Does Previous Anti-thrombotic Use Affect the Course of Coronavirus Disease-2019?

Introduction: Proinflammatory cytokines, produced as an immune response in severe acute respiratory syndrome-coronavirus 2 infection, activate the coagulation cascade as well. In this study, we investigated the difference in the clinical course of patients who had been already using anti-thrombotic therapy before coronavirus disease-2019 (COVID-19) for any reason compared to the group who had not. Methods: In this retrospective, multicenter study;patients who were hospitalized between March 11 and July 1, 2020 were divided into two main groups as who had been on anti-thrombotic therapy for any indication use previously at the time of admission or who had not been on anti-thrombotic therapy at the time of admission, and their selected clinical parameters were compared. Results: After analyzing the study population of 124 patients with a homogeneous distribution in terms of age and gender, the comparison of anti-thrombotic users and non-users showed no significant difference in hospitalization. There was a statistically significant decrease in mechanical ventilation apply rate, intensive care unit duration and mortality rate between the group using anti-thrombotic compared to the group not using it (p<0.05). Conclusion: It has already been shown that COVID-19 patients are more prone to thromboembolic events as it activates the coagulation cascade with the cytokine storm it creates and thus the mortality of COVID-19 infection increases significantly. Parallel to this fact the results of our study demonstrated that using anti-thrombotic therapy for any reason may affect the bad prognosis of the disease positively. [ FROM AUTHOR]

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.

Prognostic predictors for mortality of patients with COVID-19 in an intensive care unit.

INTRODUCTION: Fatality due to COVID-19 continues to be a challenge. Timely identification of critical COVID-19 patients is crucial for their close clinical follow-up and treatment. We aimed to identify the mortality predictors of critical COVID-19 patients. METHODOLOGY: We analyzed medical records of 232 out of 300 patients with COVID-19 hospitalized in the intensive care unit (ICU) whose medical records were available in the hospital database. Non-survivors and survivors were compared for parameters. Medical records of demographics, comorbidities, radiological signs, respiratory support, and laboratory tests on the first day of ICU admission were included. The durations of ICU stay and hospitalization were also evaluated. RESULTS: The patients with Acute Physiology and Chronic Health Evaluation II (APACHE-II) score above 28.5 and the patients with blood urea nitrogen (BUN) above 45.5 mg/dL were significantly more mortal (95% CI: 0.701, p = 0.0001; 95% CI: 0.599, p = 0.022; respectively). Partial oxygen pressure/fraction of inspired oxygen (P/F) ratio below 110.5 mmHg was a predictor for mortality (95% CI: 0.397, p = 0.018). Older age, smoking, crazy paving pattern on computed tomography (CT), and short duration of hospitalization were also predictors of mortality. The patients requiring invasive mechanical ventilation were significantly more mortal whereas the patients requiring high flow oxygen and non-invasive ventilation were significantly more likely to survive. CONCLUSIONS: We recommend evaluating APACHE-II score, BUN value, P/F ratio, age, smoking status, radiological signs on CT, length of hospitalization and modality of respiratory support upon ICU admission to identify critical patients with poor prognoses.

Co-infection of COVID-19 and Tuberculosis.

OBJECTIVE: Tuberculosis and COVID-19 diseases occur more frequently in people with similar risk factors. This study aimed to share the data on active tuberculosis patients during the severe acute respiratory syndrome coronavirus 2 pandemic. MATERIAL AND METHODS: The registration information of TB outpatient clinic between November 1, 2019, and April 20, 2020, was screened. A 7-question survey was administered to the patients who were diagnosed with active tuberculosis and who were agreed to participate in the study. RESULTS: A total of 309 patients with active tuberculosis were evaluated, the average age of the patients was 42.5 ± 18.5 years, and 70% were male. The percentage of having at least 1 comorbidity was 30.4%. The percentage of coronavirus disease 2019 disease in our study population was 1.9%; none of the patients of coronavirus disease 2019 were taken into the intensive care unit or dead due to clinical deterioration and/or respiratory failure. On the other hand, in this process it was announced that 146 457 cases were diagnosed with coronavirus disease 2019 throughout the country, of which 72% had inpatient treatment, 2% died, and 944 patients were still being treated in the intensive care unit, of which 490 were intubated. The positivity ratio of the reverse transcription-polymerase chain reaction test was 20.0% in the study group, while 20.3% in the Istanbul population. CONCLUSION: Tuberculosis patients might be more disadvantageous than the normal population in terms of the risk of exposure to severe acute respiratory syndrome coronavirus 2, but this does not cause an increase in the frequency and severity of coronavirus disease 2019 disease in active tuberculosis patients.

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.

Lifestyle Changes and Exacerbation Frequency of COPD in Times of the Pandemic.

OBJECTIVE: The objective of this study is to analyze chronic obstructive pulmonary disease exacerbation rates and the effect of patients' behavioral changes on the exacerbations during the pandemic. MATERIAL AND METHODS: This study was conducted in a reference hospital for chest diseases and patients who were hospitalized with an exacerbation of chronic obstructive pulmonary disease between March 11, 2019, and March 11, 2020, were designated. Patients' chronic obstructive pulmonary disease exacerbations requiring emergency department visits and/or hospitalization were com- pared between the pre-pandemic and pandemic periods. Each patient was surveyed with 25 questions using telemedicine. RESULTS: Of all the 256 patients, 203 (79%) were male and the mean age was 66 ± 10 years. Compared to the previous year, emer- gency department visits and hospitalizations in our hospital were significantly lower and less frequent (P < .0001, for both). Smoking habits decreased in 9% of patients, and 60% had hardly spent time outdoors. Only 3 patients reported to spend time indoors. The household mask-use rate while contacting the patient was 50%. As a chronic obstructive pulmonary disease patient, 33% expressed themselves as "feeling better." Overall, 92(36%) patients were recorded not to have any exacerbation, and 34 (13%) to have no attacks of worsening were managed at home. Novel exacerbation risk was found to independently correlate with younger age (odds ratio: 0.944, CI: 0.904-0.986, P = .010) and having more frequent episodes of exacerbation in the pre-pandemic period (odds ratio: 1.2, CI: 1.025-1.405, P = .023). CONCLUSION: Chronic obstructive pulmonary disease patients specifically benefited from confinements, restrictions, and lifestyle changes. Further studies are needed to better identify the most critical factors leading to these positive outcomes. A permanent patient management guideline for chronic obstructive pulmonary disease patients could be formulated where the weight of lifestyle factors is elevated.

Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey.

BACKGROUND: CoronaVac, an inactivated whole-virion SARS-CoV-2 vaccine, has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a good humoral response against SARS-CoV-2. We present the interim efficacy and safety results of a phase 3 clinical trial of CoronaVac in Turkey. METHODS: This was a double-blind, randomised, placebo-controlled phase 3 trial. Volunteers aged 18-59 years with no history of COVID-19 and with negative PCR and antibody test results for SARS-CoV-2 were enrolled at 24 centres in Turkey. Exclusion criteria included (but were not limited to) immunosuppressive therapy (including steroids) within the past 6 months, bleeding disorders, asplenia, and receipt of any blood products or immunoglobulins within the past 3 months. The K1 cohort consisted of health-care workers (randomised in a 1:1 ratio), and individuals other than health-care workers were also recruited into the K2 cohort (randomised in a 2:1 ratio) using an interactive web response system. The study vaccine was 3 µg inactivated SARS-CoV-2 virion adsorbed to aluminium hydroxide in a 0·5 mL aqueous suspension. Participants received either vaccine or placebo (consisting of all vaccine components except inactivated virus) intramuscularly on days 0 and 14. The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 at least 14 days after the second dose in the per protocol population. Safety analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04582344) and is active but no longer recruiting. FINDINGS: Among 11 303 volunteers screened between Sept 14, 2020, and Jan 5, 2021, 10 218 were randomly allocated. After exclusion of four participants from the vaccine group because of protocol deviations, the intention-to-treat group consisted of 10 214 participants (6646 [65·1%] in the vaccine group and 3568 [34·9%] in the placebo group) and the per protocol group consisted of 10 029 participants (6559 [65·4%] and 3470 [34·6%]) who received two doses of vaccine or placebo. During a median follow-up period of 43 days (IQR 36-48), nine cases of PCR-confirmed symptomatic COVID-19 were reported in the vaccine group (31·7 cases [14·6-59·3] per 1000 person-years) and 32 cases were reported in the placebo group (192·3 cases [135·7-261·1] per 1000 person-years) 14 days or more after the second dose, yielding a vaccine efficacy of 83·5% (95% CI 65·4-92·1; p<0·0001). The frequencies of any adverse events were 1259 (18·9%) in the vaccine group and 603 (16·9%) in the placebo group (p=0·0108) with no fatalities or grade 4 adverse events. The most common systemic adverse event was fatigue (546 [8·2%] participants in the vaccine group and 248 [7·0%] the placebo group, p=0·0228). Injection-site pain was the most frequent local adverse event (157 [2·4%] in the vaccine group and 40 [1·1%] in the placebo group, p<0·0001). INTERPRETATION: CoronaVac has high efficacy against PCR-confirmed symptomatic COVID-19 with a good safety and tolerability profile. FUNDING: Turkish Health Institutes Association.

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.

Could ferritin level be an indicator of COVID-19 disease mortality?

While the number of coronavirus disease-2019 (COVID-19) cases is increasing day by day, there is limited information known about the hematological and laboratory findings of the disease. We aimed to investigate whether serum ferritin level predicts mortality is a marker for rapid progression for inpatients. Our study included 56 patients who were died due to COVID-19 as the study group, and 245 patients who were hospitalized and recovered as the control group. The laboratory data of the patients were evaluated from the first blood tests (pre) taken from the first moment of admission to the hospital and the blood tests taken from before the patient's discharge or exitus (post) were evaluated retrospectively. The mean age of the nonsurvivor group was 62.0 ± 15.7 and the mean age of the control group was 54.34 ± 13.03. Age and length of stay are significantly higher in the nonsurvivor group. When comparing the pre- and postvalues of ferritin, according to the two groups separately, there was no significant difference in the control group and a high level of significance was observed in the nonsurvivor group (p < .01). COVID-19 disease caused by severe acute respiratory syndrome coronavirus-2 causes high mortality with widespread inflammation and cytokine storm. Ferritin is a cheap and widespread available marker, ferritin, which can be used for its predictivity of the mortality and hope it would be a useful marker for clinicians for the management of the disease.

The comparison of favipiravir and lopinavir/ritonavir combination in COVID-19 treatment

Background/aim: SARS-CoV-2, a ribonucleic acid coronavirus, rapidly spread worldwide within a short timeframe. Although different antiviral, antiinflammatory, and immunomodulatory drugs are used, current evidence is insufficient as to which drug is more efficient. Our study compared favipiravir and lopinavir/ritonavir (LPV/RTV) therapies in inpatient care for coronavirus disease 2019 (COVID-19) pneumonia. Materials and methods: Demographic data, test results, treatments, and latest status of patients receiving inpatient COVID-19 pneumonia therapy were recorded. The initial favipiravir and LPV/RTV receiving groups were compared regarding the need for intensive care units (ICU) and mortality. Logistic regression analysis was performed by including variables showing significant differences as a result of paired comparisons into the model. Results: Of the 204 patients with COVID-19 pneumonia, 59 (28.9%), 131 (64.2%), and 14 were administered LPV/RTV, favipiravir, and favipiravir with LPV/RTV, respectively. No difference was found in age, sex, presence of comorbidity, and tocilizumab, systemic corticosteroid, and plasma therapy use between patients administered with these three different treatment regimens. The mean mortality age of the patients was 71 ± 14.3 years, which was substantially greater than that of the survivors (54.2 ± 15.5 years). Compared with patients administered with LPV/RTV, ICU admission and mortality rates were lower in patients administered with favipiravir. CK-MB, AST, CRP, LDH, and creatinine levels were higher, whereas lymphocyte counts were lower in patients who died. Age, AST, CRP, LDH, and neutrophil counts were higher in patients needing ICU, and eosinophil and lymphocyte counts were significantly lower. Logistic regression analysis showed that favipiravir use independently decreased mortality (p = 0.006). Conclusion: The use of favipiravir was more effective than LPV/RTV in reducing mortality in hospitalized patients with COVID-19.

COVID-19 Pandemic and the Global Perspective of Turkish Thoracic Society.

It has been more than 3 months now since the first case of COVID-19 was reported in Turkey. Globally, the number of confirmed cases and deaths reached 9,653,048 and 491,128 respectively, as reported by 216 countries by June 27, 2020. Turkey had 1,396 new cases, 194,511 total cases, and 5,065 deaths by the same date. From the first case until today, the Turkish Thoracic Society (TTS) has been very proactive in educating doctors, increasing public awareness, undertaking academic studies, and assisting with public health policies. In the present report, social, academic, and management perspectives of the pandemic are presented under appropriate subtitles. During this critical public health crisis, TTS has once again demonstrated its readiness and constructive stance by supporting public health, healthcare workers, and the environment. This review summarizes the perspective of TTS on each aspect of the COVID-19 pandemic and casts light on its contributions.