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In total, 1,160 patients were included, and 52.2% were male, with age [median (Q1, Q3)] of 46.0 (33.0, 57.0) years. There were 341 (29.4%) patients with more than one comorbidity. Among the 1,160 patients, 158 (13.6%) were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes at the end of the two-week follow-up window. Patients with severe COVID-19 were older than those with non-severe COVID-19 (median: 57.0 vs. 44.0 years), and patients who had unfavorable outcomes were older than those with favorable outcomes (median: 60.0 vs. 46.0 years). Patients who were > 60 years of age had a higher percentage of severe illness, comorbidity, and unfavorable outcomes. Cough (49.8%) and fever (44.7%) were the two most common onset symptoms. Overall, patients with symptoms (except sore throat) had a higher percentage of severe illness and unfavorable outcomes ( Table 1).
Table 1. Characteristics of patients by clinical severity, treatment outcome and having comorbidity or not
Variables n(%) Clinical severity Treatment outcome Comorbidity or not Non-severe
cases (%)
(n = 1,002)Severe
cases (%)
(n = 158)Favorable
outcome (%)
(n= 1,128)Unfavorable
outcome (%)
(n = 32)No (%)
(n = 819)Yes (%)
(n= 341)Sex Male 606 (52.2) 519 (85.6) 87 (14.4) 594 (98.0) 12 (2.0) 412 (68.0) 194 (32.0) Female 554 (47.8) 483 (87.2) 71 (12.8) 534 (96.4) 20 (3.6) 407 (73.5) 147 (26.5) Age, median (Q1, Q3) 46.0
(33.0, 57.0)44.0
(32.0, 55.0)57.0
(45.0, 67.0)46.0
(32.0, 56.0)60.0
(46.0, 71.0)40.0
(30.0, 51.0)56.0
(48.0, 65.0)Age (categorized) < 60 917 (79.1) 828 (90.3) 89 (9.7) 901 (98.3) 16 (1.7) 717 (78.2) 200 (21.8) ≥ 60 243 (20.9) 174 (71.6) 69 (28.4) 227 (93.4) 16 (6.6) 102 (42.0) 141 (58.0) BMI, Mean (SD) 23.8 (3.4) 23.6 (3.3) 24.9 (3.7) 23.8 (3.4) 24.0 (3.2) 23.5 (3.3) 24.6 (3.4) Onset symptoms Fever No 641 (55.3) 575 (89.7) 66 (10.3) 631 (98.4) 10 (1.6) 462 (72.1) 179 (27.9) Yes 519 (44.7) 427 (82.3) 92 (17.7) 497 (95.8) 22 (4.2) 357 (68.8) 162 (31.2) Fatigue No 841 (72.5) 752 (89.4) 89 (10.6) 822 (97.7) 19 (2.3) 609 (72.4) 232 (27.6) Yes 319 (27.5) 250 (78.4) 69 (21.6) 306 (95.9) 13 (4.1) 210 (65.8) 109 (34.2) Cough No 582 (50.2) 533 (91.6) 49 (8.4) 573 (98.5) 9 (1.6) 424 (72.9) 158 (27.2) Yes 578 (49.8) 469 (81.1) 109 (18.9) 555 (96.0) 23 (4) 395 (68.3) 183 (31.7) Congestion or runny nose No 1126 (97.1) 973 (86.4) 153 (13.6) 1,096 (97.3) 30 (2.7) 780 (70.1) 332 (29.9) Yes 34 (2.9) 29 (85.3) 5 (14.7) 32 (94.1) 2 (5.9) 39 (81.3) 9 (18.8) Anorexia No 1,032 (89.0) 909 (88.1) 123 (11.9) 1,010 (97.9) 22 (2.1) 737 (71.4) 295 (28.6) Yes 128 (11.0) 93 (72.7) 35 (27.3) 118 (92.2) 10 (7.8) 82 (64.1) 46 (35.9) Sore throat No 1,046 (90.2) 895 (85.6) 151 (14.4) 1,014 (96.9) 32 (3.1) 734 (70.2) 312 (29.8) Yes 114 (9.8) 107 (93.9) 7 (6.1) 114 (100) 0 (0.0) 85 (74.6) 29 (25.4) Diarrhea No 1,113 (95.9) 963 (86.5) 150 (13.5) 1,084 (97.4) 29 (2.6) 787 (70.7) 326 (29.3) Yes 47 (4.1) 39 (83) 8 (17.0) 44 (93.6) 3 (6.4) 32 (68.1) 15 (31.9) Shortness of breath No 1,027 (88.5) 917 (89.3) 110 (10.7) 1,004 (97.8) 23 (2.2) 735 (71.6) 292 (28.4) Yes 133 (11.5) 85 (63.9) 48 (36.1) 124 (93.2) 9 (6.8) 84 (63.2) 49 (36.8) Chills No 1,095 (94.4) 951 (86.9) 144 (13.2) 1,065 (97.3) 30 (2.7) 780 (71.2) 315 (28.8) Yes 65 (5.6) 51 (78.5) 14 (21.5) 63 (96.9) 2 (3.1) 39 (60.0) 26 (40.0) Ever went to Wuhan city No 658 (56.7) 572 (86.9) 86 (13.1) 636 (96.7) 22 (3.3) 450 (68.4) 208 (31.6) Yes 322 (27.8) 287 (89.1) 35 (10.9) 315 (97.8) 7 (2.2) 235 (73.0) 87 (27.0) Note.Q1, the first quartile; Q3, the third quartile; SD, standard deviation. Hypertension (16.2%), T2DM (7.7%), and CVD (6.3%) were the three most common comorbidities. Other lung diseases (2.3%) and hepatitis B (2.1%) were common comorbidities of non-cardiometabolic disease. Around one-third of patients had one or more comorbidities (Table 2). The distribution of clinical severity and treatment outcome in the un-overlapped component of comorbidities are listed in Supplementary Table S1 (available in www.besjournal.com).
Table 2. Distribution of clinical severity and treatment outcome of COVID-19 by component and number of comorbidities
Variables n(%) Clinical severity Treatment outcome Non-severe
cases (%)Severe
cases (%)P value* Favorable
outcome (%)Unfavorable
outcome (%)P value* No comorbidity at all 819 (70.6) 758 (92.6) 61 (7.4) 808 (98.7) 11 (1.3) Had any comorbidity 341 (29.4) 244 (71.6) 97 (28.4) < 0.0001 320 (93.8) 21 (6.2) < 0.0001 Comorbidity of cardiometabolic diseases Hypertension 188 (16.2) 136 (72.3) 52 (27.7) < 0.0001 179 (95.2) 9 (4.8) 0.0023 T2DM 89 (7.7) 65 (73.0) 24 (27.0) < 0.0001 83 (93.3) 6 (6.7) 0.0004 Heart disease 53 (4.6) 32 (60.4) 21 (39.6) < 0.0001 44 (83.0) 9 (17.0) < 0.0001 Stroke 24 (2.1) 18 (75.0) 6 (25.0) 0.0017 22 (91.7) 2 (8.3) 0.0501 CVD (either heart disease or stroke) 73 (6.3) 47 (64.4) 26 (35.6) < 0.0001 63 (86.3) 10 (13.7) < 0.0001 Fatty liver 8 (0.7) 6 (75.0) 2 (25.0) 0.0626 8 (100.0) − − Hyperlipidemia 9 (0.8) 7 (77.8) 2 (22.2) 0.0964 9 (100.0) − − Hyperuricemia 7 (0.6) 6 (85.7) 1 (14.3) 0.4220 6 (85.7) 1 (14.3) 0.0977 Had hypertension and T2DM together 38 (3.3) 27 (71.1) 11 (28.9) < 0.0001 36 (94.7) 2 (5.3) 0.1098 Had hypertension and CVD together 37 (3.2) 23 (62.2) 14 (37.8) < 0.0001 32 (86.5) 5 (13.5) < 0.0001 Had CVD and T2DM together 17 (1.5) 12 (70.6) 5 (29.4) 0.0009 17 (100.0) − − Had hypertension, CVD and T2DM together 12 (1.0) 8 (66.7) 4 (33.3) 0.0009 12 (100.0) − − Comorbidity of non-cardiometabolic disease Other lung diseases 27 (2.3) 15 (55.6) 12 (44.4) < 0.0001 26 (96.3) 1 (3.7) 0.3242 Allergic diseases 7 (0.6) 1 (14.3) 6 (85.7) < 0.0001 7 (100.0) − − Hepatitis B 24 (2.1) 22 (91.7) 2 (8.3) 0.8709 24 (100.0) − − Pulmonary tuberculosis 9 (0.8) 7 (77.8) 2 (22.2) 0.0964 9 (100.0) − − Electrolyte disturbance 16 (1.4) 7 (43.8) 9 (56.3) < 0.0001 12 (75.0) 4 (25.0) 0.0001 Abnormal liver or kidney function 17 (1.5) 9 (52.9) 8 (47.1) < 0.0001 15 (88.2) 2 (11.8) 0.0266 Depression 6 (0.5) 5 (83.3) 1 (16.7) 0.3751 6 (100) − − Number of any comorbidity 0 819 (70.6) 758 (92.6) 61 (7.5) 808 (98.7) 11 (1.3) 1 230 (19.8) 168 (73.0) 62 (27.0) < 0.0001 218 (94.8) 12 (5.2) < 0.0001 2 83 (7.2) 59 (71.1) 24 (28.9) 77 (92.8) 6 (7.2) 3 28 (2.4) 17 (60.7) 11 (39.3) 25 (89.3) 3 (10.7) Note. T2DM, type 2 diabetes; CVD, cardiovascular disease. *P values were calculated by comparing the distribution of severity and treatment outcome in patients with no comorbidity at all group. Table S1. Distribution of clinical severity and treatment outcome of COVID-19 by component and number of comorbidities (un-overlapped)
Variables n (%) Clinical severity Treatment outcome Non-severe
casesSevere
casesP value Favorable
outcomeUnfavorable
outcomeP value No comorbidity at all 819 758 (92.6) 61 (7.5) 808 (98.7) 11 (1.3) Comorbidity of cardiometabolic diseases Hypertension 125 94 (75.2) 31 (24.8) < 0.0001 123 (98.4) 2 (1.6) 0.6863 T2DM 46 34 (73.9) 12 (26.1) < 0.0001 42 (91.3) 4 (8.7) 0.0002 CVD 31 20 (64.5) 11 (35.5) < 0.0001 26 (83.9) 5 (16.1) < 0.0001 Fatty liver 5 3 (60.0) 2 (40.0) 0.0457 5 (100.0) 0 (0.0) − Hyperlipidemia 5 4 (80.0) 1 (20.0) 0.2763 5 (100.0) 0 (0.0) − Hyperuricemia 2 2 (100.0) 0 (0.0) − 2 (100.0) 0 (0.0) − Hypertension + CVD 25 15 (60.0) 10 (40.0) < 0.0001 20 (80.0) 5 (20.0) < 0.0001 Hypertension + T2DM 26 19 (73.1) 7 (26.9) 0.0031 24 (92.3) 2 (7.7) 0.0577 CVD + T2DM 5 4 (80.0) 1 (20.0) 0.2763 5 (100.0) 0 (0.0) − Hypertension+ CVD + T2DM 12 8 (66.7) 4 (33.3) 0.0092 12 (100.0) 0 (0.0) − Comorbidity of non-cardiometabolic disease Other lung diseases 15 9 (60.0) 6 (40.0) < 0.0001 14 (93.3) 1 (6.7) 0.1969 Allergic diseases 4 1 (25.0) 3 (75.0) 0.0017 4 (100.0) 0 (0.0) − Hepatitis B 16 15 (93.8) 1 (6.3) 0.8563 16 (100.0) 0 (0.0) − Pulmonary tuberculosis 6 5 (83.3) 1 (16.7) 0.3067 6 (100.0) 0 (0.0) − Electrolyte disturbance 11 6 (54.6) 5 (45.5) < 0.0001 9 (81.8) 2 (18.2) 0.0115 Abnormal liver/kidney function 2 1 (50.0) 1 (50.0) 0.1398 2 (100.0) 0 (0.0) − Depression 3 3 (100.0) 0 (0.0) − 3 (100.0) 0 (0.0) − Note.T2DM, type 2 diabetes; CVD, cardiovascular disease. In addition, 1,109 (95.6%) patients received treatment with combination of Chinese and Western medicine during hospitalization, 1,012 (91.3%) patients received Qingfei Paidu decoction of Chinese medicine, and 25 (2.4%) had unfavorable outcomes. However, 2.7% of unfavorable outcomes among all patients.
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Compared with patients with no comorbidities, patients with any comorbidity had > 3-fold higher odds of being severely ill ( OR, 3.55; 95% CI, 1.94–6.50) and having unfavorable outcomes (3.65, 2.23–5.98). Patients with hypertension, T2DM, and CVD (either heart diseases or stroke) had higher odds of being severely ill, with OR (95% CI) of 3.40 (1.70, 6.80), 3.36 (1.95, 5.77), and 3.65 (2.21, 6.03), respectively. They were also more likely to have unfavorable treatment outcomes, with OR (95% CI) of 2.34 (1.44, 3.80), 4.12 (2.20, 7.72), and 4.45 (2.14, 9.26), respectively. Patients with fatty liver disease and hyperlipidemia also had an increased odd of being severely ill, although their 95% CI spanned one (Table 3).
Table 3. The odds ratio and 95% confidence interval (OR, 95% CI) between comorbidities and clinical severity and treatment outcome of COVID-19: components were overlapped
Variables Severe illness* Unfavorable outcome† Unadjusted OR Adjusted OR Unadjusted OR Adjusted OR No comorbidity at all Ref Ref Ref Ref Had any comorbidity 4.94 (2.91, 8.39) 3.55 (1.94, 6.50) 4.82 (2.77, 8.40) 3.65 (2.23, 5.98) Comorbidity of cardiometabolic disease Hypertension 4.75 (2.61, 8.66) 3.40 (1.70, 6.80) 3.69 (2.18, 6.26) 2.34 (1.44, 3.80) T2DM 4.59 (2.72, 7.74) 3.36 (1.95, 5.77) 5.31 (2.90, 9.72) 4.12 (2.20, 7.72) Heart disease 8.16 (4.86, 13.71) 4.24 (2.36, 7.62) 15.03 (9.85, 22.92) 6.31 (3.63, 10.98) Stroke 4.14 (1.60, 10.70) 3.44 (1.22, 9.66) 6.68 (2.00, 22.34) 1.84 (0.33, 10.23) CVD (either heart disease or stroke) 6.87 (4.28, 11.05) 3.65 (2.21, 6.03) 11.66 (8.17, 16.64) 4.45 (2.14, 9.26) Fatty liver 4.14 (0.95, 18.15) 3.41 (0.91, 12.75) − − Hyperlipidemia 3.55 (1.67, 7.56) 1.76 (0.97, 3.20) − − Hyperuricemia 2.07 (0.17, 25.61) 1.31 (0.1, 17.63) − − Had hypertension and T2DM together 5.06 (2.61, 9.84) 3.01 (1.19, 7.62) 4.08 (1.13, 14.76) 2.51 (0.71, 8.86) Had hypertension and CVD together 7.56 (3.76, 15.23) 4.52 (2.59, 7.87) 11.48 (4.90, 26.87) 3.96 (0.98, 16.02) Had CVD and T2DM together 5.18 (1.07, 25.00) 3.93 (0.97, 15.94) − − Had hypertension, CVD and T2DM together 6.21 (1.38, 27.90) 4.0 (1.22, 13.16) − − Comorbidity of non-Cardiometabolic disease Other lung diseases 9.94 (6.61, 14.96) 4.96 (2.51, 9.80) 2.83 (0.57, 14.13) 2.11 (0.46, 9.80) Allergic diseases − − − − Hepatitis B 1.13 (0.63, 2.03) 0.83 (0.51, 1.37) − − Pulmonary tuberculosis 3.55 (2.19, 5.76) 2.89 (1.85, 4.54) − − Electrolyte disturbance 15.98 (4.41, 57.95) 15.33 (3.54, 66.40) 15.59 (4.80, 50.66) 12.49 (5.52, 28.28) Abnormal liver/kidney function 11.05 (3.68, 33.18) 6.83 (1.44, 32.48) 9.79 (2.29, 41.89) 7.69 (2.01, 29.41) Depression − − − − Note. *Patients who were diagnosed as non-severe were used as reference group.
†Patients who had favorable outcome at end of follow-up window were used as reference group.
T2DM, type 2 diabetes; CVD, cardiovascular disease.
A short dash ‘−’ was used when there was no statistical power to estimate the association.In terms of non-cardiometabolic disease, other lung diseases (4.96, 2.51–9.80), tuberculosis (2.89, 1.85–4.54), electrolyte imbalance (15.33, 3.54–66.40), and abnormal liver/kidney function (6.83, 1.44–32.48) were linked to elevated odds of having severe illness. The latter two also had higher odds of having unfavorable treatment outcomes, with OR (95% CI) of 12.49 (5.52, 28.28) and 7.69 (2.01, 29.41), respectively (Table 3). The ORs (95% CI) between allergic diseases, hepatitis B, tuberculosis, depression, and treatment outcome were not reported due to due to the small number of patients with these morbidities.
After the associations of un-overlapped components with severity and treatment outcomes were analyzed, hypertension (2.87, 1.30–6.32), T2DM (3.57, 2.32–5.49), CVD (3.78, 1.81–7.89), fatty liver disease (7.53, 1.96–28.96), hyperlipidemia (2.15, 1.26–3.67), other lung diseases (6.00, 3.01–11.96), and electrolyte imbalance (10.40, 3.00–26.10) were independently linked to increased odds of severe illness. T2DM (6.07, 2.89–12.75), CVD (8.47, 6.03–11.89), and electrolyte imbalance (19.44, 11.47–32.96) were also strong predictors of unfavorable outcomes (Table 4).
Table 4. The odds ratio and 95% confidence interval (OR, 95% CI) of comorbidities with clinical severity and treatment outcome of COVID-19: components were un-overlapped
Variables Severe illness* Unfavorable outcome† Unadjusted OR Adjusted OR Unadjusted OR Adjusted OR No comorbidity at all Ref Ref Ref Ref Comorbidity of cardiometabolic disease Hypertension 4.10 (2.04, 8.23) 2.87 (1.30, 6.32) 1.19 (0.36, 4.00) 0.93 (0.27, 3.22) T2DM 4.39 (2.79, 6.90) 3.57 (2.32, 5.49) 7.00 (3.58, 13.69) 6.07 (2.89, 12.75) CVD (either heart disease or stroke) 6.83 (3.31, 14.12) 3.78 (1.81, 7.89) 14.13 (6.72, 29.70) 8.47 (6.03, 11.89) Fatty liver 8.28 (2.02, 33.97) 7.53 (1.96, 28.96) − − Hyperlipidemia 3.11 (1.60, 6.02) 2.15 (1.26, 3.67) − − Hyperuricemia − − − − Had hypertension and T2DM together 4.58 (1.88, 11.13) 3.04 (0.91, 10.20) 6.12 (1.42, 26.45) 4.73 (0.88, 25.37) Had hypertension and CVD together 8.28 (3.31, 20.74) 4.65 (2.00, 10.81) 18.36 (7.01, 48.11) 9.90 (3.24, 30.25) Had CVD and T2DM together 3.11 (0.42, 23.02) 1.96 (0.35, 11.13) − − Had hypertension, CVD and T2DM together 6.21 (1.38, 28.06) 3.69 (0.86, 15.79) − − Comorbidity of non-Cardiometabolic disease Other lung diseases 8.28 (4.88, 14.07) 6.00 (3.01, 11.96) 5.25 (1.1, 25.02) 3.89 (0.67, 22.61) Allergic diseases Hepatitis B 0.80 (0.30, 2.00) 0.80 (0.30, 2.35) − − Pulmonary tuberculosis 2.50 (0.60, 9.90) 1.90 (0.68, 5.08) − − Electrolyte disturbance 12.80 (5.07, 32.23) 10.40 (3.00, 26.10) 16.30 (6.60, 40.20) 19.44 (11.47, 32.96) Abnormal liver/kidney function 12.40 (0.70, 131.90) 10.50 (0.59, 87.34) − − Depression − − − − Note. *Patients who were diagnosed as non-severe were used as reference group.
†Patients who had favorable outcome at end of follow-up window were used as reference group.
T2DM, type 2 diabetes; CVD, cardiovascular disease.
A short dash ‘−’ was used when there was no statistical power to estimate the association. -
Compared with patients with no comorbidities, patients with one, two, three, or more comorbidities had increased odds of being severely ill, with OR (95% CI) of 3.43 (2.06, 5.72), 3.64 (1.07, 11.23), and 5.32 (2.16, 13.10), respectively. They also had elevated odds of having an unfavorable outcome, with OR (95% CI) of 3.00 (1.53, 5.87), 3.81 (1.60, 9.06), and 5.44 (2.48, 11.91), respectively. A dose-response trend was found between the number of comorbidities and the likelihood of being severely ill or having an unfavorable outcome (P < 0.001). Similar results were found when analyses were performed for comorbidities of cardiometabolic diseases or non-cardiometabolic diseases ( Table 5).
Table 5. The odds ratio and 95% confidence interval (OR, 95% CI) between number of comorbidities and clinical severity and treatment outcome
Number of comorbidities Severe case* Unfavorable outcome† Unadjusted OR Adjusted OR Unadjusted OR Adjusted OR Number of any comorbidity 0 Ref Ref Ref Ref 1 4.59 (2.80, 7.50) 3.43 (2.06, 5.72) 4.04 (2.08, 7.87) 3.00 (1.53, 5.87) 2 5.06 (2.00, 12.83) 3.64 (1.07, 11.23) 5.72 (2.04, 16.04) 3.81 (1.60, 9.06) 3 or more 8.04 (2.69, 24.07) 5.32 (2.16, 13.10) 8.82 (2.44, 31.89) 5.44 (2.48, 11.91) P -value for trend < 0.0001 < 0.0001 Number of cardiometabolic disease 0 Ref Ref Ref Ref 1 4.33 (2.72, 6.90) 3.10 (1.86, 5.16) 3.91 (2.02, 7.57) 2.81 (1.39, 5.68) 2 5.06 (2.02, 12.67) 3.31 (1.17, 9.41) 6.30 (2.35, 16.85) 4.24 (1.82, 9.91) 3 or more 8.04 (2.69, 24.07) 4.54 (1.57, 13.16) 8.82 (2.44, 31.90) 5.01 (2.61, 9.64) P-value for trend < 0.0001 < 0.0001 Number of non-cardiometabolic disease 0 Ref Ref Ref Ref 1 5.48 (2.36, 12.76) 5.00 (2.16, 11.59) 4.79 (1.57, 14.66) 3.85 (1.39, 10.66) 2 or more 8.75 (3.86, 18.84) 4.94 (2.02, 12.05) 5.13 (2.67, 9.86) 2.93 (1.41, 6.09) Note. *Patients who were diagnosed as non-severe were used as reference group.
†Patients who had favorable outcome at end of follow-up window were used as reference group. -
Women with comorbidities (OR, 5.46; 95% CI, 3.25–9.19) had higher odds of being severely ill than men with comorbidities did (2.46, 1.15–5.28), while men (6.58, 1.46–29.64) with comorbidities had a higher likelihood of having an unfavorable outcome than women did (2.38, 1.78–3.19). In patients aged > 60 years, CVD was highly associated with an unfavorable outcome (5.39, 1.74–16.68), and in patients aged < 60 years, T2DM was strongly correlated with unfavorable outcomes (8.03, 2.26–28.55) ( Table 6).
Table 6. The odds ratio and 95% confidence interval (OR, 95% CI) between types of comorbidities and clinical severity and treatment outcome by gender and age
Variables Gender Age Male Female < 60 ≥ 60 Being diagnosed as severe illness* No comorbidity at all Ref Ref Ref Ref Any comorbidity 2.46 (1.15, 5.28) 5.46 (3.25, 9.19) 3.54 (1.76, 7.13) 3.26 (1.56, 6.78) Hypertension 2.12 (0.84, 5.31) 5.40 (2.98, 9.80) 3.31 (1.32, 8.32) 3.05 (1.33, 7.00) T2DM 1.92 (0.87, 4.23) 5.86 (3.53, 9.75) 2.47 (1.69, 3.61) 3.95 (1.43, 10.89) CVD 1.94 (0.82, 4.58) 4.75 (2.49, 9.05) 1.57 (0.74, 3.37) 4.25 (2.26, 8.00) Having unfavorable outcome† No comorbidity at all Ref Ref Ref Ref Any comorbidity 6.58 (1.46, 29.64) 2.38 (1.78, 3.19) 4.63 (1.40, 15.27) 2.79 (1.25, 6.21) Hypertension 3.28 (0.58, 18.53) 2.11 (1.25, 3.56) 3.31 (0.76, 14.47) 2.35 (0.85, 6.54) T2DM 10.38 (2.62, 41.17) 2.72 (1.38, 5.35) 8.03 (2.26, 28.55) 1.85 (0.49, 6.92) CVD 3.75 (1.54, 9.12) 4.97 (1.89, 13.06) 3.21 (1.19, 8.65) 5.39 (1.74, 16.68) Note.*Patients who were diagnosed as non-severe were used as reference group.
†Patients who had favorable outcome at end of follow-up window were used as reference group.
T2DM, type 2 diabetes; CVD, cardiovascular disease.
doi: 10.3967/bes2020.123
Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China
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Abstract:
Objective Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients’ medical records. Multivariable logistic regression models were used to estimate the odds ratio (OR) and 95% confidence interval (95% CI) of the associations between comorbidities (cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19. Results Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30–6.32), type 2 diabetes (T2DM) (3.57, 2.32–5.49), cardiovascular disease (CVD) (3.78, 1.81–7.89), fatty liver disease (7.53, 1.96–28.96), hyperlipidemia (2.15, 1.26–3.67), other lung diseases (6.00, 3.01–11.96), and electrolyte imbalance (10.40, 3.00–26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89–12.75), CVD (8.47, 6.03–11.89), and electrolyte imbalance (19.44, 11.47–32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25–9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46–29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes. -
Key words:
- Comorbidities /
- COVID-19 /
- Severity /
- Gender /
- Age /
- Treatment outcome
注释: -
Table 1. Characteristics of patients by clinical severity, treatment outcome and having comorbidity or not
Variables n(%) Clinical severity Treatment outcome Comorbidity or not Non-severe
cases (%)
(n = 1,002)Severe
cases (%)
(n = 158)Favorable
outcome (%)
(n= 1,128)Unfavorable
outcome (%)
(n = 32)No (%)
(n = 819)Yes (%)
(n= 341)Sex Male 606 (52.2) 519 (85.6) 87 (14.4) 594 (98.0) 12 (2.0) 412 (68.0) 194 (32.0) Female 554 (47.8) 483 (87.2) 71 (12.8) 534 (96.4) 20 (3.6) 407 (73.5) 147 (26.5) Age, median (Q1, Q3) 46.0
(33.0, 57.0)44.0
(32.0, 55.0)57.0
(45.0, 67.0)46.0
(32.0, 56.0)60.0
(46.0, 71.0)40.0
(30.0, 51.0)56.0
(48.0, 65.0)Age (categorized) < 60 917 (79.1) 828 (90.3) 89 (9.7) 901 (98.3) 16 (1.7) 717 (78.2) 200 (21.8) ≥ 60 243 (20.9) 174 (71.6) 69 (28.4) 227 (93.4) 16 (6.6) 102 (42.0) 141 (58.0) BMI, Mean (SD) 23.8 (3.4) 23.6 (3.3) 24.9 (3.7) 23.8 (3.4) 24.0 (3.2) 23.5 (3.3) 24.6 (3.4) Onset symptoms Fever No 641 (55.3) 575 (89.7) 66 (10.3) 631 (98.4) 10 (1.6) 462 (72.1) 179 (27.9) Yes 519 (44.7) 427 (82.3) 92 (17.7) 497 (95.8) 22 (4.2) 357 (68.8) 162 (31.2) Fatigue No 841 (72.5) 752 (89.4) 89 (10.6) 822 (97.7) 19 (2.3) 609 (72.4) 232 (27.6) Yes 319 (27.5) 250 (78.4) 69 (21.6) 306 (95.9) 13 (4.1) 210 (65.8) 109 (34.2) Cough No 582 (50.2) 533 (91.6) 49 (8.4) 573 (98.5) 9 (1.6) 424 (72.9) 158 (27.2) Yes 578 (49.8) 469 (81.1) 109 (18.9) 555 (96.0) 23 (4) 395 (68.3) 183 (31.7) Congestion or runny nose No 1126 (97.1) 973 (86.4) 153 (13.6) 1,096 (97.3) 30 (2.7) 780 (70.1) 332 (29.9) Yes 34 (2.9) 29 (85.3) 5 (14.7) 32 (94.1) 2 (5.9) 39 (81.3) 9 (18.8) Anorexia No 1,032 (89.0) 909 (88.1) 123 (11.9) 1,010 (97.9) 22 (2.1) 737 (71.4) 295 (28.6) Yes 128 (11.0) 93 (72.7) 35 (27.3) 118 (92.2) 10 (7.8) 82 (64.1) 46 (35.9) Sore throat No 1,046 (90.2) 895 (85.6) 151 (14.4) 1,014 (96.9) 32 (3.1) 734 (70.2) 312 (29.8) Yes 114 (9.8) 107 (93.9) 7 (6.1) 114 (100) 0 (0.0) 85 (74.6) 29 (25.4) Diarrhea No 1,113 (95.9) 963 (86.5) 150 (13.5) 1,084 (97.4) 29 (2.6) 787 (70.7) 326 (29.3) Yes 47 (4.1) 39 (83) 8 (17.0) 44 (93.6) 3 (6.4) 32 (68.1) 15 (31.9) Shortness of breath No 1,027 (88.5) 917 (89.3) 110 (10.7) 1,004 (97.8) 23 (2.2) 735 (71.6) 292 (28.4) Yes 133 (11.5) 85 (63.9) 48 (36.1) 124 (93.2) 9 (6.8) 84 (63.2) 49 (36.8) Chills No 1,095 (94.4) 951 (86.9) 144 (13.2) 1,065 (97.3) 30 (2.7) 780 (71.2) 315 (28.8) Yes 65 (5.6) 51 (78.5) 14 (21.5) 63 (96.9) 2 (3.1) 39 (60.0) 26 (40.0) Ever went to Wuhan city No 658 (56.7) 572 (86.9) 86 (13.1) 636 (96.7) 22 (3.3) 450 (68.4) 208 (31.6) Yes 322 (27.8) 287 (89.1) 35 (10.9) 315 (97.8) 7 (2.2) 235 (73.0) 87 (27.0) Note.Q1, the first quartile; Q3, the third quartile; SD, standard deviation. Table 2. Distribution of clinical severity and treatment outcome of COVID-19 by component and number of comorbidities
Variables n(%) Clinical severity Treatment outcome Non-severe
cases (%)Severe
cases (%)P value* Favorable
outcome (%)Unfavorable
outcome (%)P value* No comorbidity at all 819 (70.6) 758 (92.6) 61 (7.4) 808 (98.7) 11 (1.3) Had any comorbidity 341 (29.4) 244 (71.6) 97 (28.4) < 0.0001 320 (93.8) 21 (6.2) < 0.0001 Comorbidity of cardiometabolic diseases Hypertension 188 (16.2) 136 (72.3) 52 (27.7) < 0.0001 179 (95.2) 9 (4.8) 0.0023 T2DM 89 (7.7) 65 (73.0) 24 (27.0) < 0.0001 83 (93.3) 6 (6.7) 0.0004 Heart disease 53 (4.6) 32 (60.4) 21 (39.6) < 0.0001 44 (83.0) 9 (17.0) < 0.0001 Stroke 24 (2.1) 18 (75.0) 6 (25.0) 0.0017 22 (91.7) 2 (8.3) 0.0501 CVD (either heart disease or stroke) 73 (6.3) 47 (64.4) 26 (35.6) < 0.0001 63 (86.3) 10 (13.7) < 0.0001 Fatty liver 8 (0.7) 6 (75.0) 2 (25.0) 0.0626 8 (100.0) − − Hyperlipidemia 9 (0.8) 7 (77.8) 2 (22.2) 0.0964 9 (100.0) − − Hyperuricemia 7 (0.6) 6 (85.7) 1 (14.3) 0.4220 6 (85.7) 1 (14.3) 0.0977 Had hypertension and T2DM together 38 (3.3) 27 (71.1) 11 (28.9) < 0.0001 36 (94.7) 2 (5.3) 0.1098 Had hypertension and CVD together 37 (3.2) 23 (62.2) 14 (37.8) < 0.0001 32 (86.5) 5 (13.5) < 0.0001 Had CVD and T2DM together 17 (1.5) 12 (70.6) 5 (29.4) 0.0009 17 (100.0) − − Had hypertension, CVD and T2DM together 12 (1.0) 8 (66.7) 4 (33.3) 0.0009 12 (100.0) − − Comorbidity of non-cardiometabolic disease Other lung diseases 27 (2.3) 15 (55.6) 12 (44.4) < 0.0001 26 (96.3) 1 (3.7) 0.3242 Allergic diseases 7 (0.6) 1 (14.3) 6 (85.7) < 0.0001 7 (100.0) − − Hepatitis B 24 (2.1) 22 (91.7) 2 (8.3) 0.8709 24 (100.0) − − Pulmonary tuberculosis 9 (0.8) 7 (77.8) 2 (22.2) 0.0964 9 (100.0) − − Electrolyte disturbance 16 (1.4) 7 (43.8) 9 (56.3) < 0.0001 12 (75.0) 4 (25.0) 0.0001 Abnormal liver or kidney function 17 (1.5) 9 (52.9) 8 (47.1) < 0.0001 15 (88.2) 2 (11.8) 0.0266 Depression 6 (0.5) 5 (83.3) 1 (16.7) 0.3751 6 (100) − − Number of any comorbidity 0 819 (70.6) 758 (92.6) 61 (7.5) 808 (98.7) 11 (1.3) 1 230 (19.8) 168 (73.0) 62 (27.0) < 0.0001 218 (94.8) 12 (5.2) < 0.0001 2 83 (7.2) 59 (71.1) 24 (28.9) 77 (92.8) 6 (7.2) 3 28 (2.4) 17 (60.7) 11 (39.3) 25 (89.3) 3 (10.7) Note. T2DM, type 2 diabetes; CVD, cardiovascular disease. *P values were calculated by comparing the distribution of severity and treatment outcome in patients with no comorbidity at all group. S1. Distribution of clinical severity and treatment outcome of COVID-19 by component and number of comorbidities (un-overlapped)
Variables n (%) Clinical severity Treatment outcome Non-severe
casesSevere
casesP value Favorable
outcomeUnfavorable
outcomeP value No comorbidity at all 819 758 (92.6) 61 (7.5) 808 (98.7) 11 (1.3) Comorbidity of cardiometabolic diseases Hypertension 125 94 (75.2) 31 (24.8) < 0.0001 123 (98.4) 2 (1.6) 0.6863 T2DM 46 34 (73.9) 12 (26.1) < 0.0001 42 (91.3) 4 (8.7) 0.0002 CVD 31 20 (64.5) 11 (35.5) < 0.0001 26 (83.9) 5 (16.1) < 0.0001 Fatty liver 5 3 (60.0) 2 (40.0) 0.0457 5 (100.0) 0 (0.0) − Hyperlipidemia 5 4 (80.0) 1 (20.0) 0.2763 5 (100.0) 0 (0.0) − Hyperuricemia 2 2 (100.0) 0 (0.0) − 2 (100.0) 0 (0.0) − Hypertension + CVD 25 15 (60.0) 10 (40.0) < 0.0001 20 (80.0) 5 (20.0) < 0.0001 Hypertension + T2DM 26 19 (73.1) 7 (26.9) 0.0031 24 (92.3) 2 (7.7) 0.0577 CVD + T2DM 5 4 (80.0) 1 (20.0) 0.2763 5 (100.0) 0 (0.0) − Hypertension+ CVD + T2DM 12 8 (66.7) 4 (33.3) 0.0092 12 (100.0) 0 (0.0) − Comorbidity of non-cardiometabolic disease Other lung diseases 15 9 (60.0) 6 (40.0) < 0.0001 14 (93.3) 1 (6.7) 0.1969 Allergic diseases 4 1 (25.0) 3 (75.0) 0.0017 4 (100.0) 0 (0.0) − Hepatitis B 16 15 (93.8) 1 (6.3) 0.8563 16 (100.0) 0 (0.0) − Pulmonary tuberculosis 6 5 (83.3) 1 (16.7) 0.3067 6 (100.0) 0 (0.0) − Electrolyte disturbance 11 6 (54.6) 5 (45.5) < 0.0001 9 (81.8) 2 (18.2) 0.0115 Abnormal liver/kidney function 2 1 (50.0) 1 (50.0) 0.1398 2 (100.0) 0 (0.0) − Depression 3 3 (100.0) 0 (0.0) − 3 (100.0) 0 (0.0) − Note.T2DM, type 2 diabetes; CVD, cardiovascular disease. Table 3. The odds ratio and 95% confidence interval (OR, 95% CI) between comorbidities and clinical severity and treatment outcome of COVID-19: components were overlapped
Variables Severe illness* Unfavorable outcome† Unadjusted OR Adjusted OR Unadjusted OR Adjusted OR No comorbidity at all Ref Ref Ref Ref Had any comorbidity 4.94 (2.91, 8.39) 3.55 (1.94, 6.50) 4.82 (2.77, 8.40) 3.65 (2.23, 5.98) Comorbidity of cardiometabolic disease Hypertension 4.75 (2.61, 8.66) 3.40 (1.70, 6.80) 3.69 (2.18, 6.26) 2.34 (1.44, 3.80) T2DM 4.59 (2.72, 7.74) 3.36 (1.95, 5.77) 5.31 (2.90, 9.72) 4.12 (2.20, 7.72) Heart disease 8.16 (4.86, 13.71) 4.24 (2.36, 7.62) 15.03 (9.85, 22.92) 6.31 (3.63, 10.98) Stroke 4.14 (1.60, 10.70) 3.44 (1.22, 9.66) 6.68 (2.00, 22.34) 1.84 (0.33, 10.23) CVD (either heart disease or stroke) 6.87 (4.28, 11.05) 3.65 (2.21, 6.03) 11.66 (8.17, 16.64) 4.45 (2.14, 9.26) Fatty liver 4.14 (0.95, 18.15) 3.41 (0.91, 12.75) − − Hyperlipidemia 3.55 (1.67, 7.56) 1.76 (0.97, 3.20) − − Hyperuricemia 2.07 (0.17, 25.61) 1.31 (0.1, 17.63) − − Had hypertension and T2DM together 5.06 (2.61, 9.84) 3.01 (1.19, 7.62) 4.08 (1.13, 14.76) 2.51 (0.71, 8.86) Had hypertension and CVD together 7.56 (3.76, 15.23) 4.52 (2.59, 7.87) 11.48 (4.90, 26.87) 3.96 (0.98, 16.02) Had CVD and T2DM together 5.18 (1.07, 25.00) 3.93 (0.97, 15.94) − − Had hypertension, CVD and T2DM together 6.21 (1.38, 27.90) 4.0 (1.22, 13.16) − − Comorbidity of non-Cardiometabolic disease Other lung diseases 9.94 (6.61, 14.96) 4.96 (2.51, 9.80) 2.83 (0.57, 14.13) 2.11 (0.46, 9.80) Allergic diseases − − − − Hepatitis B 1.13 (0.63, 2.03) 0.83 (0.51, 1.37) − − Pulmonary tuberculosis 3.55 (2.19, 5.76) 2.89 (1.85, 4.54) − − Electrolyte disturbance 15.98 (4.41, 57.95) 15.33 (3.54, 66.40) 15.59 (4.80, 50.66) 12.49 (5.52, 28.28) Abnormal liver/kidney function 11.05 (3.68, 33.18) 6.83 (1.44, 32.48) 9.79 (2.29, 41.89) 7.69 (2.01, 29.41) Depression − − − − Note. *Patients who were diagnosed as non-severe were used as reference group.
†Patients who had favorable outcome at end of follow-up window were used as reference group.
T2DM, type 2 diabetes; CVD, cardiovascular disease.
A short dash ‘−’ was used when there was no statistical power to estimate the association.Table 4. The odds ratio and 95% confidence interval (OR, 95% CI) of comorbidities with clinical severity and treatment outcome of COVID-19: components were un-overlapped
Variables Severe illness* Unfavorable outcome† Unadjusted OR Adjusted OR Unadjusted OR Adjusted OR No comorbidity at all Ref Ref Ref Ref Comorbidity of cardiometabolic disease Hypertension 4.10 (2.04, 8.23) 2.87 (1.30, 6.32) 1.19 (0.36, 4.00) 0.93 (0.27, 3.22) T2DM 4.39 (2.79, 6.90) 3.57 (2.32, 5.49) 7.00 (3.58, 13.69) 6.07 (2.89, 12.75) CVD (either heart disease or stroke) 6.83 (3.31, 14.12) 3.78 (1.81, 7.89) 14.13 (6.72, 29.70) 8.47 (6.03, 11.89) Fatty liver 8.28 (2.02, 33.97) 7.53 (1.96, 28.96) − − Hyperlipidemia 3.11 (1.60, 6.02) 2.15 (1.26, 3.67) − − Hyperuricemia − − − − Had hypertension and T2DM together 4.58 (1.88, 11.13) 3.04 (0.91, 10.20) 6.12 (1.42, 26.45) 4.73 (0.88, 25.37) Had hypertension and CVD together 8.28 (3.31, 20.74) 4.65 (2.00, 10.81) 18.36 (7.01, 48.11) 9.90 (3.24, 30.25) Had CVD and T2DM together 3.11 (0.42, 23.02) 1.96 (0.35, 11.13) − − Had hypertension, CVD and T2DM together 6.21 (1.38, 28.06) 3.69 (0.86, 15.79) − − Comorbidity of non-Cardiometabolic disease Other lung diseases 8.28 (4.88, 14.07) 6.00 (3.01, 11.96) 5.25 (1.1, 25.02) 3.89 (0.67, 22.61) Allergic diseases Hepatitis B 0.80 (0.30, 2.00) 0.80 (0.30, 2.35) − − Pulmonary tuberculosis 2.50 (0.60, 9.90) 1.90 (0.68, 5.08) − − Electrolyte disturbance 12.80 (5.07, 32.23) 10.40 (3.00, 26.10) 16.30 (6.60, 40.20) 19.44 (11.47, 32.96) Abnormal liver/kidney function 12.40 (0.70, 131.90) 10.50 (0.59, 87.34) − − Depression − − − − Note. *Patients who were diagnosed as non-severe were used as reference group.
†Patients who had favorable outcome at end of follow-up window were used as reference group.
T2DM, type 2 diabetes; CVD, cardiovascular disease.
A short dash ‘−’ was used when there was no statistical power to estimate the association.Table 5. The odds ratio and 95% confidence interval (OR, 95% CI) between number of comorbidities and clinical severity and treatment outcome
Number of comorbidities Severe case* Unfavorable outcome† Unadjusted OR Adjusted OR Unadjusted OR Adjusted OR Number of any comorbidity 0 Ref Ref Ref Ref 1 4.59 (2.80, 7.50) 3.43 (2.06, 5.72) 4.04 (2.08, 7.87) 3.00 (1.53, 5.87) 2 5.06 (2.00, 12.83) 3.64 (1.07, 11.23) 5.72 (2.04, 16.04) 3.81 (1.60, 9.06) 3 or more 8.04 (2.69, 24.07) 5.32 (2.16, 13.10) 8.82 (2.44, 31.89) 5.44 (2.48, 11.91) P -value for trend < 0.0001 < 0.0001 Number of cardiometabolic disease 0 Ref Ref Ref Ref 1 4.33 (2.72, 6.90) 3.10 (1.86, 5.16) 3.91 (2.02, 7.57) 2.81 (1.39, 5.68) 2 5.06 (2.02, 12.67) 3.31 (1.17, 9.41) 6.30 (2.35, 16.85) 4.24 (1.82, 9.91) 3 or more 8.04 (2.69, 24.07) 4.54 (1.57, 13.16) 8.82 (2.44, 31.90) 5.01 (2.61, 9.64) P-value for trend < 0.0001 < 0.0001 Number of non-cardiometabolic disease 0 Ref Ref Ref Ref 1 5.48 (2.36, 12.76) 5.00 (2.16, 11.59) 4.79 (1.57, 14.66) 3.85 (1.39, 10.66) 2 or more 8.75 (3.86, 18.84) 4.94 (2.02, 12.05) 5.13 (2.67, 9.86) 2.93 (1.41, 6.09) Note. *Patients who were diagnosed as non-severe were used as reference group.
†Patients who had favorable outcome at end of follow-up window were used as reference group.Table 6. The odds ratio and 95% confidence interval (OR, 95% CI) between types of comorbidities and clinical severity and treatment outcome by gender and age
Variables Gender Age Male Female < 60 ≥ 60 Being diagnosed as severe illness* No comorbidity at all Ref Ref Ref Ref Any comorbidity 2.46 (1.15, 5.28) 5.46 (3.25, 9.19) 3.54 (1.76, 7.13) 3.26 (1.56, 6.78) Hypertension 2.12 (0.84, 5.31) 5.40 (2.98, 9.80) 3.31 (1.32, 8.32) 3.05 (1.33, 7.00) T2DM 1.92 (0.87, 4.23) 5.86 (3.53, 9.75) 2.47 (1.69, 3.61) 3.95 (1.43, 10.89) CVD 1.94 (0.82, 4.58) 4.75 (2.49, 9.05) 1.57 (0.74, 3.37) 4.25 (2.26, 8.00) Having unfavorable outcome† No comorbidity at all Ref Ref Ref Ref Any comorbidity 6.58 (1.46, 29.64) 2.38 (1.78, 3.19) 4.63 (1.40, 15.27) 2.79 (1.25, 6.21) Hypertension 3.28 (0.58, 18.53) 2.11 (1.25, 3.56) 3.31 (0.76, 14.47) 2.35 (0.85, 6.54) T2DM 10.38 (2.62, 41.17) 2.72 (1.38, 5.35) 8.03 (2.26, 28.55) 1.85 (0.49, 6.92) CVD 3.75 (1.54, 9.12) 4.97 (1.89, 13.06) 3.21 (1.19, 8.65) 5.39 (1.74, 16.68) Note.*Patients who were diagnosed as non-severe were used as reference group.
†Patients who had favorable outcome at end of follow-up window were used as reference group.
T2DM, type 2 diabetes; CVD, cardiovascular disease.
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