Role of Vitamin D, ACE2 and the Proteases as TMPRSS2 and Furin on SARS-CoV-2 Pathogenesis and COVID-19 Severity.

BACKGROUND: COVID-19, the 21st century pandemic disease caused by SARS-CoV-2, has shown a wide clinical spectrum ranging from asymptomatic to deadly serious pneumonia. OBJECTIVE: In our study, the relationship between the pathogenesis and clinical severity of COVID-19 and vitamin D, ACE2, Furin and TMPRSS2 was investigated. METHODS: Serum 25(OH)D, 1,25(OH)2D and ACE2 protein were measured in 85 COVID-19 cases, divided into 5 groups, according to disease severity, from asymptomatic to severe and including a healthy control group. Expression levels of ACE2, VDR, TMPRSS2 and Furin mRNAs in PBMC were also measured. The relationship of the parameters within each group, the severity of the disease and the effect on the patients' fate were investigated. RESULTS: Statistically significant differences were found between the severity of COVID-19 and all study parameters, except for serum 25(OH)D. A strong negative correlation was found between serum ACE2 protein, 1,25(OH)2D, and ACE2 mRNA, and disease severity, length of hospital stay and death/survival rate. Vitamin D deficiency increased the death risk by 5.6-fold (95% CI 0.75-41.47), and the levels of 1,25(OH)2D lower than 1 ng/mL increased the risk of death by 3.8-fold (95% CI 1.07-13.30). CONCLUSION: This study suggests that vitamin D supplementation could be beneficial in the treatment and/or prevention of COVID-19.

Could tear be an alternative specimen for SARS-CoV-2 detection?

Objectives For a definitive diagnosis of COVID-19, respiratory tract samples are evaluated by Polymerase Chain Reaction (PCR). In our study, PCR using a tear sample was used to diagnose COVID-19, and it was questioned whether it was a screening method. Unlike the general practice, Schirmer strips were used instead of a swab for tear sample collection in this study. In addition, the diagnostic values of serum Procalcitonin (PCT), C-Reactive Protein (CRP), and Neutrophil (NEU) count in predicting COVID-19 disease from tears were also questioned. Methods A total of 94 patients who were positive for COVID-19 by PCR test were included in this study. Tear samples were obtained from patients with Schirmer strips, commonly used in eye examination, and studied with the PCR technique. CRP, PCT value, and NEU count were also compared between the positive and negative groups of the PCR. The obtained data were analyzed using the R Studio software, and the results were considered statistically significant for pResults Of these patients, 61 (64.9%) tear PCR was negative, and 33 (35.1%) tear PCR was positive. The mean age was 61.72 +/- 17.62 years. The patients were divided into two groups: tear PCR positive and negative. There was no significant age difference between these groups. As a result of ROC Analysis;When serum PCT, CRP, and NEU % values were examined in predicting COVID-19 disease from tears, it was seen that CRP (p=0.027) and especially PCT (p=0.003) values of patients with PCR-positive were significantly higher. Conclusions PCR study on tears collected with Schirmer strips is a different and non-invasive method, but it was concluded that the proposed method could not be used as a screening test. In addition, significantly higher serum PCT values were found in patients with COVID-19 positivity in tears (p<0.05).

Evaluation of the relationship between progression and SARS-CoV-2 viral load in COVID-19 cases in Ankara, Turkey.

INTRODUCTION: Patients infected with SARS-CoV-2 may present with varying clinical pictures. This study aimed to examine the relationship between viral load cycle threshold value, clinical prognosis and other laboratory parameters in initial swab samples on the day of hospitalization. METHODOLOGY: This retrospective and cross-sectional study included 112 patients, who were diagnosed with SARS-CoV-2 via the Bio-Rad CFX96 TouchTM system. Cycle threshold values for the RdRp gene obtained from reverse transcriptase polymerase chain reaction positive patients were recorded. RESULTS: The mean age of the 112 patients was 47.57 ± 17 years. No relationship was found in symptoms, pneumonia, oxygen need, follow-up in intensive care unit, and mortality between patient groups with cycle threshold values of < 30 and ≥ 30. Frequencies of thrombocytopenia (50%) and elevated LDH levels were higher in patients with cycle threshold values of ≥ 30 (p = 0.02 and p = 0.04, respectively). There was a weak but significant correlation between cycle threshold values and CRP levels (Pearson's r = 0.207, p = 0.029). CONCLUSIONS: Symptoms or clinical prognosis were not significantly related to the SARS-CoV-2 viral load levels tested at admission or for the first time within the scope of this study. Thrombocytopenia and elevated LDH rates were higher in patients with cycle threshold values of ≥ 30. A weak but significant correlation was found between the viral load and CRP levels. Large-scale studies are needed to further elucidate this subject matter.

Candidemia Among Coronavirus Disease 2019 Patients in Turkey Admitted to Intensive Care Units: A Retrospective Multicenter Study.

Background: We evaluated the epidemiology of candidemia among coronavirus disease 2019 (COVID-19) patients admitted to intensive care units (ICUs). Methods: We conducted a retrospective multicenter study in Turkey between April and December 2020. Results: Twenty-eight of 148 enrolled patients developed candidemia, yielding an incidence of 19% and incidence rate of 14/1000 patient-days. The probability of acquiring candidemia at 10, 20, and 30 days of ICU admission was 6%, 26%, and 50%, respectively. More than 80% of patients received antibiotics, corticosteroid, and mechanical ventilation. Receipt of a carbapenem (odds ratio [OR] = 6.0, 95% confidence interval [CI] = 1.6-22.3, P = .008), central venous catheter (OR = 4.3, 95% CI = 1.3-14.2, P = .02), and bacteremia preceding candidemia (OR = 6.6, 95% CI = 2.1-20.1, P = .001) were independent risk factors for candidemia. The mortality rate did not differ between patients with and without candidemia. Age (OR = 1.05, 95% CI = 1.01-1.09, P = .02) and mechanical ventilation (OR = 61, 95% CI = 15.8-234.9, P < .0001) were independent risk factors for death. Candida albicans was the most prevalent species overall. In Izmir, Candida parapsilosis accounted for 50% (2 of 4) of candidemia. Both C parapsilosis isolates were fluconazole nonsusceptible, harbored Erg11-Y132F mutation, and were clonal based on whole-genome sequencing. The 2 infected patients resided in ICUs with ongoing outbreaks due to fluconazole-resistant C parapsilosis. Conclusions: Physicians should be aware of the elevated risk for candidemia among patients with COVID-19 who require ICU care. Prolonged ICU exposure and ICU practices rendered to COVID-19 patients are important contributing factors to candidemia. Emphasis should be placed on (1) heightened infection control in the ICU and (2) developing antibiotic stewardship strategies to reduce irrational antimicrobial therapy.

Candidemia among COVID-19 patients in Turkey admitted to ICUs: A retrospective multicenter study

Objectives We evaluated the epidemiology of candidemia among COVID-19 patients admitted to intensive care units (ICUs). Methods We conducted a retrospective multicenter study in Turkey between April- December 2020. Results Twenty-eight of 148 enrolled patients developed candidemia, yielding an incidence of 19% and incidence rate of 14/1,000 patient-days. The probability of acquiring candidemia at 10, 20 and 30 days of ICU admission was 6%, 26% and 50%, respectively. Over 80% of patients received antibiotics, corticosteroid and mechanical ventilation. Receipt of a carbapenem (odds ratio and 95% confidence interval (OR, 95% CI) of 6.0 (1.6–22.3), P=0.008), central venous catheter (4.3 (1.3–14.2), P=0.02) and bacteremia preceding candidemia (6.6 (2.1–20.1), P=0.001) were independent risk factors for candidemia. Mortality rate did not differ between patients with and without candidemia. Age (1.05 (1.01–1.09), P=0.02) and mechanical ventilation (61 (15.8–234.9), P<0.0001) were independent risk factors for death. Candida albicans was the most prevalent species overall. In Izmir, C. parapsilosis accounted for 50% (2/4) of candidemia. Both C. parapsilosis isolates were fluconazole non-susceptible, harbored Erg11-Y132F mutation, and were clonal based on whole-genome sequencing. The two infected patients resided in ICUs with ongoing outbreaks due to fluconazole-resistant C. parapsilosis. Conclusions Physicians should be aware of the elevated risk for candidemia among COVID-19 patients requiring ICU care. Prolonged ICU exposure and ICU practices rendered to COVID-19 patients are important contributing factors to candidemia. Emphasis should be placed on heightened infection control in the ICU, and developing antibiotic stewardship strategies to reduce irrational antimicrobial therapy.

Investigation of Viral Load Cycle Threshold Values in Patients with SARS-CoV-2 Associated Pneumonia with Real-Time PCR Method.

INTRODUCTION: In this study, we aimed investigate the relationship of SARS-CoV-2 viral load cycle threshold (Ct) values with pneumonia. METHODOLOGY: A total of 158 patients in whom SARS-CoV-2 was confirmed in upper respiratory tract (URT) samples with molecular method and who had computed tomography (CT) of the chest, between April 2020 and June 2020 were included in this retrospective cross-sectional study. RESULTS: Mean age of 158 PCR positive patients was 45.22 ± 17.89 and 60.8% of them were male. Pneumonia was detected in 40.5% of the patients on their chest CT. A weak but significant correlation was found between SARS-CoV-2 Ct value detected with PCR in analysis of oropharyngeal/ nasopharyngeal (OP/NP) samples and chest CT score (Pearson's r: 0.197, p = 0.01). No correlation was found between the first detected viral load Ct value and age, gender and mortality. There was no significant correlation between chest CT score and mortality. While the areas remaining under ROC curve for Ct value in analysis of OP/NP samples in prediction of chest CT score ≥ 1, ≥ 5 and ≥ 10 were 0.564, 0.640 and 0.703 respectively. CONCLUSIONS: We found that the amount of SARS-CoV-2 viral load (inverse relationship with Ct) detected in OP/NP samples of patients with COVID-19 pneumonia did not reflect the increasing severity of pulmonary lesions on chest CT. Although primary target of SARS-CoV-2 is all epithelial cells of the respiratory tract we believe studies comparing viral loads in lower respiratory tract samples are needed to determine the severity of pulmonary disease.

Frequency of hepatic steatosis and its association with the pneumonia severity score on chest computed tomography in adult COVID-19 patients.

BACKGROUND: Recent studies of the coronavirus disease 2019 (COVID-19) demonstrated that obesity is significantly associated with increased disease severity, clinical outcome, and mortality. The association between hepatic steatosis, which frequently accompanies obesity, and the pneumonia severity score (PSS) evaluated on computed tomography (CT), and the prevalence of steatosis in patients with COVID-19 remains to be elucidated. AIM: To assess the frequency of hepatic steatosis in the chest CT of COVID-19 patients and its association with the PSS. METHODS: The chest CT images of 485 patients who were admitted to the emergency department with suspected COVID-19 were retrospectively evaluated. The patients were divided into two groups as COVID-19-positive [CT- and reverse transcriptase-polymerase chain reaction (RT-PCR)-positive] and controls (CT- and RT-PCR-negative). The CT images of both groups were evaluated for PSS as the ratio of the volume of involved lung parenchyma to the total lung volume. Hepatic steatosis was defined as a liver attenuation value of ≤ 40 Hounsfield units (HU). RESULTS: Of the 485 patients, 56.5% (n = 274) were defined as the COVID-19-positive group and 43.5% (n = 211) as the control group. The average age of the COVID-19-positive group was significantly higher than that of the control group (50.9 ± 10.9 years vs 40.4 ± 12.3 years, P < 0.001). The frequency of hepatic steatosis in the positive group was significantly higher compared with the control group (40.9% vs 19.4%, P < 0.001). The average hepatic attenuation values were significantly lower in the positive group compared with the control group (45.7 ± 11.4 HU vs 53.9 ± 15.9 HU, P < 0.001). Logistic regression analysis showed that after adjusting for age, hypertension, diabetes mellitus, overweight, and obesity there was almost a 2.2 times greater odds of hepatic steatosis in the COVID-19-positive group than in the controls (odds ratio 2.187; 95% confidence interval: 1.336-3.580, P < 0.001). CONCLUSION: The prevalence of hepatic steatosis was significantly higher in COVID-19 patients compared with controls after adjustment for age and comorbidities. This finding can be easily assessed on chest CT images.

Does COVID-19 cause an increase in spleen dimensions? Possible effects of immune activation, hematopoietic suppression and microthrombosis.

PURPOSE: To radiologically examine how the spleen size, which has important functions in hematological and immunological balance, is affected in COVID-19. METHODS: Between July 1 and August 31, 2020, consecutive patients diagnosed with COVID-19 were analyzed. Among these patients, those who underwent chest computed tomography (CT) examination at the time of presentation, patients with follow-up CT due to clinical deterioration were included in the study. The CTs of the patients were evaluated in terms of spleen size and volume. RESULTS: A total of 160 patients (88 females, 55%) were included in the study. The mean time between the initial and follow-up CT was 7.2 ± 2.8 days. The splenic volume (244.3 ± 136.7 vs. 303.5 ± 156.3 cm3) and splenic index (421.2 ± 235.5 vs. 523.2 ± 269.4 cm3) values were significantly higher in the follow-up CT compared to the initial CT (p < 0.001). The increase in the splenic volume and splenic index values was 59.2 ± 52.4 cm3 and 101.9 ± 90.3 cm3 (p < 0.001), respectively. The COVID-19 severity score was significantly higher in the follow-up CT compared to the initial CT (3.7 ± 4.2 vs. 12.5 ± 5.7, respectively; p < 0.001). The spleen width measured separately on the initial and follow-up CTs showed a highest positive correlation (r = 0.982, p < 0.001). CONCLUSION: Our study indicates that spleen size increases slightly-moderately in the first stages of the infection, and this increase is correlated with the COVID-19 severity score calculated on the chest CT data, and in this respect, it is similar to infections presenting with cytokine storm.