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.

COVID-19 in Familial Mediterranean Fever: Clinical Course and Complications Related to Primary Disease.

OBJECTIVE: Aim of the study is to evaluate the impact of Familial Mediterranean Fever (FMF) features on clinical course and outcomes of Coronavirus disease-19 (COVID-19) and clinical course of FMF after COVID-19. METHODS: Consecutive FMF patients with COVID-19 were enrolled from three referral hospitals. Clinical features of FMF and detailed COVID-19 information were obtained from patient interviews and medical records. RESULTS: Seventy-three FMF patients were included in the study. Sixty-nine patients had clinical symptoms of COVID-19, and 90.4% of patients received COVID-19 specific treatment. We found 24.7% hospitalization, %12.3 respiratory support, 4.1% ICU admission, 6.8% complication, and 1.4 % mortality rate in patients. Male gender and older age were significantly frequent in inpatients compared to outpatients (male gender 77.8 % vs 25.8%, p<0.001; median age 39.5 vs 32 years, p:0.043). FMF features were similar in both groups. The risk factors of hospitalization for respiratory support were male gender (OR: 7.167 (95% CI:1.368-37.535)), greater age (OR:1.067 (95% CI:1.016-1.121)) and non-adherence to colchicine treatment before the infection (OR:7.5 (95% CI: 1.348-41.722)). One-third of patients (33.3%) had reported attacks after COVID-19. The patterns of triggered attacks were fever, peritonitis, pleuritis, transient arthritis, chronic knee mono-arthritis, and protracted febrile myalgia. CONCLUSION: FMF characteristics were not associated with worse outcomes of COVID-19. Colchicine non-adherence was the risk factor of hospitalization for oxygen support. The rate of FMF attacks after COVID-19 is prominently increased with some of them be protracted and destructive.

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.

Covid-19 scientific publications from Turkey

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak poses a major global threat to the public health worldwide. The infectious disease caused by the virus that affected the entire world was named as the Coronavirus disease-2019 (COVID-19). The knowledge regarding the wide clinico-biological aspects of the COVID-19 continues to evolve very rapidly, given the growing data from all over the world. During this complicated process, healthcare professionals have benefited from each other's experiences in combatting against the COVID-19 syndrome. COVID-19 related studies have been performed by a wide variety of research groups in Turkey as well as the rest of the world. The aim of this paper is to outline Turkish COVID-19 research indexed in the LitCovid system. LitCovid is a curated literature hub for tracking up-to-date scientific data about the SARS-CoV-2. COVID-19's first case was detected in Turkey, on March 11th, 2020. Six months after the first case was observed, the total number of COVID-19 patients was reported to be as 286,455, and the total number of deaths due to SARS-CoV-2 was 6895. The genetic sequence of the novel coronavirus showed significant identity to SARS-CoV and MERS-CoV. Numerous drugs including lopinavir/ritonavir, favipiravir, neuraminidase inhibitors, remdesivir, umifenovir, azithromycin, and chloroquine have been suggested for the management of COVID-19 although the exact treatment is yet to be determined.

COVID-19 in chronic diseases

The novel coronaviruses disease, namely COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide and resulted in a crucial global health problem. Various studies and meta-analyses have demonstrated that chronic disease, including diabetes mellitus, hypertension, cardiovascular diseases, and chronic obstructive pulmonary disease, are considered as risk factors for the disease severity, poor prognosis, and mortality in COVID-19. Although the exact reasons for the association between these comorbidities and disease severity and mortality risk of COVID-19 have not clarified, immune dysregulation and hyperinflammation in these chronic diseases might be contributing factors to the progression of the COVID-19. Furthermore, most of the patients with chronic inflammatory rheumatologic disease have the impairment of immune system and inflammatory response due to underlying pathogenesis of their diseases, and thus they might be prone to SARS-CoV-2 infection. We have focused the attention on most common chronic diseases frequently observed in COVID-19 and rheumatologic diseases which may be related to infection and their association with course of COVID-19.