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 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.

Prognostic Value of Renal Dysfunction Indicators in Normotensive Patients With Acute Pulmonary Embolism.

INTRODUCTION: Glomerular filtration rate (GFR) and blood urea nitrogen (BUN) are important prognostic indicators for cardiovascular disease. However, data on the relationship between renal dysfunction (RD) and prognosis in patients with acute pulmonary embolism (APE) are limited. The estimated-GFR (eGFR), based on the Modification of Diet in Renal Disease (MDRD) equation, has been suggested as a possible prognostic marker in patients with APE; however, at present, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is thought to be more accurate than the MDRD equation for the estimation of RD. OBJECTIVE: We investigated whether eGFRCKD-EPI or BUN could predict adverse outcomes (AOs) better than eGFRMDRD in normotensive patients with APE. METHODS: Ninety-nine normotensive patients with APE (aged 22-96, 56% male) were enrolled in the study retrospectively. Adverse outcomes were defined as the occurrence of any of the following: death, cardiopulmonary resuscitation, use of vasopressors, thrombolysis, or mechanical ventilation. RESULTS: In univariate analyses, age, gender (male), heart rate (>110 bpm), serum creatinine, BUN, cardiac troponin (cTn) positivity, right ventricle-left ventricle ratio, eGFRMDRD, and eGFRCKD-EPI were found to be significantly different between those with and without AOs. Comparing area under the curves for AO, we found statistically significant differences between eGFRCKD-EPI and eGFRMDRD ( P = .01) but not between BUN and eGFRCKD-EPI or BUN and eGFRMDRD. Furthermore, 30-day mortality was 36% versus 11% in cTn-positive patients with an eGFRCKD-EPI < and ≥ 60 mL/min, respectively. CONCLUSION: There is a close relationship between RD and APE prognosis. We conclude eGFRCKD-EPI is a potential prognostic marker for risk stratification in normotensive patients with APE.

Comparison of the diagnostic value of different lymphocyte subpopulations in bronchoalveolar lavage fluid in patients with biopsy proven sarcoidosis.

BACKGROUND: Bronchoalveolar lavage is considered a helpful tool in the diagnosis of diffuse parenchimal lung diseases such as sarcoidosis. CD4/CD8 ratio is higly specific but not sensitive to distinguish sarcoidosis and other intestitial lung diseases. We aimed to compare the diagnostic value of CD4/CD8 ratio and other lmphocyte subpopulations such as CD3+16+56, CD103+, CD4+CD103+, CD8+CD103+ in bronchoalveolar lavage to distinguish sarcoidosis and other nonsarcoidosis interstitial lung diseases. METHODS: Using the bronchoscopy records from 2006 to 2013, we evaluated 68 patients with biopsy proven sarcoidosis and 72 patients with clinicoradiological and/or biopsy proven diffuse parenchimal lung diseases. Cut off values, sensitivity and specificity were given for aforementioned parameters. RESULTS: Bronchoalveolar lavage CD4/CD8 ratio, CD4+ T lymphocyte percentage, CD4+103+, CD3+CD103-, CD8+CD103+/CD103+ ratio were significantly higher in sarcoidosis than other diffuse parenchimal lung diseases whereas CD3+103+, CD3+16+56+, CD8+, CD8+CD103+, CD8+CD103+/CD8+ were significantly lower. Best cut off value of CD4/CD8 was 1.34 with sensitivity and specificity 76.4%, 79.4% respectively. The cut off values of CD4/CD8 of >3.5 and >2.5 had specificity 95.9% and 95.3%, respectively and sensitivity 52%, 41%, respectively. CONCLUSION: CD4/CD8 ratio is highly specific but not sensitive for sarcoidosis diagnosis. Thus, BAL flow cytometry is not diagnostic alone without appropriate clinicoradiological and/or histopathological findings.

Bronchoalveolar Lavage Fluid Characteristics of Patients With Sarcoidosis and Nonsarcoidosis Interstitial Lung Diseases: Ten-Year Experience of a Single Center in Turkey.

BACKGROUND: Bronchoalveolar lavage (BAL) is a noninvasive and useful technique for evaluating interstitial lung diseases (ILDs). Flow cytometric analysis of BAL fluid reveals specific diagnostic information in some unusual ILDs, and helps to narrow down the possible causes of interstitial diseases in most patients with more common disorders. A high BAL CD4/CD8 ratio is highly specific for sarcoidosis but can also be seen in other ILDs. OBJECTIVES: In this retrospective, descriptive, cross-sectional study, we compared BAL fluid characteristics and clinical variables in patients with sarcoidosis and non-sarcoidosis ILDs in a large cohort. PATIENTS AND METHODS: The study was conducted in a tertiary university hospital in Zonguldak, the biggest city of the western Black Sea region of Turkey. Between 2004 and 2014, all patients who underwent both fiberoptic bronchoscopy and BAL with a suspicion of ILD were included in the study, retrospectively. Patients were divided into two main groups: sarcoidosis and non-sarcoidosis ILDs. Non-sarcoidosis ILDs were further divided into subgroups: pneumoconiosis, tuberculosis (TB), collagen vascular diseases, idiopathic interstitial pneumonias, malignancies, and unclassified ILDs. The clinical data of patients, including age, gender, smoking status, pulmonary function tests, and BAL flow cytometric analysis results, were compared among groups. RESULTS: In total, 261 patients (119 sarcoidosis and 142 non-sarcoidosis ILDs) were enrolled. The median (interquartile range) BAL CD4/CD8 ratio and lymphocyte fraction were significantly higher in sarcoidosis than in non-sarcoidosis ILDs: 3.88 (3.76) versus 0.88 (1.01), respectively, and 20.6 (28.3) versus 6.0 (13.7), respectively. T cell receptor γ delta, CD16(+)56(+), CD103(+), CD8(+)103(+), and CD3(+)16(+)56(+) cells were significantly lower in sarcoidosis than in non-sarcoidosis ILDs. The median BAL CD4/CD8 ratios were significantly higher in patients with TB (1.87, P = 0.01) and malignancies (1.69, P = 0.03) than in other non-sarcoidosis ILDs. CONCLUSIONS: Among BAL fluid flow cytometric parameters, CD4/CD8 and lymphocyte fraction may be helpful for distinguishing sarcoidosis from other ILDs, but they are neither specific nor diagnostic for any lung disease. Thus, a multidisciplinary diagnostic discussion is required to differentiate various ILDs.

Prognostic value of serum procalcitonin and C-reactive protein levels in critically ill patients who developed ventilator-associated pneumonia.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is an important cause of mortality and morbidity in critically ill patients. We sought to determine the prognostic value of procalcitonin (PCT) and C-reactive protein (CRP) kinetics in critically ill patients who developed VAP. METHODS: Patients who were admitted to the intensive care unit (ICU) and developed VAP were eligible. Patients were followed for 28 days after the pneumonia diagnosis and blood samples for PCT and CRP were collected on the day of the pneumonia diagnosis (D0), and days 3 (D3) and 7 (D7) after the diagnosis. Patients were grouped as survivors and non-survivors, and the mean PCT and CRP values and their kinetics were assessed. RESULTS: In total, 45 patients were enrolled. Of them, 22 (48.8%) died before day 28 after the pneumonia diagnosis. There was no significant difference between the survivor and non-survivor groups in terms of PCT on the day of pneumonia diagnosis or CRP levels at any point. However, the PCT levels days 3 and 7 were significantly higher in the non-survivor group than the survivor group. Whereas PCT levels decreased significantly from D0 to D7 in the survivor group, CRP did not. A PCT level above 1 ng/mL on day 3 was the strongest predictor of mortality, with an odds ratio of 22.6. CONCLUSION: Serum PCT was found to be a superior prognostic marker compared to CRP in terms of predicting mortality in critically ill patients who developed VAP. The PCT level on D3 was the strongest predictor of mortality in VAP.

Comparison of diagnostic values of procalcitonin, C-reactive protein and blood neutrophil/lymphocyte ratio levels in predicting bacterial infection in hospitalized patients with acute exacerbations of COPD.

BACKGROUND: Viral or bacterial upper respiratory infections are the most common cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Based on available data, no reliable parameter has been presented to distinguish between bacterial and nonbacterial exacerbations. Therefore, we compared the diagnostic value of procalcitonin (PCT) level, which is a newer marker for predicting bacterial infections in patients with AECOPD, to routine parameters such as C-reactive protein (CRP) levels and the neutrophil/lymphocyte (N/L) ratio. METHODS: This study included all consecutive patients who were admitted for a diagnosis of AECOPD between January 1 and March 31, 2014. PCT, CRP, and the N/L ratio were assessed in addition to cultures from tracheal aspirates or sputum on the first day of admission. Patients with a pneumonic infiltration on chest radiographs, or an extrapulmonary infection focus, or whose blood samples were not obtained for PCT and/or CRP at the same time as sputum culture were excluded from the study. RESULTS: A total of 77 patients were included with a mean age of 71.7 ± 9.5 years. Bacteria were isolated in 37.4 % of the patients. Mean PCT levels were significantly higher in patients with positive sputum cultures than in patients with negative sputum cultures. The cut-off values for PCT, CRP, and the N/L ratio for predicting a bacterial infection were 0.40 ng/mL, 91.50 mg/L, and 11.5, respectively; sensitivity was 61, 54, and 61 % respectively; specificity was 67, 52, and 58 %, respectively; and the area under the curve (AUC) values were 0.64, 0.52, and 0.58, respectively. The AUC value of PCT was significantly better for predicting bacterial infection compared with the CRP level or the N/L ratio (p = 0.042). CONCLUSION: PCT was better than CRP and the N/L ratio for predicting a bacterial infection in hospitalized patients with AECOPD. However, we find PCT not so reliable in predicting bacterial infection in AECOPD due to sensitivity and specificity of less than 80 % and a low AUC value.