In December 2019, a new 'Coronavirus' was identified in investigations on unknown origin viral pneumonia cases in China. The virus was named "SARS-CoV-2" because of its similarity to the SARS (Severe Acute Respiratory Syndrome) virus (1). The disease spread rapidly all over the world and was declared as a pandemic by the World Health Organization (WHO) in March 2020 (2) . As of 9 September 2020, novel coronavirus disease 2019 has infected over 27 million people globally and approximately 285,000 people in Turkey (3, 4) .
Published data covers mostly information on the clinical features, laboratory findings and treatment of patients hospitalized with the diagnosis of COVID-19, however many of the COVID-19 patients were discharged with quarantine suggestions, and treatment at home.
There is limited data on whether these patients have fully recovered or if they were readmitted. The readmission data of COVID-19 patients are scarce (5-7).
The 30-day readmission rate is an important indicator of patient safety and hospital's quality performance. The '30-day readmission' is defined as 'unplanned admission for any cause to an acute care hospital within 30 days of discharge' (8). Most studies have suggested that better quality of inpatient care is associated with a lower risk of readmission (9,10).
Several studies have investigated hospital readmissions in general patient populations or among specific populations including older adults and patients with chronic conditions (such as congestive heart failure, hypertension, chronic obstructive lung disease) (11, 12) .
In this study, we aimed to find out the 30-day readmission rate of mild and moderate severity COVID-19 patients discharged from a tertiary care university hospital. Secondly, we aimed to demonstrate the characteristics and outcomes of patients who were readmitted.
This observational, single-center study was conducted in a tertiary care university hospital. Epidemiological and clinical data of patients who were hospitalized with a diagnosis of COVID-19 were retrieved from a research database where patient information was recorded prospectively. Readmission data was sought from the hospital information management system and National Health Record System (e-Pulse) to detect if the patients were readmitted to any hospital within 30 days of discharge. e-Pulse is a centralized hospital management information system owned by the Ministry of Health, which retrieves and integrates data from all of the healthcare institutions and makes them available for the patient and his/her healthcare providers. Patients and doctors (with the consent/ approval of the patient) can access the healthcare data including all admissions, laboratory results, medical images, prescription and medication details, emergency information, diagnosis details, reports and health records that contains all the details concerning the examinations via desktop and mobile platforms (13) . Each patient has a unique identity number, which is the national identity number, enabling tracking of his/her records in the healthcare system by healthcare providers given the patient has consented at the registration stage. Hence, the healthcare information of the patients in the e-Pulse system is reliable, complete and accessible except for those who haven't consented for data sharing. We retrieved the data of the patients who have consented for accessibility of their data through the e-pulse system. 30-day readmission was defined as an unplanned admission to the hospital within 30 days of discharge.
Adult patients (≥18 years-old) hospitalized in COVID-19 wards with a diagnosis of COVID-19 between March 20, 2020 (when the first case was admitted to our hospital), and April 26, 2020 were included. Among the patients who were included in the study, the first patient was discharged on March 26, and the last patient was discharged on May 01.
Critically-ill patients with sepsis and/or acute respiratory distress syndrome requiring intensive care unit (ICU) at the time of admission or those who were transferred to the ICU during the hospital stay or those who were transferred from the ICU to the COVID-19 wards were excluded considering that critically ill patients with COVID-19 might have different disease courses due to comorbidities and disease states other than COVID-19 and their mortality rate is higher than the mild and moderate cases (14) .
Diagnosis, hospitalization, treatment and discharge decisions were made by attending physicians according to the current national guidelines prepared by the Scientific Advisory Committee of the Turkish Ministry of Health. Patients who need admission to the COVID-19 wards were categorized as "probable" or "confirmed" cases. "Confirmed case" was defined as a patient who had positive polymerase chain reaction (PCR) test result for SARS-CoV-2.
"Probable case" was defined as a patient who had sudden onset of fever, cough or dyspnea without nasal discharge, with or without travel history, or who had contact with COVID-19 infected individual in the last 14 days or patients who had severe acute respiratory infections that cannot be explained with any other cause, but with negative PCR test result for SARS-CoV-2 (15) . COVID-19 cases were further classified into three categories with regards to WHO classification as mild, moderate, and severe disease. (16) .
Treatment regimens for COVID-19 and duration of treatment were also recorded.
Main categories of treatment regimens were: hydroxychloroquine(HCQ) only, HCQ+azithromycin (AZT), and favipravir (FAV) containing regimens. Some patients could also have received oseltamivir (OTV) or empirical antibacterial treatment as per the indication. Even if the patients were discharged before the treatment was completed, their medications were provided, and treatments were completed at home.
As this was an observational study, the follow-up and discharge decisions of the patients were not intervened. All patients were discharged following the instructions in the national guideline stating that ″COVID-19 patients under inpatient treatment and monitoring who have not had any fever and need for oxygen within the last 48-72 hours and who fulfil the criteria for home monitoring may be discharged after their treatment is determined by the consultant physician. Their home isolation may be terminated on the 14 th day, following the date of discharge provided not to manifest any symptoms or fever″ (15) . 
All statistical analyses were performed with SPSS statistical software package (SPSS,IBM,Armonk,NY) version 25. In descriptive statistics, number and percentage were used for categorical variables. For continuous variables with normal distribution, mean and standard deviation(SD) were used; and for continuous variables that do not show normal distribution, interquartile range(IQR) was preferred. Pearson Chi-Square Test or Fisher exact test were used in the analysis of categorical variables. Non-normally distributed numerical data were analyzed with Mann-Whitney U test or Kruskal Wallis Tests. For all comparisons P-values less than 0.05 were considered as statistically significant.
From March 26 to May 1, there were 154 mild or moderate severity (non-critical) COVID-19 patients discharged from COVID-19 wards, of which 11 (7.1%) were readmitted (Table 1) . While 98(63.6%) patients had a positive SARS-CoV-2 PCR test result (confirmed case), the rest of the patients had either compatible CT imaging results or clinical characteristics those were highly suspicious of COVID-19 (probable). Disease category (confirmed or probable) or severity (mild or moderate) were not associated with readmission.
The median length of stay (LoS) during the initial admission was 4 days (IQR=5) and was 3 days (IQR=3) among readmitted patients with no statistical difference. All but five patients (96.8%) received HCQ or HCQ based combination therapies. The characteristics of those patients who were readmitted within 30 days (n=11) and who were not (n=143) were compared in Table 1 .
All of the patients met the discharge criteria mentioned in the methods section. Nine patients had completed their first treatment course at the hospital (4 patients, 36.3%) or at home (5 patients, 45.5%) before the readmission. The median duration from discharge until readmission was 8.1(IQR=5.2) days. Two patients (18.1%) were categorized as mild disease and the remaining 9(81.9%) as moderate. Malignancy (18.7% vs 2.1%, P = 0.04) and hypertension (45.5% vs 14%, P = 0.02) were more common in those who were readmitted.
General characteristics of 11 readmitted patients are given in Table 2 .
The main reasons for readmission were prolonged fever (45.5%) and persistent cough (45.5%) ( Table 2 ). Only one patient had no complaints but was admitted due to social problems jeopardizing home isolation (Table 2, Patient 5). Among the readmitted patients, two did not receive any treatment during the initial admission period ( Table 2 ). One of the two patients who received no treatment in the initial admission period developed fever and radiological signs of pneumonia, and HCQ+AZT were initiated ( Table 2 , Patient 8). The other patient who did not receive treatment in the initial admission period was a 43-year old male patient and he was readmitted due to social problems preventing the execution of the home isolation protocol (Table 2, Patient 5). Isolation problems at home were solved and he was discharged again after 3 days.
The other patients (n=9) were treated with HCQ+AZT 5 days. Only one patient received FAV as a part of the initial treatment regimen and although this patient was readmitted with dyspnea, there was regression of pneumonia on the chest CT and the patient received no further treatment (Table 2, Patient 9). On the other hand, progression in pneumonia was detected in the CT scan of four patients who presented with either cough or fever or both (Figure 1 ). These patients who were treated with HCQ+AZT or HCQ+AZT+OTV during the initial admission were started FAV during the second admission (Table 2 , Patients 1,2,6,10).
All but two patients were discharged again. However, two patients who were over 65 years of age and had metastatic cancers developed sepsis and died in the hospital during the readmission episode. The first patient was a 67-year old female patient with a history of metastatic lung adenocancer, hypertension and chronic kidney disease presented with cough and fever (Table 2, Patient 7). Chest CT showed subpleural, multifocal noduler ground-glass opacities which were compatible with COVID-19 pneumonia in the lower lung lobes ( Figure   2 ). Her complete blood count revealed leukocytosis, neutrophilia and lymphocytopenia.
Treatment was planned as HCQ+AZT for COVID-19 pneumonia and ceftriaxone since bacterial pneumonia could not be excluded. On the 5 th day of hospitalization she developed acute kidney injury. Intravenous hydration with isotonic saline was planned, but the patient and the family rejected the treatment inspite of the acknowledgement on the risk of progression to acute renal failure. After 6 days of hospital stay, the patient was discharged at the discretion of herself and her family with a declaration to increase the volume of oral hydration. Next day, patient was back to hospital with confusion, her serum creatinine level was 3.95 mg/dl and she was hypotensive. Intravenous meropenem and hydration was started with a diagnosis of clinical sepsis, however, she had cardiac arrest and died. The 30-day readmission rate in this cohort of patient with mild to moderate COVID-19 was 7.1%. In the early stages of the pandemic, in a prospective cohort study evaluating clinical features and outcomes of discharged COVID-19 patients, 5 of 131 (3.8%) were readmitted in the first and the second week after discharge and 3 (2.29%) were readmitted in the third and the fourth week after discharge. Although not stated in the study, we calculated the 30-day readmission rate as 6.1% (22) . In a study from Spain, 61 (%4.4) of 1368 patients with laboratory confirmed SARS-CoV-2 were readmitted (23) . In a recent study, of 2864 discharged patients, 103 (3.6%) had returned for emergency care after a median of 4.5 days, with 56 had requiring inpatient readmission (24) . Readmission rate is not much different from more comprehensive and multicenter studies in the recent literature. However, as expected from the small sample of our study, the 95% confidence interval for the 7.1% readmission rate is wide. In addition, the comparison of the 30-day readmission rates between and that for other conditions in our hospital could be informative. For instance; the frequency of emergency department (ED) visits of 1570 patients discharged from the internal medicine wards were 1.3% within 7 days and were 5.2% within 30 days (12) . (25) . Several studies have been published assessing the relationship between LoS and readmission rates for different disease in the pre-pandemic periods (26) (27) (28) (29) . Shorter hospital LoS for HF was associated with increased rates of cardiovascular and HF readmissions but lower rates of non-cardiovascular readmissions (30) .
In a nation-wide study of Norwegian Hospitals, being admitted to a hospital with relatively short average LoS increased the patient's risk of early readmission significantly (31) . The results also indicated that there exists a link between the basic conditions at which the hospitals deliver the care, and the outcome of the patients measured as early readmissions.
LoS during index hospitalization (4.5 [2.9,9.1] vs 6.7 [3.5, 11.5] days; P=0.006) (24). Parra et al. also reported that readmitted COVID-19 patients had a shorter LoS (6 [4-14] vs 9 [6] [7] [8] [9] [10] [11] [12] [13] [14] days; P=0.02) (23) . LoS seems not to be the primary measure of interest in COVID-19 studies which report it, however, it can be an important parameter and can sure be related to unplanned readmissions. Hospital LoS of COVID-19 patients can be affected by many situations such as hospital bed capacity, treatment plans, quality of care and should also be an important issue that needs to be analyzed. It should be noted that the demand for hospital admissions and the learning curve of the disease has changed over the course of the epidemic, which may have had a varying impact on patient discharge.
There was a higher prevalance of readmission in hypertensive patients (p=0.02).
Similarly, the percentage of patients with an accompanying malignancy were at increased risk for readmission (18.2%vs2.1%,p=0.04). In the study from Spain, immunocompromised patients were at increased risk for readmission and there was also a trend towards a higher probability of readmission in hypertensive patients (23) . A retrospective cohort study from USA reported higher proportions of COPD (6.8% vs 2.9%) and hypertension (36% vs 22.1%) among readmitted patients compared to not readmitted patients (24) . Current data indicate HT as a risk factor for poor prognosis in COVID-19 patients (32, 33) which may be a related to the increase in readmission rates. In a nationwide analysis in China, patients with cancer were found to have a higher risk of COVID-19 than individuals without cancer and malignancy has been reported as a poor prognostic factor in COVID-19 (34) . In the present study the patients who died in the readmission period were elderly patients who had both metastatic cancers, HT and developed sepsis. Both of these patients had negative PCR test results but had CT scans compatible with COVID-19 pneumonia. Chest CT has found to have low rate of missed diagnosis of COVID-19 (3.9%, 2/51) and may be useful as a standard method for the rapid diagnosis of COVID-19 to optimize the management of patients (35, 36, 37) . However, diagnosis of COVID-19 on clinical grounds can be challenging in complex patients with multiple morbidities.
It might be argued that patients with such prognostic factors could have received FAV in the initial admission. FAV is considered as one of the potential candidates for COVID-19 treatment and used in many countries. Although, there are also several randomized controlled trials going on in China, there is not solid evidence to show in which patient group it will be used as a priority (38) .
Discussing readmission in COVID-19 is challenging, as we yet do not know the clinical characteristics of the disease and we do not have established treatment regimens and care bundles. Hence, it's difficult to analyze and discuss the factors contributing to the occurrence of readmission. Is it because of quality gaps or failed transitional care interventions in this patient population, or is it related to the natural course of the disease that may wax and wane? For instance, one patient who did not receive any treatment in the initial admission period developed fever and radiological signs of pneumonia after 9 days of home isolation, after which HCQ+AZT was initiated in the readmission period. It's hard to judge whether this readmission was due to undertreatment or short observation period of initial admission or was as a result of the natural course of the disease itself. On the other hand, four of the eleven patients were readmitted with the radiological progression of existing pneumonia without demand-for-oxygen supplementation although these patients received HCQ+AZT during the initial admission period. Lack of evidence-based therapies prevents the determination of the quality gap.
Our study has some limitations. Many features such as individual characteristics of patients, current diseases, clinical presentations, laboratory findings, and the treatments can cause readmission. We did not perform multivariable analysis to explain the causes statistically. The sample size was not enough to evaluate the predictors of hospital readmissions. We give only our observations amidst a stressful pandemic situation that we
have not yet fully understood the dynamics of the disease.
In conclusion, this is one of the first studies to report on 30-day readmission rate of COVID-19 in literature. Prolonged fever and persistent cough were the most common complaints on readmission. The percentage of patients with accompanying hypertension and malignancy were higher among readmitted patients. Two patients who died on the second admission had metastatic cancer and HT. More comprehensive studies are needed to reveal the causes and predictors of COVID-19 readmissions and to clearly demonstrate whether 30day readmission rate can be used as a quality indicator of COVID-19 care. 