Hospital Readmission in Patients With COVID-19

Objective: During the COVID-19 pandemic, the demand for hospital beds has exceeded substantially. Thus, we aimed to conduct this study to identify factors associated with the risk of readmission in order to introduce the best discharge plan for patients with high risk of hospital readmission. Method: This is a multicenter, case-control study included 1357 patients hospitalized with COVID-19 infection. Age-sex-matched case and control groups were paired at 1:2 ratios. COVID-19 readmission rate was assessed. Moreover, Logistic regression analysis was applied to determine the factors associated with readmission. Results: Of the 1357 patients, 99 (7.29%) subjects were readmitted. The most common cause of readmission was respiratory distress. The median (IQR) of the interval between hospital discharge and the second admission was 5 (2-16) days. Upon adjusting with the main risk factors, having at least one underlying disease and being treated with the corticosteroid (GC) were signicantly associated with a higher rate of readmission (OR: 2.76, 95% CI :1.30- 5.87) and (OR:8.24, 95% CI :3.72- 18.22), respectively. Conclusion: Identication of Risk factors of COVID 19 readmission will improve resource utilization and patient care.


Introduction
Coronavirus 2019 (COVID-19) is a complex health crisis caused by a new corona virus, named Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) (1). The virus was initiated at late 2019 in Hubei, China and spread rapidly all over the world and became a pandemic in January 30, 2020 (2). COVID-19 hospitalization rate is more than 70 per 100,000 patients, and 1 in 10 cases are readmitted after receiving inpatient care (3). Readmissions represent a signi cant burden on healthcare delivery systems (4). As the progression of COVID-19 remains unclear, hospital readmission becomes an emerging and costly public health concern (5). Understanding of the clinical course of COVID-19 in patients readmitted after discharge has crucial implications for policy-makers to optimize healthcare resource utilization (6). To our best knowledge, there are a few studies focusing on COVID-19 readmission. Jie Chen et al. found that 7.6% of COVID-19 patients in China, were readmitted (7). Moreover, Jeon WH et al. reported that out of the 2864 COVID-19 patients admitted to hospitals, 103 patients were readmitted after discharge mainly due to high comorbidity score. (3) Although a little is known about risk factors for re-hospitalization of patients with COVID-19, respiratory complications are found to be the main reason for readmission (8). Moreover, another study concluded readmission within the rst 12 days after discharge is more likely to directly related to the COVID-19 while at the later time it is due to other reasons such as psychiatric problems (9). However, there is still a knowledge gap on post-hospitalization outcomes in patients with COVID-19. Therefore, we aimed to conduct a study to identify the risk factors associated with readmission in order to introduce the best discharge plan for patients with high risk of hospital readmission.

Setting
This multicenter study was performed in 5 academic hospitals a liated to Iran University of Medical Sciences (IUMS) in Tehran. The study was approved by the ethics committee of the IUMS. All hospitalized patients with positive oropharyngeal or nasopharyngeal reverse transcriptase polymerase chain reaction (RT-PCR) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were considered as COVID-19. Moreover, those without laboratory con rmation for COVID-19 who presented the clinical manifestations of COVID-19 along with typical chest computed tomography (CT) ndings were also considered as having COVID-19. All patients admitted to these hospitals received standard medical treatment and respiratory support according to the national protocol of the ministry of health of Iran (10).

Study design and data collection
We retrospectively analyzed data from COVID-19 patients admitted to ve IUMS-a liated hospitals between March 2020 and September 2020. Hospital readmission was identi ed using the electronic medical records. Readmission was de ned as the hospital admission due to COVID-19-related symptoms at least 24 hours after the date of discharge. For each Patient who was re-admitted, two sex and age matched individuals with history of one admission for COVID-19 infection and discharged alive were included as the control group. Demographic and clinical characteristics of the patients were extracted from the hospital medical records. In the readmitted patients, data on the rst admission were included for the nal analysis.

Statistical analysis
Continuous and categorical variables are presented as median (interquartile range (IQR)) and number (percentage), respectively. Logistic regression analysis was applied to determine the factors associated with readmission due to COVID-19. The outcome of interest was readmission and the explanatory variables were age, sex, smoking status, opium use, underlying disease, vital signs at the time of admission, Lung involvement documented by CT images, hospital course, and medication received during the hospitalization. Statistical analyses were performed applying Stata software (version 13). All tests of signi cance were two-tailed (with 95% con dence of interval), and values of p < 0.05 were considered statistically signi cant.

Results
1357 Patients with COVID-19 infection were admitted between March 2020 and September 2020, 99 (7.29%) subjects were readmitted to the hospitals. The median (IQR) of the interval between the rst discharge and the second admission was 5 (2-16) days.

Characteristics of readmitted patients
Out of 99 readmitted patients, 12 patients were readmitted two times and the others were readmitted one time. The most common cause of readmission was respiratory distress (70.7%).
Some diseases like HTN, CAD, CKD, COPD, CVA, and Cancer increased the rate of readmission; however, their effect vanished after multivariate adjustment. Adjustment was done for the main contributing factors smoking, opium use, the number of underlying disease, ICU admission, and chest CT in ltration. After multivariate adjustment, GC therapy and the number of underlying disease ( > = 1) were associated with an increase in the rate of readmission.
The association between COVID-19 readmission and various underlying diseases has been previously reported in different studies. HTN, COPD, and pulmonary brosis have been frequently associated with a higher risk of readmission (7,12). A Spanish study showed that immunocompromised patients were also more likely to be readmitted (11). Moreover, some studies, including ours, showed the higher number of comorbidities is associated with a higher rate of readmission (3,9). In line with our results, a large Koran study showed higher risk of readmission in patients with some underlying diseases like DM, HTN, Dementia and those who had at least one underlying disease(3).
The reason why GC therapy increases readmission rate, is probably due to the fact that patients who received GC, had more severe pulmonary involvement and less oxygen saturation than patients treated with oral antiviral therapy (according to Iranian national protocol for the treatment of COVID19 (10). As it is recommended in many international guidelines, we do not start treatment with GC until oxygen saturation is decreased. As a result, patients who are candidates for treating with corticosteroids have more pulmonary involvement. Perhaps The greater risk of readmission in patients treated with GC is related to more pulmonary involvement.
In contrast of our results, prescribing GC did not increase the rate of readmission in Spanish study; This difference may be related to the time of prescription; we considered prescription of GC during the hospitalization while they included only the patients who discharged with GC (11).
The univariate analysis showed that smoking or opium use were risk factors for hospital readmission. This effect might be mediated by various factors such as socioeconomic condition, employment, education, social support, and social determinants of health (13).
As shown in previous studies, pneumonia and respiratory distress were the most common causes of readmission (9). Hospital readmitted patients with COVID-19 has not yet been widely evaluated, however, assessing the causes of readmission is necessary to identify preventable causes (9).
According to this study, patients with a medical condition have higher risk of readmission than patients with no underlying disease and this is justifying some therapeutic guidelines (like Iranian national protocol) of COVID-19 that recommends patients with at least one underlying disease were considered as the priority for hospitalization. Therefore, it seems that in the emergency department, patients with underlying diseases should be given priority to diagnostic and therapeutic procedures and also in allocation of the facilities. Also, related to use of medical treatment, the patients who received GC had a higher rate of readmission versus to the patients received Kaletra, HCQ, and Sofosbuvir. Similar to our study, the Korean one showed lower rate of readmission in patients who were treated with HCQ and Kaletra and it may be due to milder type of the disease in patients treated with oral agents(3). Similar to ours, an American study showed the type of ventilation and intubation rate had no difference between readmitted and non-readmitted patients (9).
We showed no difference in sex, age and the duration of the admission in two groups; but a Korean study showed a higher rate of readmission in male and older patients and also in those with shorter length of staying at the rst admission in readmitted group; These differences may be related to the larger number of study population in the Korean one (7590 patients) compared with ours (1357 patients) (3).

Limitations and strength
Obtaining and gathering information from several tertiary centers and including a relatively large number of patients were the strength of our study. However, there are some limitations. First of all, we could not provide more detailed information such as clinical characteristics of the patients. A lot of missing data were detected in records. Moreover, this study was conducted at the middle of the pandemic and the characteristics might be differing during the pandemic.

Conclusion
In summary we reported a relatively low rate of readmission after discharge from hospitalization of COVID-19. It seems that in the emergency department, patients with underlying diseases should be given the priority to diagnostic and therapeutic procedures and also in allocation of the facilities. Further studies are required to evaluate the risk factors of readmission and solutions to reduce the rates of patient return to the hospital. The study was performed in accordance with appropriate guidelines and reviewed and approved by the Local Ethics Committee of Iran University of Medical Sciences (Approval No: IR.IUMS.REC.1399. 053). Written consent was obtained from the patient to publish her documents.

Consent for publication
Written consent was obtained from the patient to publish her documents.
Availability of data and material The datasets generated and/or analysed during the current study are available in the database of Endocrinology & Metabolism Research Institute of Iran