Comparative clinical characteristics among different age group of adult COVID‐19 patients: A multicenter study

1 INTRODUCTION

The current outbreak of coronavirus disease (COVID-19) pandemic that was first reported from Wuhan, China, on December 31, 2019 has developed into a world-wide public health emergency. On February 26th, 2020, the World Health Organization (WHO) announced that the number of new cases of COVID-19 reported outside China had exceeded the number of new cases in China. And then they declared this viral disease a pandemic on March 11, 2020. Globally, as of 17th July 2021, there have been 188,655,968 confirmed cases of COVID-19, including 4,067,517 deaths, reported to WHO.1 In China, epidemiological evidence suggested that most of these patients had travelled to Wuhan city (Hubei province) before the onset of illness.2 Around China's spring festival in early February, rapidly increasing new cases were identified in Hubei and neighboring provinces and cities. Until 17 July 2021, cumulative reported confirmed cases was 119,614 in China, and cumulative deaths were 5612, while cumulative reported confirmed cases was 1068 in Hunan province.3

Severity assessment is the key to determining patient management, appropriate treatment, and resource allocation in epidemic events. For example, in China's experience, the Fangcang Hospital in Wuhan city is organized to treat large numbers of patients with mild and moderate COVID-19, whereas other facilities with negative-pressure isolation wards and intensive care units (ICU) serve patients with severe and critical COVID-19. Incidence and mortality of community-acquired pneumonia (CAP) is much greater in the elderly (>65 years) than in younger populations.4 Old age itself is an independent risk or prognostic factor for pneumonia.5 More frequent comorbid illness, less specific presenting clinical signs, and lowered effectiveness of therapy in older subjects also add risk.4, 6

Patients of different ages may have distinct physiological characteristics, susceptibility, clinical presentations, and response to medical treatment.7-9 Therefore, age- specific risk factors for disease severity may be useful for clinical management. To the best of our knowledge, there has been no comprehensive study regarding exploration of the associated factor of severe or critical severe type on COVID-19 cases with different age group. We report here findings describing the influence of age on clinical and laboratory features from a cross-sectional study of patients treated for COVID-19 in six University or municipal hospitals in Hubei and Hunan provinces.

2 MATERIALS AND METHODS 2.1 Study participants and procedures

A hospital-based COVID-19 disease surveillance program was established and maintained from December 2019 to March 2020. This included 6 participating hospitals (Affiliated Shaoyang Central Hospital of University of South China, The first Attached Hospital of Shaoyang University, Zhuzhou Central Hospital, Designated Hospital of Junshan District, Xiangtan Central Hospital) from Hunan Province and Puyang District People's Hospital from Hubei Province. We included patients ≥18 years who were positive for coronavirus nucleic acid detection in throat swab at admission. None of the patients were positive for Influenza A or B virus nucleic acid detection in throat swab.

This is a cross-sectional study based on review of medical records. Clinical variables were collected on standardized case report forms at each hospital. The research protocol was approved by the ethics committee of the Second Xiangya Hospital (No. 2020-010) and was approved by all other participating hospitals. We have been obtained oral consent from patients that their medical records could be potentially used for studies in the future. And then the informed consent was waived in this study approved by the ethics committee of the Second Xiangya Hospital.

2.2 Definitions

Patient variables were evaluated for all cases: Demographic characteristics (e.g., age, sex, body mass index); chronic disease history involving the central nervous system, cardiovascular system, lungs, liver, kidneys, endocrine system, autoimmune conditions; initial vital signs (e.g., temperature and respiratory rate), laboratory test results (white blood cell [WBC], lymphocyte [Lym], neutrophil [Neu], platelets [Pt], hemoglobin [Hb], Prothrombin time [PT time], activated partial thromboplastin time [APTT], D-Dimer [DD], albumin, alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatine kinase [CK], creatine kinase isoenzyme [CK-MB], total bilirubin [TBIL], K+, Na+, urea nitrogen [BUN], creatinine [Cre], blood cell sedimentation rate [ESR], Lactate dehydrogenase [LDH], Myoglobin [Mb], Random blood glucose [Glu], C-reactive protein [CRP], Procalcitonin [PCT], chest radiography); and medications. The data on initial vital signs, laboratory examinations and chest imaging results were derived from the intial results of the patients in the hospital.

For epidemiological history, patients with Wuhan travel history were defined as primary cases; patients without Wuhan travel history, but with contact with primary cases or confirmed cases, were defined as secondary cases, the remainder without definite epidemiological linkage were classified as “unknown”.

COVID-19 severity was classified into four categories. Mild: mild clinical symptoms (cough, fatigue, dyspnea) without imaging findings of pneumonia. Moderate: fever (admission temperature ≥39°C and respiratory symptoms with imaging findings of pneumonia. Severe: having any of the following criteria: (1) Respiratory distress with respiratory frequency ≥30 breaths/min; (2) Resting oxygen saturation (SpO2) ≤93% on room air; (3) PaO2/FiO2 ≤300 mmHg (1 mmHg = 0.133 kPa). Critical: having any of the flowing criteria: (1) a respiratory failure in need of mechanical ventilation; (2) shock; (3) with other significant organ dysfunction.10

Outcome was classified as cured and discharged, undergoing treatment in hospital, and deceased in-hospital. Patients were discharged from hospital upon meeting the following criteria: (1) body temperature returned to normal for more than 3 days; (2) Respiratory symptoms improved significantly; (3) Improvement in pulmonary radiographic findings; (4) Two negative throat swabs for coronavirus nucleic acid taken 24 h apart.10

2.3 Statistical analysis

Categorical variables were expressed as counts and percentages. Depending on whether it is normally distributed, continuous variables are expressed as mean ± SD or median, 25–75th interquartile range (IQR). Differences in frequencies were compared using chi-square test or Fisher's exact test. In the comparison of continuous numerical variables in independent groups, the Mann–Whitney U test was used in the case of two groups, whereas nonparametric tests with multiple independent samples corrected by Bonferroni were used three or more groups. Factors with significant (p < .05) unadjusted associations with disease severity and suspected important variables were included in subsequent multivariable logistic regression analysis (Forward method) to determine risk factors associated with disease severity, yielding adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Goodness of-fit was tested using the Hosmer-Lemeshow test [reference]. All statistical tests were two-sided, and p < .05 was considered to be statistically significant. All analyses were performed using IBM SPSS Statistics version 18.0 for Windows (IBM Corp.).

3 RESULTS 3.1 Demographic and clinical characteristics

Of 299 patients, ages ranged from 18 to 88 years with a median of 44 years (IQR: 20), and half of participants were male (Table 1). Half of patients were in the 30–50 years age groups (Figure 1).

Table 1. Baseline clinical characteristics of COVID-19 according to age groups Total <30 ≥30, <40 ≥40, <50 ≥50, <65 ≥65 n = 299 n = 41 n = 75 n = 74 n = 69 n = 40 p value Age (year) 44 (34, 54) 25 (22, 28.5) 34 (32, 37) 45 (42, 47) 54 (52, 59) 74.5 (67, 80) .000** Sex (% male) 158 (53%) 27 (66%) 42 (56%) 43 (58%) 30 (43%) 16 (40%) .061 Weight (kg) 65 (56, 74) 68 (53, 77.5) 65 (54, 75) 66 (58, 75) 64 (60, 70) 59 (50, 61) .043* Height (cm) 164 (158, 170) 170 (160, 175) 166 (160, 172) 168 (158, 170) 160 (156.5, 166.5) 158 (156, 164.5) .000** BMI (kg/m2) 23.38 (21.63, 26.08) 22.34 (20.05, 26.8) 23.13 (20.96, 25.16) 23.63 (22.38, 26.22) 24.06 (22.86, 26.37) 22.21 (20.36, 24.52) .063 Total number of chronic disease 0 (0, 1) 0 (0, 0) 0 (0, 0) 0 (0, 1) 0 (0, 1) 1 (1, 2) .000** Temp (°C) 36.75 (36.5, 37.2) 37 (36.7, 37.3) 36.8 (36.5, 37.2) 36.7 (36.5, 37.23) 36.6 (36.4, 37.1) 36.6 (36.43, 37) .026* HR (min−1) 86 (78, 96) 87.5 (83.5, 100) 82 (76, 95.25) 85 (77.5, 92) 88.5 (82, 98) 90 (78.25, 99) .036* RR (min−1) 20 (20, 20) 20 (18, 20) 20 (19.75, 20) 20 (19.75, 20) 20 (20, 20) 20 (20, 21) .025* Chronic disease 105 (35%) 2 (5%) 12 (16%) 25 (34%) 36 (52%) 30 (75%) .000** DM 35 (12%) 1 (2%) 4 (5%) 7 (9%) 10 (14%) 13 (33%) .000** hypertension 53 (18%) 0 (0%) 2 (3%) 12 (16%) 16 (23%) 23 (58%) .000** Chronic heart disease 14 (5%) 0 (0%) 1 (1%) 2 (3%) 6 (9%) 5 (13%) .013* Chronic pulmonary disease 17 (6%) 1 (2%) 2 (3%) 1 (1%) 9 (13%) 4 (10%) .011* Cancer 5 (2%) 0 (0%) 0 (0%) 2 (3%) 2(3%) 1(3%) .549 Chronic nervous system disease 8 (3%) 0 (0%) 2 (3%) 0 (0%) 4(6%) 2(5%) .147 Chronic liver disease 8 (3%) 0 (0%) 3 (4%) 4 (5%) 1 (1%) 0 (0%) .265 Chronic kidney disease 1 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (3%) .134 Endocrine and immune disease 5 (2%) 0 (0%) 1 (1%) 2 (3%) 1 (1%) 1 (3%) .878 Bilateral involvement on chest radiographs 236 (79%) 25 (61%) 55 (73%) 61 (82%) 59 (86%) 36 (90%) .005** Epidemiological history Primary case 117 (39.13%) 15 (36.59%) 40 (53.33%) 37 (50%) 25 (36.23%) 0 (0%) .000** Secondary case 111 (37.12%) 18 (43.9%) 20 (26.67%) 22 (29.73%) 29 (42.03%) 22 (55%) Unknown case 71 (23.75%) 8 (19.51%) 15 (20%) 15 (20.27%) 15 (21.74%) 18 (45%) Note: *p < .05, **p < .01. Abbreviations: DM, diabetes mellitus; HR, heart rate; RR: respiratory rate; Temp, temperature. image

The distribution of patients in different age group

One-third of participants had one or more chronic disease. The total number of chronic diseases differed significantly (p < .001) between age groups, with elderly have more chronic disease. Older age groups had more patients with at least one or more chronic disease (5%, 16%, 34%, 52%, and 75% in <30, 30–40, 40–50, 50–65, and ≥65 age groups, respectively; p < .001). Older age groups had higher prevalence of diabetes mellitus (DM) history (p < .001) and hypertension history (p < .001), chronic heart disease history (p = .013), and chronic pulmonary disease history (p = .011). Prevalence of bilateral radio graphic pneumonia findings was high in all five age groups (overall, 79%) and was increased significantly with older age (61%, 73%, 82%, 86%, and 90% in <30, 30–40, 40–50, 50–65, and ≥65 age groups, respectively; p = .005). 71 (23.75%) patients could not provide a definite contact or exposure history with confirmed or suspected COVID-19 infection. A total of 53.33% of 30–40 years and 50% of 40–50 years were primary cases, and none of the elderly were primary cases. Percentage of secondary cases were 55% among elderly, 42.03% in 50–65 years and 43.9% in <30 years. Temperature, heart rate, respiratory rate on admission were slightly increased in older age groups (Table 1).

3.2 Symptoms

The most common symptoms were cough in 216 (72%) patients, fever in 202 (68%), expectoration in 139 (46%), fatigue in 117 (39%), dry cough in 77 (26%) and were of comparable prevalence in all age groups. Only dyspnea was significantly different between elderly group and other groups (p = .001) (Figure 2).

image

Symptoms of COVID-19 according to age groups

3.3 Comparison of laboratory testing profile

As shown in Table 2, age ≥65 had significant lower lymphocyte percentage compared to age <30 and age 30–40 (19.25 vs. 32.75, p = .003; 19.25 vs. 29.1, p = .015). Age <30 had significantly higher levels of lymphocyte counts compared to age 30–40, 40–50, 50–65, ≥65 (1.6 vs. 1.2, p = .009; 1.6 vs. 1.15, p = .002; 1.6 vs. 1.29, p = .021; 1.6 vs. 1.06, p < .001). The level of ESR and PCT of age ≥65 were the highest among all groups; these values were higher than level of ESR and PCT of age <30, 30–40, 40–50, and 50–65 with statistically significant differences (p < .001). Age ≥65 had significantly higher levels of CRP compared to age 30–40 (13.9 vs. 5, p = .002). The decrease in lymphocyte count and the increase in ESR and PCT may be attributed to the dysregulation of the immune status and the intensified response to proinflammatory cytokines.

Table 2. Laboratory testing profile of COVID-19 according to age groups Total <30 ≥30, <40 ≥40, <50 ≥50, <65 ≥65 n = 299 n = 41 n = 75 n = 74 n = 69 n = 40 p value WBC (×109) 4.97 (3.86, 6.49) 5.34 (4.18, 7.82) 4.7 (3.64, 5.8) 4.79 (3.62, 5.84) 4.95 (3.97, 6) 5.59 (3.87, 7.73) .151 N (×109) 3.09 (2.32, 4.54) 2.95 (2.16, 4.23) 2.97 (2.31, 3.93) 2.98 (2.29, 3.96) 3.13 (2.34, 4.6) 3.86 (2.4, 6.17) .242 N% 63.9 (56, 72.3) 57.8 (51.6, 66.7) 61.8 (56, 73.8) 65.1 (56.2, 71.9) 64.5 (55.5, 72.38) 69.25 (61.15, 82.53) .006** L (×109) 1.22 (0.84, 1.63) 1.6 (1.23, 2.31) 1.2 (0.8, 1.62) 1.15 (0.85, 1.52) 1.29 (0.87, 1.64) 1.06 (0.63, 1.49) .000** L% 27 (19.3, 35) 32.75 (23.58, 42.93) 29.1 (21.8, 35.4) 26.1 (19.35, 35.95) 27.45 (19.85, 36.35) 19.25 (11.55, 27.6) .003** Hb (g/L) 134 (123, 147.5) 146 (132.25, 158) 140 (129, 150) 141 (129, 152) 126 (119, 138) 122.5 (118, 131) .000** Pt (×109) 206 (161, 253) 245 (195, 273.5) 214 (172, 248) 216.5 (159.25, 259.25) 184 (146.5, 239) 175.5 (144.75, 228.75) .01** PT time (s) 12.3 (11.1, 12.99) 12.6 (10.83, 13.3) 12.3 (10.9, 12.8) 12.34 (11, 13.08) 12.03 (11.07, 12.9) 12.65 (11.73, 13.28) .558 APTT (s) 32.7 (29.1, 37.2) 30.9 (27, 33.69) 34.12 (30.2, 38.14) 32.3 (29.4, 37.03) 33.9 (27.8, 37.1) 31.64 (28.7, 39.66) .189 DD (mg/L) 0.32 (0.2, 0.49) 0.29 (0.13, 0.4) 0.28 (0.18, 0.4) 0.31 (0.2, 0.44) 0.35 (0.2, 0.5) 0.66 (0.4, 1.46) .000** albumin (g/L) 42.25 (38.57, 45.7) 45.36 (42.15, 49) 44 (41.22, 46.7) 42.6 (38.98, 45.72) 40.9 (36.6, 43.7) 36.92 (32.35, 40.4) .000** ALT (U/L) 21.6 (14.95, 35) 19.25 (13.08, 28.9) 22 (15, 38.7) 27 (16.98, 43.1) 22.4 (15, 34.3) 17.85 (12.58, 24.85) .024* AST (U/L) 23 (18.1, 30.8) 21.85 (18.25, 26) 22 (17, 29) 23 (19.68, 32.73) 24 (18, 30.9) 25.3 (19.33, 39.8) .122 CK (U/L) 67.1 (46.08, 103) 72 (51.1, 100) 64 (48.4, 103) 63.5 (43.5, 109.5) 67 (45.5, 96.31) 88.5 (47.48, 145.23) .419 CK-MB (U/L) 8 (2.5, 11.93) 6 (2.5, 9) 9 (2.5, 11.93) 8 (2.5, 10.63) 8 (2.5, 11.8) 11 (4.85, 17) .088 TBIL 11.55 (8.18, 18.49) 11.95 (7.4, 19.78) 11.9 (8.02, 18.43) 10.2 (8.25, 18.6) 13.12 (9.02, 18.78) 10.24 (7.12, 15.23) .528 K (mmol/L) 4.14 (3.79, 4.5) 4.13 (3.75, 4.47) 4.02 (3.75, 4.58) 4.18 (3.8, 4.46) 4.19 (3.81, 4.45) 4.1 (3.9, 4.56) .981 Na (mmol/L) 139.8 (137.8, 141.5) 139.2 (137.95, 142.6) 139.8 (138.4, 141) 139.25 (137.8, 141.03) 140.1 (137.9, 141.87) 139.69 (136.38, 142.45) .747 BUN (mmol/L) 3.95 (3.15, 4.94) 3.82 (3.15, 4.33) 3.7 (2.86, 4.4) 3.7 (3.13, 4.94) 4.34 (3.28, 5.45) 5.12 (3.6, 7.35) .000** Cr (µmol) 67.5 (56, 80) 70.5 (56.1, 81.75) 67 (57.1, 81.5) 69.15 (55.08, 79.38) 64.2 (55.75, 76.7) 71.45 (56.75, 81.8) .562 LDH (U/L) 177.5 (153, 219.25) 169 (147, 209.5) 175 (146.5, 203.75) 187 (160.75, 228.25) 172.5 (148.5, 196.5) 198 (159, 303) .07 Mb (µg/L) 36 (30, 57) 37.35 (30, 43.73) 35 (30, 47.9) 33.5 (30, 52.89) 39 (30, 61.63) 86.25 (41.15, 202.95) .002** Glu (mmol/L) 5.45 (4.95, 6.45) 5.13 (4.9, 5.52) 5.44 (4.75, 6) 5.62 (5.08, 6.94) 5.51 (5.08, 6.83) 5.43 (5.12, 9.31) .229 ESR (mm/h) 20.45 (8, 44.88) 14.5 (6, 39.25) 19.3 (6, 40) 17 (11.25, 39.75) 20 (8, 44.13) 69.8 (30, 85) .000** CRP (mg/L) 5.19 (5, 16.6) 5 (5, 13.62) 5 (2.51, 11.74) 5 (3.69, 18.6) 5.6 (5, 16.61) 13.9 (5, 48.55) .003** PCT (ng/ml) 0.06 (0.05, 0.1) 0.05 (0.03, 0.1) 0.06 (0.05, 0.1) 0.05 (0.05, 0.1) 0.05 (0.05, 0.1) 0.1 (0.07, 0.13) .000** Note: *p < .05, **p < .01. Abbreviations: ALT, alanine aminotransferase; APTT, activated partial thromboplastin time; AST, aspartate aminotransferase; BUN, urea nitrogen; CK, creatine kinase; CK-MB, creatine kinase isoenzyme; Cre, creatinine; CRP, C-reactive protein; DD, D-Dimer; ESR, blood cell sedimentation rate; Glu, random blood glucose; Hb, hemoglobin; L, lymphocyte; LDH, lactate dehydrogenase; Mb, myoglobin; N, neutrophil; PCT, procalcitonin; Pt, platelets; PT, Prothrombin time; TBIL, Total bilirubin; WBC, white blood cell.

Measurements such as BUN (5.12 vs. 3.82, p = .008; 5.12 vs. 3.7, p = .001; 5.12 vs. 3.7, p = .018) and Mb (86.25 vs. 37.35, p = .006; 86.25 vs. 35, p = .007; 86.25 vs. 33.5, p = .004) of age ≥65 were significantly higher than those of age <30, 30–40 and 40–50. In addition, levels of DD of age ≥65 was significantly higher than those of age <30, 30–40 and 40–50 and 50–65 (0.66 vs. 0.29, p < .001; 0.66 vs. 0.28, p < .001; 0.66 vs. 0.31, p < .001; 0.66 vs. 0.35, p < .001). Levels of platelets of age ≥65 and 50–65 was significantly lower than those of age <30 (175.5 vs. 245, p = .037; 184 vs. 245, p = .019) (Table 2 and Figure 3). These changes suggesting potentially heart, kidney and coagulation function damage in the oldest age group. The levels of WBC, N, PT time, APTT, AST, CK, CKMB, TBIL, K, Na, Cr, LDH, and Glu of the groups were not statistically different among different age groups.

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Comparison of Lab tests according to age groups

3.4 Medical treatments and outcomes of COVID-19 among the age groups

80% received Interferon alpha inhalation (239/299), 76% of the patients received Lopinavir/ritonavir (228/299), 57% received Arbidol (169/299), and 52% received Lianhua Qingwen Capsule treatment (Chinese medicine). Combination use of Arbidol, Lopinavir/ritonavir or Interferon alpha inhalation was also common. Empirical antibiotic treatment was used when bacterial infection was suspected, which may reference for elevated Neu, PCT value and sputum. 42% were received antibiotic (126/299). Percentage of corticosteroid (17/57, 43%) and Immunoglobulin (19/56, 48%) treatment was highest in age ≥65 (Table 3).

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