Acute kidney injury in patients with COVID-19: a retrospective cohort study from Switzerland.

BACKGROUND: Data about patients in Europe with corona virus disease-2019 (COVID-19) and acute kidney injury (AKI) are scarce. We examined characteristics, presentation and risk factors of AKI in patients hospitalised with COVID-19 in a tertiary hospital in Switzerland. METHODS: We reviewed health records of patients hospitalised with a positive nasopharyngeal polymerase chain reaction test for SARS-CoV2 between 1 February and 30 June 2020, at the University Hospital of Basel. The nadir creatinine of the hospitalisation was used as baseline. AKI was defined according the KDIGO guidelines as a 1.5× increase of baseline creatinine and in-hospital renal recovery as a discharge creatinine <1.25× baseline creatinine. Least absolute shrinkage and selection operator (LASSO) regression was performed to select predictive variables of AKI. Based on this a final model was chosen. RESULTS: Of 188 patients with COVID-19, 41 (22%) developed AKI, and 11 (6%) required renal replacement therapy. AKI developed after a median of 9 days (interquartile range [IQR] 5-12) after the first symptoms and a median of 1 day (IQR 0-5) after hospital admission. The peak AKI stages were stage 1 in 39%, stage 2 in 24% and stage 3 in 37%. A total of 29 (15%) patients were admitted to the intensive care unit and of these 23 (79%) developed AKI. In-hospital renal recovery at discharge was observed in 61% of all AKI episodes. In-hospital mortality was 27% in patients with AKI and 10% in patients without AKI. Age (adjusted odds ratio [aOR] 1.04, 95% confidence interval [CI] 1.01­1.08; p = 0.024), history of chronic kidney disease (aOR 3.47, 95% CI 1.16­10.49;p = 0.026), C-reactive protein levels (aOR 1.09, 95% CI 1.03­1.06; p = 0.002) and creatinine kinase (aOR 1.03, 95% CI 1.01­1.06; p = 0.002) were associated with development of AKI. CONCLUSIONS: AKI is common in hospitalised patients with COVID-19 and more often seen in patients with severe COVID-19 illness. AKI is associated with a high in-hospital mortality.

Derivation and external validation of a simple risk score to predict in-hospital mortality in patients hospitalized for COVID-19: A multicenter retrospective cohort study.

ABSTRACT: As severe acute respiratory syndrome coronavirus 2 continues to spread, easy-to-use risk models that predict hospital mortality can assist in clinical decision making and triage. We aimed to develop a risk score model for in-hospital mortality in patients hospitalized with 2019 novel coronavirus (COVID-19) that was robust across hospitals and used clinical factors that are readily available and measured standardly across hospitals.In this retrospective observational study, we developed a risk score model using data collected by trained abstractors for patients in 20 diverse hospitals across the state of Michigan (Mi-COVID19) who were discharged between March 5, 2020 and August 14, 2020. Patients who tested positive for severe acute respiratory syndrome coronavirus 2 during hospitalization or were discharged with an ICD-10 code for COVID-19 (U07.1) were included. We employed an iterative forward selection approach to consider the inclusion of 145 potential risk factors available at hospital presentation. Model performance was externally validated with patients from 19 hospitals in the Mi-COVID19 registry not used in model development. We shared the model in an easy-to-use online application that allows the user to predict in-hospital mortality risk for a patient if they have any subset of the variables in the final model.Two thousand one hundred and ninety-three patients in the Mi-COVID19 registry met our inclusion criteria. The derivation and validation sets ultimately included 1690 and 398 patients, respectively, with mortality rates of 19.6% and 18.6%, respectively. The average age of participants in the study after exclusions was 64 years old, and the participants were 48% female, 49% Black, and 87% non-Hispanic. Our final model includes the patient's age, first recorded respiratory rate, first recorded pulse oximetry, highest creatinine level on day of presentation, and hospital's COVID-19 mortality rate. No other factors showed sufficient incremental model improvement to warrant inclusion. The area under the receiver operating characteristics curve for the derivation and validation sets were .796 (95% confidence interval, .767-.826) and .829 (95% confidence interval, .782-.876) respectively.We conclude that the risk of in-hospital mortality in COVID-19 patients can be reliably estimated using a few factors, which are standardly measured and available to physicians very early in a hospital encounter.

Clinical characteristics and factors associated with acute kidney injury among patients hospitalized with coronavirus disease: an observational retrospective study.

BACKGROUND: Coronavirus disease 19 (COVID-19) is a multisystemic disease with high incidence of acute kidney injury (AKI). OBJECTIVE: To describe the clinical characteristics and factors associated with AKI among patients hospitalized with COVID-19. DESIGN AND SETTING: Retrospective cohort conducted at Hospital Civil de Culiacan, Mexico. METHODS: We included 307 patients hospitalized due to COVID-19. AKI was defined and staged based on serum creatinine levels in accordance with the criteria of the Acute Kidney Injury Network (AKIN). Multivariate logistic regression analysis was used to determine factors associated with AKI. RESULTS: The patients' age was 56 ± 15 years (64.5% male). The incidence of AKI was 33.6% (n = 103). Overall, 53.4% of patients had community-acquired AKI, and 46.6% had hospital-acquired AKI. Additionally, 15.5% of them presented AKIN stage 1; 34% had AKIN stage 2; and 50.5% had AKIN stage 3. Hemodialysis was required for 10.7% of the patients. The factors associated with AKI were chronic kidney disease (odds ratio, OR: 10.8; P = 0.04), use of norepinephrine (OR: 7.3; P = 0.002), diabetes mellitus (OR: 2.9; P = 0.03), C-reactive protein level (OR: 1.005; P = 0.01) and COVID-19 severity index based on chest tomography (OR: 1.09; statistical trend, P = 0.07). Hospital stay (11 ± 7 days; P < 0.001) and mortality (83.5 versus 31.4%; P < 0.05) were greater among patients with AKI. CONCLUSION: AKI was a frequent and serious complication in our cohort of patients hospitalized with COVID-19, which was associated with high mortality and long hospital stay.

SARS-CoV-2 infection increases risk of acute kidney injury in a bimodal age distribution.

BACKGROUND: Hospitalized patients with SARS-CoV2 develop acute kidney injury (AKI) frequently, yet gaps remain in understanding why adults seem to have higher rates compared to children. Our objectives were to evaluate the epidemiology of SARS-CoV2-related AKI across the age spectrum and determine if known risk factors such as illness severity contribute to its pattern. METHODS: Secondary analysis of ongoing prospective international cohort registry. AKI was defined by KDIGO-creatinine only criteria. Log-linear, logistic and generalized estimating equations assessed odds ratios (OR), risk differences (RD), and 95% confidence intervals (CIs) for AKI and mortality adjusting for sex, pre-existing comorbidities, race/ethnicity, illness severity, and clustering within centers. Sensitivity analyses assessed different baseline creatinine estimators. RESULTS: Overall, among 6874 hospitalized patients, 39.6% (n = 2719) developed AKI. There was a bimodal distribution of AKI by age with peaks in older age (≥60 years) and middle childhood (5-15 years), which persisted despite controlling for illness severity, pre-existing comorbidities, or different baseline creatinine estimators. For example, the adjusted OR of developing AKI among hospitalized patients with SARS-CoV2 was 2.74 (95% CI 1.66-4.56) for 10-15-year-olds compared to 30-35-year-olds and similarly was 2.31 (95% CI 1.71-3.12) for 70-75-year-olds, while adjusted OR dropped to 1.39 (95% CI 0.97-2.00) for 40-45-year-olds compared to 30-35-year-olds. CONCLUSIONS: SARS-CoV2-related AKI is common with a bimodal age distribution that is not fully explained by known risk factors or confounders. As the pandemic turns to disproportionately impacting younger individuals, this deserves further investigation as the presence of AKI and SARS-CoV2 infection increases hospital mortality risk.

Using dipstick urinalysis to predict development of acute kidney injury in patients with COVID-19.

BACKGROUND: Acute kidney injury (AKI) is a common complication in patients hospitalized with COVID-19 and may require renal replacement therapy (RRT). Dipstick urinalysis is frequently obtained, but data regarding the prognostic value of hematuria and proteinuria for kidney outcomes is scarce. METHODS: Patients with positive severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) PCR, who had a urinalysis obtained on admission to one of 20 hospitals, were included. Nested models with degree of hematuria and proteinuria were used to predict AKI and RRT during admission. Presence of Chronic Kidney Disease (CKD) and baseline serum creatinine were added to test improvement in model fit. RESULTS: Of 5,980 individuals, 829 (13.9%) developed an AKI during admission, and 149 (18.0%) of those with AKI received RRT. Proteinuria and hematuria degrees significantly increased with AKI severity (P < 0.001 for both). Any degree of proteinuria and hematuria was associated with an increased risk of AKI and RRT. In predictive models for AKI, presence of CKD improved the area under the curve (AUC) (95% confidence interval) to 0.73 (0.71, 0.75), P < 0.001, and adding baseline creatinine improved the AUC to 0.85 (0.83, 0.86), P < 0.001, when compared to the base model AUC using only proteinuria and hematuria, AUC = 0.64 (0.62, 0.67). In RRT models, CKD status improved the AUC to 0.78 (0.75, 0.82), P < 0.001, and baseline creatinine improved the AUC to 0.84 (0.80, 0.88), P < 0.001, compared to the base model, AUC = 0.72 (0.68, 0.76). There was no significant improvement in model discrimination when both CKD and baseline serum creatinine were included. CONCLUSIONS: Proteinuria and hematuria values on dipstick urinalysis can be utilized to predict AKI and RRT in hospitalized patients with COVID-19. We derived formulas using these two readily available values to help prognosticate kidney outcomes in these patients. Furthermore, the incorporation of CKD or baseline creatinine increases the accuracy of these formulas.

Frequency of deranged renal profile in patients with COVID-19: Tertiary Care Experience from a developing country.

Coronavirus disease-2019 (COVID-19) is a global pandemic, also affecting Pakistan with its first case reported on February 26, 2020. Since then, it has been declared a pandemic by the World Health Organization. Our study aimed to evaluate the renal derangements associated with COVID-19 infection in our population. A retrospective, observational study was conducted to include all the admitted patients having COVID-19 positive, and evaluated those for derangements of renal function (n = 362). Out of the 362 patients, 229were admitted in the ward, 133 were in intensive care unit (ICU), 258 of them recovered, while 104 deaths reported. At admission, the renal profile was deranged in almost one-half of ICU admissions and mortalities which increased to two-third during the hospital stay, with around 80% of deaths reported with increased urea and creatinine levels. Among the deceased patients, around one-third of the mortalities developed renal profile derangements during the hospital stay although they were admitted with a normal renal profile. An estimated glomerular filtration rate showed a mean increase of 13.37 mL/min/1.73 m2 during the hospital stay of surviving patients, while a decline of 19.92 in nonsurviving patients. A hazard ratio of 3.293 (P <0.001) for admitting serum urea and 3.795 (P = 0.009) at discharge and for serum creatinine at 5.392 (P <0.001) on discharge was associated significantly with mortality. Kaplan-Meier plot showed a significant decline in days of survival with deranged urea and creatinine (P <0.001). The deranged renal function in COVID-19 patients is associated with an increased number of ICU admissions as well as mortalities.

Gross hematuria after SARS-CoV-2 vaccination: questionnaire survey in Japan.

BACKGROUND: Recent clinical reports indicate a correlation between gross hematuria after the coronavirus 2019 (COVID-19) vaccination in patients with glomerulonephritis, especially immunoglobulin A nephropathy (IgAN). Furthermore, healthcare workers in Japan were initially vaccinated with an mRNA vaccine from February 17, 2021, and some of them experienced gross hematuria after receiving the vaccination. METHODS: We conducted a web-based survey of the councilor members of the Japanese Society of Nephrology (581 members, 382 facilities) to elucidate the relationship between gross hematuria and COVID-19 vaccination. RESULTS: In the first survey, 27 cases (female: 22, 81.5%) of gross hematuria were reported after receiving a COVID-19 vaccination. Of them, 19 (70.4%) patients were already diagnosed with IgAN at the occurrence of gross hematuria. Proteinuria appeared in eight of the 14 (57.1%) cases with no proteinuria before vaccination and hematuria in five of the seven (71.4%) cases with no hematuria before vaccination. The second survey revealed that a renal biopsy was performed after vaccination in four cases, all of whom were diagnosed with IgAN. Only one case showed a slightly increased serum creatinine level, and no patients progressed to severe renal dysfunction. CONCLUSION: This study clarified the clinical features of gross hematuria after a COVID-19 vaccination. Because there was no obvious progression to severe renal dysfunction, safety of the COVID-19 vaccination is warranted at least in the protocol of inoculation twice.

Effects of hydroxychloroquine and its metabolites in patients with connective tissue diseases.

Hydroxychloroquine has attracted attention in the treatment of COVID-19. Many conflicting findings have been reported regarding the efficacy and safety of this drug, which has been used safely in the rheumatological diseases for years. However, these studies lacked measurement methods that allow accurate assessment of hydroxychloroquine and its metabolite levels. The aim of this study was to measure hydroxychloroquine and its metabolite levels in whole blood samples of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SS) and scleroderma (Scl) by a robust, simple and accurate validated tandem mass spectrometric method, and to investigate the relationship between these levels with drug-related adverse effects and disease activity scores. The validated LC-MS/MS method was applied to measure blood hydroxychloroquine and its metabolite levels of patients with RA, SLE, SS, Scl. Various haematological and biochemical parameters were measured with Beckman-Coulter AU 5800 and Beckman Coulter LH 780 analyzers, respectively. QTc intervals were calculated with Bazett's formula, and the patients were followed up by clinicians in terms of clinical findings and adverse effects. Hydroxychloroquine levels of patients were similar to previous studies. There was a negative correlation between disease activity scores and hydroxychloroquine levels, while the highest correlation was between QTc interval, creatinine and GFR levels with desethylchloroquine. Bidetylchloroquine had the highest correlation with RBC count and liver function tests. Our findings showed that hydroxychloroquine and its metabolite levels were associated with disease activity scores, renal, hepatic function, QTc prolongation, and hematological parameters.

Lithium toxicity at therapeutic doses as a fallout of COVID-19 infection: a case series and possible mechanisms.

Lithium, a mood stabilizer used in the treatment of bipolar disorder is known for its anti-inflammatory properties with the discussion of its potential use in COVID-19 infection. The SARS-CoV-2 virus causing COVID-19 infection is known to enter the target cells through angiotensin converting enzyme-2 receptors present in abundance in the lung and renal tissue. Recent research supports the evidence for direct renal injury by viral proteins. Here we report two patients with bipolar disorder presenting with lithium toxicity in the presence of COVID-19 infection. Two patients with bipolar disorder, maintaining remission on lithium prophylaxis, presented to the psychiatric emergency with recent-onset fever and altered sensorium. Both the patient's investigations revealed lithium toxicity, elevated serum creatinine, urea and inflammatory markers. Hypernatremia, hyperkalaemia, and hyperchloremia were seen in one patient. Lithium and other psychotropic medications were stopped immediately, and COVID-19 treatment was initiated. Patient with clinical signs of lithium toxicity, hypernatremia, hyperkalaemia, and hyperchloremia developed ventricular tachycardia. He survived and regained consciousness after 2 weeks of aggressive conservative management. However, another patient died of acute respiratory failure on day 3. Possible direct infection of the kidney by SARS-CoV-2 viral proteins can manifest with acute kidney injury and lithium toxicity among patients on long-term lithium therapy. Health professionals treating COVID-19 infection among individuals on lithium therapy should be aware of the possibility of lithium toxicity in the background of renal injury.

Nutritional status in patients with COVID-19 and cancer: the experience of the National Cancer Institute in Mexico.

INTRODUCTION: Background: nutritional status might vary according to different underlying illnesses such as cancer or infectious diseases, including COVID-19. In this context, data from developing countries remain scarce. Objectives: the objective of this study was to assess the nutritional status and outcomes of Mexican cancer patients diagnosed with COVID-19 at a tertiary care center. Methods: this was a retrospective study including 121 consecutive cancer patients diagnosed with COVID-19 at the National Cancer Institute, Mexico City, during four months. Results: the most frequent oncological diagnoses were gynecological (19 %) and hematological (17 %). Most patients were overweight (35 %). In the univariate analysis, ≥ 65 years, intubation, hypoalbuminemia, high creatinine, lymphopenia, nutrition-impact symptoms, and ECOG 2-4 were statistically associated with lower survival. The median survival of the cohort was 41 days. Conclusions: to our best knowledge, this is the first study of its kind performed in Mexico, and as other studies from other regions, our results might aid in identifying cancer patients most at risk for severe COVID-19, and could be potentially useful to enhance public health messaging on self-isolation and social distancing among Mexican cancer patients.

INTRODUCCIÓN: Antecedentes: el estado nutricional puede variar según las diferentes enfermedades subyacentes, como el cáncer o las enfermedades infecciosas, por ejemplo, la COVID-19. En este contexto, los datos de los países en desarrollo siguen siendo escasos. Objetivos: el objetivo de este estudio fue evaluar el estado nutricional y los resultados de pacientes mexicanos con cáncer diagnosticados de COVID-19 en un centro de atención terciaria. Métodos: se trata de un estudio retrospectivo que incluyó a 121 pacientes consecutivos con cáncer diagnosticados de COVID-19 en el Instituto Nacional del Cáncer de la Ciudad de México durante cuatro meses. Resultados: los diagnósticos oncológicos más frecuentes fueron los ginecológicos (19 %) y hematológicos (17 %). La mayoría de los pacientes tenían sobrepeso (35 %) y obesidad (31 %). En el análisis univariado, ≥ 65 años, intubación, hipoalbuminemia, creatinina alta, linfopenia, síntomas de impacto nutricional y ECOG 2-4 se asociaron estadísticamente con una menor supervivencia. La mediana de supervivencia de la cohorte fue de 41 días. Conclusiones: hasta donde sabemos, este es el primer estudio de este tipo realizado en México y, al igual que otros estudios de otras regiones, nuestros resultados podrían ayudar a identificar a los pacientes con cáncer y mayor riesgo de COVID-19 grave; también podrían ser potencialmente útiles para mejorar los mensajes de salud sobre el autoaislamiento y el distanciamiento social entre los pacientes mexicanos con cáncer.

Negative effects of iodine-based contrast agent on renal function in patients with moderate reduced renal function hospitalized for COVID-19.

BACKGROUND: Kidney disease and renal failure are associated with hospital deaths in patients with COVID - 19. We aimed to test if contrast enhancement affects short-term renal function in hospitalized COVID - 19 patients. METHODS: Plasma creatinine (P-creatinine) was measured on the day of computed tomography (CT) and 24 h, 48 h, and 4-10 days after CT. Contrast-enhanced (n = 142) and unenhanced (n = 24) groups were subdivided, based on estimated glomerular filtration rates (eGFR), > 60 and ≤ 60 ml/min/1.73 m2. Contrast-induced acute renal failure (CI-AKI) was defined as ≥27 µmol/L increase or a > 50% rise in P-creatinine from CT or initiation of renal replacement therapy during follow-up. Patients with renal replacement therapy were studied separately. We evaluated factors associated with a > 50% rise in P-creatinine at 48 h and at 4-10 days after contrast-enhanced CT. RESULTS: Median P-creatinine at 24-48 h and days 4-10 post-CT in patients with eGFR> 60 and eGFR≥30-60 in contrast-enhanced and unenhanced groups did not differ from basal values. CI-AKI was observed at 48 h and at 4-10 days post contrast administration in 24 and 36% (n = 5/14) of patients with eGFR≥30-60. Corresponding figures in the eGFR> 60 contrast-enhanced CT group were 5 and 5% respectively, (p < 0.037 and p < 0.001, Pearson χ2 test). In the former group, four of the five patients died within 30 days. Odds ratio analysis showed that an eGFR≥30-60 and 30-day mortality were associated with CK-AKI both at 48 h and 4-10 days after contrast-enhanced CT. CONCLUSION: Patients with COVID - 19 and eGFR≥30-60 had a high frequency of CK-AKI at 48 h and at 4-10 days after contrast administration, which was associated with increased 30-day mortality. For patients with eGFR≥30-60, we recommend strict indications are practiced for contrast-enhanced CT. Contrast-enhanced CT had a modest effect in patients with eGFR> 60.

Eosinophil: A Nonnegligible Predictor in COVID-19 Re-Positive Patients.

Although vaccine resources are being distributed worldwide, insufficient vaccine production remains a major obstacle to herd immunity. In such an environment, the cases of re-positive occurred frequently, and there is a big controversy regarding the cause of re-positive episodes and the infectivity of re-positive cases. In this case-control study, we tracked 39 patients diagnosed with COVID-19 from the Jiaodong Peninsula area of China, of which 7 patients tested re-positive. We compared the sex distribution, age, comorbidities, and clinical laboratory results between normal patients and re-positive patients, and analysed the correlation between the significantly different indicators and the re-positive. Re-positive patients displayed a lower level of serum creatinine (63.38 ± 4.94 U/L vs. 86.82 ± 16.98 U/L; P =0.014) and lower albumin (34.70 ± 5.46 g/L vs. 41.24 ± 5.44 g/L, P =0.039) at the time of initial diagnosis. In addition, two positive phases and the middle negative phase in re-positive patients with significantly different eosinophil counts (0.005 ± 0.005 × 109/L; 0.103 ± 0.033 × 109/L; 0.007 ± 0.115 × 109/L; Normal range: 0.02-0.52 × 109/L). The level of eosinophils in peripheral blood can be used as a marker to predict re-positive in patients who once had COVID-19.

Chronic kidney disease linked to SARS-CoV-2 infection: a case report.

BACKGROUND: The recent COVID-19 pandemic has raised concerns about patient diagnosis and follow-up of chronically ill patients. Patients suffering from chronic illnesses, concomitantly infected by SARS-CoV-2, globally tend to have a worse prognosis and poor outcomes. Renal tropism and acute kidney injury following SARS-CoV-2 infection has recently been described in the literature, with elevated mortality rates. Furthermore, patients with pre-existing chronic kidney disease, infected by SARS-CoV-2, should be monitored carefully. Here, we report the case of a 69-year-old patient with splenic marginal zone lymphoma, suffering from longstanding chronic kidney disease following SARS-CoV-2 infection. CASE PRESENTATION: A 69-year-old male patient previously diagnosed with pulmonary embolism and splenic marginal zone lymphoma (Splenomegaly, Matutes 2/5, CD5 negative and CD23 positive), was admitted to the hospital with shortness of breath, fever and asthenia. A nasopharyngeal swab test was performed in addition to a CT-scan, which confirmed SARS-CoV-2 infection. Blood creatinine increased following SARS-CoV-2 infection at 130 µmol/l, with usual values at 95 µmol/l. The patient was discharged at home with rest and symptomatic medical treatment (paracetamol and hydration), then readmitted to the hospital in August 2020. A kidney biopsy was therefore conducted as blood creatinine levels were abnormally elevated. Immunodetection performed in a renal biopsy specimen confirmed co-localization of SARS-CoV2 nucleocapsid and protease 3C proteins with ACE2, Lewis x and sialyl-Lewis x antigens in proximal convoluted tubules and podocytes. Co-localization of structural and non-structural viral proteins clearly demonstrated viral replication in proximal convoluted tubules in this chronically ill patient. Additionally, we observed the co-localization of sialyl-Lewis x and ACE2 receptors in the same proximal convoluted tubules. Reverse Transcriptase-Polymerase Chain Reaction test performed on the kidney biopsy was negative, with very low Ct levels (above 40). The patient was finally readmitted to the haematology department for initiation of chemotherapy, including CHOP protocol and Rituximab. CONCLUSIONS: Our case emphasizes on the importance of monitoring kidney function in immunosuppressed patients and patients suffering from cancer following SARS-CoV-2 infection, through histological screening. Further studies will be required to decipher the mechanisms underlying chronic kidney disease and the putative role of sialyl-Lewis x and HBGA during SARS-CoV-2 infection.

Could urinary kidney injury molecule-1 be a good marker in subclinical acute kidney injury in mild to moderate COVID-19 infection?

PURPOSE: To evaluate urinary kidney injury molecule-1 (uKIM-1), which is a proximal tubule injury biomarker in subclinical acute kidney injury (AKI) that may occur in COVID-19 infection. METHODS: The study included proteinuric (n = 30) and non-proteinuric (n = 30) patients diagnosed with mild/moderate COVID-19 infection between March and September 2020 and healthy individuals as a control group (n = 20). The uKIM-1, serum creatinine, cystatin C, spot urine protein, creatinine, and albumin levels of the patients were evaluated again after an average of 21 days. RESULTS: The median (interquartile range) uKIM-1 level at the time of presentation was 246 (141-347) pg/mL in the proteinuric group, 83 (29-217) pg/mL in the non-proteinuric group, and 55 (21-123) pg/mL in the control group and significantly high in the proteinuric group than the others (p < 0.001). Creatinine and cystatin C were significantly higher in the proteinuric group than in the group without proteinuria, but none of the patients met the KDIGO-AKI criteria. uKIM-1 had a positive correlation with PCR, non-albumin proteinuria, creatinine, cystatin C, CRP, fibrinogen, LDH, and ferritin, and a negative correlation with eGFR and albumin (p < 0.05). In the multivariate regression analysis, non-albumin proteinuria (p = 0.048) and BUN (p = 0.034) were identified as independent factors predicting a high uKIM-1 level. After 21 ± 4 days, proteinuria regressed to normal levels in 20 (67%) patients in the proteinuric group. In addition, the uKIM-1 level, albuminuria, non-albumin proteinuria, and CRP significantly decreased. CONCLUSIONS: Our findings support that the kidney is one of the target organs of the COVID-19 and it may cause proximal tubule injury even in patients that do not present with AKI or critical/severe COVID-19 infection.

Lymphocytes screening on admission is essential for predicting in-hospital clinical outcome in COVID-19 patients: A retrospective cohort study.

INTRODUCTION: We aimed to identify the associations between the lymphocytes (LYM) absolute count on admission and clinical outcomes in COVID-19 patients. METHODS: In this retrospective study, 224 COVID-19 patients who were admitted to General Hospital of Central Theater Command of the PLA from January 22 to April 4, 2020, were consecutively included. These patients were divided into the lymphopenia group and the nonlymphopenia group according to whether the LYM count on admission was below the normal range. RESULTS: During hospitalization, patients in the lymphopenia group have a much higher all-cause mortality (14.5% vs 0.0%; P < .001) and an evidently longer length of hospital stay (24.0 vs 17.5 days; P < .001) than patients in the nonlymphopenia group. The correlation analysis results indicated that the LYM count was negatively correlated with the values of NEU (R = -.2886, P < .001), PT (R = -.2312, P < .001), FIB (R = -.2954, P < .001), D-D (R = -.3554, P < .001), CRP (R = -.4899, P < .001), IL-6 (R = -.5459, P < .001), AST (R = -.2044, P < .01), Cr (R = -.1350, P < .05), CPK (R = -.2119, P < .01), CK-Mb (R = -.1760, P < .01), and LDH (R = -.4330, P < .001), and was positively correlated with the count of PLT (R = .2679, P < .001). In addition, LYM as a continuous variable was associated with 97% decreased risk of in-hospital mortality in the fully adjusted models (OR = 0.03, 95%CI, 0.00-0.37, P < .001). DISCUSSION: LYM screening on admission is a critical predictor for assessment of disease severity and clinical outcomes in patients with COVID-19, and lymphopenia substantially correlates with poor clinical outcomes.

Specific cytokines in the inflammatory cytokine storm of patients with COVID-19-associated acute respiratory distress syndrome and extrapulmonary multiple-organ dysfunction.

BACKGROUND: To date, specific cytokines associated with development of acute respiratory distress syndrome (ARDS) and extrapulmonary multiple organ dysfunction (MOD) in COVID-19 patients have not been systematically described. We determined the levels of inflammatory cytokines in patients with COVID-19 and their relationships with ARDS and extrapulmonary MOD. METHODS: The clinical and laboratory data of 94 COVID-19 patients with and without ARDS were analyzed. The levels of inflammatory cytokines (interleukin 6 [IL-6], IL-8, IL-10, and tumor necrosis factor α [TNF-α]) were measured on days 1, 3, and 5 following admission. Seventeen healthy volunteers were recruited as controls. Correlations in the levels of inflammatory cytokines with clinical and laboratory variables were analyzed, furthermore, we also explored the relationships of different cytokines with ARDS and extrapulmonary MOD. RESULTS: The ARDS group had higher serum levels of all 4 inflammatory cytokines than the controls, and these levels steadily increased after admission. The ARDS group also had higher levels of IL-6, IL-8, and IL-10 than the non-ARDS group, and the levels of these cytokines correlated significantly with coagulation parameters and disseminated intravascular coagulation (DIC). The levels of IL-6 and TNF-α correlated with the levels of creatinine and urea nitrogen, and were also higher in ARDS patients with acute kidney injury (AKI). All 4 inflammatory cytokines had negative correlations with PaO2/FiO2. IL-6, IL-8, and TNF-α had positive correlations with the APACHE-II score. Relative to survivors, non-survivors had higher levels of IL-6 and IL-10 at admission, and increasing levels over time. CONCLUSIONS: The cytokine storm apparently contributed to the development of ARDS and extrapulmonary MOD in COVID-19 patients. The levels of IL-6, IL-8, and IL-10 correlated with DIC, and the levels of IL-6 and TNF-α were associated with AKI. Relative to survivors, patients who died within 28 days had increased levels of IL-6 and IL-10.

Hemophagocytic histiocytosis in severe SARS-CoV-2 infection: A bone marrow study.

INTRODUCTION: The clinical and laboratory features of severe COVID-19 infection overlap with those of hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory disorder often associated with several viral infections. The clinical syndrome of HLH encompasses fever, organomegaly, cytopenias, hyperferritinemia, hypertriglyceridemia, raised transaminases, hypofibrinogenemia, absent natural killer (NK) cell activity, increased soluble CD25 and hemophagocytic lymphohistiocytosis in bone marrow, spleen, and lymph nodes. METHODS: We analyzed clinicopathological and laboratory features of thirteen patients with severe COVID-19 infection suspected to have HLH and found to have hemophagocytic histiocytosis on bone marrow examination (BME). RESULTS: Five of thirteen (38.46%) patients fulfilled five of eight HLH 2004 criteria and/or had a H-score ≥169. Three (23.08%) satisfied four of eight and remainder five (38.46%) satisfied three of eight HLH 2004 criteria. Fever, raised serum ferritin (13/13, 100%), transaminases (9/13, 69.23%), triglycerides (4/13, 30.76%), cytopenias (5/13, 38.46%), hypofibrinogenemia (2/13, 15.38%), and organomegaly (1/13, 7.69%) were observed in our patients. BME showed hemophagocytic histiocytosis without lymphocytosis in all. Contrary to HLH, lymphocytopenia (11/13, 84.61%), leukocytosis (7/13, 53.84%), neutrophilia (7/13, 53.84%), and hyperfibrinogenemia (7/13, 53.84%) were observed. Serum CRP, LDH, and plasma D-dimer were elevated in all, while serum albumin was decreased in 12 of 13 (92.3%) patients. Five patients recovered with high-dose pulsed corticosteroid therapy. CONCLUSION: The immune response associated with severe COVID-19 infection is similar to HLH with few differences. HLH should be suspected in severe COVID-19 infection although all patients may not fulfill required HLH diagnostic criteria. BME should be done in suspected cases so that appropriate therapy may be initiated early.

Acute kidney injury in children with COVID-19: a retrospective study.

BACKGROUND: Acute kidney injury (AKI) is a complication of coronavirus disease 2019 (COVID-19). The reported incidence of AKI, however, varies among studies. We aimed to evaluate the incidence of AKI and its association with mortality and morbidity in children infected with severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) who required hospital admission. METHODS: This was a multicenter retrospective cohort study from three tertiary centers, which included children with confirmed COVID-19. All children were evaluated for AKI using the Kidney Disease Improving Global Outcomes (KDIGO) definition and staging. RESULTS: Of 89 children included, 19 (21 %) developed AKI (52.6 % stage I). A high renal angina index score was correlated with severity of AKI. Also, multisystem inflammatory syndrome in children (MIS-C) was increased in children with AKI compared to those with normal kidney function (15 % vs. 1.5 %). Patients with AKI had significantly more pediatric intensive care admissions (PICU) (32 % vs. 2.8 %, p < 0.001) and mortality (42 % vs. 0 %, p < 0.001). However, AKI was not associated with prolonged hospitalization (58 % vs. 40 %, p = 0.163) or development of MIS-C (10.5 % vs. 1.4 %, p = 0.051). No patient in the AKI group required renal replacement therapy. Residual renal impairment at discharge occurred in 9 % of patients. This was significantly influenced by the presence of comorbidities, hypotension, hypoxia, heart failure, acute respiratory distress, hypernatremia, abnormal liver profile, high C-reactive protein, and positive blood culture. CONCLUSIONS: AKI occurred in one-fifth of children with SARS-CoV-2 infection requiring hospital admission, with one-third of those requiring PICU. AKI was associated with increased morbidity and mortality, and residual renal impairment at time of discharge.