ABSTRACT

Background and Objectives:

The severity and mortality of coronavirus disease 19 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 is associated with underlying diseases such as hypertension, diabetes mellitus, and chronic kidney disease (CKD). To this end, the aim of this study was to assess the clinical characteristics, laboratory outcomes, and results in patients hospitalized with coronavirus disease 2019 (COVID-19) and those without CKD.

Methods:

This cross-sectional matched study was conducted on patients with confirmed COVID-19 and patients without CKD who were hospitalized at Baqiyatallah Hospital in Tehran, Iran from February 26, 2020, to March 26, 2020. These patients were homogeneous in terms of age, sex, body mass index, and underlying diseases such as hypertension and diabetes mellitus. Demographic data, clinical symptoms, laboratory, and radiological findings were collected from the patient's medical records and compared according to the patient's CKD status.

Results:

Among COVID-19 patients, 56 and 97 patients with and without CKD were investigated, respectively. In general, 111 (72.5%) patients were male with a mean age of 55 years. Patients with CKD had higher levels of blood urea nitrogen, creatinine, and red blood cell distribution width (p<0.05). No differences were found in COVID-19 patients with and without CKD regarding chest computed tomography findings, ICU admission, and death.

Conclusions:

Overall, the findings support the use of erythrocyte distribution width, blood urea nitrogen, and creatinine to monitor patients with CKD with COVID-19 and to assess the risk of disease progression. Ultimately, management of comorbidities including hypertension and diabetes will reduce the severity of COVID-19 in CKD.

Keywords: chronic kidney disease, clinical characteristics, COVID-19, hospitalized, Cistanche extract

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1. Introduction

The coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) has affected multiple populations worldwide. As of April 18, 2021, the virus has resulted in 140,332,386 confirmed cases and more than 3 million deaths, and this number is still increasing. To date, there are no approved antivirals to fight this infectious disease, and treatment is only supportive and symptomatic.

COVID-19 can cause a range of diseases, from mild to severe respiratory infections and multi-organ dysfunction, and in some cases can be transmitted asymptomatically from person to person. According to numerous reports, the severity and mortality of the pandemic were positively correlated with the underlying diseases. Hypertension, chronic kidney disease (CKD), and diabetes mellitus are the most common underlying diseases in patients with COVID-19, and these patients are more likely to develop severe cases.

In this regard, it has been reported that high expression of angiotensin-converting enzyme is a cellular entry route for SARSCoV-2 in the kidney. In addition, SARS-CoV-2 has been identified in urine and kidney tissue from some COVID-19 patients, suggesting that the kidney is a potential target of the virus. In a study of 701 patients with COVID-19, 13.1% and 14.4% had increases in blood urea nitrogen (BUN) and serum creatinine. In addition, 33.7% of patients with increased baseline serum creatinine died, highlighting the importance of COVID-19 for patients with preexisting renal disease. However, there are limited data on the clinical characteristics of patients with CKD who are infected with COVID-19. Clinical characteristics of CKD patients infected with COVID-19 for better control of the disease. Thus, the current work aimed to assess and compare the laboratory findings, clinical features, and consequences of COVID-19. Laboratory results, clinical features, and consequences of COVID-19 infection. Laboratory results, clinical characteristics, and consequences of hospitalized patients with COVID-19 at different medical centers.

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2. Methods

2.1 Participants and Research Design

This cross-sectional study included 153 consecutive adult patients with confirmed COVID-19 admitted at Baqiyatallah Hospital, a hospital that treats patients with COVID-19 according to government standards, from March 12 to April 10, 2020. Among the patients, 56 adult patients with COVID-19 combined with CKD and 97 controls without CKD were homogenized with respect to age, body mass index, sex, and underlying diseases (e.g., diabetes and hypertension). detection of COVID-19 was based on interim guidelines issued by the World Health Organization. All COVID-19 patients were diagnosed by the reverse transcription-polymerase chain reaction of SARS-CoV- 2 RNA from nasopharyngeal specimens and followed up for clinical outcomes until April 18, 2020. This study was conducted under the approval of the Ethics Committee of Baqiyatallah University of Medical Sciences, Iran (IR.BMSU.REC.1399.171). Based on the retrospective design of this study, all patients signed a written informed consent.

2.2 Data Collection & Statistical Analysis

The demographic data, chest computed tomography (CT)scans, laboratory findings, clinical symptoms, and outcome-related data of all patients were obtained from electronic medical records. The patients with missing data on the studied criteria and kidney transplant recipients were excluded from the study. Patients with CKD were identified based on the self-declaration form or medical documents confirmed by a nephrologist. Based on the Kidney Disease: Improving global outcomes, CKD was defined as the glomerular filtration rate(<60 mL/min/1.73 m2) for a minimum of three months [11]. Eventually, patients’ clinical outcomes were evaluated by experienced clinicians.

Categorical and continuous variables were expressed as the percentage (%) and mean ± standard deviation (SD), respectively. In addition, categorical and continuous variables were analyzed by the chi-square test/Fisher’s exact test and independent t-test/Mann-Whitney U test, respectively. A Pvalue less than 0.05 represented a statistically significant difference. Finally, SPSS software (version 22.0, IBM) was used to analyze the obtained data.

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3. Results

In general, 153 patients (56 and 97 patients with and without CKD, respectively) suffering from confirmed COVID-19 were included in this cross-sectional study. Table 1 represents the demographic and clinical characteristics of COVID-19 hospitalized patients with and without CKD. Based on the results, no differences were found between the two groups in terms of age, gender, and underlying comorbidities (i.e., hypertension and diabetes) due to the matching design (p≥0.05). The mean (±SD) age of patients with and without CKD was 56.79 (±11.93) and 54.35 (±13.20) years, respectively, and most patients (72.5%) were males. Furthermore, no considerable differences were observed regarding clinical symptoms between the groups at the time of admission (p≥0.05).

Table 2. The radiographic and laboratory results among COVID-19 hospitalized patients with and without CKD

Table 2 summarizes the comparison results of laboratory and radiographic findings between patients with and without CKD. The erythrocyte sedimentation rate (ESR, 43.68±24.61 mm/h), C-reactive protein (CRP, 44.34±22.58 mg/L), blood sugar (BS, 153.5±84.34 mg/dL), BUN (19.38±7.63 mg/dL), creatinine (1.58±0.18 mg/dL), aspartate aminotransferase (AST, 39.76±25.24 U/L), and lactate dehydrogenase (LDH, 666.9±207.27 U/L) were above the normal range in CKD patients. Based on laboratory findings, COVID-19 patients with CKD were at higher risk of inflammatory responses and myocardial and hepatic damage, leading to an unfavorable prognosis of COVID-19.

Regarding laboratory results on admission, CKD patients also demonstrated higher levels of BUN (19.38±7.63 vs. 13.16±4.57 mg/dL, p<0.001), creatinine (1.58±0.18 vs. 1.06±0.28 mg/dL, p<0.001), and red cell distribution width (RDW-CV, 13.68±1.67 vs. 13.06±0.99, p=0.013) compared to patients without CKD. Nonetheless, the values of hematological parameters (Table 2) were lower, including hemoglobin (13.55±2.15 vs. 14.61±1.48 g/dL, p=0.003), hematocrit (40.17±5.37% vs. 42.38±3.72%, p=0.014), mean corpuscular hemoglobin (MCH, 28.35±3.67 vs. 29.68±2.26 pg, p=0.026), and mean corpuscular hemoglobin concentration (MCHC, 33.64±1.87 vs. 34.45±1.19 g/dL, p=0.008).

Table 3. Clinical outcomes of COVID-19 hospitalized patients with and without CKD

On admission, chest CT abnormalities were detected in most patients. There was no significant difference between the CT or chest radiography results of COVID-19 patients with and without CKD (Table 3). Based on the results, bilateral lung involvement and ground-glass opacities were the most prevalent CT abnormalities. According to data in Table 3, no significant difference was found in mortality rates, ICU admission, and length of hospital stay between patients with and without CKD.

4. Discussion

COVID-19 is a highly contagious and newly evolved disease related to the enhanced rates of hospitalization and mortality, especially in individuals with underlying diseases. Limited data exist on the clinical characteristics of COVID-19 hospitalized patients with CKD. The present paper sought to discuss and compare the clinical characteristics and differences between COVID-19 patients with and without CKD.

Based on the results, the proportions of male patients in the present work (72.5%) were higher compared to females, which is in line with the findings of previous studies. They also suffered from more severe symptoms that were related to old age, nicotine dependence, and a higher number of comorbidities.

According to recent studies, CKD is among the most widespread comorbidities in COVID-19 patients. In the current study, hypertension and diabetes between patients with and without CKD were matched for assessing the direct impact of CKD on the severity and death of COVID-19. No considerable differences were found in the clinical manifestation, radiological findings, and mortality rates between patients with and without CKD. These data revealed that the increased severity and mortality rate of the disease in COVID-19 patients with CKD, which was reported in other studies, may not be directly related to CKD per se. This means that other comorbidities, especially hypertension, and diabetes, have great impacts on the undesirable outcomes of COVID-19 patients with CKD.

Laboratory findings in all admitted patients indicated higher CRP, LDH, and ESR rates than the normal range, revealing a severe status and multi-organ damage, which is consistent with the findings of earlier studies. Moreover, kidney damage indexes (i.e., the level of BUN and creatinine) were higher than the normal range and were also considerably higher in patients with CKD in comparison with patients without CKD. Conversely, the RDW-CV value significantly increased in patients with CKD compared to ones without CKD. This was reported as an important predictor for the severity of COVID-19 patients in previous studies. However, other observed RBC indexes were significantly lower in CKD patients.

In the present study, although chest radiographic findings showed pulmonary involvement in all patients, there was no significant difference regarding the type of pulmonary manifestations between COVID-19 patients with and without CKD.

Additionally, no considerable differences were detected in the length of hospital stay, ICU admission, rate of hospital discharge, and mortality between the two groups during the follow-up. These results could highlight the importance of other comorbidities on the severity of COVID-19 infections in our study population.

This study has some limitations. The related data were only obtained from patients from a single center in Tehran. Accordingly, it would be more valuable to achieve more complete results by conducting larger studies in a multicenter manner. In addition, the data were acquired via electronic medical records, thus this study might not be unbiased regarding the missing data.

5. Conclusions

Overall, RDW-CV, BUN, and creatinine were essential laboratory indicators for monitoring patients with COVID-19 combined CKD and assessing the risk of disease progression in this study. disease severity and hospital morbidity and mortality in patients with COVID-19 combined CKD may be associated with other comorbidities, particularly hypertension, and diabetes, rather than CKD itself. Therefore, optimal management of these risk factors will be effective in preventing the development of critical conditions and implementing effective therapeutic measures.

REFERENCES

1. World Health Organization (WHO). Coronavirus disease 2019 (COVID-19): Weekly epidemiological update on COVID-19-20 April 2021.

2. Arons MM, Hatfield KM, Reddy SC, et al. Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facility. N Engl J Med 2020;382(22):2081-90.

3. Corbellini C, Villafane J, Gugliotta E, et al. Late breaking abstract-Pulmonary rehabilitation in post-COVID subjects with moderate lung restriction, a case series. Eur Respir J 2021;58:PA2003.

4. Reviriego GB, Pascual BP, Ruiz AR, et al. Spanish experience of pulmonary rehabilitation efficacy for patients affected by the novel SARS-CoV-2 (COVID-19): A case report. Top Geriatr Rehabil 2020;36(4):212-4.

5. Farnoosh G, Akbariqomi M, Badri T, Bagheri M, Izadi M, Saeedi-Boroujeni A, et al. Efficacy of a low dose of melatonin as an adjunctive therapy in hospitalized patients with COVID-19: A randomized, double-blind clinical trial. Arch Med Res. 2021 Jun 23.

6. Emami A, Javanmardi F, Pirbonyeh N, Akbari A. Prevalence of underlying diseases in hospitalized patients with COVID-19: A systematic review and meta-analysis. Arch Acad Emerg Med 2020;8(1):e35.

7. Flythe JE, Assimon MM, Tugman MJ, et al. Characteristics and outcomes of individuals with pre-existing kidney disease and COVID-19 admitted to intensive care units in the United States. Am J Kidney Dis 2021;77(2):190-203.e1.

8. Akbariqomi M, Hosseini MS, Rashidiani J, et al. Clinical characteristics and outcome of hospitalized COVID-19 patients with diabetes: A single-center, retrospective study in Iran. Diabetes Res Clin Pract 2020;169:108467.

9. Fan C, Lu W, Li K, Ding Y, Wang J. ACE2 Expression in kidney and testis may cause kidney and testis infection in COVID-19 patients. Front Med 2021;7:563893.

10. Cheng Y, Luo R, Wang K, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int 2020;97(5):829-38.

11. Levin A, Stevens PE, Bilous RW, et al. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013;3(1):1-150.

12. Peckham H, de Gruijter NM, Raine C, et al. Male sex was identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission. Nat Commun 2020;11(1):6317.

13. Jin J-M, Bai P, He W, et al. Gender differences in patients with COVID-19: Focus on severity and mortality. Front Public Health 2020;8:152.

14. Council E-E, Group EW. Chronic kidney disease is a key risk factor for severe COVID-19: A call to action by the ERA-EDTA. Nephrol Dial Transplant 2020;36(1):87-94.

15. Gansevoort RT, Hilbrands LB. CKD is a key risk factor for COVID-19 mortality. Nat Rev Nephrol 2020;16(12):705-6.

16. Gasparini M, Khan S, Patel JM, et al. Renal impairment and its impact on clinical outcomes in patients who are critically ill with COVID-19: A multicentre observational study. Anaesthesia 2021;76:320-6.

17. Pranata R, Supriyadi R, Huang I, et al. The association between chronic kidney disease and new-onset renal replacement therapy on the outcome of COVID-19 patients: A meta-analysis. Clin Med Insights Circ Respir Pulm Med 2020;14:1179548420959165.

18. Mokhtari T, Hassani F, Ghaffari N, Ebrahimi B, Yarahmadi A, Hassanzadeh G. COVID-19 and multiorgan failure: A narrative review on potential mechanisms. J Mol Histol 2020;51(6):613-28.

19. Ghahramani S, Tabrizi R, Lankarani KB, et al. Laboratory features of severe vs. non-severe COVID-19 patients in Asian populations: A systematic review and meta-analysis. Eur J Med Res 2020;25(1):30.

20. Henry BM, Benoit JL, Benoit S, et al. Red blood cell distribution width (RDW) predicts COVID-19 severity: A prospective, observational study from the Cincinnati SARSCoV-2 Emergency Department Cohort. Diagnostics 2020;10(9):618.

21. Wang C, Zhang H, Cao X, et al. Red cell distribution width (RDW): A prognostic indicator of severe COVID-19. Ann Transl Med 2020;8(19):1230.

22. Wang C, Deng R, Gou L, et al. Preliminary study to identify severe from moderate cases of COVID-19 using combined hematology parameters. Ann Transl Med 2020;8(9):593. https://doi.org/10.21037/atm-20-3391 PMid:32566620 PMCid:PMC7290538.