USA | 2541 | 63.7±16.5 | 1298 (51.1) | Retrospective cohort study | Cardiovascular Comorbidity | 222 (8.7) | HR 1.062 (0.8-1.410) | Death | HCQ alone (vs. neither medication), azithromycin alone (vs. neither medication), HCQ+AZM (vs. neither medication), age, gender, ethic, BMI,lung comorbidity,CKI comorbidity,COPD, HTN,asthma, COPD,cancer,diabetes, percent O2 saturation < 95, admission to ICU, ventilator, given steroid, given tocilizumab | 7 |
San Román et al. (2020) [34] | Spain | 522 | 68±15 | 294 (56) | NR | Heart disease | 68 (13.02) | OR 2.017 (1.050-3.876) | Severity | Age, SatO2 <90%, creatinine > 1.5 mg/dL, c-reactive protein> 10 mg/L | 7 |
Cheng et al. (2020) [35] | China | 456 | 54.97±18.59 | 211 (46.27) | Retrospective cohort study | CVD | 52 (11.4) | OR 1.204 (0.554-2.619) | Any in-hospital disease progression | Age, gender, HTN, diabetes, CKD, neural system diseases, pulmonary disease, cancer, laboratory findings(leucocytes count, neutrophil count, lymphocyte count, NLR, platelet count, albumin, APTT, prothrombin time, INR, D-dimer, aspartate aminotransferase, creatinine, potassium, creatine kinase, lactate dehydrogenase, procalcitonin, C-reactive protein, erythrocyte sedimentation rate, IL-6 | 8 |
Oussalah et al. (2020) [36] | France | 149 | 65 (54–77) | 91 (61.1) | Retrospective, longitudinal cohort study | CVD | 38 (25.5) | OR 2.35 (0.35-15.68) | Death | Age, COPD, gender, creatinine >10.1 mg/L, HTN | 8 |
Kim et al. (2020)[37] | Korea | 9148 | 51* | 3556 (38.9) | Observational Study | Heart failure | 124 (1.4) | OR 3.17 (1.88–5.34) | Mortality | Gender, age, type of distiricts, high epidemic region and socio-economic status | 8 |
Chen et al. (2020) [38] | China | 3309 | 62(49-69) | 1642 (49.6) | Retrospective | CVD | 242 (7.3) | OR 1.41 (0.94-2.13) | Death | Age, gender, HTN, diabetes, cerebrovascular disease, malignancy, CKI, COPD, days from onset to clinics (vs ≤5d), days from onset to admission (vs ≤12d) | 9 |
Ferrante et al. (2020) [39] | Italy | 332 | 66.9 (55.4-75.5) | 237 (71.4) | Single-center cohort study | CAD | 49 (14.5) | OR 2.14 (0.99-4.63) | Death | Age, HTN, CVA, Cancer, eGFR, PaO/FiO2 ratio, PA diameter, baseline ACEI/ARB use | 7 |
Rastad et al. (2020) [40] | Iran | 2597 | 54.8±16.9 | 1589 (53.7) | Retrospective cohort study | CVD | 314 (10.6) | OR 0.61 (0.30, 1.24) | In-hospital mortality | WBC, neutrophils, lymphocytes, serum concentrations, creatinine, LDH, AST, ALT, Hb, ESR, CRP, age | 8 |
Hwang et al. (2020) [41] | South Korea | 103 | 67.62±15.32 | 52 (50) | Retrospective cohort study | CVD | 12 (12) | HR 2.556 (0.535–12.207)) | Mortality | Age, diabetes, CLD, Alzheimer’s dementia, stroke | 7 |
Grasselli ei al. (2020) [42] | Italy | 3988 | 63 (56-69) | 3188 (79.9) | Retrospective, observational cohort study | Heart disease | 533 (13.4) | HR 1.08 (0.91-1.29) | Death | Age, gender, respiratory support, HTN, hypercholesterolemia, type 2 diabetes, Malignancy, COPD, ACE inhibitor therapy, ARB therapy, statin, diuretic, PEEP at admission, FiO2 at admission, PaO2/FiO2 at admission | 8 |
Deng et al. (2020) [43] | China | 264 | 64.5 (53.3-74.0) | 130 (49.2) | Retrospective study | Coronary heart disease | 32 (12.1) | HR 1.855 (1.006-3.421) | Death | Age, gender, HTN, cTnI-ultra, CK-MB, MYO, NT-proBNP, Cr | 7 |
AI-Salameh et al. (2020) [44] | France | 433 | 72±14.3 | 226 (52.1) | Observational cohort | CVD | 99 (31.2) | HR 1.84 (1.1-3.08) | Death | Age, diabetes, gender, abnormal LFTs | 7 |
Atkins et al. (2020) [45] | UK | 507 | 74.3±4.5 | 311 (61.3) | NR | CHD | 108 (21.5) | OR 0.86 (0.55-1.36) | Death | Age, gender, race, education, atrial fibrillation, stroke, HTN, diabetes (type 2), CKD, depression, dementia, asthma, COPD, osteoporosis, osteoarthritis, delirium, pneumonia, falls/fragility fractures | 8 |
Yao et al. (2020) [46] | USA | 242 | 66.1±18.3 | 104 (42.98) | Single-institution retrospective study | Heart Disease | 39 (13.6) | HR 0.94 (0.43-2.07) | Mortality | Zinc sulfate (yes vs no), age, gender, COPD, clinical severity, lopinavir/ritonavir, steroids, IL-6 receptor inhibitors, | 8 |
Pinto et al. (2020) [47] | Italy | 1226 | 71.7±14.5 | 733 (59.8) | Observational cohort Study | CVD | NR (NR) | OR 1.58 (0.68–3.68) | Death | Age, sex, presence of metastatic disease, time since cancer diagnosis | 7 |
Chilimuri et al. (2020) [48] | USA | 375 | 63.0 (52.0-72.0) | 236 (63) | Retrospective cohort study | CVD | 62 (17) | OR 1.56 (0.78-3.11) | Mortality | Age, gender, HTN, lymphocyte, creative protein, alanine aminotransferase, aspartate aminotransferase, creatine kinase | 8 |
Lian et al. (2020) [49] | China | 232 | NR | 108 (46.5) | Retrospective study | Heart disease | 31 (13.36) | HR 2.587 (1.156-5.787) | Severity | Age, NLR, multiple mottling and ground-glass opacity | 8 |
Zhao et al. (2020) [50] | USA | 641 | 58.9±17.5 | 358 (55.85) | Retrospective study | Heart failure | 20 (3.12) | OR 33.48 (4.99-224.45) | Mortality | LDH, procalcitonin, smoking history, SpO2, lymphocyte count, procalcitonin, LDH, COPD, SpO2, heart rate, age | 8 |
Wang et al. (2020) [51] | USA | 1827 | 52.7±21.1 | 500 (32.6) | NR | CVD | 589 (32.2) | OR 2.21 (1.21-4.04) | Severity | Gender, race, marital status, Insurance type, smoking history, BMI, comorbidities (diabetes, COPD, CKD, CLD, HTN, allergic rhinitis), SABA, combination | 7 |
Garcia-Azoin et al. (2020) [52] | Spain | 576 | 67.18±14.75 | 326 (56.6) | Retrospective cohort study | Cardiac disease | 154 (26.7) | OR 1.20 (0.730-1.999) | Mortality | mRS≥3, age, gender, HTN, diabetes, smoking, pulmonary disorders, cancer, chronic neurological disorders, immunosuppression | 7 |
Alkhatib et al. (2020) [53] | USA | 158 | 57±15.1 | 61 (38.6) | Retrospective cross-sectional analysis | Heart Failure | 21 (13.3) | OR 2.4 (0.734-7.845) | Severity | Age, gender, diabetes, HTN, lung disease, CKD, BMI | 7 |
Hernández-Galdamez et al. (2020) [54] | Mexico | 211003 | 45.7±16.3 | 115442 (54.71) | Cross-sectional study | CVD | 4949 (2.35) | OR 0.93 (0.87-1.00) | Death | At least one comorbidity/risk, CKD, immunosuppression, diabetes, COPD, HTN, asthma, obesity, smoking | 8 |
Bellmann-Weiler et al. (2020) [55] | Australia | 259 | 66.8±14.3 | 157 (60.62) | Retrospective | CVD | 152 (58.62) | OR 2.127 (0.309–14.647) | Death | Age, CKD, COPD, eGFR, leukocytes, PCT, anemia, | 8 |
Berenguer et al. (2020) [56] | Spain | 4035 | 70 (56 – 80) | 2433 (61) | Retrospective nationwide cohort study | Chronic heart disease | 932 (23.3) | HR 1.58 (1.38-1.81) | Death | Gender, age, HTN, diabetes, COPD, obesity, CKI stage 4, liver cirrhosis, chronic neurological disorder, cancer, dementia, headache, myalgia/arthralgia, anosmia, cough, sputum production, dyspnea, chest pain, vomiting/nausea, altered consciousness, low SaO2, WBC count, neutrophil-to-lymphocyte ratio, platelets, prolonged APTT, eGFR, ALT, CRP | 7 |
Gottlieb et al. (2020) [57] | USA | 8673 | 41 (29 – 54) | 4045 (46.6) | Retrospective case-control study t | Congestive Heart Failure | 218 (14.7) | OR 1.45 (1.00-2.12) | Critical Illness | Age, gender, race, COPD, HTN, hyperlipidemia, diabetes, prior CVA, CKD, current ESRD, obstructive sleep apnea, bloodborne cancer, symptoms (anosmia, cough, headache, myalgias), labs(WBC, ALC,ANC/ALC, total Bilirubin, albumin, AST, ALT, LDH, lactate, D-Dimer, CRP, ferritin, troponin) | 8 |
Agarwal et al. (2020) [58] | USA | 1126 | 67.9±13.7 | 630 (49.3) | Retrospective | CVD | 754 (59) | OR 1.18 (0.88-1.57) | Mortality | Treatment regimen (noninsulin only, insulin 1 noninsulin, insulin only), HTN, CKD, COPD | 7 |
Shang et al. (2020) [59] | China | 2529 | 66 | 73 (64.6) | Retrospective | CHD | 28 (24.8) | OR 5.611 (1.392-22.623) | Death | Age, D-dimer, PCT, LYM, diabetes, CRP, BUN | 8 |
Shi et al. (2020)[60] | Iran | 386 | 59.46±15.82 | 236 (61.1) | Prospective, single-center study | CVD | 97(25.1) | HR 1.121 (0.565-2.226) | Death | Age, diabetes, malignancy, CKD, CVA/TIA, previous ACEI/ARB use, ARDs, AKI | 7 |
Posso et al. (2020) [62] | Spain | 834 | 60 | 400 (46.5) | Retrospective | Heart Failure | 37 (37.4) | OR 1.6 (1.01-2.55) | Death | Age, gender | 7 |
Shu et al. (2020) [63] | China | 571 | 50.0 (38.0-59.0) | 278 (48.7) | Single-center, retrospective cohort study | Coronary heart disease | 12 (2.1) | OR 6.75 (0.629-72.61) | Severity | Smoke, HTN, diabetes, dyspnea, consolidation, interstitial abnormalities, lymphocyte counting | 8 |
Parra-Bracamonte et al. (2020) [64] | Mexico | 142690 | 45 (34.0-57.0) | 79280 (56) | NR | Cardiopathy | 3521 (2.0) | OR 1.012 (0.92-1.112) | Mortality | Age, gender, smoking, hospitalized, pneumonia, comorbidity (HTN, obesity, diabetes, COPD, asthma, immunosuppressed, CKD, other complication) | 8 |
Pablos et al. (2020) [65] | Spain | 456 | 65±17.9 | 182 (41) | Retrospective observational matched cohort study | Heart failure | 106 (23.2) | OR 1.57 (0.93-2.66) | Composite severe COVID-19 outcome | CTD, age, gender, obesity, diabetes, glucocorticoids (any dose), antivirals | 8 |
Zhang et al. (2020) [66] | China | 461 | 51 (38-64) | 264 (57.3) | Multicenter study | Coronary heart disease | 25 (5.4) | OR 0.382 (0.096-1.526) | Critical illness | Age, gender, comorbidities (HTN, diabetes, CLD), types of previous surgery (gastrointestinal surgery, urogenital surgery, skeletal surgery, cardiovascular surgery, others), WBC, neutrophil, lymphocyte, LDH, hemoglobin, platelet, albumin, AST, ALT, DBIL, IBIL, TBIL, APTT, PT, D-dimer, creatinine, hs-CRP, procalcitonin, urea nitrogen, FBG, CT score) | 8 |
Fox et al. (2020) [67] | USA | 389 | 66.2±14.2 | 208 (46.5) | Single-center retrospective analysis | CAD | 77 (19.79) | OR 1.579 (0.562–4.436) | In-hospital mortality | Age, BMI, gender, ethnic, Hispanic, others, COPD, asthma, CAD, HTN, atrial fibrillation, CKD | 7 |
Vena et al. (2020) [68] | Italy | 317 | 71 (60-82) | 213 (67.2) | Retrospective study | CVD | 63 (19.9) | OR 2.58 (1.07-6.25) | All-cause in-hospital mortality | AKI, age, CRP, IL-6 | 7 |
Ng et al. (2020) [69] | USA | 10482 | 66 | 6239 (59.5) | Retrospective study | Heart Failure | 920 (8.78) | OR 1.32 (1.14-1.53) | Death | Age, sex, race/ethnicity, BMI, diabetes mellitus, HTN, cancer, mechanical ventilation, use of vasoactive medication, hemoglobin, lymphocyte, blood urea nitrogen, albumin, C-reactive protein and ferritin | 8 |
He et al. (2020) [70] | China | 288 | 48.5 (34.3-62) | 131(45.5) | Single-center, retrospective cohort study | CVD | 85 (29.5) | OR 0.986 (0.052-18.588) | Death | Age, CKD, exposure history in Wuhan >2 weeks, diarrhea, WBC count, lymphocyte count, creatinine, PCT, | 8 |
Gupta et al. (2020) [71] | USA | 2626 | 63.99±16.49 | 1497(57.00) | Retrospective study | CAD | 516 (19.6) | OR 1.179 (0.844-1.647) | In-hospital mortality | Age, gender, CKD, exposure history in Wuhan >2 weeks, diarrhea, white blood cell count, lymphocyte count, creatinine | 6 |
Czernichow et al. (2020) [72] | Europe | 5795 | 59.8±13.6 | 3791 (65.4) | Prospective cohort study | HF | 264 (4.55) | OR 1.15 (0.82-1.59) | Body mass index, age, diabetes, hypertension, dyslipidemia, sleep apnea, CKD, malignancies, history of smoking, gender | 8 | |
Sisó-Almirall et al. (2020) [73] | Spain | 322 | 56.7±17.8 | 161 (50.0) | Multicenter, observational descriptive study | HF | 25(7.8) | OR 1.92 [0.74–4.84] | Death or ICU admission | Age, gender | 7 |
Brenner et al*. (2020) [74] | Germany | 9548 | 62.1 | 4182 (43.8) | Ongoing statewide cohort study | CVD | 4186 (43.8) | HR 1.285 (0.936–1.763) | Mortality | Any cause, age, gender, cancer, respiratory disease, Season | 8 |
De Rossi et al. (2020) [75] | Italy | 158 | 66.38±13.44 | 113 (71.52) | Retrospective cohort study | Heart disease | 33 (20.89) | HR 3.001 (1.422-6.332) | Mortality | GROUP, age, gender, diabetes, HTN, CRP at admission, time to hospitalization, Time to hospitalization | 7 |
Nimkar et al. (2020) [76] | USA | 327 | 71 (59–82) | 182 (55.7) | Retrospective case series | Cardiac Disease | 98 (29.9) | OR 1.7 (0.7–3.9) | Mortality | AKI, ARDS, demographics (age, gender, race), HTN, diabetes mellitus, overweight (25 - 29.9), obese ( >= 30), underweight < 18.5 | 7 |
Klang et al. (2020) [77] | USA | 1320 | 74.48±12.88 | 772 (58.48) | Multicenter observational retrospective study | CHD | 258 (19.55) | OR 1.00 (0.8–1.4) | Death | Age, CAD, HTN, diabetes, CKD, COPD, cancer, obesity, smoking | 7 |
Emami et al. (2021) [78] | Iran | 1239 | 51.48±19.54 | 692 (55.9) | NR | CVD | 132 (10.7) | HR 3.52 (1.23–11.15) | Mortality | Age, diabetes, chronic liver disease, cancer, HIV, smoking, asthma, immunodeficiency disease | 5 |
Liu et al. (2020) [79] | China | 2044 | 62.0 (51.0-70.0) | 1000 (48.92) | Mini-national multicenter, retrospective, cohort study | CHD | 199 (9.76) | OR 1.65 (1.02-2.66) | Critical disease (vs. moderate and severe disease) | Factors with effect modification, HTN, COPD, age, diabetes, tumor, CKD, cough | 6 |
Giorgi et al. (2020) [61] | Italy | 2653 | 63.2 | 1328 (50.1) | Population-based prospective cohort | CHD | 168 (7.1) | HR 1.7 (1.2–2.5) | Death | Age, gender | 7 |
Feng et al. (2020) [81] | China | 114 | 63.96±13.41 | 71 (62.3) | Single-center, prospective study | CVD | 31 (27.2) | HR 1.062 (0.380–2.970) | Poor outcome | Age, gender | 7 |
Li et al. (2020) [82] | China | 199 | 67 (61-78) | 89 (44.7) | Retrospective study | CVD | NR (NR) | OR 0.250 (0.020-3.155) | Death | Age, CKD, HTN, Diabetes, d-dimer at admission, lymphocyte count at admission, fasting plasma glucose at admission, treatment with low molecular weight heparin, Antidiabetic drugs | 7 |
Seiglie et al. (2020) [83] | USA | 450 | 63.32±17.13 | 259 (57.5) | Observational study | CHF | 52 (11.56) | OR 1.94 (0.78-4.85) | Death | Diabetes, BMI category (overweight, Obese), age, male, race/ethnicity (Hispanic, African American, other, unknown/missing), HTN, COPD/asthma, cancer (active), liver disease, renal disease | 7 |
Tural Onur et al. (2020) [84] | Turkey | 301 | 57±18 | 206 (68.4) | Retrospectively | CVD | 19 (6.3) | OR 15.331 (3.394-69.272) | Death | Age, length of stay, lung cancer | 7 |
Anzola et al. (2020) [85] | Italy | 431 | 65±16 | 263 (61) | Prospective study | CVD | 77 (18) | OR 0.618 (0.297-1.285) | Death | Age, lymphocyte count, creatinine, AST, CRP, diabetes, HTN, gender (male), | 7 |
Ioannou et al. (2020) [86] | USA | 10131 | 61.6±15.9 | 9221 (91.0) | Longitudinal cohort study | CAD | 2203 (21.7) | HR 1.02 (0.88-1.18) | Death | Diabetes, cancer, HTN, congestive heart failure, cerebrovascular disease, dialysis, chronic kidney disease, cirrhosis, asthma, COPD, obstructive sleep apnea, obesity, hypoventilation, alcohol dependence, smoking, Charlson comorbidity body index score | 9 |
Bahl et al. (2020) [87] | USA | 1461 | 62.0 (50.0–74.0) | 770 (52.7) | Multicentered cohort study | CVD | 163 (11.2) | HR 1.32 (0.95–1.83) | Mortality | Age, gender, race (Black/African American, White/Caucasian, other), diabetes mellitus, HTN, respiratory rate, blood oxygen saturation White blood cell count, hemoglobin, ALT, creatinine, d-dimer, procalcitonin, lactic acid | 6 |
Kabarriti et al. (2020) [88] | USA | 5902 | 58 (44-71) | 2768 (46.9) | Cohort study | CVD | 1306 (22.1) | HR 1.20 (1.03-1.41) | Death | Age, gender, socioeconomic status (Lowest quartile, Second quartile, third quartile, highest quartile) | 8 |
Jackson et al. (2020) [89] | USA | 51 | 60 (45–69) | 29 (56.9) | Retrospective observational cohort | CAD | 10 (19.6) | OR 2.37 (1.08–5.23) | Death | End-stage renal disease, neurologic disorders, | 6 |
Desai et al. (2020) [90] | Italy | 575 | 64.8 (27-93) | 380 (66.09) | Single-center, retrospective, observational study | CVD | 155 (27.1) | HR 1.78 (1.21–2.61) | Death | Age, ACEi, therapy: LMWH | 8 |
Wang et al. (2021) [91] | China | 663 | 58 (44-69) | 321 (48.4) | Retrospective | CVD | 164 (24.7) | OR 1.66 (0.82-3.47) | Poor therapeutic effect | Age, gender, respiratory diseases, urinary diseases, T2DM, severe and critical condition, Fever, Expectoration, dyspnea, chest tightness, muscle aches, dizziness, neutrophil count >6.3 × 10 per L, Lymphocyte count <1.1 × 10 per L, Hemoglobin <115 g/L, ALT >40 U/L, ALT >40 U/L, Cr >73 mmol/L, Cr >73 mmol/L, albumin <35 g/L, LDH >300 U/L, CRP >10 mg/L | 8 |
Solerte et al. (2020) [92] | Italy | 169 | 69±1.0 | 115 (68) | Multicenter, case-control, retrospective, observational study | CVD | 53 (38) | OR 2.5 (1.30–4.81) | Mortality | Treatment with sitagliptin, age, gender, cancer, chronic kidney disease, use of hydroxychloroquine use of antiviral agents | 8 |
Hayek et al. (2020) [93] | USA | 5019 | 60.42±14.86 | 3165 (63.06) | Multicenter cohort study | CAD | 676 (13.47) | OR 1.13 (0.87-1.47) | In-hospital cardiac arrest | Number of intensive care unit beds ( ≥100 (reference), 50-99, <50), age, gender, Black compared with non-Hispanic white, Hispanic compared with non-Hispanic white, body mass index per 5 kg/m2,current or former tobacco use, diabetes mellitus, HTN, coronary artery disease, congestive heart failure, kidney disease (chronic or end stage), COPD, active malignancy, mSOFA score per 2 units | 8 |
Chen et al. (2020) [94] | China | 2828 | 60.0 (50.0-68.0) | 1442 (51.0) | single-center Retrospective cohort study | CHD | 181 (6.4) | OR 3.09 (1.69-5.64) | Adverse outcomes ( death, ARDS, respiratory failure and septic shock during hospitalization, mechanical ventilation, ICU admission, as well as clinical cure and discharges) | Age, COPD, AKI, Hs-CRP, neutrophil, lymphocyte, blood pressure | 5 |
Lee et al. (2020) [95] | South Korea | 5061 | 45.44±17.92 | 2,229 (44%) | Retrospective cohort study | CVD | 49 (0.97) | HR 2.316 (1.053-5.094) | Mortality | Age, gender, cerebrovascular disease, HTN, diabetes, pulmonary disease, malignancy, CKD | 8 |
Nachega et al. (2020) [96] | South Africa | 766 | 46 (34–58) | 500 (65.6) | Retrospective cohort study | Heart disease | 30 (3.9) | HR 1.40 (0.68–2.88) | Death | Age, gender, clinical stage at admission (mild or moderate, Severe or critical, HTN, diabetes, obesity, asthma/chronic obstructive pulmonary, chronic kidney disease, cancer, HIV, current tuberculosis, chloroquine/azithromycin–based, received oxygen | 8 |
Rozaliyani et al. (2020) [97] | India | 4052 | 45.8±16.3 | 2169 (53.5) | Retrospective cohort study | Heart disease | 148 (6.9) | OR 1.43 (0.85-2.41) | Death | Age, gender, registered address (West Jakarta, Central Jakarta, South Jakarta, East Jakarta, North Jakarta, outside Jakarta, citizenship, foreigner), Symptoms (cough, fever, malaise, dyspnea, headache, nausea/emesis, Sore throat, cold/runny nose, myalgia, chills, abdominal pain, diarrhea, pneumonia), temperature, comorbidity (HTN, COPD, diabetes, renal disease, malignancy, immunological disorder, liver failure, Obesity) | 7 |
Wang et al. (2020) [98] | China | 293 | 59.2 (42.8-73.1) | 138 (47.1) | Retrospective study | Coronary heart disease | 21 (7.2) | HR 1.771 (1.013-3.097) | Mortality | Age, gender, fever, cough, expectoration, dyspnea, catarrhal symptoms, neuromuscular symptoms, digestive symptoms, comorbidity, Hypertension, diabetes, cerebrovascular disease, COPD, chronic renal disease, chronic liver disease, malignancy, only one comorbidity, ≥2 comorbidities, complications, shock, acute cardiac injury, acute renal injury, acute liver injury, Only one complication, ≥2 complications | 8 |
Liu et al. (2020) [99] | China | 77 | 63.6±3.6 | 48 (62) | Retrospective study | CVD | 15 (20) | HR 2.533 (1.108-6.306) | In-hospital death | HbA1C, age, gender, CRD | 8 |
Al Kuwari et al. (2020) [100] | Qatar | 5685 | 35.8±12.0 | 5052 (88.9) | Case series | CVD | 250 (4.4) | OR 0.54 (0.24-1.22) | Severe or critical illness | Age, gender, Qatari nationality, HTN, diabetes mellitus, chronic lung disease, chronic kidney disease, cancer | 8 |
Balbi et al. (2020) [101] | Italy | 340 | 68 (57–76) | 252 (74) | Retrospective observational study | CVD | 86 (25) | OR 3.21 (1.28–8.39) | Death | Age, SpO2, PaO2/FiO2 ratio, Brixia score | 6 |
Calmes et al. (2021) [102] | Belgium | 493 | 58 ± 19 | 244 (49.49) | NR | Cardiopathy | 88 (18) | OR 0.94 (0.53-1.7) | Intensive care unit stay | Age, gender | 8 |
Talavera et al. (2020) [103] | Spain | 576 | 67.18±14.75 | 325 (56.6) | Retrospective cohort study | Cardiological disorders | 154 (26.7) | OR 1.201 (0.716-2.016) | Mortality | Age, sex, hypertension, diabetes, smoking habit, cardiological disorders, pulmonary disorders, cancer, and chronic neurological disorders | 6 |
Zinellu et al. (2020) [104] | Italy | 105 | 72.0 (59.5-80.0) | 70 (66.67) | Retrospective | CVD | 59 (56.19) | HR 2.53 (0.80-7.99) | In-hospital mortality | Age, gender, smoking status, intensity of care, respiratory disease, kidney disease, diabetes, cancer, De Ritis index ≥ 1.63 | 7 |
Mallow et al. (2020) [105] | USA | 21676 | 64.9±17.2 | 11442 (52.8) | Retrospective cohort study | Severe heart disease | 12000 (55.4) | OR 1.27 (1.16-1.40) | Mortality | Age, gender, insurance (Medicaid as any payer), teaching status (nonteaching hospital vs teaching hospital), hospital bed Size, chronic lung disease, moderate to severe asthma, immunocompromised, obesity, diabetes, CKD with dialysis, liver disease, HTN, DNR, statin use in hospital | 8 |
Abbasi et al. (2020) [106] | Iran | 262 | 58 (43–67) | 172 (65.6) | Retrospective cohort study | CAD | 78 (29.8) | OR 6.7 (1.08–42.2) | Mortality | Age, HTN, diabetes, chronic renal failure, hypoxia at admission, WBC, LYM count, LYM% less than 20%, Hb, Plt, AST, ALT, LDH, CRP, ESR, Cr, CT severity score | 6 |
Craig-Schapiro et al. (2021) [107] | USA | 136 | 56.24±35.04 | 93 (68.38) | NR | CVD | 52 (38.23) | OR 0.76 (0.26-2.23) | Mortality | Waitlist status, age, gender, BMI, black, diabetes, pulmonary disease, history of stroke, smoking history, ACE / ARB use | 7 |
Ryan et al. (2020) [108] | USA | 556 | 57±17 | 296 (53) | Retrospective case-control study | CVD | 71 (13) | OR 1.41 (0.77–2.58) | Composite of ICU Admission, Mechanical Ventilation, and Death | Age, immunocompromised status, dyspnea, vomiting, chronic kidney disease, COPD, diabetes mellitus, ACE inhibitor, gender, obesity, current or former smoker, obstructive sleep apnea, HTN, hyperlipidemia | 6 |
Serin et al. (2020) [109] | Turkey | 2217 | 47.66±17.23 | 1175 (53) | NR | CAD | 165 (7.4) | HR 1.726 (0.645−4.618) | Mortality | COPD, chronic heart failure, HTN, diabetes mellitus, chronic renal failure, malignancy, without Involvement in CT, unilaterally, bilaterally, WBC, neutrophil, hemoglobin, C-Reactive Protein, D-Dimer, urea, aspartate aminotransferase, Lactate Dehydrogenase/Lymphocyte | 5 |
Cao et al. (2020) [110] | China | 101 | 56.6±15.1 | 67 (66.3) | Retrospective, two-center study | CVD | 21 (20.8) | OR 0.439 (0.081–2.387) | Mortality | Age, respiratory rate, dyspnea, acute respiratory distress syndrome, diabetes, HTN, chronic pulmonary disease, bacterial infection | 7 |
Gupta et al. (2020) [111] | USA | 3099 | 62 (51–71) | 2003 (64.6) | Multicenter cohort study | CAD | 390 (12.6) | OR 1.17 (0.65-2.13) | 28-day mortality | Age, gender, Non–white race, HTN, diabetes mellitus, BMI, chronic kidney disease, congestive heart failure, active malignancy, ≤3 days from hospital to ICU admission, lymphocyte count <1,000 mm3, PaO2:FiO2, altered mental status, ICU Day 1, secondary Infection, ICU Day 1, vasopressors, coagulation Component of SOFA Score, Liver component of SOFA Score, urine output (ml/day), initial RRT modality initial RRT modality, hospital size (no. pre-COVID ICU beds), regional density of COVID-19 (quartiles) | 7 |
Raparelli et al. (2021) [112] | Italy | 3517 | 77.64±11.51 | 2346 (66.7) | Retrospective analysis | Congestive Heart Failure | 539 (15.7) | OR 0.75 (0.56-1.00) | Death | AGE, IHD, T2DM, dementia, COPD, CLD, CKD, AD, fever, SOB, cough, admission in ICU, AKI, acute cardiac injury, shock, antivirals, tocilizumab, length of stay | 6 |
Chinnadurai et al. (2020) [113] | UK | 215 | 74 (60–82) | 133 (61.9) | Single-center observational study | CVD | 93 (43.3) | OR 1.20 (0.61–2.40) | Mortality | Age, care home resident, frailty, smoking, respiratory diseases | 6 |
Rajter et al. (2020) [114] | USA | 280 | 59.6±15.9 | 153 (64.6) | NR | Cardiac Disease | 43 (15.4) | OR 1.51 (0.43-5.22) | Mortality | Treatment group (Ivermectin VS Control), age, gender, current or former smoker, Race (Black, Hispanic, Other, White), comorbidities (diabetes, pulmonary, HTBN, No comorbidities), BMI, severe presentation, Intubated at study entry, MAP < 70 mm Hg, corticosteroid treatment, peripheral white cell count, lymphocyte count | 7 |
Naaraayan ey al. (2020) [115] | USA | 362 | 71 (59–82) | 200 (55.3) | Retrospective case series | Cardiac diseases | 119 (32.9) | OR 0.9 (0.5–1.4) | In-hospital mortality | age, sex, hypertension, diabetes, race, chronic obstructive pulmonary disease, renal disease and obesity | 6 |
Cherri et al. (2020) [116] | Italy | 53 | 75 (68–83) | 32 (60.4) | Retrospective study | Cardiopathy | 20 (37.7) | OR 1.15 (0.187-7.13) | Mortality | Age, BMI, diabetes, active oncological disease | 7 |
Rodríguez-Molinero et al. (2020) [117] | Spain | 418 | 65.4±16.6 | 238 (56.9) | Observational cohort study | Heart failure | 26 (6.22) | OR 1.16 (0.44–3.06) | Case fatality | Age, gender, diabetes mellitus, obesity, chronic kidney disease, HTN, atrial fibrillation, dementia, OSAS, Auto-immune disease | 6 |
Clift et al. (2020) [118] | UK | 8256158 | 44.33±27.42 | 4111197 (49.8) | Cohort study | Heart failure | 96225 (1.17) | HR 1.14 (1.08–1.20) | Death | No learning disability, learning disability apart from down syndrome, down syndrome, males vs. females, Townsend material deprivation score (5-unit increase), White, Indian British, Pakistani British, Bangladeshi British, Other Asian British, Caribbean British, Black British, Chinese British, other ethnic group, not in care home or homeless, lives in residential or nursing home, Homeless according to GP records, No kidney failure, chronic kidney disease stage, chemotherapy grad, blood cancer, bone marrow or stem cell transplant in past 6 month, respiratory tract cancer, Radiotherapy in past 6 month, Solid organ transplant (excluding kidney and bone marrow), immunosuppressant drug, ≥4 scripts from GP in past 6 mo, Leukotriene or LABA, ≥4 scripts in past 6 month, Oral steroids, ≥4 scripts in past 6 month, Sickle celI disease or severe immunodeficiency, type 1 diabetes, type 2 diabetes, COPD, asthma, rare lung conditions (bronchiectasis, CF, or alveolitis), pulmonary hypertension or pulmonary fibrosis, coronary heart disease, stroke, atrial fibrillation, congestive heart failure, thromboembolism, peripheral vascular disease, congenital heart disease, dementia, Parkinson disease, Epilepsy MND, MS, myasthenia gravis, or Huntington disease, Cerebral palsy, severe mental illness, osteoporotic fracture (hip, spine, wrist, or humerus), rheumatoid arthritis or SLECirrhosis | 9 |
Clift et al. (2020) [119] | UK | 6083102 | 48.21±18.57 | 3035409 (49.90) | Population based cohort study | Coronary heart disease | 215069 (3.54) | HR 1.24 (1.10-1.40) | Death | No learning disability, learning disability apart from down syndrome, down syndrome, males vs. females, Townsend material deprivation score (5-unit increase), White, Indian British, Pakistani British, Bangladeshi British, Other Asian British, Caribbean British, Black British, Chinese British, Other ethnic group, not in care home or homeless, lives in residential or nursing home, homeless according to GP records, No kidney failure, chronic kidney disease stage, chemotherapy grad, blood cancer, bone marrow or stem cell transplant in past 6 month, respiratory tract cancer, radiotherapy in past 6 month, solid organ transplant (excluding kidney and bone marrow), immunosuppressant drug, ≥4 scripts from GP in past 6 month, Leukotriene or LABA, ≥4 scripts in past 6 month, Oral steroids, ≥4 scripts in past 6 month, sickle celI disease or severe immunodeficiency, type 1 diabetes, type 2 diabetes, COPD, asthma, rare lung conditions (bronchiectasis, CF, or alveolitis), pulmonary hypertension or pulmonary fibrosis, coronary heart disease, stroke, atrial fibrillation, congestive heart failure, thromboembolism, peripheral vascular disease, congenital heart disease, dementia, Parkinson disease, epilepsy MND, MS, myasthenia gravis, or Huntington disease, cerebral palsy, severe mental illness, osteoporotic fracture (hip, spine, wrist, or humerus), rheumatoid arthritis or SLEcirrhosis | 9 |
Gamberini et al. (2020) [120] | Italy | 2540 | 66 (59–72) | 300 (76.7) | Multicenter prospective observational study | Chronic ischemic heart disease | 35 (9) | HR 0.277 (0.181–0.423) | Mechanical ventilation | Age, SOFA score at ICU admission, renal replacement therapy during ICU stays, lowest PaO2/FiO2 within 5 days, CRS < 40 mL/cmH2O within 5 days, neurologic complications | 7 |
Omrani et al. (2020) [121] | Qatar | 1409 | 39.82±14.2 | 1167 (82.8) | Retrospective cohort study | Coronary artery disease | 31 (2.4) | OR 1.090 (0.449–2.643) | Admission to ICU | Age, gender, diabetes mellitus, HTN, chronic liver disease, chronic kidney disease, BMI | 6 |
Yahyavi et al. (2020) [122] | Iran | 2553 | 58.1±17.9 | 1498 (58.7) | Retrospective cohort study | CVD | 942 (36.9) | OR 1.1 (0.8-1.5) | Mortality | angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, chronic kidney disease, chronic pulmonary disease, diabetes mellitus, intensive care unit, diuretics, beta-blockers, and calcium channel blockers | 7 |
Guisado-Vasco et al. (2020) [135] | Spain | 607 | 69±22.0 | 394 (65.02) | Retrospective, observational, longitudinal study | Chronic cardiac disease | 133 (22.62) | OR 1.956 (0.778-4.922) | In-hospital death | Age, gender, Chest X-ray score, hydroxychloroquine, tocilizumab, lopinavir/ritonavir, cyclosporine A, Glucocorticoids, Lymphocyte count at admission, Ferritin at admission, C-reactive protein at admission, lactate dehydrogenase (LDH) at admission, d-dimer at admission, Creatinine at admission, arterial hypertension, diabetes mellitus, chronic respiratory disease, PaO2/FiO2 | 7 |
Izzy et al.* (2020) [124] | USA | 5190 | 52 (36–66) | 2378 (46) | NR | Coronary artery disease | 257 (5) | OR 0.52 (0.323–0.835) | ICU Admission | Age, gender, smoking status, last BMI, comorbidities (diabetes mellitus, hyperlipidemia, HTN, obstructive lung disease, interstitial lung disease, cerebrovascular disease, obstructive sleep apnea, CKD, transplantation, auto-immune diseases, malignancy), total comorbidities (0, 1–2, >2) | 8 |
Chow et al. (2020) [125] | USA | 412 | 55 (41-66) | 244(52.9) | Retrospective, observational cohort study | CAD | 52 (12.62) | HR 1.91 (1.06-3.42) | In-hospital death | Age, gender, BMI, Ethnicity (African American, Asian, Hispanic/Latino), HTN, DM, renal disease, aspirin use | 6 |
Raines et al. (2020) [126] | USA | 440 | 60.8±14.07 | 393 (89.32) | Retrospective | CVD | 364 (82.73) | OR 0.9 (0.47-1.73) | Mortality | Age, gender, race, BMI, immunodeficiency syndromes, pulmonary diseases, oncologic diseases, gastrointestinal diseases, renal diseases, hematologic diseases, endocrine diseases, neurologic problems, lifetime tobacco user | 7 |
Ramos-Rincon et al. (2020) [123] | Spain | 2772 | 86.3 (83.2-89.6) | 1367 (49.4) | Nationwide, multicenter, retrospective, observational study | CVD | 855 (30.8) | OR 1.22 (0.96-1.54) | Mortality | Age, gender, degree of dependence (independent or mild, moderate, Severe), comorbidities ( Charlson comorbidity Index, non-atherosclerotic cardiovascular disease, atherosclerotic cardiovascular diseases, dementia, obesity, moderate-severe renal disease), symptoms (shortness of breath, anorexia, diarrhea), physical exam (Oxygen saturation < 90% (pulsi oximetry), temperature 37.8 ºC, HTN (systolic blood pressure<100 mmHg), tachycardia (>100 beats per minute), Tachypnoea (20 breaths per minute), confusion, pulmonary rales, qSOFA score 2 (high risk)), chest X-ray (normal, unilateral infiltrates, bilateral infiltrates), laboratory findings (leukocytes 10.0 x103/L, neutrophils 7.5 x103/L, Lymphocytes<0.800 x103/L, monocytes<0.500 x103/L, pH<7.40, PO2, PO2/FiO2 ratio < 200, glucose > 126 mg/dL, eGFR < 45ml/min/1.73m2, lactate dehydrogenase 500 U/L, AST,ALT, CRP, venous lactate, procalcitonin, interleukin-6, d-dimer, serum ferritin) | 6 |
Zhang et al. (2021) [127] | China | 222 | 51.5 (34.0-65.3) | 90(40.54) | NR | Chronic cardiovascular disease | 44 (19.82) | HR 3.616 (1.111-11.776) | Mortality | Dyspnea, pharyngalgia, COPD, elevated myocardial enzymes, acute liver dysfunction, acute kidney injury | 6 |
de Souza et al. (2020) [128] | Brazil | 9807 | 70.21±8.37 | 4662 (47.5) | Retrospective population-based study | CVD | 1192 (12.2) | OR 1.15 (0.95–1.39) | Mortality | Age, gender, initial symptoms reported (initial symptoms reported, fever, fatigue, headache, myalgia, odynophagia, dyspnea, diarrhea), comorbidities (diabetes, HTN, chronic lung disease, chronic kidney disease, obesity) | 8 |
Kolhe et al. (2020) [129] | UK | 1161 | 72.1±16.0 | 657 (56.59) | Retrospective cohort study | Congestive cardiac failure | 207 (17.83) | OR 1.38 (0.95-1.99) | Mortality | Age, gender, ethnicity (White, Asian, Black, mixed, others, not stated), cerebrovascular disease, Dementia, chronic lung disease, connective tissue disorder, Diabetes with complication, paraplegia, chronic kidney disease, chronic liver disease, Cancer, treatment (ACEI or ARB use, ACEI or ARB use), AKI | 8 |
Kim et al. (2021) [130] | USA | 10861 | 65 (54-77) | 6468(59.6) | NR | CAD | 1447 (13.3) | OR 1.02 (0.90-1.17) | Death | Age, gender, race/ethnicity, BMI, HTN, DM,CKD, end stage renal disease, cancer, asthma, COPD, smoking status, hospital type | 6 |
Giustino et al. (2020) [131] | New York City & Milan | 305 | 63 (53–73) | 205 (67.2) | International, multicenter cohort study | Heart failure | 24 (7.9) | OR 5.38 (1.65-17.54) | In-Hospital Death | Age, Hispanic ethnicity, history of heart failure, cardiocirculatory shock, acute respiratory distress syndrome, acute kidney injury stage II or III, no cardiac injury (No cardiac injury vs cardiac injury with echocardiographic abnormalities) | 7 |
An et al. (2020) [132] | Korea | 228 | 44.97±19.79 | 107 (46.9) | Cohort study | CVD | 70 (30.7) | HR 1.23 (0.89-1.70) | Mortality | Age, gender, income level, residence, household type, disability, symptom, infection route, underlying medical condition (none, HTN, diabetes mellitus, hyperlipidemia, cerebrovascular disease, cancer, chronic lung disease or asthma, chronic renal disease, mental illness, chronic liver disease) | 6 |
Piazza et al. (2020) [133] | USA | 1114 | 50.6±18.3 | 511 (45.9) | Retrospective observational cohort analysis | CAD | 90 (8.1) | OR 1.09 (0.38–3.16) | Death | Major arterial or venous thromboembolic event (Age, gender, VTE prophylaxis, ARDS, d-dimer (decile)) | 7 |
Rao et al. (2020) [134] | China | 240 | 48 (23–87) | 111 (46.250 | Retrospective cohort study | CVD | 43 (17.9) | OR 3.326 (0.721-15.336) | Severe pneumonia | Age | 7 |
Tehrani et al. (2021) [136] | Sweden. | 255 | 66±17 | 150 (59) | Retrospective analysis | Chronic heart failure | 34 (13) | OR 1.01 (0.42-2.42) | Death | Age, HTN, chronic kidney disease, previous stroke | 8 |
Hyman et al. (2020) [137] | USA | 755 | 63±13 | 483 (64.0) | Retrospective cohort study | Congestive heart failure or valve disorder | 30 (4.3) | HR 1.39 (0.87–2.23) | Mortality | Hospital site, baseline demography, preexisting comorbidities, laboratory findings at admission, maximum vital sign values | 7 |
Hamilton et al. (2020) [138] | UK | 1032 | 71 (56–83) | 569 (55.1) | Retrospective review | Congestive Heart Failure | 129 (12.5) | HR 2.01 (1.51-2.67) | Mortality | AKI, cancer, other ethnicity, diabetes, gender, RAASi, race, dementia, myocardial infarction, age | 6 |
Liu et al. (2020) [139] | China | 774 | 64 (54–73) | 452 (58.4) | Multicenter retrospective observational study | Chronic cardiac disease | 91 (11.8) | HR 1.12 (0.68–1.84) | Mortality | Time-varying exposure, age, gender, APACHE II score, COPD, diabetes, HTN, chronic kidney disease, chronic liver disease, stroke, malignancy, immunosuppression, fever at admission, systolic pressure at admission, leukocytes, hemoglobin, platelets, lymphocytes, d-dimer, total bilirubin, serum creatinine, procalcitonin, corticosteroids, corticosteroids, human immunoglobulin | 8 |
Ganatra et al. (2020) [140] | USA | 2467 | 59 (18–101) | 1032 (42) | Retrospective study | CAD | 184 (7.0) | OR 0.92 (0.66–1.27) | Severe disease | Age, prior/current smoker, β-blockers, history of cancer, gender, diabetes mellitus, ACEi or ARB, HTN, COPD, CKD | 4 |
Rubio-Rivas et al. (2020) [141] | Spain | 12066 | 68 (56–79) | 7052 (58.5) | Cohort study | Chronic heart failure | 809 (6.7) | OR 1.16 (1.02–1.32) | In-hospital mortality | Age, gender, BMI, clusters, comorbidity (Arterial hypertension, diabetes mellitus, hyperlipidemia, hyperlipidemia, chronic kidney disease, chronic hepatopathy, active cancer), Charlson’s index, heart rate upon admission, respiratory rate upon admission > 20 bpm, PaO2/FiO2 upon admission, lab test upon admission (CRP mg/L, LDH U/L), treatments during admission (Redeliver, tocilizumab, corticosteroids) | 9 |
Mendes et al. (2020) [142] | Switzerland | 235 | 86.3±6.5 | 102 (43.4) | Retrospective monocentric cohort study | Heart failure | 66 (28.1) | OR 1.51 (0.95-2.40) | Mortality | Gender | 6 |
Nemer et al. (2020) [143] | USA | 350 | 64±16 | 194 (55) | Prospective | Congestive heart failure | 42 (12) | OR 0.76 (0.17-3.39) | Primary composite outcome was defined as death, ICU transfer, or increased oxygen requirement. | Age, BMI, COPD, peripheral oxygen saturation on room air, CRP, lactate dehydrogenase level, abnormal troponin T level, abnormal d-dimer level, Abnormal chest x-ray findings | 8 |
Guo et al. (2020) [144] | China | 350 | 43(32–56) | 173(49.4) | Retrospective, multicenter study | CVD | 15 (4.3) | OR 1.81 (0.42–7.84) | Severe COVID-19 | Age, gender, Wuhan exposure, family cluster case, smoking, comorbidity (HTN, diabetes, chronic kidney disease, chronic liver disease, cerebral infarction) | 6 |
Hilbrands et al. (2020) [145] | Netherlands | 305 | 60±13 | 189(62) | Observational study | Heart failure | 64 (21) | OR 1.39 (1.02–1.89) | 28-day case-fatality | Age, gender | 5 |
Wang et al. (2020) [146] | China | 7283 | 64 (53–71) | 3732 (51.2) | Retrospective observational study | CVD | 161 (2.2) | HR 1.83 (1.33-2.51) | Death | Age, gender, location (central area in Wuhan, Other areas), occupation (medical workers, retirees, others), diabetes, HTN, respiratory disease, number of symptoms at admission, date of onset (Dec 2019–9 Jan 2020, 10–22 Jan 2020, 23 Jan–1 Feb 2020, 2–25 Feb 2020) | 9 |
Tang et al. (2020) [147] | USA | 752 | 73.9 (21.9-105.4) | 323 (43) | Cohort study | Coronary heart disease | 240 (31.91) | HR 0.83 (0.58-1.19) | Death | Age, gender, race, and facility | 8 |
Annweiler et al. (2020) [173] | France | 77 | 88 (85−92) | 39 (50.6) | Retrospective quasi-experimental study | Cardiomyopathy | 42 (54.5) | HR 4.04 (0.81-20.30) | 14-day mortality | Age, gender, Iso resource groups score, severe undernutrition, history of cancer, history of HTN, glycated hemoglobin, number of acute health issue, use antibiotics, use of systemic corticosteroids, use treatments of respiratory disorder | 5 |
Huang et al. (2020) [148] | China | 676 | 56.0 (39.0–68.0) | 314 (46.4) | Retrospective study | Heart Disease | 71 (10.5) | HR 1.40 (0.76–2.47) | Hospital mortality | Age, gender, HTN, Diabetes, cancer, d-dimer, CRP, PCT, LDH | 6 |
Poterucha et al. (2021) [149] | USA | 887 | 64.1 | 513 (58) | Retrospective study | CAD | 104 (12.0) | HR 1.56 (1.04-2.33) | Mortality | AF/AFL, QRS abnormality, ST-T wave abnormality, Initial hs-cTnT ≥ 20 ng/L, age, gender, Hypertension, Diabetes, CKD, primary lung disease, Obesity, HFrEF, HFpEF, active cancer, history of cancer | 6 |
Li et al. (2020) [150] | China | 100 | 62.0 (51.0–70.8) | 56 (56.0) | NR | CVD | 15 (15.0) | HR 3.73 (0.41–33.84) | Cardiac damage | Age, gender, Hypertension, diabetes, hyperlipidemia, white blood count, prothrombin time, d-dimer, creatinine interleukin-6, procalcitonin, hs-CRP | 6 |
Prado-Galbarro et al. (2020) [151] | Mexico | 9487 | 31.37 (41.13-51.18) | 5050 (53.2) | Observational study | CVD | 171(1.8) | HR 0.85 (0.67-1.06) | Mortality | Age, gender, indigenous ethnicity, pneumonia, COPD, diseases associated with immunosuppression, additional comorbidity (Chronic diseases interaction, HTN, diabetes, obesity, chronic kidney disease, intensive care unit), region, density, mode of transport (driving, public transport, walking) | 8 |
Shah et al. (2020) [152] | USA | 487 | 68.53±16.66 | 273 (56.06) | Retrospective review | Cardiomyopathy | 16 (3.28) | OR 3.33 (1.07-10.41) | Mortality | Age, gender, patient admitted from home, PMH HTN, PMH hyperlipidemia, PMH A. fib, , PMH CVA, PMH diabetes, PMH dementia, PMH active cancer, AKI, Dyspnea in ED noted as positive, initial CXR/CT findings | 7 |
Botta et al. (2021) [153] | Netherlands | 553 | 67.0 (59.0–73.0) | 417 (75) | National, multicenter, observational cohort study | Heart failure | 25 (5.0) | OR 0.73 (0.26-2.08) | 28-day mortality | Ventilatory variables on day 0 (positive end-expiratory pressure, tidal volume, respiratory system compliance), PaO2/FiO2, laboratory tests on day 0* pH, Lactate, Creatinine), vital signs on day 0 (Heart rate, mean arterial pressure), organ support on day 0 (use of vasopressor, fluid balance), demographic characteristics (age, gender, BMI, HTN, diabetes, chronic kidney disease, COPD, use of angiotensin-converting enzyme inhibitor, use of angiotensin II receptor blocker) | 6 |
Di Domenico et al. (2020) [154] | France | 310 | 64 (52–76) | 200 (64.5) | Single‑center retrospective study | Heart disease | 50 (16.2) | HR 1.921 (0.893-4.135) | Death | Age, diabetes, HTN, CKD, obesity, vascular disease, ever been a smoker | 7 |
Ayaz et al. (2020) [155] | Pakistan | 66 | 50.6±19.1 | 40 (61) | Retrospective cohort study | Ischemic heart disease | 10 (15) | OR 26.5 (4.7–147.8) | Mortality | Age, diabetes, HTN, ICU admission, mechanical ventilation, bilateral infiltrates on chest radiography, neutrophil to lymphocyte ratio ≥3.3, INR ≥1.2 | 6 |
Hippisley-Cox et al. (2020) [156] | UK | 8275949 | 48.47±18.41 | 4115973 (49.73) | Prospective cohort study | CVD | 433631 (5.24) | HR 0.85 (0.66-1.10) | Admission to ICU | ACE inhibitor, angiobrnsin enzyme blocker, gender, material deprivation, ethnicity, geographical region, smoking status, BMI, chronic renal disease, atrial fibrillation, type 1 diabetes, type 2 diabetes, hypertension, asthma, COPD, Beta-blockers, calcium channel blockers, other diabetes drugs, sulfonylureas, biguanides, anticoagulants, antiplatelets, statins, statins, potassium-sparing diuretics | 9 |
Tomasoni et al. (2020) [157] | Italy | 692 | 66.5±13.3 | 415 (68.9) | Multicenter study | CAD | 148 (21.4) | HR 1.20 (0.67-2.14) | In-hospital mortality | Age, gender, smoker, HTN, hyper dyslipidemia, Diabetes, atrial fibrillation, COPD, CKD, Treatment before hospitalization (ACE-i/ARBs/ARNI, mineralocorticoids, Beta-blockers, direct oral anticoagulants, warfarin, Statins), baseline findings (heart rate, Oxygen saturation), laboratory measurements (PaO2/FiO2, red blood cell count, hemoglobin, hematocrit, lymphocytes count, platelets count, creatinine, eGFR (CKD-EPI), CRP on admission, procalcitonin, troponin, NT-proBNP, d-dimer, aspartate transaminase, albumin, international normalized Ratio) | 7 |
Elmunzer et al. (2020) [158] | North American | 1846 | 59.9±16.4 | 1044 (56.6) | Large-scale retrospective cohort study | Congestive Heart Failure | 284 (15.4) | OR 1.60 (1.12-2.28) | Death | H2RA Use, PPI Use, age, gender, race, dementia, number of comorbidities, WBC at admission, platelets at admission, AST at admission, albumin at admission | 6 |
Polverino et al. (2020) [159] | Italy | 3179 | 2171 (68.3) | Nationwide observational study | Coronary artery disease | 359 (11.3) | OR 1.11 (0.83-1.49) | Death | Age, gender, atrial fibrillation, blood cancer, COPD chronic renal failure, diabetes, HTN, obesity, organ cancer, stroke | 5 | |
Sharp et al. (2020) [160] | USA | 21280 | 50 (34-66) | 9053 (42.5) | Retrospective cohort study | Congestive Heart Failure | NA (NA) | OR 1.45 (1.18–1.77) | Adverse outcomes (death, ARDS, respiratory failure and septic shock during hospitalization, mechanical ventilation, ICU admission, as well as clinical cure and discharges) | Age, gender, BMI, coagulopathy, diabetes, fluid and electrolyte disorders, other neurological disorders, weight Loss, heart rate, systolic BP, oxygen saturation, respiratory rate | 8 |
Stebbing et al. (2020) [161] | Italy&Spain | 166 | 74.05±13.06 | 85 (51.2) | Observational studies | CVD | 48 (28.9) | HR 1.41 (0.68-2.92) | Death & admission to ICU | Age, gender, HTN, diabetes, chronic Obstructive Lung disease, cronic kidney disease, Solid cancer, Charlson Comorbidity Index, baseline PaO2/FiO2, lymphocyte count (/mcL), alanine aminotransferase, hydroxychloroquine, lopinavir/ritonavir, glucocorticoids, low molecular weight heparin, antibiotics | 6 |
Fu et al. (2020) [162] | China | 355 | 43.5* | 193 (54.37) | Hospital-Based Retrospective Cohort Study | Heart disease | 20 (6.2) | OR 0.454 (0.102-2.010) | Myocardial injury | Age, gender, HTN, diabetes | 7 |
Sheshah et al. (2020) [163] | Saudi Arabia | 300 | 49.7±13.2 | 259 (86.3) | Single-center, retrospective study | Coronary Artery Disease | 10 (3.3) | OR 19.4 (1.5-260) | Mortality | Age, gender, HTN, type 2 diabetes mellitus, chronic kidney disease, acute kidney injury, stroke, methylprednisolone, dexamethasone, hydroxychloroquine, azithromycin | 6 |
Bowe et al. (2020) [164] | USA | 5216 | 70 (61–76) | 4908 (94) | Cohort study | CVD | 1588 (30.0) | OR 0.87 (0.76-1.01) | Severe AKI | Age, gender, race, Smoking status, HTN, diabetes mellitus type 2, ACEI/ARB, diuretics, anticoagulant, immunosuppressants, b-blocker, aspirin, eGFR category | 8 |
Cheng et al. (2020) [165] | China | 220 | 59.5 (48.3-70.0) | 106 (48.2) | Retrospective, observational study | CAD | 22 (10.0) | HR 0.97 (0.35-2.68) | In-hospital death | Hypertension, history of cerebrovascular disease, History of diabetes mellitus, history of diabetes mellitus | 4 |
Neumann-Podczaska et al. (2020) [166] | Poland | 50 | 74.8±9.4 | 35 (70.0) | Retrospective | Heart disease | 26 (52.0) | HR 2.61 (0.92–7.39) | 60-day mortality | Age, functional Capacity, Diabetes | 6 |
Ken-Dror et al. (2020) [167] | UK | 429 | 70±18 | 242 (56.4) | Prospective cohort study | Chronic cardiac disease/congenital heart disease | 103 (31.3) | OR 3.43 (2.1-5.63) | Mortality | Self-reported feverishness 38°C, cough self-report, oxygen saturation, history of fever, cough, sore throat, chest pain, muscle aches myalgia, altered consciousness confusion, obesity as defined by clinical staff, diabetes with complications, dementia, malnutrition, current admission to ICU/IMC/HDU, non-invasive ventilation BIPAP/CPAP, invasive ventilation, high flow nasal canula oxygen therapy, clinical pneumonia, inotropes vasopressors, viral pneumonia, bacterial pneumonia, anemia | 7 |
Iannelli et al. (2020) [168] | France | 8286 | 59.1±12.6 | 4296 (51.8) | Retrospective | Cardiac failure | 569 (6.9) | OR 1.53 (1.24–1.89) | Death | Age, gender, cancer, diabetes, bariatric surgery | 9 |
Sharifpour et al. (2020) [169] | USA | 268 | 63±15 | 149 (55.6) | Cohort analysis | CAD | 36 (13.4) | OR 1.381 (0.498–3.826) | Mortality | Age, CRP Slope d1to7, CRP tests (count d1 to 7), CRRT, CRP Max d1to7, obesity (BMI> = 30kg/m2), intubation, SOFA score, HTN | 6 |
Martins-Filho et al. (2020) [170] | Northeast Brazil | 1207 | 60 (46–73) | 724 (60) | Retrospective cohort study | Heart failure | 102 (8.45) | OR 2.00 (1.31–3.04) | Mortality | Infectious disease, kidney disease, age | 6 |
Lee et al. (2020) [171] | Korea | 7339 | 47.1±19.0 | 2970 (40.1) | Nationwide Population-Based Retrospective Study | CVD | 455 (6.1) | OR 0.95 (0.64–1.40) | Death | Influenza, tuberculosis, COPD, pneumonia, asthma, DM, CKD, Chronic liver disease, HTN, malignancies, HIV infection, lopinavir/ritonavir, Hydroxychloroquine, ribavirin, type I interferon, Human immunoglobulin G, Oseltamivir, antibiotics, age, gender | 8 |
Loffi et al. (2020) [172] | Italy | 1252 | 64.7±15.5 | 798 (63.74) | Retrospective, observational, single-center study | CAD | 124 (9.9) | HR 1.14 (0.79-1.63) | Death | Age, gender, LVEF<35%, CVA, atrial fibrillation, diabetes mellitus, hypertension, smoking, CKD | 5 |
Grodecki et al. (2021) [175] | USA | 109 | 63.74±15.11 | 68 (62.39) | Prospective | Heart failure | 16 (14.68) | OR 3.5 (1.1-8.2) | Death | Age, gender, diabetes mellitus, hypertension, smoking history, chronic lung disease, history of coronary artery disease, epicardial adipose tissue volume (mL), epicardial adipose tissue attenuation, total pneumonia burden | 7 |
Rossi et al. (2020) [80] | Italy | 590 | 76.2 (68.2–82.6) | 399 (67.6) | Retrospective observational study | CVD | 95 (16.1) | HR 1.180 (0.855–1.628) | Mortality | Age, gender, vital signs at admission (temperature, PaO2/FiO2, PaO2/FiO2<300), laboratory parameters (LDH, CRP, white blood cell count, lymphocyte’s rate), chronic diseases (hyperlipidemia, diabetes, atrial fibrillation, COPD, CKD, stroke, malignancy, 3 or more comorbidities), chronical drugs intake (ACEi, ARBs, CCBs, Alpha blockers, Diuretics, Beta blockers) | 6 |
Khan et al. (2020) [177] | Saudi Arabia | 648 | 34±19 | 342 (52.8) | Retrospective cohort study | Cardiac diseases | 23 (3.5) | OR 3.05 (1.16-8.02) | ICU admission | Age, gender, smoker, comorbidities (one or more comorbidity, two or more comorbidity, diabetes mellitus, HTN, CRD, chronic kidney diseases, cancer/immunodeficiency), symptoms (fever, cough, sore throat, runny nose, headache, GI symptoms, myalgia), vital signs (temperature (≥38), heart rate ≥100, respiratory rate, respiratory rate, respiratory rate, DBP, oxygen saturation, oxygen saturation) | 7 |
Rutten et al. (2020) [178] | Netherlands | 1538 | 84±8.7 | 554 (36.02) | Prospective cohort study | CVD | 53 (3.47) | HR 1.15 (0.97-1.35) | Mortality | Age, gender, comorbidity (Dementia, cerebrovascular disease, diabetes mellitus, chronic respiratory disease, reduced kidney function, Parkinson’s disease) | 6 |
Schuelter-Trevisol et al. (2020) [179] | Brazil | 211 | 51.2* | 113 (53.6) | Cohort study | Chronic heart disease | 27 (12.9) | OR 0.98 (0.31-3.10) | Death | Age, gender, comorbidities (arterial hypertension, diabetes mellitus, obesity, neurologic/psychiatric diseases, chronic lung diseases, dyslipidemia, smoking habits, cancer, chronic kidney diseases, vascular diseases) | 6 |
FAI2R /SFR/SNFMI/SOFREMIP/CRI/IMIDIATE (2020) [174] | France | 694 | 56.1±16.4 | 232 (33.4) | Observational, multicenter, French national cohort study | Coronary heart diseases | 68 (9.8) | OR 1.86 (0.97–3.56) | Severity | Age, gender | 8 |
Nyaberaet al. (2020) [181] | USA | 290 | 77.6±8.3 | 150 (51.7) | Single-center retrospective cohort study | CAD | 80 (27.6) | OR 0.91 (0.52-1.62) | Mortality | BMI, age, COPD, asthma, DM, HTN, end-stage renal disease | 4 |
Ozturk et al. (2021) [182] | Turkey | 1160 | 60.5 (47–71) | 627 (54.1) | Multicenter, retrospective, observational study | CVD | NR (NR) | HR 1.242 (0.850–1.815) | Death | Age, gender, diabetes mellitus, HTN, COPD, albumin, hemoglobin, lymphocyte count, platelet count, CRP increase, clinic presentation, COVID-19 diagnosis by RT-PCR, patient group, control group (HD group, RT group, CKD group) | 5 |
Druyan et al. (2021) [183] | Israel | 181 | 62.71* | 107(59.1) | Single center study | Heart failure | 10 (5.52) | OR 2.35 (0.24-18.64) | Severe, critical or fatal COVID19 | Gender, AID, HTN, dyslipidemia, diabetes, malignancy, IHD, arrhythmia, obesity, pulmonary disease, smoking, CVA, renal failure, older age | 5 |
Alguwaihes et al. (2020) [184] | Saudi Arabia | 439 | 55 (19–101) | 300 (68.3) | Single-center retrospective study | CVD | 44 (10.0) | HR 1.8 (0.7–4.4) | Death | Age, gender, comorbidities (obesity, HTN, diabetes mellitus, chronic kidney disease, congestive heart failure, stroke, smoking), medications (β-Blocker use, ACE inhibitor use, ARB Use), laboratory investigations (RBG, FPG, HbA1c>9.0%, bilateral lung infiltrates, neutrophil count>7.5, creatinine>90 μmol/l, ALT>65 U/l, 25(OH)D<12.5 nmol/l) | 7 |
Özdemir et al. (2021) [185] | Turkey | 101 | 49.60±18 | 55 (54.4) | Retrospective study | Chronic heart failure | 10 (9.9) | HR 1.02 (0.98 – 1.10) | QTc prolongation | Baseline QTc, HCQ alone, HCQ + AZM | 6 |
Gue et al. (2020) [186] | UK | 316 | 73.42±15.97 | 192 (61.1) | Single-center retrospective cohort | CAD | 48 (15.19) | OR 1.62 (0.76–4.07) | 30-day mortality | Age, gender, HTN, atrial fibrillation, oral anticoagulants, modified sepsis-induced coagulopathy score | 7 |
Galiero et al. (2020) [187] | Italy | 618 | 65±15.2 | 379 (61.3) | Multicenter retrospective observational cohort study | Chronic Cardiac Disease | 166 (26.9) | OR 0.96 (0.53-1.76) | Mortality | Age, gender, Glasgow Coma Score/15, respiratory severity Scale, CKD, CLD, chronic respiratory disease, malignancies | 6 |
Rosenthal et al. (2020) [188] | USA | 64781 | 56.1±19.9 | 31968 (49.3) | Retrospective cohort study | Myocardial infarction | 3717 (5.7) | OR 1.47 (1.34-1.62) | In-Hospital Mortality | Age, gender, race, payer type, admission point of origin, hospital region, hospital beds, hospital teaching status, hospital teaching status, Sepsis, acute kidney failure, hypokalemia, acidosis, acute liver damage, neurological disorder, baseline comorbidities (Cerebrovascular disease, COPD, dementia, diabetes, any malignant neoplasm, metastatic solid tumor, hemiplegia, AIDS, HTN, Hyperlipidemia) | 9 |
Rethemiotaki et al. (2020) [189] | the World Health Organization dataset and Chi nese Center for Disease Control and Preventio | 44672 | 71* | 22981 (51.44) | NR | CVD | 92 (15.9) | OR 13.6 (10.3–17.9) | Death | Age, gender, occupation (service industry, farmer/laborer, health worker, retiree, other/none), province: (Hubei, Other), Wuhan-related exposure, comorbid condition (HTN, diabetes, chronic respiratory disease, cancer (any), none) | 8 |
Pantea Stoian et al. (2020) [176] | China | 432 | NR | NR | Multiple-case, multiple-center | Heart failure | 30 (6.94) | OR 2.990 (1.612–5.546) | Death | Age, gender, HTN, obesity, diabetes type 2, dialysis, chronic kidney disease, COPD, supraventricular tachyarrhythmia, respiratory failure, Intercept | 7 |
Zhou et al. (2020) [191] | China | 134 | 62.08±14.38* | 85 (63.4) | Retrospective | Coronary heart disease | 16 (11.94) | OR 1.098 (0.202–5.959) | Death | Gender, age, HTN, coronary heart disease, neutrophil, lymphocyte, ALT, IL-2, IL-6, TNF-α, D-dimer, and total CT score | 6 |
Stefan et al. (2021) [192] | Romania | 37 | 64 (55–71) | 19 (51) | Retrospective, observational, single-center study | Coronary heart disease | 19 (51.0) | HR 0.98 (0.05–17.54) | In-hospital death | Age, hemodialysis vintage, obesity, current smoker, diabetes mellitus, Charlson comorbidity index, basal oxygen saturation, hemoglobin, lymphocytes, CRP, serum albumin, LDH, Lopinavir–ritonavir, Tocilizumab, hydroxychloroquine, glucocorticoids | 7 |
Ahnach et al. (2021) [180] | Morocco | 101 | 50 (32–63) | 75 (51.72) | Retrospective study | CVD | 16 (11.03) | OR 3.74 (0.76–18.29 | Disease severity | Age, gender, HTN, diabetes, other disease, respiratory symptom, neutrophil, lymphocyte, eosinophil, CRP | 6 |
Eshrati et al. (2020) [193] | Iran | 3188 | 55.05 ± 0.31 | 1925 (60.4) | Retrospective cohort study | CVD | 401 (12.6) | HR 0.60 (0.83-1.13) | death | Age, gender, immune disease, diabetes, liver disease, kidney disease, ,COPD, cancer, chronic nervous disease, type of treatment | 8 |
Özyılmaz et al. (2020) [194] | Turkey | 105 | 45 (20–87) | 76 (72.3) | Single-center, retrospective, observational study | CAD | 14 (13.3) | OR 0.024 (0.000–1.207) | Mortality | Troponin I, C-Reactive protein, lymphocyte count, shortness of breath, HTN, hyperlipidemia, diabetes mellitus | 7 |
Tan et al. (2020) [195] | China | 163 | 69.0 (62.0-78.0) | 109 (66.9) | Retrospective study | Chronic cardiac injury | 25 (15.3) | OR 2.660 (1.034-6.843) | Mortality | Age, gender, HTN, diabetes | 5 |
Ling et al. (2020) [196] | UK | 444 | 74 (63-83) | 245 (55.2) | Cross-Sectional Multi-Centre Observational Study | Heart failure | 54 (12.2) | OR 1.61 (0.87–2.99) | Mortality | Age, gender, diabetes, non-Caucasian ethnicity, baseline serum 25(OH)D levels, vitamin D deficiency, treatment with cholecalciferol booster therapy, admission SpO2 < 96%, admission CRP > 73 mg/L, admission creatinine > 83 μmol/L, received CPAP, length of stay >11 days, diabetes (types 1 and 2 combined), admission glucose > 6·9 mmol/L, COPD, asthma, IHD, current or previous ACS, HTN, current or previous TIA or stroke, dementia, obesity, malignancy of solid organ, malignancy of skin, hematological malignancy, solid organ transplant, inflammatory arthritis, inflammatory bowel disease | 5 |
Zhong et al. (2020) [197] | China | 126 | 66.3±10.6 | 56 (44.4) | Retrospective observational study | CVA | 21 (16.7) | OR 2.03 (0.45-9.08) | Death | Age, gender, ACEI/ARB, stains | 5 |
Izurieta et al. (2020) [198] | USA | 12613 | 80.5* | 6496 (51.5) | Retrospective cohort study | Congestive Heart Failure | 3557 (28.2) | OR 1.30 (1.23, 1.36)) | Death | Age, gender, reason for entering medicare, ADI national rank, logged COVID-19 circulation rate by 100,000, logged population density by county, vaccination, presence of medical conditions (HTN, obesity, diabetes, hospitalized stroke/TIA, coronary revascularization, atrial fibrillation, hospitalized AMI, other cerebrovascular disease, COPD, asthma without COPD, interstitial lung disease, hypersensitivity pneumonitis, bronchiectasis, chronic liver disease, neurological/neurodevelopmental conditions), frailty conditions, immunocompromised status, estimated overall, interaction effects of age, dual-eligibility, and race, 80 years old vs. 65 years old, dual-eligible vs. non-dual-eligible, dual-eligible vs. non-dual-eligible, effects of being dual-eligible, by race, non-whites vs. whites, non-dual-eligible, non-whites vs. whites, dual-eligible | 8 |
Burrell et al. (2021) [199] | Australia | 304 | 63.5 (53–72) | 140 (69%) | Prospective, observational cohort study | Chronic cardiac disease | 40 (20) | HR 3.38 (1.46–7.83) | Mortality | Age, gender, APACHE-II score on ICU day 1, comorbid conditions (comorbid conditions), | 5 |
Li et al. (2020) [190] | China | 123 | 64.43±14.02 | 62 (50.41) | Retrospective study | CVD | 26 (21.14) | OR 0.686 (0.227–2.076) | Unfavorable clinical outcomes | Age, gender, diabetes, HTN, COPD, CT severity score, GGO volume, GGO volume percentage, consolidation volume, consolidation volume percentage | 4 |
Caliskan et al. (2020) [200] | Turkey | 56 | 48±19.664 | NR | Retrospective observational study | CAD | 42 (7.4) | OR 6.252 (2.171-18.004) | Mortality | Former smoker, current smoker, age, COPD, diabetes, dementia, HTN, chronic renal failure, arrhythmia | 5 |
Vafadar et al. (2021) [201] | Iran | 219 | 57.8±16.5 | 137 (62.6) | Retrospective cohort | Ischemic heart disease | 46 (22.37) | HR 1.98 (0.94–4.17) | Mortality | Respiratory rate, SpO2 ≤ 90%, WBC count, NLR, age | 6 |
Working group for the surveillance and control of COVID-19 in Spain et al. (2020) [202] | Spain | 2612 | 83 (75–89) | 14680 (56.2) | NR | CVD | 11444 (59.9) | OR 1.32 (1.23-1.42) | Death | Gender, age, pneumonia, acute respiratory distress syndrome, acute renal failure, Diabetes, HTN, chronic lung disease, chronic renal disease, healthcare worker | 6 |
Rashidi et al. (2021) [203] | Iran, Germany, USA | 1529 | 56 (32–80) | 832 (54.4) | Multi-center prospective study | Cardiac disease | 149 (9.7) | OR 0.80 (0.36–1.76) | Death | Age, gender, recent cancer, COPD, CKD, smoking, diabetes mellitus, HTN | 5 |
Chaudhri et al. (2020) [204] | USA | 317 | 59.16±17.5 | 166 (52.37) | Single-center cohort study | Coronary artery disease | 27 (12) | OR 0.92 (0.39-2.17) | Key outcomes | Age, gender, history of ARB use,history of ACEI use, HTN, diabetes, CKD | 5 |
Huh et al. (2021) [205] | South Korea | 219961 | 49.4 (18–116) | 104331 (47.4) | Retrospective case-control study | Chronic heart disease | 32457 (14.76) | OR 1.31 (1.04-1.65) | The requirement of any one of the following or death: supplementary oxygen, high-flow nasal cannula, non-invasive ventilation, mechanical ventilation, and extracorporeal membrane oxygenation | Drugs commonly used for chronic conditions (angiotensin receptor blockers, angiotensin converting enzyme inhibitors, metformin, thiazolidinedione, Statins, NSAIDs), drugs with potential therapeutic effect, drugs with potential therapeutic effect, comorbidities (Charlson comorbidity index, mean (SD), Diabetes, HTN, chronic lung disease, asthma and allergic rhinitis, chronic liver disease, Chronic kidney disease, Malignancy, RA, SLE, GCA, and JIA, other connective tissue disease, chronic neurologic disease, Pancreatitis), healthcare utilization | 8 |
Orioli et al. (2021) [206] | Belgium | 73 | 69±14 | 48 (66.67) | Retrospective study | CVD | 32 (43.8) | HR 3.54 (1.60-7.82) | In-hospital death | Diabetes, cognitive impairment, area of lung injury >50% | 6 |
Gude-Sampedro et al. (2021) [207] | Spain | 10454 | 58.0±20.0 | 4172 (39.9) | Retrospective cohort study | Ischemic heart disease | OR 1.61 (1.20-2.33) | Death | Age, gender, lymphoma/leukemia, dementia, COPD, diabetes, chronic kidney disease | 9 | |
Monteiro et al. (2020) [208] | USA | 112 | 61 (45–74) | 74 (66) | Retrospective, observational cohort study | CAD | 17 (15) | OR 0.48 (0.08–3.08) | Requiring mechanical ventilation | Age, gender, past medical history (obesity, diabetes, HTN, CKD), Tobacco exposure history | 4 |
Lano et al. (2020) [209] | France | 122 | 73.5 (64.2–81.2) | 79 (65) | Observational cohort multicenter study | Congestive heart failure | 13 (11) | OR 1.222 (0.309–4.649) | Mortality | Age, atrial fibrillation, ARBs (current medication) | 8 |
Lanini et al. (2020) [210] | Italy | 379 | 61.67±15.60 | 273 (72.03) | Longitudinal cohort study | CVD | 19 (5.01) | OR 2.79 (1.29-6.03) | Death | Age, gender, diabetes, neoplasm, obesity, chronic renal failure, COPD | 4 |
Schwartz et al. (2020) [212] | Canada | 56606 | 31* | 29205 (51.59) | Cross-sectional study | CVD | 4465 (7.89) | OR 1.10 (0.99–1.22) | Death | Healthcare worker, age, comorbidities (asthma, COPD, renal conditions, diabetes, immune compromise or cancer, obesity, other medical conditions None), exposed to long-term care home, symptoms (fever and/or cough, other symptoms, missing, asymptomatic) | 9 |
Sun et al. (2021) [213] | China | 3400 | 61 (50-68) | 1649 (48.5) | Retrospective cohort study | CVD | 343 (10.1) | OR 2.85 (1.65-4.94) | Death | Comorbid conditions (Neither HTN nor T2DM, Hypertension alone, T2DM alone, HTN and T2DM), age, gender, cerebrovascular disease, chronic kidney disease, chronic liver disease, chronic lung disease, endocrine/Immune system disease, tumor, ACEIs/ARBs treatment | 6 |
McGurnaghan et al. (2021) [214] | Scotland | 319349 | 79.9 (71.4–85.7) | 180486 (56.5) | Cohort study | Any heart disease | 696 (64.3) | OR 2.425 (2.135–2.754) | Fatal or critical care unit-treated COVID-19 | Sociodemographic (age, gender, diabetes type, diabetes duration, care home resident, any hypoglycemia admission in past 5 years, deprivation index, ethnicity, comorbidities (any diabetic ketoacidosis admission in past 5 years, any hypoglycemia admission in past 5 years, ever admitted to hospital in past 5 years, asthma or chronic lower airway disease, neurological and dementia (excluding epilepsy),liver disease, immune disease or on immunosuppressants, any listed condition), other clinical measures (insulin pump use, flash glucose monitor use, HbA1c, BMI, systolic blood pressure, diastolic blood pressure, total cholesterol, Estimated glomerular filtration rate, albuminuria grade, retinopathy grading, tobacco smoking), drug exposures (any lipid lowering, any proton pump inhibitor, any non-steroidal anti-inflammatory drugs, any anticoagulants, Any antihypertensive, number of ATC level 3 drug classes (excluding for diabetes), number of diabetes drug classes prescribed) | 8 |
Cetinkal et al. (2020) [215] | Turkey | 349 | 68.3±13.3 | 176 (50.43) | Retrospective single-center study | Heart failure | 38 (10.89) | OR 2.40 (0.82-7.01) | In-hospital mortality | Neutrophil to lymphocyte ratio, gender, age, diabetes mellitus, Use of RAAS blockers, chronic kidney disease, Smoking, COPD, d-dimer, LDH, procalcitonin, Ferritin | 6 |
Xu et al. (2020) [216] | China | 61 | 63.62±10.78 | 33 (54.1) | Retrospective | Heart diseases | 7 (11.5) | OR 2.94 (0.42-21.78) | Severity | Age, gender, diabetes, HTN, hepatic dysfunction, mild-nonlung involvement | 4 |
Lv et al. (2021) [217] | China | 409 | 50.47±12.43 | 188 (46) | Retrospective cohort Study | Heart disease | 51 (12.5) | HR 2.650 (1.079–6.510) | Death | Age, gender, fever, cough, sputum, tiredness, body aches, diarrhea, number of symptoms, HTN, diabetes, pulmonary disease, other comorbidities, CT ground-glass, opacity, CT bilateral pulmonary infiltration | 5 |
Guerra et al. (2021) [218] | Spain | 447 | 55.0±22.5 | 190 (46.4) | Retrospective single center study | Coronary artery disease | OR 4.95 (1.51-16.27) | Mortality | Gender, HTN, COPD, cancer, diabetes, obesity, CLD, age | 6 |
Table 2
The results of subgroup analysis
Variables | Effects | NO. Of studies | Subgroup analysis | Prediction interval | |
|---|---|---|---|---|---|
Pooled ES (95% CI) | I²,Tau², P value | ||||
Sample size | |||||
>=1000 | HR | 24 | 1.16 (1.03-1.32) | I² = 88%, τ² = 0.0697,P < 0.01 | 0.66-2.04 |
OR | 53 | 1.41 (1.32-1.51) | I² = 84%, τ² = 0.0694,P < 0.01 | 0.84-2.39 | |
<1000 | HR | 41 | 1.63 (1.41-1.88) | I² = 64%, τ² = 0.0957,P < 0.01 | 0.86-3.10 |
OR | 83 | 1.57 (1.40-1.77) | I² = 57%, τ² = 0.0967, P < 0.01 | 0.84-2.95 | |
Age | |||||
>=60 | HR | 41 | 1.42 (1.25-1.61) | I² = 73%,τ² = 0.0914, P < 0.01 | 0.76-2.65 |
OR | 78 | 1.49 (1.34-1.65) | I² = 86%, τ² = 0.1144,P < 0.01 | 0.75-2.95 | |
<60 | HR | 23 | 1.18 (1.04-1.33) | I² = 81%, τ² = 0.0181,P < 0.01 | 0.77-1.80 |
OR | 58 | 1.30 (1.19-1.42) | I² = 76%, τ² = 0.0379,P < 0.01 | 0.87-1.94 | |
NR | HR | 1 | 2.59 (1.16-5.79) | - | - |
OR | 2 | 1.75 (0.67-4.61) | I² = 88%, τ² = 0.4301,P < 0.01 | - | |
Male (%) | |||||
>=50 | HR | 44 | 1.41 (1.23-1.60) | I² = 83%, τ² = 0.1123,P < 0.01 | 0.71-2.80 |
OR | 94 | 1.33 (1.23-1.44) | I² = 78%, τ² = 0.0558,P < 0.01 | 0.83-2.14 | |
<50 | HR | 21 | 1.25 (1.13-1.38) | I² = 55%, τ² = 0.0179,P < 0.01 | 0.92-1.69 |
OR | 36 | 1.42 (1.27-1.58) | I² = 56%, τ² = 0.0431,P < 0.01 | 0.92-2.20 | |
NA | HR | 0 | - | - | - |
OR | 8 | 2.25 (0.87-5.79) | I² = 98%, τ² = 1.6735,P < 0.01 | 0.08-65.97 | |
Study design | |||||
Retrospective/case series | HR | 38 | 1.50 (1.30-1.73) | I² = 81%, τ² = 0.1067,P < 0.01 | 0.76-2.96 |
OR | 88 | 1.37 (1.28-1.47) | I² = 65%, τ² = 0.0269,P < 0.01 | 0.98-1.91 | |
Prospective study | HR | 9 | 1.11 (0.74-1.67) | I² = 88%, τ² = 0.2724,P < 0.01 | 0.28-4.39 |
OR | 7 | 1.31 (0.84-2.06) | I² = 77%, τ² = 0.2451,P < 0.01 | 0.32-5.34 | |
Others | HR | 19 | 1.25 (1.12-1.39) | I² = 63%, τ² = 0.0214,P < 0.01 | 0.90-1.74 |
OR | 43 | 1.45 (1.24-1.70) | I² = 93%, τ² = 0.1725,P < 0.01 | 0.62-3.42 | |
Region | |||||
Europe | HR | 27 | 1.31 (1.17-1.47) | I² = 83%,τ² = 0.0462, P < 0.01 | 0.83-2.08 |
OR | 54 | 1.47 (1.33-1.64) | I² = 75%, τ² = 0.0725,P < 0.01 | 0.85-2.56 | |
North America | HR | 12 | 1.16 (1.02-1.33) | I² = 52%,τ² = 0.0234, P = 0.02 | 0.80-1.69 |
OR | 42 | 1.18 (1.08-1.29) | I² = 77%, τ² = 0.0333,P < 0.01 | 0.81-1.72 | |
Asia | HR | 24 | 1.64 (1.24-2.16) | I² = 81%,τ² = 0.3015, P < 0.01 | 0.51-5.30 |
OR | 37 | 1.55 (1.29-1.87) | I² = 68%, τ² = 0.1272,P < 0.01 | 0.73-3.29 | |
Others | HR | 2 | 2.12 (0.89-5.01) | I² = 59%, τ² = 0.2289,P = 0.12 | - |
OR | 5 | 3.54(0.86-14.60) | I² = 92%, τ² = 2.2249,P < 0.01 | 0.02-691.66 | |
Disease | |||||
CVD | HR | 27 | 1.36 (1.15-1.61) | I² = 79%, τ² = 0.1154,P < 0.01 | 0.66-2.80 |
OR | 41 | 1.48 (1.24-1.76) | I² = 91%, τ² = 0.1984,P < 0.01 | 0.59-3.70 | |
Cardiac disease | HR | 25 | 1.40 (1.17-1.69) | I² = 77%, τ² = 0.1141,P < 0.01 | 0.68-2.90 |
OR | 38 | 1.43 (1.25-1.64) | I² = 84%, τ² = 0.0762,P < 0.01 | 0.80-2.55 | |
HF | HR | 4 | 1.23 (1.05-1.44) | I² = 89%, τ² = 0.0173,P < 0.01 | 0.63-2.39 |
OR | 31 | 1.46 (1.31-1.62) | I² = 59%, τ² = 0.0290,P < 0.01 | 1.01-2.10 | |
CAD | HR | 9 | 1.48 (1.14-1.93) | I² = 70%, τ² = 0.0957,P < 0.01 | 0.67-3.29 |
OR | 26 | 1.17 (1.02-1.35) | I² = 52%,τ² = 0.0416, P < 0.01 | 0.75-1.83 | |
Others | HR | - | - | - | |
OR | 2 | 1.63 (1.05-2.53) | I² = 33%, τ² = 0.0585,P = 0.22 | - | |
Outcomes | |||||
Mortality | HR | 55 | 1.39 (1.27-1.53) | I² = 76%, τ² = 0.0597,P < 0.01 | 0.85-2.30 |
OR | 98 | 1.44 (1.32-1.56) | I² = 84%, τ² = 0.0840, P < 0.01 | 0.80-2.57 | |
Severity | HR | 7 | 1.06 (0.70-1.60) | I² = 88%, τ² = 0.2418,P < 0.01 | 0.30-3.68 |
OR | 25 | 1.22 (1.03-1.43) | I² = 66%, τ² = 0.0575,P < 0.01 | 0.72-2.06 | |
Disease progression | HR | 3 | 1.65 (1.20-2.27) | I² = 0%, τ² = 0.000,P = 0.56 | 0.21-12.92 |
OR | 15 | 1.63 (1.31-2.04) | I² = 68%, τ² = 0.0858,P < 0.01 | 0.84-2.39 | |
Totally, our results revealed that COVID-19 patients who suffered from CVD tended more to adverse outcomes (pooled ORs = 1.41, 95% CIs: 1.32-1.51, prediction interval: 0.84-2.39; pooled HRs = 1.34, 95% CIs: 1.23-1.46, prediction interval: 0.82-2.21 Fig. 2). Subgroup analysis by sample size showed consistent results (pooled HRs = 1.16, 95% CIs: 1.03-1.32, prediction interval: 0.66-2.04; pooled ORs = 1.41, 95% CIs: 1.32-1.51, prediction interval: 0.84-2.39 for sample size >= 1000; pooled HRs = 1.63, 95% CIs: 1.41-1.88, prediction interval: 0.86-3.10; pooled ORs: 1.57, 95% CIs: 1.40-1.77, prediction interval: 0.84-2.95 for sample size < 1000; Table 2 and Fig. A1). The positive association between pre-existing CVD and adverse outcomes in COVID-19 patients was also observed in subgroup analysis by disease types (Table 2 and Fig. A2): cardiac disease (pooled HRs = 1.40, 95% CIs: 1.17-1.69, prediction interval: 0.68-2.90; pooled ORs = 1.43, 95% CIs: 1.25-1.64, prediction interval: 0.80-2.55), HF (pooled HRs = 1.23, 95% CIs: 1.05-1.44, prediction interval: 0.63-2.39; pooled ORs = 1.46, 95% CIs: 1.31-1.62, prediction interval: 1.01-2.10), and CAD (pooled HRs = 1.48, 95% CIs: 1.14-1.93, prediction interval: 0.67-3.29; pooled ORs = 1.17, 95% CIs:1.02-1.35, prediction interval: 0.75-1.83). In addition, subgroup analyses stratified by age, the proportion of males, region, disease outcomes and study design supported the above positive associations (Table 2 and Fig. A3-7). Sensitivity analysis indicated that our result was robust (Fig. 3A and B). There was no publication bias was detected by Begg’s test (OR: P = 0.233, HR: P = 0.054; Fig. 4A and B), while significant publication bias was found by Egger’s test (OR: P = 0.000, HR: P = 0.000; Fig. 4C and D). Therefore, the trim-and-fill method was adopted for further analysis. The results for HR showed that with the addition of 21 more studies, the results of the meta-analysis would be more robust but not reversed (pooled HRs = 1.11, 95% CIs: 1.01-1.14, fixed-effects model; pooled HRs = 1.16, 95% CIs: 1.06-1.26, random-effects model), and the OR results (pooled ORs: 1.18, 95% CIs: 1.16-1.20, fixed-effects model; pooled ORs: 1.21, 95% CIs: 1.12-1.30, random-effects model) showed that the results would be equally robust after adding 29 studies. However, there was high heterogeneity in our study. To find sources of heterogeneity, we conducted a meta-regression. However, adjustments for multivariate regression coefficients for sample size, age, proportion of males, study design, region, disease types, disease outcomes were not statistically significant (Table 3), suggesting that these were not sources of heterogeneity identified.
Fig. 2
Forest plot of adjusted pooled effects for adverse outcomes associated with CVD in patients with COVID-19. A) Pooled OR; B) Pooled HR
Table 3
The result of meta-regression
Variables | HR | OR | ||||
|---|---|---|---|---|---|---|
Tau² | t-value | P-value | Tau² | t-value | P-value | |
Sample size | 0.0753 | -0.3248 | 0.0007 | 0.0931 | -0.1552 | 0.0449 |
>=1000 | ||||||
<1000 | ||||||
Age | 0.0552 | - | 0.1123 | 0.0746 | - | 0.3495 |
>=60 | 0.1404 | 0.1206 | 0.1006 | 0.1674 | ||
<60 | ||||||
NR | 0.7562 | 0.1143 | 0.1713 | 0.5027 | ||
Male (%) | 0.0734 | 0.0351 | 0.7253 | 0.0997 | - | 0.0086 |
>=50 | -0.0678 | 0.4355 | ||||
<50 | ||||||
NR | 0.4272 | 0.0119 | ||||
Study design | 0.0774 | - | 0.0828 | 0.0796 | - | 0.8863 |
Retrospective/case series | 0.1064 | 0.3152 | -0.0034 | 0.9647 | ||
Prospective study | 0.1064 | 0.1628 | -0.0823 | 0.6301 | ||
Others | ||||||
Region | 0.0651 | - | 0.1800 | 0.0601 | - | <0.0001 |
Europe | -0.1169 | 0.2910 | -0.0307 | 0.7439 | ||
North America | -0.2287 | 0.0746 | -0.2362 | 0.0132 | ||
Asia | ||||||
Others | 0.3260 | 0.3447 | 1.3471 | <0.0001 | ||
Disease | 0.0702 | - | 0.8655 | 0.1005 | - | 0.4005 |
CVD | -0.1123 | 0.4286 | 0.1737 | 0.1365 | ||
Cardiac disease | -0.0681 | 0.6418 | 0.1620 | 0.1741 | ||
HF | -0.1221 | 0.5212 | 0.2230 | 0.0640 | ||
CAD | ||||||
Others | 0.82 | 0.413 | ||||
Outcomes | 0.0694 | - | 0.0375 | 0.0810 | - | 0.1400 |
Mortality | -0.0990 | 0.6880 | -0.1298 | 0.2733 | ||
Severity | -0.4713 | 0.0915 | -0.2786 | 0.0528 | ||
Disease progression | ||||||
Fig. 3
Sensitivity analysis for pooled OR (A) and HR (B)
Fig. 4
Publication bias for pooled OR (A and B) and HR (C and D)
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Discussion
Many countries have been hit by the pandemic caused by SARS-CoV-2, numerous people lost their lives because of this. Meanwhile, health systems in every country were under so unprecedented strain that it was very important to find an effective marker to help implement bed grading management. What called for special attention was that earlier studies have shown COVID-19 patients with at least one underlying conditions, such as chronic kidney disease, HIV, diabetes and other comorbidities, have a poor disease course [2, 29, 211, 219, 220], which means that those patients with underlying diseases should be monitored more carefully in case of disease getting worse. Furthermore, it was reported that the risk of primary respiratory syndrome severity and adverse outcomes was increased in Middle East respiratory syndrome (MERS) patients with pre-existing CVD. The research by Li et al. [8] with unadjusted effect estimates showed that there was a positive association between CVD and adverse outcomes in patients with COVID-19, but the association might be confounded by other factors such as age, gender and comorbidities. Thus, we performed a quantitative meta-analysis on the basis of adjusted effect estimates to clarify whether pre-existing CVD was an independent risk factor associated with adverse outcomes in COVID-19 patients.
Our results based on adjusted effect estimates revealed that pre-existing CVD was significantly related to adverse outcomes in COVID-19 patients on the basis of 203 eligible studies with 24,032,712 cases. The significant association between pre-existing CVD and adverse outcomes in COVID-19 patients was still existent in further subgroup analyses stratified by the proportion of males, study design, disease types, sample size, region and disease outcomes, which suggests that our findings are relatively stable.
Similar to other meta-analyses, several limitations should be acknowledged in this present study. Firstly, data on drug and supportive treatments are not clear in the selected studies presently, thus, we could not evaluate the effects of treatments on the association between co-existing CVD and adverse outcomes in COVID-19 patients. Secondly, statistically significant results were more likely to be accepted and published than non-statistically significant results in similar studies, but in fact, the data of the meta-analysis mainly derived from the studies which have been published, which may lead to publication bias. Thirdly, the causal relationship of CVD and adverse outcomes in patients with COVID-19 cannot be confirmed on account of the inherent limitation of the observational study. Therefore, well-designed studies with larger sample sizes are needed for further verification.
Conclusions
In conclusion, our findings indicated that pre-existing CVD was an independent risk factor associated with adverse outcomes among COVID-19 patients. COVID-19 patients with a history of CVD might need more attention.
Acknowledgements
We would like to thank Jian Wu, Yang Li and Hongjie Hou (All are from Department of Epidemiology, School of Public Health, Zhengzhou University) for their kind help in searching articles and collecting data, and valuable suggestions for data analysis.
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The authors declare not any potential conflict of interest.
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