Favipiravir for the treatment of COVID-19 pneumonia: Can we predict the response to treatment?

INTRODUCTION: Early experience with favipiravir in the treatment of COVID-19 is promising, but no clinical data have been published in medical journals. This study aimed to review the experience with favipiravir treatment for COVID-19 pneumonia and to examine whether there are any predictors of treatment response. METHODOLOGY: Fifty-six patients with severe or progressive pneumonia associated with COVID-19 who were treated with favipiravir monotherapy for at least five days were included in this retrospective study. Treatment response was defined as clinical recovery without any need for admission into the intensive care unit and/or anti-cytokine therapy. The demographic, clinical, laboratory and radiographic features of the patients were compared between favipiravir-responders and non-responders. RESULTS: Of the 56 patients, 34 patients (60.7%) responded to treatment and recovered. There was no difference in the demographic, clinical, and radiographic findings between the responders and non-responders. The inflammatory biomarkers were also similar except for the CRP levels on the day favipiravir was started [74 (36-111) vs. 118.5 (46.5-203) mg/L, respectively, p = 0.043]. There was also a significant difference in the median time to defervescence [1 (1-2) vs. 3.5 (1.75-9.25) days, respectively]. Of clinical interest, 27 (79.4%) and 31 (91.2%) of the responders became afebrile within two and four days, respectively. The response rate was lower in patients who presented severe pneumonia associated with respiratory failure. CONCLUSIONS: Patients with non-severe pneumonia at admission and whose fever resolved within two days of treatment are more likely to improve with favipiravir.

The Efficacy of Hydroxychloroquine and Azithromycin Combination Therapy on Hospital Mortality in COVID 19 Pneumonia Patients.

BACKGROUND/AIM: Effective therapeutic approaches for SARS-CoV-2 pandemic are urgently needed. Hydroxychloroquine (HCQ) alone or in combination with azithromycin has been used in several countries, without any clear evidence. This study aimed to determine the effectiveness and safety of hydroxychloroquine as compared to hydroxychloroquine and azithromycin combination in patients with COVID-19 pneumonia. MATERIALS AND METHODS: This retrospective study evaluated all patients admitted to two university hospitals between 18 March and 20 May 2020 with the diagnosis of COVID-19 pneumonia. Out of 496 patients, 370 met the eligibility criteria and were included in the final analysis. The primary outcome was in-hospital mortality. Secondary outcomes were time to recovery, presence of severe acute respiratory infection (SARI), the requirement for oxygen therapy, and/or mechanical ventilation, length of hospital stay, and adverse events. RESULTS: A total of 222 patients received hydroxychloroquine and 148 were treated with HCQ and azithromycin combination. The in-hospital mortality rates were similar in the two groups (10.8% vs. 6.8%, respectively, p=0.186). Additionally, the needs for oxygen therapy, invasive mechanic ventilation (IMV) and intensive care unit (ICU) admission were not different. The rate of the requirement of non-invasive mechanic ventilation (NIV) was higher in patients receiving HCQ plus azithromycin (10.1% vs. 4.5%, p=0.035). Time to recovery was 3.5 days in HCQ and 5.0 days in HCQ plus azithromycin group (p<0.001). The median length of hospital stay was longer in patients with the combination therapy (7.0 vs. 5.5 days, p<0.001). Amongst all patients, only 3 patients developed electrocardiographic changes needing discontinuation of therapy. LIMITATIONS: Observational design of the study is the main limitation. CONCLUSIONS: The present findings suggest that adding azithromycin to HCQ is not associated with any improvement in clinical outcome and mortality in patients with COVID-19 pneumonia and supports the current knowledge not to include azithromycin in the initial treatment of COVID-19.

Communication: The Follow-Up of Biomarkers Better Predicts the Poor Outcome in COVID-19 Patients.

OBJECTIVE: To investigate the course of biomarkers on admission and follow-up in order to identify early predictors for poor outcome in COVID-19 patients. METHODS: In this study, 132 COVID-19 patients were classified as good outcome (n=62) and poor outcome (n=70) groups. Laboratory parameters were evaluated on admission and within 5-7 days after hospitalization. RESULTS: Baseline levels of neutrophil-lymphocyte ratio, CRP, procalcitonin, ferritin, D-dimer and LDH were higher (p<0.01); lymphocyte count was lower in the poor outcome patients. During follow-up there was a larger decrease in lymphocyte count and more prominent increases in other biomarkers (p<0.001). In ROC analysis, the AUCs strongly indicated the poor outcome on days 5-7 of the hospitalization. CONCLUSIONS: This study suggests that the follow-up measurements of the biomarkers better predict the poor outcome in COVID-19 pneumonia.

[Pneumococcal infections and protection with vaccination in adult chronic lung diseases]. / Eriskin kronik akciger hastaliklarinda pnömokok infeksiyonu ve asi ile korunma.

Pneumococcal infections are an important cause of mortality and morbidity in Chronic Lung Diseases. However, exacerbations, which make the treatment of diseases very difficult, and corticosteroids used during treatment carry a great risk of pneumococcal infection and adversely affect the treatment. The most rational way to reduce the negative impact of pneumococcal infections on the clinical and economic burden of Chronic Lung Diseases is vaccination of the risky population. Although, vaccination recommendations are well defined, recommended by national and international guidelines and are paid by health authorities, in Turkey, vaccination rates in adults with chronic lung disease is far below the expected. Since physicians are considered to be the most important and reliable resource that can guide their patients in vaccination, applying pneumococcal vaccination routinely in all patients with chronic lung diagnosis and making it a part of daily practice will greatly contribute to reducing the clinical and economic burden of pneumococcal infections in these patients. In this review, the effects of pneumococcal diseases on chronic lung diseases, the risk and clinical burden of pneumococcal diseases in chronic lung diseases are discussed in the light of guidelines and current literature, and the importance of protection from pneumonia in these patients is emphasized. In addition to general information and efficacy data about pneumococcal vaccines available in our country, application methods and access routes to vaccines are also described.

Factors affecting TST level in patients undergoing dialysis: a multicenter study.

INTRODUCTION: The risk of TB is increased in patients with chronic kidney disease (CKD) when compared with individuals with normal renal function. We aimed to determine tuberculin skin test (TST) response and the factors which might affect the response in patients with CKD undergoing dialysis in this study. METHODS: The purified protein derivative solution was administered to the patients and the diameter of induration was measured. Additionally, the age, gender and smoking status of the patients were interrogated. Comorbidities were recorded both by patients' self-reports and data from the hospital files. The number of Bacille Calmette-Guerin (BCG) scars was recorded by checking both shoulders. FINDINGS: The study was conducted with a total of 371 patients (194 men and 177 women). The mean age was 60.09 ± 15.88, TST was 6.99 ± 6.9, duration of dialysis was 4.44 ± 4.5 (3.8-0.1,24). A total of 229 patients have comorbodities (61.7%, the most frequent was hypertension). Logistic regression model was performed. Gender, vitamin D treatment and high parathormone (PTH) levels remained in the final stage of the analysis and vitamin D intake and PTH levels were detected to be statistically significant (P = 0.002, 0.007, respectively). DISCUSSION: This study is the first study which showed a correlation between TST negativity and increased PTH levels and receiving vitamin D treatment. Starting from this point, it was concluded that PTH may suppress the immune system and especially cellular immunity.

Role of Toll-Like Receptors in Tuberculosis Infection.

BACKGROUND: One-third of the world's population is infected with Mycobacterium tuberculosis. Investigation of Toll-like receptors (TLRs) has revealed new information regarding the immunopathogenesis of this disease. Toll-like receptors can recognize various ligands with a lipoprotein structure in the bacilli. Toll-like receptor 2 and TLR-4 have been identified in association with tuberculosis infection. OBJECTIVES: The aim of our study was to investigate the relationship between TLR polymorphism and infection progress. METHODS: Twenty-nine patients with a radiologically, microbiologically, and clinically proven active tuberculosis diagnosis were included in this 25-month study. Toll-like receptor 2 and TLR-4 polymorphisms and allele distributions were compared between these 29 patients and 100 healthy control subjects. Peripheral blood samples were taken from all patients. Genotyping of TLR-2, TLR-4, and macrophage migration inhibitory factor was performed. The extraction step was completed with a Qiagen mini blood purification system kit (Qiagen, Ontario, Canada) using a peripheral blood sample. The genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: In total, 19 of the 29 patients with tuberculosis infection had a TLR-2 polymorphism, and 20 of the 100 healthy subjects had a TLR-2 polymorphism (P < 0.001). The TLR-4 polymorphism and interferon-γ allele distributions were not statistically correlated. CONCLUSIONS: Toll-like receptor 2 polymorphism is a risk factor for tuberculosis infection. The limiting factor in this study was the lack of investigation of the interferon-γ and tumor necrosis factor-α levels, which are important in the development of infection. Detection of lower levels of these cytokines in bronchoalveolar lavage specimens, especially among patients with TLR-2 defects, will provide new data that may support the results of this study.

Clinical factors and comorbidities affecting the cost of hospital-treated COPD.

PURPOSE: We aimed to assess the effects of comorbidities on COPD costs and to investigate the relationship between comorbidities and clinical variables. PATIENTS AND METHODS: All patients hospitalized with a diagnosis of COPD exacerbation between January 1, 2014, and December 31, 2014, at all state hospitals of Aydin province, a city located in the western part of Turkey, were included in this study. The costs examined in the study pertained to medications, laboratory tests, hospital stays, and other treatment-related factors, such as consumption of materials, doctor visits, and consultation fees. RESULTS: A total of 3,095 patients with 5,237 exacerbations (mean age, 71.9±10.5 years; 2,434 males and 661 females) were evaluated. For 880 of the patients (28.9%), or 3,852 of the exacerbations (73.1%), at least one comorbid disease was recorded. The mean cost of each exacerbation was $808.5±1,586, including $325.1±879.9 (40.7%) for hospital stays, $223.1±1,300.9 (27.6%) for medications, $46.3±49.6 (0.9%) for laboratory expenditures, and $214±1,068 (26.5%) for other treatment-related factors, such as consumption of materials, doctor visits, and consultation fees. The cost of each exacerbation was $1,014.9 in patients with at least one comorbidity, whereas it was $233.6 in patients without comorbidity (P<0.001). Age >65 years, female gender, hospitalization in an intensive care unit, invasive or noninvasive mechanical ventilation, and a long duration of hospitalization were all found to be significant factors in increasing total costs during the exacerbations requiring hospitalization (P<0.05 for all). CONCLUSION: Comorbidities have an important role in the total costs of acute exacerbations of COPD. Strategies for the prevention, diagnosis, and effective management of comorbidities would decrease the overall financial burden associated with acute exacerbations of COPD.

ERCC1 expression does not predict survival and treatment response in advanced stage non-small cell lung cancer cases treated with platinum based chemotherapy.

BACKGROUND: ERCC1 is considered as a promising molecular marker that may predict platinum based chemotherapy response in non small cell lung cancer patients. We therefore investigated whether its expression is indeed associated with clinical outcomes in advanced stage NSCLC patients. MATERIALS AND METHODS: Pretreatment tumor biopsy samples of 83 stage 3B and 4 non-small cell lung cancer patients treated with platinum based chemotherapy were retrospectively analyzed for immunohistochemical ERCC1 expression. None of the patients received curative surgery or radiotherapy. RESULTS: By calculating H- scores regarding the extent and intensity of immunohistochemical staining of tumor biopsy samples, ERCC1 expression was found to be positive in 50 patients (60.2%). ERCC1 positive and negative groups had no statistically significant differences regarding treatment response, progression free survival and overall survival (respectively p=0.161; p=0.412; p=0.823). CONCLUSIONS: In our study we found no association between ERCC1 expression and survival or treatment response. The study has some limitations, such as small sample size and retrospective analysis method. There is need of more knowledge for use of ERCC1 guided chemotherapy regimens in advanced stage NSCLC.

Can impairments of thyroid function test affect prognosis in patients with respiratory failure?

Thyroid function test (TFT) impairments can be detected in extrathyroidal dysfunction, primarily in chronic obstructive pulmonary disease (COPD) with acute respiratory failure (RF). The aims of this study were to: (i) evaluate TFT impairments in patients with RF, (ii) compare TFT results to a control group without RF and (iii) assess the effects of thyroid dysfunction on clinical outcome and prognosis of RF. The TFT parameters were assessed in 65 patients (65.0 +/- 10.0 years, 49 males) with RF and compared to 18 patients (64.4 +/- 9.8 years, 13 males) with lung disease and no RF (p> 0.05). Arterial blood gas analysis, free T3 (FT3), free T4 (FT4) and TSH levels were all measured. The impairments of TFT were demonstrated in 34 (52.3%) patients with RF and 8 (44.4%) patients without RF (p> 0.05). The most common finding was a decrease in at least one of the TFT parameters in both groups (43.1% vs. 44.4%, respectively). In RF group, there was no significant association between TFT results and gender, age, diagnosis and co-morbid disease. However, need for invasive mechanical ventilation was higher both in patients with low FT3 and low FT4 when compared to those with normal TFT results (p= 0.001 and p= 0.003, respectively). In-hospital mortality rate was also higher both in the patients with low FT3 and low FT4 than the others (p= 0.006 and p= 0.01, respectively). We conclude that TFT impairments are not observed more frequently in patients with RF when compared to the patients without RF. However, low FT3 and FT4 levels increase the rates of invasive mechanical ventilation and mortality.

Exudative pleural effusion due to brucellosis in a patient with chronic obstructive pulmonary disease.

Pleural involvement is a rare presentation of brucellosis. We report a patient referred for the evaluation of fever, right-sided pleural effusion and hilar lymph node enlargement. The pleural fluid revealed exudative characteristics with the predominance of neutrophils. Brucella melitensis was isolated from bone marrow, pleural effusion and blood cultures. The diagnosis was also confirmed by demonstration of a high Brucella agglutinin titre. The patient was successfully treated with rifampicin and doxicycline for three months.