key: cord-0970991-2676aeyd
authors: Sami, Ramin; Karbasi, Maryam; Haji Ahmadi, Somayeh; Mansourian, Marjan; Dehghan, Mehrnegar; Khademi, Nilufar; Eslami, Mohammad Javad; Ghasemi, Khojasteh
title: Age-Dependent Clinical Features and Prognosis of COVID-19 Patients
date: 2021-03-03
journal: Tanaffos
DOI: nan
sha: 6c783ad36b263e9eb445f5c118faf09684b37a56
doc_id: 970991
cord_uid: 2676aeyd

BACKGROUND: The clinical and paraclinical symptoms of COVID-19 differ across age groups. This study investigated the differences between these parameters and their outcomes in young, middle-aged, and elderly patients admitted to a COVID-19 referral center. MATERIALS AND METHODS: This retrospective study encompassed patients with COVID-19 hospitalized at Khorshid Hospital (Isfahan, Iran) during February 23 to April 30, 2020. The patients' predisposing conditions, clinical and paraclinical findings, and outcomes were compared among three young, middle-aged, and elderly groups. RESULTS: Of the 1185 hospitalized patients with suspected COVID-19, 1065 were discharged or died at the end of the study. Among these 1065 patients, 654 patients with the mean age of 57.7 years had positive PCR results or typical CT scans and were included in the study, of whom 77 (11.8%), 353 (54%), and 234 (34.2%) patients were assigned into the young, middle-aged, and elderly groups, respectively. There was no statistically significant difference among the three groups regarding the prevalence of clinical symptoms. Moreover, CRP, ESR, WBC, BUN, Cr, and lymphocytes were higher in the elderly group. The ground-glass opacity (GGO) (24.1%), GGO-consolidation (27.4%), and consolidation (10.3%) were the most common CT scan findings in the young, middle-aged, and elderly groups, respectively. Fifty-three patients (8.1%) died, and the mortality rates were 10.36%, 7.27%, and 3.8% in the elderly, middle-aged, and young groups, respectively. CONCLUSION: COVID 19 symptoms do not depend on age; however, paraclinical findings differ across young, middle-aged, and elderly patients.

The first patient with a definitive diagnosis of COVID-19 was reported in Iran on February 18, 2020 (1) . At the beginning of the pandemic, the symptoms were mainly limited to respiratory tract infection; however, other symptoms such as gastrointestinal, cutaneous, and neurological symptoms gradually emerged (2) .

Age is an important host factor in response to infections (3) . Asymptomatic carriers are mainly observed in the middle-aged group in close contact with the families of the infected (4) . Although an acceptable prognosis is provided for most patients, the elderly with underlying chronic diseases have a poor prognosis (5) . Several studies have examined the symptoms, clinical course, and outcome of COVID-19 (5) ; however, few studies have addressed and compared these variables among different age groups.

The present study examined the demographics, clinical symptoms, paraclinical findings, and outcomes of COVID- 19 in different age groups. Examining the virus behavior in different age groups, the present study aimed to determine the diagnostic key factors leading to the diagnosis of COVID-19 at different age groups. Furthermore, by detecting the predictor factors for fatality among these patients, it is possible to identify high-risk groups and reduce the fatality rate by focusing on their treatment.

In this prospective cohort study, the required data were obtained from patients with COVID-19 admitted to Khorshid Hospital (Isfahan, Iran) during February 23 and April 30, 2020 (6) . All the patients were included in the study when they were either discharged from the hospital or passed away. All patients aged above 18 years, who were hospitalized with clinical symptoms of COVID-19 for more than a night and had positive RT-PCR test results (7) or typical COVID-19 CT scan findings (according to the benchmarks of Society of Radiology) (8) , were included in this study. This study was supported by the Isfahan The clinical data were extracted from the patients' medical history and then recorded. The collected data encompassed demographic information, comorbidity, home medication, clinical symptoms, initial laboratory, CT scan findings, and outcomes (i.e., intubation, admission to ICU, length of stay in ICU, length of stay in the ward, and fatality rate). In this regard, the patients who died immediately after intubation were classified as nonintubated. The primary objective of this study was to compare the clinical and paraclinical symptoms among three young, middle-aged, and elderly groups, and the secondary objective of the research was to evaluate the outcomes in these three groups.

One-way analysis of variance (ANOVA) was applied for continuous variables as means and standard deviations, while categorical variables were compared by chi-squared tests. The Cox proportional hazards model was employed for the classified variables to compare groups of time with event data. The statistically significant hazard ratios were considered in a 95% confidence interval. The linear regression model was adopted for a continuous outcome at p < 0.05 was considered a statistically significant beta coefficient. All the statistical data were processed for analysis and visualization using IBM SPSS software version 26.0 and MS-Excel.

Out of the 1185 patients with suspected COVID-19, 1065 patients were discharged or died. Among the 1065 patients, 654 patients had positive PCR results (N=451) and typical CT-scan findings and were thus included in the study (median age: 57.7 years; range: 18-99 years). Table 1 presents the participants' baseline characteristics. As presented in Table 1 , 77 (11.8%), 353 (54%), and 234 (34.2%) patients were assigned into the young, middle-aged, and elderly groups, respectively. Above 80% of the young patients self-reported that they had been in close contact with the infected individuals; however, the rates were 65.2% and 18.2% for the middle-aged and elderly groups, respectively (p=0.017). The time interval between symptom onset and hospitalization was significantly shorter in the young group than in the middle-aged and elderly groups (p=0.009). Table 2 presents the clinical and paraclinical findings.

As it can be noticed, there are no statistically significant differences in clinical symptoms among the three age groups. Dry coughing was the most common symptom observed in the elderly and middle-aged groups (76.3% and 77.14%, respectively), while fever was the most common symptom in the young group (77.7%). Among the laboratory findings (Table 3 ), significant differences were observed in C-reactive protein (CRP) (p=0.023) and ESR (p=0.001); however, not such a difference was noticed among the three groups in terms of ferritin (p=0.094).

Although the severity of involvement in the CT scans of young patients (6±7.67) was less than that of middle-aged (9.6±5.2) and elderly (9.23±5.67) patients, this difference was not statistically significant among the research groups (p=0.142). Ground-glass opacity (GGO), consolidation, and GGO-consolidation were the most common findings in the elderly (p=0.013), young (p=0.024), and middle-aged (p=0.004) groups, respectively (Table 3) .

Of the 654 patients, 88 persons (13.5%) were admitted to the ICU, 23 persons (5.1%) were intubated, and 53 individuals (8.1%) died ( Table 4 ). The intubation rates in the young, middle-aged, and elderly groups were 2.3%, 1.38%, and 6.4%, respectively (p≤0.001). In the Cox model, the young group was considered the reference group, and the hazard ratio was estimated in comparison with each of the other categories ( Table 5 ). The first model was a raw model for all the outcomes. Although the estimated hazard ratios were not significant, admission to the ICU and fatality rate in the middle-aged group were 29% and 27% higher than those ratios in the young group, respectively. However, the intubation rate in the middle-aged group was 66% less than that in the young group. The hazard ratio of admission to ICU in the middle-aged to young groups was 0.96%. The outcomes of fatality and intubation in the elderly group increased by 0.06% and 0.82%, respectively, compared to the young group. The effect of gender and main variables (in the groups of contact variables, vital symptoms, comorbidities, and biochemistry parameters) on the desired outcome was eliminated in the second to fourth models. Although the results were not significant in the fourth model, the hazard ratios of the length of stay in the hospital were 1.10 and 3.27 in the elderly and middle-aged groups compared to the young group, respectively. Moreover, the hazard ratios of fatality rate in the middle-aged and elderly groups were 1.65 and 2.40 times higher than those in the young group, respectively. The hazard ratio of intubation in the middle-aged group decreased by 25% compared to the young group; however, the difference was not statistically significant. In contrast, as a statistically non-significant finding, the hazard ratio of intubation in the elderly group was 4.8 times higher than that in the young group.

The regression coefficients estimated by the linear regression model for the outcomes of the length of stay at hospital and ICU showed that the length of stay at hospital increased by about half a day with aging in each age group at a statistically significant p-value. On the other hand, the length of stay in ICU decreased by about two days with increasing age in each age group, at a statistically nonsignificant value. These results are reported in Table 5 in the form of four fitted models. The first model did not adjust the effect of any of the variables. In the three other models, the effects of gender and significant variables on contact variables, vital symptoms, comorbidities, and biochemistry parameters were adjusted in the three groups, respectively. (2, (9) (10) (11) (12) . The prevalence of SARS and MERS infections was also higher among men (13, 14) . (15) (16) (17) . Different fever prevalence may be due to differences in the mean ages of the studied population or in the days of fever screening. It can be predicted that the lower prevalence of fever in the elderly due to underlying diseases or weakened immune probably are the nature of the disease and the excessive secretion of inflammatory cytokines (19) .

In this study, some factors providing the grounds for virus transmission were evaluated, which encompassed the house area, being in close contact with the infected, and a history of traveling to areas with a high prevalence of COVID-19. In general, 80% of the young patients reported close contact with infected persons, while only 18% of the elderly had experienced such close contact. Furthermore, the area of the house was larger for the elderly group.

These findings suggest that the elderly are much more prone to infection than the young and middle-aged.

Coronaviruses are usually transmitted through the air or close contact (20) . Our study revealed that about one-third and twothirds of the patients had RR <20 and HR <100

beats/minute at the triage, respectively. This finding is consistent with other studies' findings (9, 21) , implying that normal vital signs do not rule out COVID-19-induced pneumonia at any age. Although the prevalence of hypoxia at the triage was higher in the elderly than in the other groups, the difference was not statistically significant.

According to the findings of our study, in all three age groups, among the vital signs, RR and sataO2 were the most sensitive criteria for suspected COVID-19 patients with pulmonary involvement.

In our patients, the average number of WBCs was significantly higher in the elderly than in other groups;

however, leukocytosis was prevalent in none of the study group. Unlike Liu's et al. study (16) , the present study concluded that the prevalence of lymphopenia was higher in the middle-aged and elderly groups. The prevalence of lymphopenia has been 30-80% among the COVID-19

patients (9, 10, 21 In our study, the elderly patients were intubated or hospitalized in ICU more frequently than the other groups, and this finding was consistent with other studies (3, 9, 10, 21) . Although the length of hospital stay was longer in the elderly group, the mean length of ICU stay in the young group was twice as long as that of the elderly group.

Young patients are usually admitted to ICU when they are under critical conditions; however, older individuals are transferred to ICU when their condition is not much severe or critical because of the complications of their disease. In other words, older individuals discharge from ICU sooner.

This study had several limitations. First, due to the lack of diagnostic kits for PCR at the beginning of the outbreak in Iran, including all the patients in the study was impossible. As a result, several hospitalized patients with COVID-19 symptoms were not included. Second, since we compared only the three age groups, this analogy cannot be generalized to out-patients. Third, the number of patients was not similar in the research groups. Fourth, although the treatment protocols were the same, the effect of medication on the outcomes was not considered.

The present study showed that elderly patients were more likely to develop COVID-19, while they may have no close contact with other patients and may even live in larger houses. Although there was no significant difference in the clinical symptoms and some paraclinical findings among the age groups, an increase in CRP, ESR, WBC, Bun, Cr, and lymphocytes was mainly observed in the elderly. No significant difference was also observed in the involvement on CT scans of the patients in different age groups; however, the type and pattern of involvement differed. Finally, the length of hospital stay was longer in the elderly group; however, the length of ICU stay was more prolonged in the young group.

This study is financially supported by Vice-Chancellor in Research Affairs, Medical University of Isfahan (199139).

Coronavirus disease (COVID-19)

Clinical Characteristics of Coronavirus Disease 2019 in China

Analysis of Epidemiological and Clinical Features in Older Patients With Coronavirus Disease 2019 (COVID-19) Outside Wuhan

Clinical Outcomes in 55 Patients With Severe Acute Respiratory Syndrome Tanaffos

Coronavirus 2 Who Were Asymptomatic at Hospital Admission in Shenzhen

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

A one-year hospital-based prospective COVID-19 open-cohort in the Eastern Mediterranean region: The Khorshid COVID Cohort (KCC) study

Genetic Analysis Tracks SARS-CoV-2 Mutations in Human Hosts

High-resolution computed tomography manifestations of COVID-19 infections in patients of different ages

Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Clinical Characteristics of Covid-19 in New York City

Sexual Dimorphism in Innate Immunity

Prevalence of comorbidities in the Middle East respiratory syndrome coronavirus (MERS-CoV): a systematic review and meta-analysis

Sex-Based Differences in Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection

Clinical characteristics of older patients infected with COVID-19: A descriptive study

Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients

Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: A systematic review and meta-analysis

Clinical characteristics of 145 patients with corona virus disease 2019 (COVID-19

Safety and efficacy of the neuraminidase inhibitor GG167 in experimental human influenza

Routes of transmission of influenza A H1N1, SARS CoV, and norovirus in air cabin: Comparative analyses

Caution on kidney dysfunctions of COVID-19 patients

Cytokine Release Syndrome in COVID-19 Patients, A New Scenario for an Old Concern: The Fragile Balance between Infections and Autoimmunity

Radiological Society of North America Expert Consensus Document on Reporting Chest CT Findings Related to COVID-19: Endorsed by the Society of Thoracic Radiology, the American College of Radiology, and RSNA. Radiol Cardiothorac Imaging