Figure 1 shows the PRISMA flow diagram of the study selection process. A total of 1942 articles were identified in the initial search. After removing duplicates, 1880 were screened by titles and abstracts. Articles which were not available in English were translated with the help of Google Translate(22). After screening by abstract and title, 253 articles were selected for full-text assessment. Out of these 253 articles, 206 articles were excluded after full-text review and finally 46 articles were included.
Out of 46 studies, most studies were limited to China (n = 26, 14 from Wuhan) followed by USA (n = 8), South Korea (n = 3), Italy (n = 3), one each from France, Spain and Iran. Two of them were multicentric studies which included patients from various American, Asian and European countries and one was from Diamond Princess Cruise ship. A total of 13,624 older patients were included. Supplementary Table S1 presents various characteristics of all the studies included in meta-analysis. The proportion of males in the studies ranged from 36% − 86%. Most studies were in the hospital setting (n = 38), while remaining included both inpatients and outpatients (n = 8). Most of the studies were of low (n = 14) or intermediate quality (n = 26) (Supplementary Table S1). 33 studies reported follow up; minimum follow up duration ranged from 0 to 35 days. The remaining 13 studies didn’t report duration of follow up. 15 studies didn’t have any minimum follow up period (0 days) i.e. the final date of enrolment was as same as the final date of outcome. As evident from the funnel plots (Supplementary figures S11-S18) and Egger’s regression analysis, there was publication bias for all variables.
Severity of illness and outcome
Table 1 provides details of severity of illness and outcomes in included studies. Overall, 50% (95% CI – 36–65%, I2 – 95%) of 2049 patients developed severe illness while 23% (95% CI – 16–31%, I2- 88%) of 5280 progressed to critical illness. 43% (95% CI – 3–88%, I2- 100%) of 6901 patients were discharged. Overall, the WPP of mortality was 11% (95% CI – 4–20%, I2- 98%) among all 12,060 older patients included in the study. (Table 2)
Table 1
Severity of illness and outcomes of COVID-19 in included studies
Author name | n | Severe | Critical | Death | Discharged |
Bhatraju, P K et al. | 18 | .. | .. | 9 | 1 |
Bialek, S et al. | 278 | .. | 64 | 35 | .. |
Burrer, S et al.* | 238 | .. | .. | 10 | .. |
Burrer, S et al.* | 219 | .. | 35 | .. | .. |
Catellani, F et al. | 16 | .. | .. | 7 | .. |
Chen, T (a) | 55 | 48 | 24 | 19 | 36 |
Chen, T (b) | 153 | .. | .. | 94 | .. |
Chow, N et al. | 715 | .. | 232 | .. | .. |
Du, R-H et al. | 65 | .. | .. | 17 | .. |
Feng, Y et al. | 118 | 45 | 25 | 18 | 87 |
Fernández-Ruiz, M et al. | 15 | 3 | .. | 5 | 6 |
Grasselli, G et al. | 958 | .. | .. | 322 | 111 |
Grein, J et al. | 18 | .. | .. | 7 | .. |
Guan, W-J et al. | 153 | 44 | 32 | .. | .. |
Kang, Y-J et al. | 1825 | .. | .. | 67 | .. |
KCDC | 1679 | .. | .. | 58 | .. |
Li, J et al. | 259 | 135 | .. | 65 | 194 |
Lian, J et al. | 136 | 33 | 13 | 0 | 31 |
Liu, K et al. | 18 | 4 | .. | 1 | 17 |
Liu, Y et al. | 85 | .. | .. | 9 | 76 |
Lodigiani, C et al. | 22 | .. | 4 | 7 | 11 |
Mehta, V et al. | 138 | .. | .. | 49 | .. |
Nikpouraghdam, M et al. | 1164 | .. | .. | 160 | .. |
Pereira, M R et al. | 43 | 19 | .. | .. | .. |
Richardson, S et al.* | 3368 | .. | .. | 466 | 959 |
Richardson, S et al.* | 2582 | .. | 613 | .. | .. |
Russell, TW et al. | 200 | .. | .. | 7 | .. |
Tian, S et al. | 48 | 20 | .. | 2 | .. |
Wang, D et al. | 36 | | .. | 16 | 20 |
Wang, L et al. | 339 | 239 | 80 | 65 | 91 |
Yang, R et al. | 62 | .. | .. | 17 | .. |
Yao, Q et al. | 17 | 9 | .. | 6 | .. |
Yu, X et al. | 107 | 21 | .. | .. | .. |
Zhang, G et al. (a) | 17 | 7 | 7 | 4 | .. |
Zhang, G et al. (b) | 62 | 24 | .. | .. | .. |
Zhang, J et al. | 315 | 246 | 67 | 19 | .. |
Zhang, L et al. | 19 | 11 | 11 | .. | .. |
Zhang, Y T et al. | 312 | 114 | 36 | 6 | .. |
Zhao, X-Y et al. | 16 | 8 | .. | .. | .. |
*Data for critical illness was not available for all patients; KCDC - Korea Centers for Disease Control and Prevention; ICU – Intensive care unit |
Table 2
Weighted pooled prevalence (WPP) of comorbidities, clinical features, severity of illness and outcome in older patients with COVID-19
Variable | Number of studies | Number of patients | WPP | 95% CI | p-value for Cochran’s Q | I2 | Egger’s test* (p-value) |
Severity of illness |
Severe | 18 | 2049 | 0.50 | 0.36–0.65 | 0.00 | 95 | < 0.001 |
Critical | 14 | 5280 | 0.23 | 0.16–0.31 | 0.00 | 88 | < 0.001 |
Outcomes |
Discharged | 14 | 6901 | 0.43 | 0.03–0.88 | 0.00 | 100 | < 0.001 |
Dead | 30 | 12060 | 0.11 | 0.04–0.20 | 0.00 | 98 | < 0.001 |
Comorbidities |
≥ 1 comorbidity | 12 | 1888 | 0.81 | 0.68–0.93 | 0.00 | 92 | < 0.001 |
Hypertension | 17 | 2245 | 0.48 | 0.36–0.60 | 0.00 | 92 | < 0.001 |
Diabetes Mellitus | 17 | 1804 | 0.22 | 0.13–0.32 | 0.00 | 86 | 0.004 |
Cardiovascular disease | 13 | 1679 | 0.19 | 0.11–0.28 | 0.00 | 85 | 0.002 |
Hypothyroid | 3 | 99 | 0.11 | 0.01–0.25 | 0.16 | 45 | .. |
Neurological disease | 9 | 871 | 0.09 | 0.06–0.13 | 0.02 | 55 | .. |
Malignancy | 12 | 1476 | 0.09 | 0.03–0.15 | 0.00 | 80 | 0.014 |
Chronic lung disease | 14 | 1748 | 0.08 | 0.03–0.13 | 0.00 | 82 | 0.004 |
Cerebrovascular disease | 9 | 814 | 0.08 | 0.06–0.11 | 0.23 | 24 | .. |
Kidney disease | 14 | 1591 | 0.05 | 0.01–0.09 | 0.00 | 77 | 0.066 |
Liver disease | 11 | 1416 | 0.03 | 0.01–0.05 | 0.01 | 58 | 0.018 |
Autoimmune diseases | 3 | 473 | 0.02 | 0.00-0.06 | 0.06 | 65 | .. |
Clinical Features |
Fever | 11 | 782 | 0.83 | 0.66–0.97 | 0.00 | 91 | < 0.001 |
Cough | 11 | 782 | 0.60 | 0.50–0.70 | 0.00 | 71 | < 0.001 |
Dry cough | 4 | 432 | 0.56 | 0.43–0.69 | 0.08 | 56 | .. |
Sputum production | 8 | 654 | 0.28 | 0.17–0.39 | 0.00 | 70 | .. |
Dyspnoea | 11 | 782 | 0.42 | 0.19–0.67 | 0.00 | 94 | 0.020 |
Fatigue | 9 | 691 | 0.33 | 0.16–0.52 | 0.00 | 88 | .. |
Anorexia | 3 | 470 | 0.31 | 0.01–0.67 | 0.00 | 96 | .. |
Chest discomfort | 5 | 500 | 0.26 | 0.01–0.57 | 0.00 | 93 | .. |
Diarrhoea | 6 | 575 | 0.18 | 0.02–0.39 | 0.00 | 91 | .. |
Myalgia | 9 | 746 | 0.15 | 0.01–0.33 | 0.00 | 93 | .. |
Abdominal pain | 4 | 219 | 0.11 | 0.02–0.22 | 0.00 | 80 | .. |
Sore Throat | 5 | 639 | 0.10 | 0.00-0.25 | 0.00 | 94 | .. |
Headache | 7 | 714 | 0.09 | 0.00-0.24 | 0.00 | 94 | .. |
Nausea-Vomiting | 4 | 543 | 0.08 | 0.00-0.23 | 0.00 | 93 | .. |
Gastrointestinal symptoms | 3 | 169 | 0.15 | 0.00-0.79 | 0.00 | 94 | .. |
Baseline characteristics and comorbidities
On analysing comorbidities, 81% (95% CI – 68–93%, I2- 92%) of older patients had at least one comorbidity. Hypertension was the most common comorbidity (48%, 95% CI – 36–60%, I2- 92%) followed by diabetes mellitus (22%, 95% CI – 13–32%, I2- 86%) and cardiovascular disease (19%, 95% CI – 11–28%, I2- 85%) (Table 2). Two studies broadened their definitions of cardiovascular disease to include hypertension(23) or CVA(24) and hence were excluded from the analyses of these variables.
Clinical features
Most common symptoms were fever (83%, 95% CI – 66–97%, I2- 91%), cough (60%, 95% CI – 50–70%, I2- 71%), dyspnoea (42%, 95% CI – 19–67%, I2- 94%) and fatigue (33%, 95% CI- 16–52%, I2- 88%). Among gastrointestinal symptoms, anorexia (31%, 95% CI – 1–67%, I2- 96%) followed by diarrhoea (18%, 95% CI- 2–39%, I2- 91%) were most common ones (Table 2). In some studies, presence or absence of gastrointestinal symptoms were reported without any additional details or specific information. These have reported as ‘gastrointestinal symptoms’ only. Wherever, specific information was available, it was reported and analysed separately.
Laboratory and radiological findings
Lymphopenia (52%, 95% CI – 24–81%, I2- 94%) and leukopenia (20%, 95% CI – 6–38%, I2- 89%) were most commonly reported haematological findings while bilateral lung infiltrates (76%, 95% CI – 44–100%, I2- 97%) was the most common radiologic finding (Supplementary Table S7).
Complications
Most common complications observed in these patients were secondary infection (34%, 95% CI – 6–66%, I2- 91%), AKI (26%, 95% CI 0–65%, I2-98%) (Supplementary Table S7).
Respiratory support
The WPP of requirement for oxygen support was 84% (95% CI – 60–100%, I2- 81%). Overall, 21% (95% CI – 0–49%, I2- 91%) required invasive mechanical ventilation (Supplementary Table S7). One study reported 68.4% mortality rate(13) while in the other one, out of two patients on mechanical ventilator, one died while the other one was in ICU for 21 days(25).
Sensitivity analysis was done by excluding outliers for severe illness, diabetes mellitus, chest discomfort, abdominal pain, sore throat, headache and lymphopenia. The pooled results did not change substantially. We further did analyses in which the studies which including only ICU patients(26, 27) or with clinical data for only dead patients(23, 24, 28–31) were excluded. No significant difference was seen in the pooled prevalence. We did a subgroup analysis according to the location of study (China vs. outside China) of the variables (Table 3). Death rate was similar in studies from China (15%, 95% CI – 5–26%, I2- 96%) and outside China (11%, 95% CI – 3–20%, I2- 98%) (p = 0.56). Similarly, the WPP of comorbidities and clinical features were similar in both locations.
Table 3
Subgroup analysis of studies from China and outside China
Variable | China | Outside China | p-value for interaction |
Number of studies/patients | Prevalence (95% CI) | p-value (Cochran’s Q); I2 | Number of studies/patients | Prevalence (95% CI) | p-value (Cochran’s Q); I2 |
Death | 16/2035 | 0.15 (0.05–0.26) | 0.00; 96% | 14/10025 | 0.11 (0.03–0.20) | 0.00; 98% | 0.56 |
≥ 1 comorbidity | 6/410 | 0.68 (0.53–0.82) | 0.00; 85% | 6/1478 | 0.84 (0.72–0.95) | 0.00; 91% | 0.09 |
Hypertension | 11/1387 | 0.42 (0.28–0.57) | 0.00; 91% | 6/858 | 0.57 (0.39–0.74); | 0.00; 81% | 0.20 |
Diabetes Mellitus | 10/921 | 0.22 (0.10–0.36); | 0.00; 90% | 7/883 | 0.22 (0.12–0.33) | 0.01; 65% | 1.00 |
Cardiovascular disease | 9/901 | 0.14 (0.08–0.20) | 0.00; 72% | 4/778 | 0.26 (0.11–0.43) | 0.00; 79% | 0.17 |
Chronic Lung disease | 9/883 | 0.07 (0.04–0.11) | 0.02; 56% | 6/865 | 0.08 (0.00-0.26) | 0.00; 91% | 0.88 |
Malignancy | 7/702 | 0.05 (0.03–0.07) | 0.30; 17% | 5/774 | 0.13 (0.01–0.28) | 0.00; 78% | 0.25 |
Kidney disease | 8/720 | 0.04 (0.01–0.07) | 0.06; 48% | 6/871 | 0.06 (0.00-0.18) | 0.00; 87% | 0.68 |
Liver disease | 6/582 | 0.02 (0.00-0.06) | 0.02; 62% | 5/834 | 0.04 (0.01–0.07) | 0.09; 50% | 0.85 |
Fever | 6/583 | 0.85 (0.56-1.00) | 0.00; 95% | 5/199 | 0.77 (0.67–0.87) | 0.08; 58% | 0.42 |
Cough | 6/583 | 0.57 (0.47–0.67) | 0.03; 61% | 5/199 | 0.71 (0.61–0.81) | 0.11; 12.47% | 0.05 |
Dyspnoea | 6/583 | 0.36 (0.07–0.68) | 0.00; 95% | 5/199 | 0.63 (0.45–0.80) | 0.00; 78% | 0.13 |
The overall quality of evidence for all outcomes was low because of study design (observational studies only), lack of consistency of methodology, presence of publication bias and significant heterogeneity in all effect estimates.