Evaluation of symptoms, radiological findings, laboratory data and outcome in COVID-19 patients with chronic kidney disease at Tehran, Iran


 Background: Chronic kidney disease (CKD) patients are a large population and of significant importance. Except for having an underlying disease, they have some other risk factors, for example, old age, impaired immune function, and other comorbidities that make them more susceptible to the new SARS-COV2 infection.Methods: As data on CKD patients with SARS-CoV-2 Infection is limited, we decided to carry out a cross-sectional study at Labbafinezhad Hospital on 78 CKD patients with approved COVID-19 infection either on dialysis or not. We have also incorporated CKD patients with kidney transplant history. Results: The mean age of the patients was 64.04 years, including 53 women and 25 men. Among all symptoms, dyspnea (19.2%) was the most prevalent one. Laboratory data analysis shows an increase in LDH, Creatinine, and ESR and CRP levels. The most common finding on chest CT-Scan was bilateral ground-glass opacity detected in 31 (86.1%) patients, followed by pleural effusion (12.8%) and atelectasis (19%). Among included patients, 53 (74.6%) had hypoxia (o2 saturation 94% and lower), 47 (81%) had tachypnea (respiratory rate over 16) and 9 (23.1%) had some reduction in the level of consciousness (GCS lower than 15). Conclusion: Due to the important effect of underlying medical conditions on the outcome of COVID-19 patients, evaluation of clinical manifestations, radiologic findings, laboratory data, and outcome of COVID-19 patients with chronic kidney disease is important to establish a perspective for physicians to manage CKD patients.


Introduction
Today's world is facing a huge wave of COVID-19 virus disease. Thirty years after the virus was first discovered in the 1930s, evidence of its pathogenicity has been established in humans (1). In December 2019, a viral outbreak of the same family was reported from Wuhan, China (2,3), and the spread of the disease has since infected more than 14 million people and killed more than 600,000 worldwide (4).
The presence of underlying diseases such as diabetes, hypertension, cardiovascular disorders as well as COPD can affect the severity of the disease in different people and the mortality rate (5 -7). Chronic kidney disease (CKD) is a common disease that can lead to impaired renal function by reducing the glomerular filtration rate (GFR) (8). Statistics show that in 2017, over 5 million patients worldwide were suffering from the disease (9). Old age and the presence of underlying diseases in most patients with this disease are among the factors that make CKD patients more susceptible to  In CKD, the glomerular filtration rate decreases due to a decrease in the number of nephrons. Adaptive responses are then generated by factors such as vasoactive hormones, growth factors, and cytokines (8). The presence of cytokines causes a cytokine storm, activating the angiotensin II pathway, which eventually leads to increased blood coagulation and microangiopathy (10). Studies have shown that ICU hospitalization rates, as well as mortality in CKD patients, are significantly higher due to symptoms such as cough, severe shortness of breath, and extreme fatigue (11,12). Also, the results of laboratory tests of these patients have shown that ferritin and CRP in CKD patients are associated with a significant increase, which can be related to their severe inflammatory status (13).
Despite a large number of CKD patients, research in this area has been relatively largely neglected. In this study, we describe 78 patients in the Labafinejad Hospital in Tehran, Iran. Clinical manifestations, radiological findings, laboratory data, and results are reviewed to provide insights for physicians in managing patients with chronic kidney disease infected with COVID-19.

Study design
This study, which is designed as a cross-sectional study from March 2, 2020, to May 9, 2020, has been approved by the Ethics Committee in Biomedical Research of Shahid Beheshti University of Medical Sciences with the code (IR.SBMU.REC.1399.018). Patients with novel coronavirus (COVID-19) referred to Labbafinezhad Hospital in Tehran were included in the study if they met the inclusion criteria (cough, fever, fatigue, myalgia, chest pain, dyspnea, other upper respiratory symptoms, and gastrointestinal symptoms).Diagnosis of COVID-19 patients was based on the WHO interim guidance, a confirmed COVID-19 patient defined as an individual with a positive reverse transcriptase-polymerase chain reaction (RT-PCR) result or a patient with common COVID-19 symptoms and a computed tomography scan (CT-scan) compatible to COVID-19 pattern confirmed by experts [14].The written informed consent form was obtained from all patients by the Ethics Commission of the hospital.
A total of 91 patients presented within the specified time period, out of 78 patients who were eligible for the study. Patients are divided into 4 subgroups ( fig 1): 1) patients who were not on dialysis 2) patients on maintenance dialysis 3) patients who underwent dialysis following COVID-19 and 4) patients with a history of a kidney transplant. After reviewing clinical charts, nursing records, laboratory findings, radiological reports and other medical records of CKD patients with COVID-19 confirmed infection, clinical presentation, laboratory data, radiology findings and results were extracted from documented medical records using data collection forms. laboratory tests were performed again before discharge. The quick COVID-19 Severity Index (qCSI) was used to assess the severity of COVID-19 in patients. The qCSI ultimately requires only 3variables, all of which are accessible at the bedside [26].

Statistical Analysis
The collected data were summarized as descriptive profiles by using mean, median, standard deviation, and variance. The percentage, mean, median, standard deviation of patients were calculated within different groups for specific variables. Independent t-test, paired t-test, and chisquare were used to compare the clinical features of patients with COVID-19. A P. value of less than 0.05 was considered to indicate statistical significance. All the statistical analyses were performed by the Statistical Package for Social Sciences (SPSS Inc., Chicago, Illinois, USA) version 26.0.

Result
Based on the results in Table 1 Comparison of blood, inflammatory, biochemical and clinical indices between the four groups in patients shows that LDH (P=0.022), AST (P=0.038) and ALT (P= 0.004) indices were significantly different between groups of patients.   According to the results in Table 3, Unilateral ground glass opacity (GGO) in the radiological findings of the Non dialysis CKD group was significantly (P=0.50) higher than the other groups. However, other radiological indices did not differ significantly between different groups. On the other hand, no significant difference was observed in the type of drug used by the groups.

Discussion
COVID-19 can cause a variety of symptoms in patients. And these clinical symptoms have different severity and nature depending on the history of underlying diseases, physiology and severity of infection in each patient. The results indicate that in this study the most common symptom in all patients was dyspnea. Also, dyspnea was the most common symptom in all patients on dialysis too, who were on maintenance dialysis or underwent dialysis following COVID-19. A previous study including five patients on hemodialysis with COVID-19 revealed that diarrhea and non-respiratory symptoms were the most common symptoms [15]. Another case report similarly reported that nausea and vomiting were the first symptoms of on dialysis COVID-19 patients [16]; however, in this study, the prevalence of gastrointestinal symptoms was only 25%. Also, in patients with a history of a kidney transplant, 52.6% had dyspnea while the study of Akaline et al. declares that, the initial symptom in these patients was fever [17]. However, given the nature and target tissue of the COVID-19 infectious agent, the prevalence of respiratory disorders can be predictable.
Contrary to the previous COVID-19 studies, in this study there were more women (68.8%) than men (31.2%) [18][19][20][21]. However, looking at the mortality rate of patients, it can be seen that the number of deaths in women (52.8%) in the study was more than men (44%) which according to the changes in sex hormone levels among female patients with end-stage renal disease, these differences can be justified [22].
Based on present study, 89.7% of patients had a history of underlying diseases. Most patients with severe conditions had diabetes, hypertension, and coronary diseases; which is aligned with the data that have been reported [21,23] so that, Comorbidities in patients with kidney disease are risk factors for poor outcomes in COVID-19 [5].
This study declares that, even with the higher O2 saturation (mean=91.2) and normal respiratory rate (mean=16.71) in patients who underwent dialysis following COVID-19, the mortality rate was 80%. While in patients without dialysis who had the lowest O2 saturation (mean=86.73%) and the highest respiratory rate (mean=22.86), the mortality rate was only 45.5%.
In terms of laboratory data, the average level of creatinine in all patients was 4.37 mg/dl and between subgroups, patients on maintenance dialysis had the highest average creatinine level (5.74 mg/dl), contrary to the study of Ajaimy et al. which the median of creatinine in COVID-19 patients with kidney disease was 2mg/dl [23]. It cannot be said that there is a strong correlation between albumin levels and patient outcome [24]. It is worth mentioning that in our study the mean LDH level in all patients was 667.058 U/L while in previous studies, the mean LDH level in COVID-19 patients without kidney disease was 261 U/L and in patients with CKD was 264 U/L [13,21]. On the other hand, in our study, the mean level of LDH in patients with a history of kidney transplantation at the time of admission was 815 U/L and at the time of discharge was 119.66 U/L, which is much higher than the amount reported in the same study (mean LDH level=336 U/L) [17]. Also, in line with other studies, the LDH level was higher in patients who died and patients admitted to ICU which shows the correlation between the high level of LDH and poor outcome of patients [25].
Taking the patients' CT-Scan into consideration, align with other studies, bilateral ground-glass opacity was the most radiological finding [21,23].
The implementation of the present study was accompanied by limitations that, for example, the evaluation of serum antibodies for COVID-19 (IgG and IgM) and hematologic tests have not been conducted to determine viremia have not been carried out which might have some useful information regarding patients' outcomes. Finally, our explanation may be restricted because of the small sample size.

Conclusion
According to the results, dyspnea was the most common symptom in patients in this study, while the levels of LDH, AST and ALT had the most changes. Also, the most common finding on a shelf CT scan is bilateral dimming of the ground glass. Also, the most common finding on chest CT-Scan is bilateral ground-glass opacity. on the other hand, due to the number of deaths and ICU admissions, it can be concluded that CKD is one of the important factors that can cause poor prognosis in COVID-19 patients. For this reason, it can be said that, it is important to evaluate clinical manifestations, radiologic findings, laboratory data, and outcome of COVID-19 patients with CKD, to establish a perspective for physicians to manage patients.