Figure 1
Flow chart of study selection.
Table 1
Summary of 25 studies included in systematic review.
| Reference | Journal | Region | Setting | Sample size | Severe, n (%) | Age median (IQR) or mean (SD) in y | Male, n (%) | Current smoking, n (%) | HTN, n (%) | DM, n (%) | CVD, n (%) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Bhatraju PK | NEJM | USA | 9 Seattle-area hospitals | 24 | 18 (75) | 64 (18) | 15 (63) | 5 (22)* | – | 14 (58) | 2 (8) |
| Cao J | Intensive Care Med | China | Zhongnan Hospital | 102 | 18 (18) | 54 (37–67) | 53 (52) | – | 28 (28) | 11 (11) | 5 (5) |
| Chen J | J Infect | China | Shanghai Public Health Clinical Center | 249 | 22 (9) | 51 (36–64) | 126 (51) | – | – | – | 55 (22) |
| Chen T | BMJ | China | Tongji Hospital | 274 | 196 (72) | 62 (44–70) | 170 (62) | 11 (4) | 93 (34) | 47 (17) | 22 (8) |
| Cheng Y | Kidney International | China | Tongji Hospital | 701 | 113 (16) | 63 (50–71) | 367 (52) | – | 233 (33) | 100 (14) | |
| China CDC | CCDC | China | China National Data | 44,672 | 8,255 (19) | – | 22,981 (51) | – | 2,683 (13) | 1,102 (5) | 873 (4) |
| Deng Y | Chin Med J | China | Tongji Hospital and Central Hospital of Wuhan | 225 | 109 (48) | – | 124 (55) | – | 58 (26) | 26 (12) | 17 (8) |
| Guan W | NEJM | China | 552 hospitals in 30 provinces | 1099 | 67 (6) | 47 (35–58) | 637 (58) | 137 (13) | 165 (15) | 81 (7) | 27 (3) |
| Guo T | JAMA Cardiol | China | Seventh Hospital of Wuhan | 187 | 43 (23) | 59 (15) | 91 (49) | 18 (10) | 61 (33) | 28 (15) | 21 (11) |
| Huang C | Lancet | China | Jinyintan Hospital | 41 | 13 (32) | 49 (41–58) | 30 (73) | 3 (7) | – | – | 6 (15) |
| Lian J | Clin Infect Dis | China | Hospitals in Zhejiang province | 788 | 77 (10) | 46 (15) | 407 (52) | 54 (7) | 126 (16) | 57 (7) | 11 (1) |
| Liang W | Lancet Oncology | China | 575 hospitals across China | 1,590 | 131 (8) | 49 ± 16 | 909 (57) | 111 (7) | – | – | – |
| Onder G | JAMA | Italy | Italy National Data | 22,512 | 1,625 (7) | – | – | – | – | – | – |
| Ruan Q | Intensive Care Med | China | Jinyintan Hospital and Tongji Hospital | 150 | 67 (45) | – | 102 (68) | – | 52 (35) | – | 13 (9) |
| Shi S | JAMA Cardiol | China | Zhejiang Province | 416 | 97 (23) | 64 (21–95) | 205 (49) | – | 127 (31) | 60 (14) | 44 (11) |
| Tang N | J Thromb Haemost | China | Tongji Hospital | 183 | 21 (12) | 54 ± 16 | 98 (54) | – | – | – | – |
| US CDC | MMWR | US | US National Data | 2,449 | 121 (5) | – | – | – | – | – | – |
| US CDC_2 | MMWR | USA | US National Data | 6,637 | 457 (6) | – | – | 86 (1) | 106 (2) | 723 (11) | 597 (9) |
| Wang D | JAMA | China | Zhongnan Hospital | 138 | 36 (26) | 56 (42–68) | 75 (54) | – | 43 (31) | 14 (10) | 20 (15) |
| Wang L | J Infect | China | Renmin Hospital of Wuhan University | 339 | 80 (24) | 69 (65–76) | 166 (49) | – | 138 (41) | 54 (16) | 53 (16) |
| Wu C | JAMA Intern Med | China | Jinyintan Hospital, Wuhan | 201 | 84 (42) | 51 (43–60) | 128 (64) | – | 39 (19) | 22 (11) | 8 (4) |
| Yang X | Lancet Respir | China | Jinyintan Hospital, Wuhan | 52 | 35 (67) | 60 (13) | 35 (67) | 2 (4) | – | 9 (17) | 5 (10) |
| Yuan M | PLoS One | China | Central Hospital of Wuhan | 27 | 10 (41) | 60 (47–69) | 12 (45) | – | 5 (19) | 6 (22) | 3 (11) |
| Zhang L | Ann Oncol | China | Tongji Sino-French New Town Hospital, Union Red Cross Hospital and Union West Hospital | 28 | 15 (54) | 65 (56–70) | 17 (61) | – | – | 4 (14) | 4 (14) |
| Zhou F | Lancet | China | Jinyintan Hospital and Wuhan Pulmonary Hospital | 191 | 59 (31) | 56 (46–67) | 119 (62) | 11 (6) | 58 (30) | 36 (19) | 15 (8) |
[i] All studies were published in 2020.
Abbreviations: COVID-19: coronavirus disease 2019; CVD: cardiovascular disease; DM: diabetes; HTN: hypertension; NR, not reported.
* Current or former smoking.
Table 2
Relative risk estimates of severe COVID-19 by age in eligible studies.
| Study | No. of events | Age, per-year increment | Across categories | |
|---|---|---|---|---|
| Reference | Comparison | |||
| Bhatraju PK | 18 cases with mechanical ventilation | – | <60 | Unadjusted OR: 60–70: 3.50 (0.24–51.90) 70–80: NA >80: 0.33 (0.03–3.93) |
| Chen J | 22 cases with ICU admission | Unadjusted OR: 1.08 (1.04–1.13) Adjusted* OR: 1.06 (1.00–1.12) | – | – |
| Chen T | 113 deaths | – | <60 | Unadjusted OR: ≥60: 8.55 (4.75–15.40) |
| Cheng Y | 113 deaths | – | ≤65 | Unadjusted HR: >65: 2.43 (1.66–3.56) |
| China CDC | 1,023 deaths | – | 20–29 | Unadjusted HR: 30–39: 1.23 (0.51–2.94) 40–49: 2.29 (1.03–5.15) 50–59: 6.79 (3.17–14.54) 60–69: 19.3 (9.1–40.8) 70–79: 44.6 (21.1–94.6) ≥80: 89.4 (42.0–190.5) |
| Lian J | 58 cases with ARDS | – | <60 | Unadjusted OR: ≥60: 3.59 (2.04, 6.30) |
| Liang W | 131 composite end points (ICU admission requiring invasive ventilation or death) | Adjusted OR†: 1.048 (1.033–1.064) | – | – |
| Onder G | 1,625 deaths | – | 30–39 | Unadjusted OR: 40–49: 1.33 (0.42–4.26) 50–59: 3.36 (1.20–9.37) 60–69: 12.05 (4.45–32.63) 70–79: 48.77 (18.20–130.63) ≥80: 84.10 (31.43–225.06) |
| Shi S | 57 deaths | Adjusted HR‡: 1.02 (0.99–1.05) | – | – |
| US CDC | 121 cases with ICU admission | – | 20–44 | Unadjusted OR: 45–54: 2.80 (1.43–5.49) 55–64: 2.41 (1.21–4.83) 65–74: 4.33 (2.29–8.20) 75–84: 5.78 (2.90–11.51) ≥85: 3.29 (1.40–7.76) |
| US CDC_2 | 457 cases with ICU admission | – | 19–64 | Unadjusted OR: ≥65: 1.21 (0.96–1.52) |
| Wang L | 65 deaths | Unadjusted HR: 1.08 (1.06–1.11)Adjusted HR§: 1.06 (1.03–1.10) | – | – |
| Wu C | 84 cases with ARDS | – | <65 | Unadjusted HR: ≥65: 3.26 (2.08–5.11) |
| Yang X | 32 deaths | – | 30–49 | Unadjusted OR: 50–59: 6.75 (1.16–39.20) 60–69: 5.50 (1.06–28.42) ≥70: 27.00 (2.34–311.17) |
| Zhang L | 15 composite events of ICU admission, use of mechanical ventilation or death | Adjusted HR||: 1.46 (0.48–4.43) | – | – |
| Zhou F | 54 deaths | Unadjusted OR: 1·14 (1·09–1·18) Adjusted OR#: 1.10 (1.03–1.17) | – | – |
[i] Abbreviations: ARDS: acute respiratory distress syndrome; COVID-19: coronavirus disease 2019; ICU: intensive care unit.
* Adjusted for gender, comorbidity, WBC, lymphocytes, CRP, albumin, aspartate aminotransferase, lactate dehydrogenase, eGFR, CD4 cell counts.
† Adjusted for age, sex, cancer, HTN, COPD, DM.
‡ Adjusted for age, cardiovascular disease, cerebrovascular disease, diabetes, COPD, renal failure, cancer, ARDS, cardiac injury, creatinine ≥1.50 mg/dL, NT-proBNP ≥900pg/mL.
§ Adjusted variables unclear.
|| Adjusted for age, receiving anti-tumor treatment within 14 days, and patchy consolidation on admission CT scan.
# Adjusted for age, lymphocyte count, d-dimer, SOFA score, coronary heart disease.
Figure 2
Forest plots of unadjusted relative risk estimates of severe COVID-19 according to gender (A), smoking status (B) and (C) based on restrictive meta-analysis.
Figure 3
Forest plots of unadjusted relative risk estimates of severe COVID-19 according to hypertension (A), diabetes (B), and prior CVD (C) on restrictive meta-analysis.
Figure 4
Forest plots of adjusted relative risk estimates of severe COVID-19 according to prior CVD.
Figure 5
Meta-regression of unadjusted relative risk of severe COVID-19 for hypertension (A), diabetes (B), and CVD (C) by age difference between severe vs. non-severe COVID-19 based on restrictive meta-analysis.