Abstract
Introduction
This study evaluated the incidence, clinical characteristics, and risk factors of kidney involvement in patients with the Omicron variant infection in the post-acute treatment phase in Tianjin, China.
Methods
Data were collected from 430 patients with Omicron variant infection in Tianjin, China. Demographics, comorbidities, laboratory blood tests, urinalysis, vaccination status, and COVID-19 clinical classification were assessed. Patients were grouped based on kidney involvement, and associated risk factors of kidney involvement were also investigated.
Results
Asymptomatic, mild, ordinary, and severe patients with Omicron COVID-19 variant comprised 1.5%, 49.1%, 48.9%, and 0.5% of the sample population, respectively, without critical illness or death. The incidences of hematuria, proteinuria, and concurrent hematuria and proteinuria were 14.7%, 14.2%, and 5.1%, respectively. Patients with and without kidney involvement differed in age, body mass index (BMI), comorbidity, creatinine levels, estimated glomerular filtration rate, and C-reactive protein (CRP) levels. Age, hypertension, higher CRP levels, and higher BMI were linked with kidney involvement.
Conclusion
The majority of the patients suffered from mild or ordinary symptoms of Omicron COVID-19 infection. The primary kidney involvement was hematuria and proteinuria. Proteinuria was significantly associated with Omicron variant infection, and patients with hypertensive comorbidity, higher CRP, and higher creatinine levels were at increased risk of proteinuria after Omicron variant infection.
Keywords: Omicron, Kidney involvement, Proteinuria, Hematuria
Introduction
Coronavirus disease 2019 (COVID-19) is a contagious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes severe pulmonary diseases and several extrapulmonary symptoms [1]. COVID-19 has high morbidity and mortality as it affects the cardiovascular, hematologic, renal, endocrinologic, neurologic, gastrointestinal and hepatobiliary, ophthalmologic, and dermatologic systems [2, 3]. SARS-CoV-2 can cause acute kidney injury (AKI), proteinuria, and hematuria [4, 5]. Kidney injury is linked to poor clinical outcomes; proteinuria and hematuria in noncritical patients are independently linked to disease progression, whereas AKI occurs primarily in critical patients. New-onset AKI patients have higher mortality rates than those without AKI, predicting worse short-term outcomes [2].
As of January 2022, COVID-19 had spread rapidly throughout the world, resulting in 5.27 million cases and over 6 million deaths [6]. As it spreads, the virus evolves and produces new variants. The new SARS-CoV-2 Omicron strain is contagious and spreads faster than other COVID-19 strains. The Omicron variant can evade immune system defenses, and the COVID-19 vaccination also has a limited effect on the strain [7]. However, most patients suffering from the Omicron variant have milder symptoms and need less oxygen support than those affected by previous variants.
On January 8, 2022, China reported its first Omicron case. In the next 2 months, Omicron replaced the Delta variant throughout the country. Despite numerous clinical reports on COVID-19, little is known about the Omicron variant, particularly how it affects the kidneys. The present study aimed to fill this gap in the literature. After 7–14 days of acute phase treatment at Tianjin Haihe Hospital, the first batch of 430 Omicron patients from China was admitted to Tianjin First Central Hospital. Based on hospitalization data, this study evaluated the incidence, clinical characteristics, and risk factors of kidney involvement in patients with the Omicron variant in the post-acute phase of treatment.
Methods
Study Participants
At Tianjin Haihe Hospital, 430 patients with Omicron COVID-19 infection underwent acute phase treatment. From January 21, 2022, to March 7, 2022, these patients were transferred to Tianjin First Central Hospital for rehabilitation after receiving acute phase treatment. In the present cohort study, we retrospectively selected hospitalized post-acute phase patients with at least one urinalysis and one serum creatinine level measurement. Patients aged <1 year or with chronic kidney disease (CKD) were excluded. Nucleic acid was extracted from respiratory samples using commercial kits (Zybio, 5203050). The WHO protocol was used to identify two target genes, the open reading frame of 1ab (ORF1ab) and the nucleocapsid protein (N), using reverse transcription-polymerase chain reaction [8].
Data Collection
We collected patients' demographic and clinical data from electronic medical records, including sex, age, height, body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), and comorbid conditions such as hypertension, diabetes mellitus, and cardiovascular and cerebrovascular diseases (CVD). Blood pressure was measured at admission to the hospital. Blood and urine samples were collected in the morning 2 days after admission, and hematological, biochemistry, and urinalysis tests were performed. Hematological parameters included hemoglobin, white blood cells (WBCs), platelets, alanine transaminase, aspartate aminotransferase, blood urea nitrogen (BUN), creatinine, sodium, C-reactive protein (CRP), and interleukin 6 (IL-6). A routine dipstick urine examination and a microscopic examination of urine sediment were performed. After ruling out urinary tract infection, the presence of 1+ protein or greater in urinalysis was defined as proteinuria. Hematuria was defined as urine red blood cell count >13.1/μL in males and >30.7/μL in females according to the diagnostic criteria of routine urine tests in the central laboratory of Tianjin First Central Hospital (UF-1000i, Sysmex Corporation, Kobe, Japan) [9]. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation for adult patients and the Schwartz-Lyon equation [10] for patients aged ≤18 years.
COVID-19 clinical classification, vaccination dose, and types were recorded. According to Chinese recommendations for diagnosis and treatment of novel coronavirus (SARS-CoV-2) infection (trial 8th version), we classified all patients as asymptomatic, mild, ordinary, or severe patients with COVID-19 [11]. Asymptomatic refers to a positive nucleic acid test with no clinical symptoms. Mild patients have mild clinical symptoms with no pneumonia on imaging. Ordinary indicates obvious clinical symptoms associated with pneumonia on imaging. Severe patients with COVID-19 have any of the following: (1) respiratory rate ≥30 times/minute; (2) oxygen saturation during air intake ≤93% in the resting state; (3) partial pressure of arterial blood oxygen/concentration ≤300 mm Hg; (4) progressive aggravation of clinical symptoms and pulmonary imaging >50% within 24–48 h.
Statistical Analysis
Normally distributed continuous variables were presented as mean ± standard deviation, non-normally distributed continuous variables (CRP and IL-6) as medians and interquartile ranges, and categorical variables as frequencies and percentages. Independent samples t test or Mann-Whitney U test compared continuous variables between groups. If appropriate, the categorical variables were compared using the χ2 test or Fisher's exact test. The associated risk factors for hematuria and proteinuria were identified using univariable and multivariable logistic regression in a stepwise forward manner. Parameters with p value < 0.05 in the univariable model were included in the multivariable model. The odds ratio and 95% confidence interval were determined. The correlations between kidney injury indicators and the clinical classification of Omicron variant infection were examined using Pearson correlation tests. All statistical analyses were conducted using SPSS, version 22 (IBM, Japan) and STATA, version 14 (StataCorp LP, College Station, TX, USA). A p value < 0.05 was considered statistically significant.
Results
Demographic and Clinical Characteristics of Patients
This study included 409 patients, excluding 1 patient aged <1 year, 8 patients with CKD, and 12 patients without urinalysis results. Table 1 shows the demographic and clinical characteristics of patients. The mean age was 36.54 ± 21.44 years, and the mean body mass index (BMI) was 23.62 ± 5.47. There were 177 male and 232 female patients. The proportion of comorbidity was 19.6% (80/409) for hypertension, 8.3% (34/409) for diabetes, and 5.6% (23/409) for CVD. The types of kidney involvement included hematuria, proteinuria, and concurrent hematuria and proteinuria, with kidney involvement incidences at 14.7% (60/409), 14.2% (58/409), and 5.1% (21/409), respectively. The mean serum creatinine level was 54.31 ± 15.47 μmol/L, and eGFR was 112.43 ± 18.06 mL/min/1.73 m2. However, no cases of AKI were observed. Table 2 shows the vaccine and clinical classifications of COVID-19. The overall vaccination rate was 91.4%: 4.9% (20/409), 49.9% (204/409), and 36.7% (150/409) of the patients received one, two, and three doses, respectively. Sinovac and Sinopharm were the most commonly used vaccines for immunization: 47.9% (179/409) of patients received multiple doses of Sinopharm, and 37.7% (141/409) were treated with Sinovac. As for COVID-19 clinical classification, asymptomatic, mild, ordinary, and severe patients with COVID-19 accounted for 1.5% (6/409), 49.1% (201/409), 48.9% (200/409), and 0.5% (2/409), respectively, without critical cases or death.
Table 1.
Demographic and clinical characteristics in all patients and patients with kidney involvement
| Variables | All patients (n = 409) | Hematuria |
Proteinuria |
Hematuria and proteinuria |
||||||
|---|---|---|---|---|---|---|---|---|---|---|
| yes (n = 60) | no (n = 349) | p valuea | yes (n = 58) | no (n = 351) | p valuea | yes (n = 21) | no (n = 388) | p valuea | ||
| Demographics | ||||||||||
| Age, years (n = 409) | 36.54±21.44 | 43.70±17.85 | 35.31±21.78 | 0.022 | 48.93±20.91 | 34.50±20.85 | <0.001 | 47.24±20.76 | 35.96±21.35 | 0.019 |
| Categorical of ages (n = 409) | 0.002 | <0.001 | 0.081 | |||||||
| ≤18 years, n (%) | 112(27.4) | 6(10.0) | 106(30.4) | 6(10.3) | 106 (30.2) | 2 (9.5) | 110(28.4) | |||
| 19–59 years, n (%) | 233 (57.0) | 46 (76.7) | 187(53.6) | 34 (58.6) | 199 (56.7) | 13 (61.9) | 220 (56.7) | |||
| ≥60 years, n (%) | 64(15.6) | 8(13.3) | 56(16.0) | 18(31.0) | 46(13.1) | 6 (28.6) | 58(14.9) | |||
| BMI, Kg/m2 (n = 409) | 23.62±5.47 | 25.41±5.05 | 23.31±5.49 | 0.348 | 26.35±5.41 | 23.17±5.36 | <0.001 | 27.44±5.53 | 23.41±5.40 | 0.001 |
| Comorbidities | ||||||||||
| Hypertension, n (%) (n = 409) | 80(19.6) | 22 (36.7) | 58(16.6) | 0.001 | 28 (48.3) | 52(14.8) | <0.001 | 10(47.6) | 70(18.0) | 0.003 |
| Diabetes, n (%) (n = 409) | 34 (8.3) | 5 (8.3) | 29 (8.3) | 1.000 | 12(20.7) | 22 (6.3) | 0.001 | 3(14.3) | 31 (8.0) | 0.403 |
| CVD, n (%) (n = 409) | 23 (5.6) | 3 (5.0) | 20 (5.7) | 1.000 | 8(13.8) | 15 (4.3) | 0.009 | 3 (14.3) | 20 (5.2) | 0.106 |
| Vital signs | ||||||||||
| SBP, mm Hg (n = 409) | 126.01±18.90 | 131.25±17.06 | 125.11±19.07 | 0.509 | 134.95±17.07 | 124.54±18.80 | <0.001 | 136.86±15.97 | 125.43±18.88 | 0.007 |
| DBP, mm Hg (n = 409) | 84.14±11.94 | 88.08±9.51 | 83.46±12.20 | 0.005 | 88.64±10.70 | 83.40±11.99 | 0.002 | 91.05±7.76 | 83.77±12.02 | 0.006 |
| Laboratory parameters | ||||||||||
| HGB, g/L (n = 408) | 128.14±16.61 | 129.97±18.79 | 127.83±16.22 | 0.076 | 127.78±19.09 | 128.21±16.20 | 0.855 | 128.53±21.61 | 128.12±16.33 | 0.915 |
| WBC, × 109/L (n = 408) | 6.65±2.14 | 7.06±2.57 | 6.58±2.05 | 0.026 | 6.98±2.51 | 6.59±2.07 | 0.211 | 7.64±3.41 | 6.60±2.04 | 0.030 |
| PLT, ×109/L (n = 408) | 281.15±73.87 | 266.00±59.59 | 283.83±75.87 | 0.100 | 281.60±75.77 | 281.08±73.65 | 0.960 | 268.19±73.54 | 281.87±73.92 | 0.409 |
| ALT, U/L (n = 408) | 47.98±65.03 | 50.99±41.88 | 47.47±68.26 | 0.302 | 56.14±71.37 | 46.63±63.92 | 0.303 | 46.85±30.50 | 48.05±66.41 | 0.935 |
| AST, U/L (n = 400) | 37.76±44.79 | 33.36±17.73 | 38.54±47.98 | 0.156 | 38.68±39.09 | 37.43±45.27 | 0.724 | 30.03±10.37 | 38.19±45.91 | 0.417 |
| BUN, mmol/L (n = 407) | 4.11±1.24 | 4.32±1.27 | 4.07±1.24 | 0.403 | 4.69±1.53 | 4.01±1.16 | <0.001 | 5.06±1.46 | 4.05±1.21 | <0.001 |
| Cr, µmol/L (n = 407) | 54.31±15.47 | 57.47±15.56 | 53.76±15.42 | 0.791 | 60.70±15.23 | 53.25±15.28 | 0.001 | 63.26±16.78 | 53.82±15.27 | 0.006 |
| eGFR, mL/min/1.73 m2 (n = 407) | 112.43±18.06 | 111.27±15.05 | 112.63±18.55 | 0.034 | 108.81±23.30 | 127.77±31.44 | <0.001 | 107.74±20.62 | 126.01±31.32 | 0.009 |
| Na, mmol/L (n = 400) | 140.58±1.93 | 140.78±1.67 | 140.55±1.97 | 0.289 | 140.70±1.93 | 140.56±1.93 | 0.610 | 140.76±1.81 | 140.57±1.94 | 0.661 |
| CRP, mg/L (n = 409) | 0.70 [0.26–1.66] | 0.97 [0.42–2.10] 0.63 [0.24–1.48] | 0.016 | 1.43 [0.51–2.70] | 0.58 [0.24–1.43] <0.001 | 1.43 [0.67–2.27] | 0.64 [0.25–1.53] | 0.010 | ||
| IL-6, pg/mL (n = 409) | 0.00 [0.00–1.83] | 0.00 [0.00–1.77] 0.00 [0.00–1.87] | 0.637 | 0.00 [0.00–2.39] | 0.00 [0.00–1.69] | 0.252 | 0.00 [0.00–1.93] | 0.00 [0.00–1.91] | 0.972 | |
BMI, body mass index; CVD, cardiovascular and cerebrovascular diseases; SBP, systolic blood pressure; DBP, diastolic blood pressure; HGB, hemoglobin; WBC, white blood cell; PLT, platelets; ALT, alanine transaminase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; Cr, creatinine; eGFR, estimated glomerular filtration rate; CRP, C-reactive protein; IL-6, interleukin 6.
Independent sample f test, Mann-Whitney U test, χ2 test, or Fisher's exact test as appropriate.
Table 2.
COVID-19 vaccine and clinical classifications in all patients and patients with kidney involvement
| Variables | All patients (n = 409) | Hematuria |
Proteinuria |
Hematuria and proteinuria |
||||||
|---|---|---|---|---|---|---|---|---|---|---|
| yes (n = 60) | no (n = 349) | p valuea | yes (n = 58) | no (n = 351) | p valuea | yes (n = 21) | no (n = 388) | p valuea | ||
| Vaccine dosage (n = 409), n (%) | ||||||||||
| Unvaccinated | 35 (8.6) | 2 (3.3) | 33 (9.5) | 0.374 | 8(13.8) | 27 (7.7) | 0.345 | 2 (9.5) | 33 (8.5) | 0.645 |
| One dose | 20 (4.9) | 2 (3.3) | 18(5.2) | 3 (5.2) | 17 (4.8) | 1 (4.8) | 19(4.9) | |||
| Two doses | 204 (49.9) | 31 (51.7) | 173 (49.6) | 24(41.4) | 180 (51.3) | 13(61.9) | 191 (49.2) | |||
| Three doses | 150 (36.7) | 25(41.7) | 125 (35.8) | 23 (39.7) | 127(36.2) | 5 (23.8) | 145(37.4) | |||
| Vaccine type (n = 374), n (%) | ||||||||||
| Sinovac vaccine | 141 (37.7) | 24 (41.4) | 117(37.0) | 0.335 | 20 (40.0) | 121 (37.3) | 0.853 | 8(42.1) | 133 (37.5) | 0.544 |
| Sinopharm vaccine | 179 (47.9) | 23 (39.7) | 156 (49.4) | 24 (48.0) | 155(47.8) | 7 (36.8) | 172 (48.5) | |||
| Others | 54(14.4) | 11 (19.0) | 43(13.6) | 6(12.0) | 48(14.8) | 4(21.1) | 50(14.1) | |||
| Clinical classification (n = 409), n (%) | ||||||||||
| Asymptomatic cases) | 6(1.5) | 1 (1.7) | 5(1.4) | 0.619 | 0 (0.0) | 6(1.7) | 0.079 | 0 (0.0) | 6(1.5) | 0.169 |
| Mild type | 201 (49.1) | 27 (45.0) | 174 (49.9) | 21 (36.2) | 180 (51.3) | 6 (28.6) | 195(50.3) | |||
| Ordinary type | 200 (48.9) | 32 (53.3) | 168 (48.1) | 37 (63.8) | 163(46.4) | 15(71.4) | 185 (47.7) | |||
| Severe type | 2(0.5) | 0 (0.0) | 2 (0.6) | 0 (0.0) | 2 (0.6) | 0 (0.0) | 2 (0.5) | |||
χ2 test or Fisher's exact test as appropriate.
Comparison of Clinical Features between Patients with or without Kidney Involvement
Patients with hematuria at admission were older and had a higher prevalence of hypertension, lower eGFR, and higher CRP than those without hematuria. Patients with proteinuria were older and had a higher prevalence of hypertension, diabetes, and CVD; higher SBP and DBP; higher BUN and creatinine levels; lower eGFR; and higher CRP levels than those without proteinuria. Except for the complications related to hypertension, higher BMI, and higher WBC count, the clinical characteristics of patients with concurrent hematuria and proteinuria were identical to those of proteinuria patients. The above results are listed in Table 1. Vaccine dosage, type, and clinical classification of COVID-19 did not change between the two groups in the three types of kidney involvement (Table 2).
Univariable and Multivariable Logistic Regression Analysis of Clinical Factors Associated with Kidney Involvement
To find the factors associated with kidney involvement, we first included clinical indicators of hematuria and proteinuria in the univariable logistic regression model. Age, BMI, and hypertension all affected hematuria. Age, BMI, hypertension, diabetes, CVD, SBP, DBP, eGFR, BUN levels, creatinine levels, CRP levels, and clinical classification of COVID-19 affected proteinuria. Concurrent hematuria and proteinuria were linked to age, BMI, hypertension, SBP, DBP, eGFR, WBC counts, BUN levels, and creatinine levels (Table 3).
Table 3.
Associated clinical factors for kidney involvement by univariate logistic regression analysis
| Variables | Hematuria |
Proteinuria |
Hematuria and proteinuria |
|||
|---|---|---|---|---|---|---|
| OR (95% CI) | p value | OR (95% CI) | p value | OR (95% CI) | p value | |
| Sex (male, %) | 0.926 (0.531–1.613) | 0.785 | 1.167 (0.668–2.038) | 0.587 | 1.471 (0.610–3.545) | 0.390 |
| Age, years | 1.019 (1.005–1.032) | 0.006 | 1.034 (1.019–1.049) | <0.001 | 1.025 (1.004–1.048) | 0.022 |
| Categorical of ages | ||||||
| ≤18 years | Reference | Reference | Reference | |||
| 19–59 years | 4.346 (1.796–10.514) | 0.001 | 3.018 (1.228–7.419) | <0.001 | 5.690 (1.113–29.086) | 0.037 |
| ≥60 years | 2.524 (0.834–7.635) | 0.101 | 6.913 (2.577–18.542) | 0.016 | 3.250 (0.721–14.656) | 0.125 |
| BMI, Kg/m2 | 1.072 (1.019–1.127) | 0.007 | 1.113 (1.055–1.175) | <0.001 | 1.129 (1.047–1.217) | 0.002 |
| Hypertension, n (%) | 2.905 (1.601–5.271) | <0.001 | 5.367 (2.965–9.713) | <0.001 | 4.130 (1.688–10.103) | 0.002 |
| Diabetes, n (%) | 1.003 (0.372–2.703) | 0.995 | 3.901 (1.810–8.409) | 0.001 | 1.919 (0.536–6.877) | 0.317 |
| CVD, n (%) | 0.866 (0.249–3.009) | 0.821 | 3.584 (1.445–8.886) | 0.006 | 3.067 (0.834–11.280) | 0.092 |
| SBP, mm Hg | 1.017 (1.003–1.032) | 0.021 | 1.029 (1.014–1.044) | <0.001 | 1.030 (1.008–1.053) | 0.008 |
| DBP, mm Hg | 1.036 (1.010–1.062) | 0.006 | 1.041 (1.015–1.068) | 0.002 | 1.059 (1.016–1.103) | 0.006 |
| HGB, g/L | 1.008 (0.991–1.025) | 0.357 | 0.998 (0.982–1.015) | 0.855 | 1.001 (0.975–1.028) | 0.914 |
| WBC, ×109/L | 1.094 (0.977–1.226) | 0.120 | 1.076 (0.958–1.208) | 0.217 | 1.162 (1.005–1.344) | 0.043 |
| PLT, ×109/L | 0.997 (0.993–1.000) | 0.085 | 1.000 (0.996–1.004) | 0.960 | 0.997 (0.991–1.004) | 0.407 |
| ALT, U/L | 1.001 (0.997–1.005) | 0.699 | 1.002 (0.998–1.005) | 0.311 | 1.000 (0.993–1.007) | 0.935 |
| AST, U/L | 0.995 (0.982–1.007) | 0.394 | 1.001 (0.996–1.006) | 0.726 | 0.982 (0.950–1.015) | 0.288 |
| BUN, mmol/L | 1.162 (0.943–1.430) | 0.158 | 1.478 (1.201–1.820) | <0.001 | 1.636 (1.235–2.167) | 0.001 |
| Cr, µmol/L | 1.015(0.998–1.033) | 0.087 | 1.031 (1.013–1.050) | 0.001 | 1.038 (1.010–1.068) | 0.008 |
| eGFR, mL/min/1.73 m2 | 0.996 (0.981–1.011) | 0.590 | 0.972 (0.956–0.989) | 0.001 | 0.974 (0.948–0.999) | 0.044 |
| Na, mmol/L | 1.064 (0.920–1.231) | 0.401 | 1.039 (0.898–1.202) | 0.609 | 1.053 (0.835–1.328) | 0.660 |
| CRP, mg/L | 1.011 (0.975–1.049) | 0.543 | 1.045 (1.013–1.078) | 0.005 | 1.026 (0.981–1.073) | 0.263 |
| IL-6, pg/mL | 1.008 (0.956–1.062) | 0.773 | 1.018 (0.965–1.074) | 0.512 | 1.055 (0.994–1.120) | 0.079 |
| Vaccine dosage | 1.352 (0.945–1.934) | 0.099 | 0.888 (0.650–1.214) | 0.457 | 0.824 (0.513–1.323) | 0.423 |
| Vaccine type | 1.022 (0.679–1.538) | 0.918 | 0.888 (0.572–1.380) | 0.599 | 1.051 (0.537–2.058) | 0.885 |
| Clinical classification | 1.067 (0.813–1.400) | 0.639 | 1.335 (1.007–1.769) | 0.044 | 1.544 (0.969–2.460) | 0.068 |
OR, odds ratio; CI, confidence interval.
The significant indicators from the univariable logistic regression model were integrated into the multivariable logistic regression model in a stepwise forward manner. Age and hypertension were linked to hematuria. Patients aged 19–59 years had a considerably higher risk of hematuria than those aged ≤18 years. Higher CRP, higher creatinine levels, and hypertension were associated with proteinuria. Hypertension, higher BMI, and higher WBC count were independent predictors of concurrent hematuria and proteinuria (Table 4).
Table 4.
Associated clinical factors for kidney involvement by multivariate logistic regression analysis
| Variables | Hematuria |
Variables | Proteinuria |
Variables | Hematuria and proteinuria |
|||
|---|---|---|---|---|---|---|---|---|
| OR (95% CI) | p value | OR (95% CI) | p value | OR (95% CI) | p value | |||
| Hypertension, n (%) | 3.094(1.575–6.080) | 0.001 | Hypertension (n, %) | 4.616(2.501–8.519) | <0.001 | Hypertension n (%) | 3.130(1.218–8.045) | 0.018 |
| Categorical of ages | CRP, mg/L | 1.041 (1.007–1.077) | 0.018 | BMI, Kg/m2 | 1.109(1.022–1.204) | 0.013 | ||
| ≤18 years | Reference | Cr, µmol/L | 1.025(1.006–1.046) | 0.011 | WBC, ×109/L | 1.911 (1.023–1.388) | 0.024 | |
| 19–59 years | 3.409(1.382–8.411) | 0.008 | ||||||
| ≥60 years | 1.195 (0.352–4.059) | 0.775 | ||||||
OR, odds ratio; CI, confidence interval.
Associations between Kidney Injury Indicators and Omicron Variant Infection
Pearson correlation tests were used to examine the associations between kidney injury indicators (hematuria, proteinuria, concurrent hematuria and proteinuria) and Omicron variant infection. The results showed that proteinuria was significantly associated with Omicron variant infection (p = 0.043) (Table 5).
Table 5.
Associations between kidney injury indicators and Omicron variant infection
| Kidney injury indicators | Pearson coefficient (95% CI) | p value |
|---|---|---|
| Hematuria | 0.023 (−0.073–0.117) | 0.640 |
| Proteinuria | 0.100 (0.003–0.195) | 0.043 |
| Hematuria and proteinuria | 0.093 (0.005–0.179) | 0.061 |
CI, confidence interval.
Discussion
COVID-19 is a prevalent infectious disease. Although it primarily affects the lungs, it can also affect the kidneys. Severe patients with COVID-19 often have increased creatinine levels, BUN levels, hematuria, proteinuria, and AKI [12]. However, the effect of the Omicron variant on kidneys has not been reported. More research is required on kidney involvement and associated risk factors in patients with Omicron variant infection.
AKI, the most fatal SARS-CoV-2 complication, has garnered increasing attention. AKI incidence varies substantially between studies, from 8% to 50% [4, 13, 14, 15, 16, 17]. COVID-19 patients with AKI have a high mortality risk [2, 16, 18, 19]. In this study, only 2 severe patients with COVID-19 had a better prognosis. There were no critical cases or deaths; no patients needed mechanical ventilation and intensive care unit treatment; none had abnormal BUN and creatinine levels; no patients satisfied AKI diagnostic criteria. Renal dysfunction or AKI was not the predominant kidney involvement in this cohort of Omicron variant infection. Our data confirm that Omicron patients had mild or moderate symptoms, and their hospital stays were shorter.
It should be noted that the patients in this cohort were not in the acute phase of Omicron variant infection. Medical ethics and patient data confidentiality prevent us from obtaining these patients' clinical examination results from another facility. We do not know whether the patients had transient renal function changes in the acute phase. Our clinical data comprise the short-term follow-up observations of the post-acute phase. AKI did not occur in the post-acute rehabilitation phase.
Patients suffering from COVID-19 had exhibited kidney damage in two-thirds of cohort studies [16, 17, 20, 21, 22, 23, 24]. However, previous studies focused on AKI and overlooked proteinuria and microscopic hematuria. Proteinuria and hematuria are common in China [16, 17, 20] and were seen in 86% and 82% of COVID-19-related deaths, respectively, during hospitalization [17]. COVID-19 patients with kidney involvement exhibited a higher mortality rate (11.2%) than those without kidney involvement (1.2%) [20]. Cheng et al. [16] analyzed data from 701 Chinese patients and found symptoms of proteinuria (43.9%) and hematuria (26.7%). A study in India found urine abnormalities in 71%, proteinuria in 58.2%, hematuria in 17.3%, pyuria in 8.2%, and concurrent proteinuria and hematuria in 13.6% of patients [21]. A study in Spain reported proteinuria in 88.9% and hematuria in 79.4% of patients [22]. Other studies showed proteinuria prevalence in 36.1–59% and hematuria in 6–50% of patients [14, 23, 24].
In the present study, we identified 14.7% cases of hematuria, 14.2% of proteinuria, and 5.1% of concurrent hematuria and proteinuria. This proportion is smaller than the data mentioned above [16, 17, 20, 21, 22, 23, 24], suggesting that Omicron variant infection causes lighter urine abnormalities such as hematuria and proteinuria than SARS-CoV-2 and other variants. We excluded CKD participants from the analysis. Nonetheless, we cannot determine whether hematuria or proteinuria occurred upon admission or during the hospital stay. The incidence of hematuria and proteinuria has reached 14.7% and 14.2%, respectively, higher than the prevalence of CKD at 10.8%, in the general population in China [25], indicating that Omicron infection may cause new-onset kidney involvement.
Proteinuria and hematuria are not as critical clinically as AKI, but their influence on COVID-19 prognosis cannot be overlooked. Proteinuria and hematuria can be used as independent predictors of COVID-19 severity [26, 27]. Our study demonstrated that proteinuria was significantly associated with Omicron variant infection. A prospective cohort study showed that 62.4% of COVID-19 patients had proteinuria upon admission and 37.5% developed proteinuria during hospitalization. The overall prognosis is poor in patients with newly developed proteinuria [28]. Even in patients with mild symptoms, there is an increased risk of long-term renal damage [29]. The direct infection of renal cells and lipid mediator storm caused by SARS-Cov-2 can promote tubulointerstitial fibrosis at the molecular level, which increases the possibility of acute kidney involvement and CKD [30, 31]. Although the incidence of hematuria and albuminuria is not high in this study, the kidney involvement represented by hematuria and albuminuria is likely to be the starting point of adverse renal outcomes in long-term follow-up. Therefore, it is suggested that albuminuria and hematuria should be monitored throughout the clinical process of Omicron infection including follow-up.
Risk factors of proteinuria and hematuria in COVID-19 patients are unknown. This study found that older age, hypertension, higher CRP levels, and higher BMI were linked with kidney involvement. In the general population, hypertension is one of the risk factors for proteinuria. In this study, we reached a similar conclusion: hypertensive comorbidity would increase the risk of proteinuria when infected with the Omicron variant. CRP levels indicate inflammation, which increases the risk of renal impairment. Hematuria and proteinuria may result from severe renal inflammation [18, 32].
SARS-CoV-2 binding to angiotensin-converting enzyme 2 (ACE2) on endothelial cells may cause a systemic vasculitis-like syndrome [33]. Virus particles in renal endothelial cells suggest that viremia may cause kidney endothelial damage and kidney injury [34]. Cytokine storm may cause kidney immune inflammatory damage and endothelial cell dysfunction, similar to severe influenza virus infection [35]. Proteinuria may be caused by kidney endothelial cells, according to autopsy findings. Endothelial dysfunction or podocyte damage may cause transient high albuminuria [24]. Severe proximal tubular injury can also impair receptor-mediated endocytosis [36]. Furthermore, tubular blockage and heme pigment-induced renal inflammation could cause hematuria or proteinuria [37].
Hematuria and proteinuria were linked to increased BMI in this study. This is consistent with previous research that found obesity to be a risk factor for kidney injury in COVID-19 patients [38, 39, 40]. Higher BMI or obesity was associated with increased severity and a worse prognosis in COVID-19 patients. This is due to an increase in the individual's inflammatory state (dysregulation of adipokines and greater release of IL-6 and tumor necrosis factor-alpha), a compromised immune response, an increased thrombotic risk, and detrimental effects on pulmonary mechanics. Furthermore, ACE2 receptors are found in adipose tissue, which is thought to be a significant viral reservoir [39, 41].
This study has some limitations. Although we have excluded patients with a history of CKD, we cannot completely determine that proteinuria is only related to Omicron infection and has no correlations with other risk factors such as hypertension, diabetes, and older age. It is suggested that we pay special attention to screening kidney damage indicators in patients with hypertension, diabetes, and old age when infected with Omicron.
Conclusion
This study is one of the first to report on kidney involvement of 409 post-acute phase Omicron patients and analyze the associated risk factors. The majority of the patients suffered from mild or ordinary symptoms of Omicron infection. The primary renal involvement was hematuria and proteinuria. Proteinuria was significantly associated with Omicron variant infection, and patients with hypertensive comorbidity, higher CRP, and higher creatinine levels were at increased risk of proteinuria after Omicron variant infection. This study is a short-term follow-up observational study with a large sample size. Standardized follow-up strategies should be implemented to closely monitor the long-term renal outcomes of Omicron patients.
Statement of Ethics
This study has been granted an exemption from requiring written informed consent for it is a retrospective medical chart review. Before analysis, the patient records and information were anonymized and de-identified. This study was approved by the Tianjin First Center Hospital's Institutional Review Board (IRB; ethics approval document no. 22HHXBJC00001) and was conducted following the principles of the Helsinki Declaration.
Conflict of Interest Statement
The authors declare no potential conflicts of interest concerning the research, authorship, and publication of this article.
Funding Sources
The Haihe Laboratory of Cell Ecosystem Innovation Fund provided funding for this study.
Author Contributions
Research idea and study design: Lanbo Teng and Wenxiu Chang; data collection and manuscript writing: Lanbo Teng; data analysis/interpretation and statistical analysis: Wenxiu Chang. All authors read and approved the final version of the manuscript.
Data Availability Statement
This paper contains all of the data generated or analyzed during the study. Any further queries should be directed to the corresponding author.
Acknowledgments
We express our gratitude to everyone involved in medical care and epidemic prevention for their tireless efforts during the COVID-19 pandemic. We thank everyone at Tianjin First Central Hospital.
Funding Statement
The Haihe Laboratory of Cell Ecosystem Innovation Fund provided funding for this study.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
This paper contains all of the data generated or analyzed during the study. Any further queries should be directed to the corresponding author.