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.

Unclear Issues Regarding COVID-19.

Scientists from all over the world have been intensively working to discover different aspects of Coronavirus disease 2019 (COVID-19) since the first cluster of cases was reported in China. Herein, we aimed to investigate unclear issues related to transmission and pathogenesis of disease as well as accuracy of diagnostic tests and treatment modalities. A literature search on PubMed, Ovid, and EMBASE databases was conducted, and articles pertinent to identified search terms were extracted. A snow-ball search strategy was followed in order to retrieve additional relevant articles. It was reported that viral spread may occur during the asymptomatic phase of infection, and viral load was suggested to be a useful marker to assess disease severity. In contrast to immune response against viral infections, cytotoxic T lymphocytes decline in SARS-CoV-2 infection, which can be partially explained by direct invasion of T lymphocytes or apoptosis activated by SARS-CoV-2. Dysregulation of the urokinase pathway, cleavage of the SARS-CoV-2 Spike protein by FXa and FIIa, and consumption coagulopathy were the proposed mechanisms of the coagulation dysfunction in COVID-19. False-negative rates of reverse transcriptase polymerase chain reaction varied between 3% and 41% across studies. The probability of the positive test was proposed to decrease with the number of days past from symptom onset. Safety issues related to infection spread limit the use of high flow nasal oxygen (HFNO) and continuous positive airway pressure (CPAP) in hypoxic patients. Further studies are required to elucidate the challenging issues, thus enhancing the management of COVID-19 patients.

What We Learned about COVID-19 So Far? Notes from Underground.

The novel coronavirus pandemic poses a major global threat to public health. Our knowledge concerning every aspect of COVID-19 is evolving rapidly, given the increasing data from all over the world. In this narrative review, the Turkish Thoracic Society Early Career Taskforce members aimed to provide a summary on recent literature regarding epidemiology, clinical findings, diagnosis, treatment, prevention, and control of COVID-19. Studies revealed that the genetic sequence of the novel coronavirus showed significant identity to SARS-CoV and MERS-CoV. Angiotensin-converting enzyme 2 receptor is an important target of the SARS-CoV-2 while entering an organism. Smokers were more likely to develop the disease and have a higher risk for ICU admission. The mean incubation period was 6.4 days, whereas asymptomatic transmission was reported up to 25 days after infection. Fever and cough were the most common symptoms, and cardiovascular diseases and hypertension were reported to be the most common comorbidities among patients. Clinical manifestations range from asymptomatic and mild disease to severe acute respiratory distress syndrome. Several patients showed typical symptoms and radiological changes with negative RT-PCR but positive IgG and IgM antibodies. Although radiological findings may vary, bilateral, peripherally distributed, ground-glass opacities were typical of COVID-19. Poor prognosis was associated with older age, higher Sequential Organ Failure Assessment score, and high D-dimer level. Chloroquine was found to be effective in reducing viral replication in vitro. Likewise, protease inhibitors, including lopinavir/ritonavir, favipiravir, and nucleoside analogue remdesivir were proposed to be the potential drug candidates in COVID-19 management. Despite these efforts, we still have much to learn regarding the transmission, treatment, and prevention of COVID-19.