Severe Coronavirus disease 2019 pneumonia patients showed signs of aggravated renal impairment

Abstract Background This objective of this study was to identify a sensitive indicator of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Methods Samples were collected from 136 patients with Coronavirus disease 2019 (COVID‐19) pneumonia admitted to the Shanghai public health clinical center (116 mild, 20 severe). The concentrations of serum urea, Uric Acid (UA), Creatinine (CREA), Erythrocyte sedimentation rate (ESR), high‐sensitivity C‐reactive protein (hs‐CRP), procalcitonin (PCT), and urine protein (Pro) have been tested in this study. Results Higher levels of urea (female 7.00 ± 3.31, male 8.87 ± 5.18) Pro (female7/7, male 12/13), hs‐CRP (female 2/7, male 5/13) ESR (female 94.43 ± 33.26, male 67.85 ± 22.77) were found in severe patients compared with the mild (urea: female 3.71 ± 1.00, male 4.42 ± 1.14; Pro: female 3/46, male 12/70; hs‐CRP: female 1/46, male 3/70; ESR: female 43.32 ± 33.24, male 21.64 ± 21.82). UA is lower in the severe group (female 146.90 ± 54.01, male 139.34 ± 66.95) than in mild group (female 251.99 ± 64.35, male 339.81 ± 71.32). CREA and PCT did not show a significant difference between mild and severe patients, but the difference among the five biological markers (urea, Pro, hs‐CRP, ESR, and UA) between mild and severe patients we tested was small (P < .05). Conclusion Severe COVID‐19 patients had higher levels of urea and Pro, while their UA levels were lower, reflecting poor kidney function in severe patients. However, higher levels of hs‐CRP, ESR indicated that inflammatory responses were more active in severe patients.


| INTRODUC TI ON
Severe acute respiratory syndrome coronavirus 2 (SARS-  belongs to the β-genus of the coronavirus family, containing an envelope of single-stranded RNA virus that is contagious to humans. 1 The outbreak of SARS-CoV-2 constitutes a public health emergency of international concern, the disease triggered by the latest coronavirus 2019 (COVID- 19) is spreading rapidly across the world. [2][3][4] Recently, Charleen and his colleagues found SARS-CoV-2 RNA in patient stool samples and also detected in urine. 5 Previous studies have shown that the SARS-CoV-2 can be transmitted via contact or fomites and also possible to spread by the fecal-oral route. 5 But there is no evidence of the capacity of vertical transmission. 6 Wan et al 1 proposed that the human-to-human transmission ability of 2019-nCoV-2 be acquired through the 2019-nCoV-2 RBD sequence and its receptor-binding motif (RBM) that directly contacts ACE2. The incubation period for COVID-19 is approximately 5-6 days, and the serial interval range estimates from 4.4 to 7.5 days. [7][8][9] Meanwhile, Zou et al 10 pointed out the possibility that viremia might be high enough to trigger transmission for 1-2 days before onset. Recent research has identified the evolution of SARS-CoV-2, leading to the outbreaks and described the potential for viral spread from animals to humans. 11 Quarantine, social distancing, and isolation of infected populations can contain the epidemic. 12 Fever, cough, dyspnea, and radiographic findings of pneumonia are the main clinical characteristics of patients with COVID-19. [13][14][15] Some less common symptoms have been sputum, producing headache, hemoptysis, and gastrointestinal symptoms. 13 Evidence shows that SARS-CoV-2 may cause cardiac injury. 16 Globally, there have been 12 401 262 confirmed cases of COVID-19 by July 12, 2020, including 559 047 deaths, as reported by WHO. In particular, the major risk factors for COVID-19 mortality are considered to be the advanced age (>60 years), male sex, and presence of comorbidities. 17 Previous research found that acute renal impairment was uncommon in SARS but had a remarkably high mortality rate (91.7%, 33 of 36 cases). 18 However, different results are derived based on research that showed more than 40% of patients had clinical renal disease symptoms and observed a significantly higher in-hospital death rate in patients with renal abnormalities. 19 Wang et al 20  In order to investigate the relationship between COVID-19 infection and renal function, multiple clinical diagnostic parameters, including CREA, UA, urea, Pro, ESR, hs-CRP, and PCT, were compared between patients with mild and severe symptoms. We believe that the present study may help to gain a deeper understanding of the pathogenicity of SARS-CoV-2. The hs-CRP, Pro, and PCT data were analyzed with the chi-squared test. Graph Pad Prism version 5.0 (Graph Pad software) was used for preparing all the figures. Significant differences have been identified, as P < .05.

| RE SULTS
Due to the difference between male and female biomarkers, we compared all data in the severe and mild groups according to gender.

| Analysis of parameters related to kidney function: Female
We obtained 53 samples from females, including 7 mild cases and 46 severe cases. Our results showed that CREA levels of the above two cases (mild 55.78 ± 9.36, severe 60.47 ± 21.00) were not significantly different (P = .5812, Figure 1A). The UA level was considerably  Figure 1B). The average urea level of the severe group (7.00 ± 3.31) was significantly higher than that of the mild group (3.71 ± 1.00; P = .04, Figure 1C). The chi-squared test reveals the significant effects of Pro seen in severe cases (P < .0001, Table 2).

| Analysis of parameters related to kidney function: Male
Seventy samples were obtained from mild patients, and 13 from severe patients. The independent samples t test was used for evaluating quantitative variables.

| Analysis of inflammatory markers
We classified as normal and abnormal samples within the normal range of hs-CRP or PCT. The chi-square test analyzed the data of hs-CRP and PCT.

| Analysis of inflammatory markers: Male
The hs-CRP (Table 3) and ESR levels were significantly different between two groups (mild 21.64 ± 21.82, severe 67.85 ± 22.77; P < .0001, Figure 2D). The results were higher in severe cases, while there is no significant difference found in PCT (P > .05, Table 3).

| D ISCUSS I ON
According to a previous report, 19% (   Note: There was significant difference in hs-CRP between the severe and mild groups (Female: P = .0335, Male: P = .0019). No significant difference showed in PCT between the severe and mild groups (Female: P = .2319, Male: P = .0625).
Abbreviations: hs-CRP, hypersensitivity C -reactive protein; PCT, serum procalcitonin; The mild, the mild group; The severe, the severe group.

ACK N OWLED G M ENTS
The materials used in this study were provided by the department of Laboratory Medicine, Shanghai Public Health Clinical Center, to which we are grateful. The technical assistance of Professor Zhaoqin Zhu was greatly appreciated.

CO N FLI C T O F I NTE R E S T
The authors report no conflicts of interest in this work.

E TH I C A L A PPROVA L
This study was approved by the Research Ethics Review Committee of the Shanghai Public Health Clinical Center (2020-Y025-01).