Erratum: Evaluation of prevalence and risk factors for bloodstream infection in severe coronavirus disease 2019 (COVID-19) patients - CORRIGENDUM.

[This corrects the article DOI: 10.1017/ash.2021.254.].

Correction: Serial measurement of cytokines strongly predict COVID-19 outcome.

[This corrects the article DOI: 10.1371/journal.pone.0260623.].

The Prognostic Value of Lung Injury and Fibrosis Markers, KL-6, TGF-ß1, FGF-2 in COVID-19 Patients.

Background: Biomarkers of lung injury and interstitial fibrosis give insight about the extent of involvement and prognosis in well-known interstitial lung diseases (ILD). Serum Krebs von den Lungen-6 (KL-6) reflects direct alveolar injury and, transforming growth factor-beta1 (TGF-ß1) and fibroblast growth factor-2 (FGF-2) are principal mediators of fibrosis in ILD and in almost all fibrotic diseases. In this sense, we aimed to assess associations of these biomarkers with traditional inflammatory markers and clinical course of COVID-19. Methods: Patients with COVID-19 who had confirmed diagnosis with SARS-CoV-2 nucleic acid RT-PCR were enrolled and followed up prospectively with a standardized approach one month after diagnosis. Patients were divided into severe and non-severe groups according to National Institutes of Health criteria. Outcome was assessed for the requirement of intensive care unit (ICU) admission, long term respiratory support and death. Blood samples were collected at enrollment and serum levels of KL-6, TGF-ß1, FGF-2 were determined by ELISA. Association between these markers with other prognostic markers and prognosis were analyzed. Results: Overall 31 severe and 28 non-severe COVID-19 patients were enrolled and were compared with healthy control subjects (n = 30). Serum KL-6 levels in COVID-19 patients were significantly higher (median [IQR]; 11.54 [4.86] vs 8.54 [3.98] ng/mL, P = .001] and FGF-2 levels were lower (median [IQR]; 76.84 [98.2] vs 101.62 [210.6] pg/mL) compared to healthy control group. A significant correlation was found between KL-6 values and CRP, fibrinogen, d-dimer and lymphocyte counts. However, we did not find an association between these markers and subsequent severity of COVID-19, mortality and long-term prognosis. Conclusions: Serum KL-6 levels were significantly elevated at the diagnosis of COVID-19 and correlated well with the other traditional prognostic inflammatory markers. Serum levels of principal fibrosis mediators, TGF-ß1, FGF-2, were not elevated at diagnosis of COVID-19, therefore did not help to anticipate long term prognosis.

The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort.

Background and objectives: Although several repurposed antiviral drugs have been used for the treatment of COVID-19, only a few such as remdesivir and molnupiravir have shown promising effects. The objectives of our study were to investigate the association of repurposed antiviral drugs with COVID-19 morbidity. Methods: Patients admitted to 26 different hospitals located in 16 different provinces between March 11-July 18, 2020, were enrolled. Case definition was based on WHO criteria. Patients were managed according to the guidelines by Scientific Board of Ministry of Health of Turkey. Primary outcomes were length of hospitalization, intensive care unit (ICU) requirement, and intubation. Results: We retrospectively evaluated 1,472 COVID-19 adult patients; 57.1% were men (mean age = 51.9 ± 17.7years). A total of 210 (14.3%) had severe pneumonia, 115 (7.8%) were admitted to ICUs, and 69 (4.7%) were intubated during hospitalization. The median (interquartile range) of duration of hospitalization, including ICU admission, was 7 (5-12) days. Favipiravir (n = 328), lopinavir/ritonavir (n = 55), and oseltamivir (n = 761) were administered as antiviral agents, and hydroxychloroquine (HCQ, n = 1,382) and azithromycin (n = 738) were used for their immunomodulatory activity. Lopinavir/ritonavir (ß [95% CI]: 4.71 [2.31-7.11]; p = 0.001), favipiravir (ß [95% CI]: 3.55 [2.56-4.55]; p = 0.001) and HCQ (ß [95% CI]: 0.84 [0.02-1.67]; p = 0.046) were associated with increased risk of lengthy hospital stays. Furthermore, favipiravir was associated with increased risks of ICU admission (OR [95% CI]: 3.02 [1.70-5.35]; p = 0.001) and invasive mechanical ventilation requirement (OR [95% CI]: 2.94 [1.28-6.75]; p = 0.011). Conclusion: Our findings demonstrated that antiviral drugs including lopinavir, ritonavir, and favipiravir were associated with negative clinical outcomes such as increased risks for lengthy hospital stay, ICU admission, and invasive mechanical ventilation requirement. Therefore, repurposing such agents without proven clinical evidence might not be the best approach for COVID-19 treatment.

The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort

Background and objectives Although several repurposed antiviral drugs have been used for the treatment of COVID-19, only a few such as remdesivir and molnupiravir have shown promising effects. The objectives of our study were to investigate the association of repurposed antiviral drugs with COVID-19 morbidity. Methods Patients admitted to 26 different hospitals located in 16 different provinces between March 11–July 18, 2020, were enrolled. Case definition was based on WHO criteria. Patients were managed according to the guidelines by Scientific Board of Ministry of Health of Turkey. Primary outcomes were length of hospitalization, intensive care unit (ICU) requirement, and intubation. Results We retrospectively evaluated 1,472 COVID-19 adult patients;57.1% were men (mean age = 51.9 ± 17.7years). A total of 210 (14.3%) had severe pneumonia, 115 (7.8%) were admitted to ICUs, and 69 (4.7%) were intubated during hospitalization. The median (interquartile range) of duration of hospitalization, including ICU admission, was 7 (5–12) days. Favipiravir (n = 328), lopinavir/ritonavir (n = 55), and oseltamivir (n = 761) were administered as antiviral agents, and hydroxychloroquine (HCQ, n = 1,382) and azithromycin (n = 738) were used for their immunomodulatory activity. Lopinavir/ritonavir (β [95% CI]: 4.71 [2.31–7.11];p = 0.001), favipiravir (β [95% CI]: 3.55 [2.56–4.55];p = 0.001) and HCQ (β [95% CI]: 0.84 [0.02–1.67];p = 0.046) were associated with increased risk of lengthy hospital stays. Furthermore, favipiravir was associated with increased risks of ICU admission (OR [95% CI]: 3.02 [1.70–5.35];p = 0.001) and invasive mechanical ventilation requirement (OR [95% CI]: 2.94 [1.28–6.75];p = 0.011). Conclusion Our findings demonstrated that antiviral drugs including lopinavir, ritonavir, and favipiravir were associated with negative clinical outcomes such as increased risks for lengthy hospital stay, ICU admission, and invasive mechanical ventilation requirement. Therefore, repurposing such agents without proven clinical evidence might not be the best approach for COVID-19 treatment.

Evaluation of long-term antibody kinetics in healthcare workers vaccinated with inactivated COVID-19 Vero cell vaccine (CoronaVac), a propensity score-matched observational study.

OBJECTIVES: This study aimed to evaluate the long-term antibody kinetics after vaccinating with an inactivated COVID-19 Vero cell vaccine (CoronaVac) in healthcare workers (HCWs) at a single center in Turkey. METHODS: For this prospective observational study, Chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) were used for the determination of binding antibodies (bAb) and neutralizing antibodies (nAb), respectively. Antibody kinetics were compared for the potential influencing factors, and propensity score analysis was performed to match the subcohort for age. RESULTS: Early bAb and nAb response was achieved in all 343 participants. Titers of bAbs against SARS-CoV-2 on 42 days post-vaccination (dpv) were higher in HCWs who were aged <40 years and who had a history of COVID-19. SARS-CoV-2 bAb levels in HCWs on days 42 (n = 97), 90 (n = 97), and 180 (n = 97) were 175 IU/ml (3.9-250), 107 IU/ml (2.4-250), and 66.1 IU/ml (2.57-250), respectively (p<0.001). SARS-CoV-2 bAb (p<0.001) and nAb (p<0.001) titers decreased significantly over time. There was a high negative correlation between SARS-CoV-2 antibody titers and inverse optic density of nAb responses (Pearson correlation coefficient: -0.738, p<0.001). CONCLUSIONS: When the antibody responses were compared, it was seen that the vaccine immunogenicity was better in those who had prior COVID-19 history and were aged <40 years. In the course of time, it was determined that there was a significant decrease in bAb and nAb responses after the 90th day. These results may guide approval decisions for booster COVID-19 vaccines.

Evaluation of prevalance and risk factors for bloodstream infection in severe coronavirus disease 2019 (COVID-19) patients.

Objectives: In this study, we sought to determine the prevalence of bloodstream infection (BSI) in severe coronavirus disease 2019 (COVID-19) patients and to determine the risk factors of BSI in critical COVID-19 patients. Design: Retrospective, descriptive study between March 2020 and January 2021. Setting: An 1,007-bed university hospital. Participants: Patients who were hospitalized due to severe COVID-19 disease and had an aerobic blood culture taken at least once during hospitalization. Methods: Case definitions were made according to National Institutes of Health clinical definitions. According to the blood culture results, the patients were grouped as with and without BSIs, and compared for BSIs risk factors. Results: In total, 195 patients were included in the study. Blood culture positivity was detected in 76 (39.0%) of 196 patients. Excluding blood culture positivity considered as contamination, the prevalence of BSI in all severe COVID-19 cases was 18.5% (n = 36). In intensive care unit patients the prevalence of BSI was 30.6% (n = 26). In multivariate analyses, central venous catheter (odds ratio [OR], 8.17; 95% confidence interval [CI], 2.46-27.1; P < .01) and hospitalization in the multibed intensive care unit (OR, 4.28; 95% CI, 1.28-14.3; P < .01) were risk factors associated with the acquisition of BSI. Conclusion: The prevalence of BSI in COVID-19 patients is particularly high in critically ill patients. The central venous catheter and multibed intensive care follow-up are risk factors for BSI. BSIs can be reduced by increasing compliance to infection control measures and central venous catheter insertion-care procedures. The use of single-bed intensive care units where compliance can be achieved more effectively is important for the prevention of BSIs.

Severity Assessment in COVID-19 Pneumonia: Comparison of Semi-Quantitative and Quantitative CT Analyses

Objective: To investigate the performance of semi-quantitative CT (SCT) and automated quantitative CT (QCT) analyses for differentiating mild disease from the severe disease in COVID-19 pneumonia. Materials and Methods: Sixty-seven laboratory confirmed COVID-19 patients were enrolled. The patients were grouped into mild and severe disease regarding clinical features. CT images were evaluated by three observers independently. Three different SCT scoring methods and QCT analysis were performed. The two disease groups were compared in terms of SCT and QCT parameters. Intraclass correlation coefficient was used to investigate inter-rater reliability. The performance of SCT and QCT in the differentiation of mild disease and severe disease was evaluated using receiver operating characteristics (ROC) analysis. Results: Inter-rater reliability was excellent for all SCT scores. SCT and QCT scores were significantly different between two disease groups (p<0.05). Five-point score showed the best performance regarding to area under curve (AUC) values. The cut-off value of >7 for 5-point score had 88.89% sensitivity and 82.76% specificity and cut-off value of >10.29% for QCT score (%) had 75.00% sensitivity and 98.04% specificity for differentiating the mild disease from severe disease. Conclusion: QCT may play an important role in the management of COVID-19 pneumonia with its high specificity values. (English) [ FROM AUTHOR] Amaç: COVID-19 pnömonisinde hafif hastalığı şiddetli hastalıktan ayırt etmede semi-kantitatif BT (SBT) ve kantitatif-BT (KBT) analizlerinin performansını karşılaştırmak. Yöntem: Çalışmaya 67 laboratuvar tarafından doğrulanmış COVID-19 hastası dahil edildi. Hastalar klinik özelliklerine göre hafif ve ağır hasta olarak gruplandırıldı. BT görüntüleri bağımsız olarak üç gözlemci tarafından değerlendirildi. Üç farklı SBT skorlama yöntemi ve KBT analizi uyulandı. Íki hastalık grubu SBT ve KBT parametreleri açısından karşılaştırıldı. Gözlemciler arası güvenilirliği araştırmak için sınıf içi korelasyon katsayısı kullanıldı. Hafif hastalık ve ağır hastalık ayrımında SBT ve KBT'nin performansı, ROC analizi kullanılarak değerlendirildi. Bulgular:Gözlemciler arası güvenilirlik, tüm SBT skorları için mükemmeldi. SBT ve KBT değerleri hafif ve ağır hastalık grupları arasında anlamlı olarak farklıydı (p<0.05). Eğri altındaki alan (EAA) göz önüne alındığında SBT skorlama yöntemleri arasında beşli skorlama en iyi performansı gösterdi. ROC analizinde beşli skorlama için en uyun kesim noktası 7 olarak belirlenmiş olup bu değere ait duyarlılık %88.89, özgüllük %82.76 olarak hesaplanmıştır. KBT değeri (%) için kesim noktası %10.29 olarak belirlendiğinde duyarlılık değeri %75.00, özgüllük değeri ise %98.04 olarak hesaplanmıştır. Sonuç:KBT, yüksek özgüllük değerleri ile COVID-19 pnömonisinin yönetiminde önemli bir rol oynayabilir. (Turkish) [ FROM AUTHOR] Copyright of Gazi Medical Journal is the property of Gazi Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Assessment of olfactory and gustatory functions in COVID-19 patients

Background/aim: This study aims to evaluate of olfactory and gustatory functions of COVID-19 patients and possible risk factors for olfactory and gustatory dysfunctions. Materials and methods: The cross-sectional study included adult patients who were diagnosed with COVID-19 in Gazi University Hospital between April 2020 and June 2020. Volunteered patients participated in a survey in which olfactory and gustatory functions and various clinical information were questioned. Sinonasal Outcome Test-22 was also administrated to all patients. Results: A hundred and seventy-one patients participated in this study. Olfactory and gustatory dysfunctions rates were 10.5% (n: 18) and 10.5% (n: 18), respectively. Patients without any symptom other than smell and taste dysfunctions were clustered as group 1 and patients who are clinically symptomatic were clustered as group 2. Olfactory dysfunction occurred in 8% of group 1 and 17.4% of group 2 (p = 0.072). Gustatory dysfunction rate of smokers was 19.7% and significantly higher than gustatory dysfunction rate of nonsmokers (5.5%) (p = 0.007). Twenty-seven-point-eight percent of the patients with olfactory dysfunction (n = 5) were male and 72.2% (n: 13) were female. Sex did not show significant effect on rate of olfactory dysfunction. Twenty-five patients participated in psychophysical olfactory function test. No participant reported olfactory dysfunction at the time of test. Of the participants, 64% (n: 16) were normosmic and 36% (n: 9) were hyposmic according to Sniffin' Stick test. Conclusion: Olfactory and gustatory dysfunctions are more common in patients who are clinically symptomatic than those diagnosed during contact tracing. Objective tests may show that frequency of olfactory dysfunction is greater than frequency of self-reported olfactory dysfunction.

Serial measurement of cytokines strongly predict COVID-19 outcome.

PURPOSE: Cytokines are major mediators of COVID-19 pathogenesis and several of them are already being regarded as predictive markers for the clinical course and outcome of COVID-19 cases. A major pitfall of many COVID-19 cytokine studies is the lack of a benchmark sampling timing. Since cytokines and their relative change during an infectious disease course is quite dynamic, we evaluated the predictive value of serially measured cytokines for COVID-19 cases. METHODS: In this single-center, prospective study, a broad spectrum of cytokines were determined by multiplex ELISA assay in samples collected at admission and at the third day of hospitalization. Appropriateness of cytokine levels in predicting mortality were assessed by receiver-operating characteristic (ROC) analyses for both sampling times in paralel to conventional biomarkers. RESULTS: At both sampling points, higher levels of IL-6, IL-7, IL-10, IL-15, IL-27 IP-10, MCP-1, and GCSF were found to be more predictive for mortality (p<0.05). Some of these cytokines, such as IL-6, IL-10, IL-7 and GCSF, had higher sensitivity and specificity in predicting mortality. AUC values of IL-6, IL-10, IL-7 and GCSF were 0.85 (0.65 to 0.92), 0.88 (0.73 to 0.96), 0.80 (0.63 to 0.91) and 0.86 (0.70 to 0.95), respectively at hospital admission. Compared to hospital admission, on the 3rd day of hospitalization serum levels of IL-6 and, IL-10 decreased significantly in the survivor group, unlike the non-survivor group (IL-6, p = 0.015, and IL-10, p = 0.016). CONCLUSION: Our study results suggest that single-sample-based cytokine analyzes can be misleading and that cytokine levels measured serially at different sampling times provide a more precise and accurate estimate for the outcome of COVID-19 patients.

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.

Relationship between chest computed tomography findings and clinical conditions of coronavirus disease (COVID-19): A multicentre experience.

AIMS: This study aimed to investigate the clinical and chest computed tomography (CT) features associated with clinical parameters for coronavirus disease (COVID-19) in the capital of Turkey, Ankara. MATERIALS AND METHODS: Epidemiological, clinical features, laboratory findings and radiological characteristics of 1563 hospitalised patients with COVID-19 in Ankara were collected, reviewed and analysed in this study. The risk factors associated with disease severity were investigated. RESULTS: Non-severe (1214; 77.7%) and severe cases (349; 22.3%) were enrolled in the study. Compared with the non-severe group, the severe group were significantly older and had more comorbidities (ie, hypertension, diabetes mellitus, cardiovascular disease and chronic kidney disease). Smoking was more common in the severe group. Severe patients had higher respiratory rates and higher incidences of cough and dyspnoea compared with non-severe patients. Compared with the non-severe patients, the severe patients had increased C-reactive protein (CRP), procalcitonin, neutrophil to lymphocyte ratio (NLR) and CRP/albumin ratio and decreased albumin. The occurrence rates of consolidation, subpleural sparing, crazy-paving pattern, cavity, halo sign, reversed halo sign, air bronchogram, pleural thickening, micronodule, subpleural curvilinear line and multilobar and bilateral involvement in the CT finding of the severe patients were significantly higher than those of the non-severe patients. CONCLUSIONS: Many factors are related to the severity of COVID-19, which can help clinicians judge the severity of the patient and evaluate the prognosis. This cohort study revealed that male sex, age (≥55 years), patients with any comorbidities, especially those with cardiovascular disease, dyspnoea, increased CRP, D-dimer and NLR, and decreased lymphocyte count and CT findings of consolidation and multilobar involvement were predictors of severe COVID-19.

The predictors of COVID-19 mortality in a nationwide cohort of Turkish patients.

The COVID-19-related death rate varies between countries and is affected by various risk factors. This multicenter registry study was designed to evaluate the mortality rate and the related risk factors in Turkey. We retrospectively evaluated 1500 adults with COVID-19 from 26 centers who were hospitalized between March 11 and July 31, 2020. In the study group, 1041 and 459 cases were diagnosed as definite and highly probable cases, respectively. There were 993 PCR-positive cases (66.2%). Among all cases, 1144 (76.3%) were diagnosed with non-severe pneumonia, whereas 212 (14.1%) had severe pneumonia. Death occurred in 67 patients, corresponding to a mortality rate of 4.5% (95% CI:3.5-5.6). The univariate analysis demonstrated that various factors, including male sex, age ≥65 years and the presence of dyspnea or confusion, malignity, chronic obstructive lung disease, interstitial lung disease, immunosuppressive conditions, severe pneumonia, multiorgan dysfunction, and sepsis, were positively associated with mortality. Favipiravir, hydroxychloroquine and azithromycin were not associated with survival. Following multivariate analysis, male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were found to be independent risk factors for mortality. Among the biomarkers, procalcitonin levels on the 3rd-5th days of admission showed the strongest associations with mortality (OR: 6.18; 1.6-23.93). This study demonstrated that the mortality rate in hospitalized patients in the early phase of the COVID-19 pandemic was a serious threat and that those patients with male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were at increased risk of mortality; therefore, such patients should be closely monitored.

The prognostic role of neopterin in COVID-19 patients.

In Coronavirus disease-2019 (COVID-19) cases, hyper inflammation is associated with the severity of the disease. High levels of circulating cytokines were reported in severe COVID-19 patients. Neopterin produced by macrophages on stimulation with interferon-gamma, which is an important cytokine in the antiviral immune response, hence it can be used to predict the severity of disease in COVID-19 cases. In this study, it was aimed to determine the prognostic value of the neopterin for the prediction of severe disease in patients with COVID-19. This single-center, prospective study was conducted in hospitalized COVID-19 patients and healthy volunteers. Severe and mild COVID-19 cases were compared in terms of clinical and laboratory findings as well as serum neopterin levels on hospital admission. To assess the prognostic utility of neopterin between the severe and mild COVID-19 groups, a receiver-operating characteristic (ROC) curve was generated, and the area under the curve (AUC) was calculated. The median serum neopterin level was four times higher in COVID-19 patients than the healthy controls (46 vs. 12 nmol/L; p < .001). The AUC value of serum neopterin was 0.914 (95% confidence interval, 0.85-0.97). The sensitivity and specificity of serum neopterin for the cut-off value of 90 nmol/L to identify severe COVID-19 cases were 100% and 76%, respectively. Serum neopterin levels on hospitalization were significantly higher in severe COVID-19 disease than mild COVID-19 patients. Neopterin levels can be used as an early prognostic biomarker for COVID-19 on admission.

Early predictors of acute kidney injury in COVID-19 patients.

AIM: This study aims to determine the frequency of COVID-19 related AKI and to identify the early predictors of AKI. METHODS: This study is a single-center, retrospective, observational study. Hospitalized COVID-19 patients between 24/03/2020 and 31/05/2020 were included in the study. All patients were evaluated for renal dysfunctions with urine dipstick, protein/creatinine ratio, albumin/creatinine ratio in spot urine, serum cystatin C, serum creatinine level on hospital admission, and 28th day of hospital admission. To assess the utility of these parameters to predict AKI, a receiver-operating characteristic curve was generated and the area under the curve (AUC) was calculated. RESULTS: 348 patients were included. The average incidence of AKI was 4.9% (n = 17). The incidence of AKI in mild, moderate and severe COVID-19 cases was 1.3% (n = 4), 9.0% (n = 3) and 76.9% (n = 10), respectively. Proteinuria was detected in 7.8% (n = 27) of patients with a urine dipstick test. In spot urine analysis, proteinuria was found in 20.1% (n = 70) of patients. The frequency of persistent proteinuria was 5.2% (n = 18). The AUC alue of serum cystatin C, D-dimer and albumin/creatinine ratio to predict COVID-19 related AKI were 0.96 (0.90 to 1.0), 0.94 (0.89-0.98), and 0.95 (0.91-0.98). CONCLUSION: In COVID-19 patients with normal serum creatinine levels on hospital admission, albuminuria, serum cystatin C and D-dimer levels may be an early predictor of COVID-19 related AKI and these patients should be monitored closely for AKI. Since the sample size in the AKI group was small, our study results should be confirmed with larger cohort studies.

The assessment of serum ACE activity in COVID-19 and its association with clinical features and severity of the disease.

Angiotensin-converting enzyme (ACE)/Angiotensin (Ang) II pathway has crucial regulatory effects on circulatory hemostasis and immune responses. This pathway has a major role in the development of acute lung injury and acute respiratory distress syndrome (ARDS), which is a devastating complication of SARS-CoV-2 infection. The aim of this study is to investigate the serum ACE activity and its correlation with clinical features and the disease severity in patients with COVID-19. Patients with confirmed COVID-19 by detecting SARS-CoV-2 nucleic acid RT-PCR were included in the study. Demographic data, clinical features, laboratory and radiologic investigations were recorded. Patients were classified by disease severity; asymptomatic, mild, and severe pneumonia. The serum ACE activity was evaluated with an autoanalyzer based on a spectrophotometric method. Fifty-five patients (50.9% female) and 18 healthy subjects (33.3 % female) were enrolled in the study. The median age of patients was 40 years, ranging from 22 to 81 years. Eighteen healthy subjects were served as the control group. The baseline characteristics were comparable between groups. The median serum ACE activity of patients and controls (38.00 [IQR 21] U/L and 32.00 [IQR 24] U/L, respectively) and of between patients grouped by disease severity (38.5 [IQR 19], 36 [IQR 25], and 38 [IQR 22] U/L, asymptomatic, mild and severe pneumonia group, respectively) were similar. There was no correlation between the serum ACE activity and conventional inflammatory markers. In this study, we did not find an association between serum ACE activity and COVID-19 and serum ACE activity on admission did not reflect disease severity.

Prognostic value of interleukin-18 and its association with other inflammatory markers and disease severity in COVID-19.

BACKGROUND: The effectual immune response is crucial to defeat viral infections. However, exuberant immune response with features of macrophage activation syndrome (MAS) lead detrimental consequences in COVID-19 patients. Interleukin (IL)-18 is one of the leading cytokines in MAS which has not been studied in COVID-19. OBJECTIVE: To investigate the association of IL-18 with the other inflammatory markers and disease severity in COVID-19 for predicting disease prognosis. METHODS: Patients with COVID-19 who had confirmed diagnosis with SARS-CoV-2 nucleic acid RT-PCR were enrolled into the study. Data on demographic and clinical characteristics, and laboratory values of CRP, ferritin, d-dimer and procalcitonin were measured on admission. Patients were followed up prospectively with a standardized approach until hospital discharge or death. Individuals were classified as asymptomatic, mild and severe pneumonia according to their clinical, laboratory and radiological characteristics. Worse outcome was defined as requirement of intensive care unit (ICU) admission or death. Blood samples were collected at enrollment and serum levels of IL-6 and IL-18 were determined by ELISA. Association between IL-18 and other inflammatory markers and prognosis were analyzed. RESULTS: There were 58 COVID-19 patients (50% male) with a median age of 43 (min 22-max 81) years. Twenty age and sex matched healthy subjects were served as control group. The study population was divided into three groups according to disease severity: asymptomatic (n = 20), mild pneumonia group (n = 27) and a severe group (n = 11). During follow up nine (15.5%) patients required ICU admission and three of them were died eventually. Serum IL-18 were correlated with other inflammatory markers and biochemical markers of organ injury; creatinine, liver enzymes and troponin. Serum IL-18 levels were remarkably higher in COVID-19 patients compared to healthy subjects with being highest in severe pneumonia group (p < 0.001). IL-18 serum concentrations were almost four-fold higher in patients with worse outcome compared to good outcome (p < 0.001). Serum IL-18 above the cut off value of 576 pg/mL on admission was associated with 11.7 fold increased risk of ICU admission. CONCLUSIONS: The serum concentrations of IL-18 correlate with other inflammatory markers and reflect disease severity. Results of the present study shed light on role of IL-18 on COVID-19 pathogenesis and might provide an evidence for the clinical trials on IL-18 antagonists for the treatment of severe COVID-19 patients.

The factors predicting pneumonia in COVID-19 patients: preliminary results from a university hospital in Turkey

Background/aim: Pneumonia is the most serious clinical presentation of COVID-19. This study aimed to determine the demographic, clinical, and laboratory findings that can properly predict COVID-19 pneumonia. Materials and methods: This study was conducted in the Gazi University hospital. All hospitalized patients with confirmed and suspected SARS-CoV-2 infection between 16 March 2020 and 30 April 2020 were analyzed retrospectively. COVID-19 patients were separated into two groups, pneumonia and nonpneumonia, and then compared to determine predicting factors for COVID-19 pneumonia. Variables that had a P-value of less than 0.20 and were not correlated with each other were included in the logistic regression model. Results: Of the 247 patients included in the study 58% were female, and the median age was 40. COVID-19 was confirmed in 70.9% of these patients. Among the confirmed COVID-19 cases, 21.4% had pneumonia. In the multivariate analysis male sex (P = 0.028), hypertension (P = 0.022), and shortness of breath on hospital admission (P = 0.025) were significant factors predicting COVID-19 pneumonia. Conclusion: Shortness of breath, male sex, and hypertension were significant for predicting COVID-19 pneumonia on admission. Patients with these factors should be evaluated more carefully for diagnostic procedures, such as thorax CT.