Mortality Predictors Of Pre-variant SARS-CoV-2 Infected ARDS Patients Receiving Favipiravir and Tocilizumab (preprint)

Objective In this study, viral clearance (oronasopharyngeal swab RT-PCR negativity) and intensive care outcomes and risk factors affecting mortality of critically ill patients with COVID-19-related acute respiratory distress syndrome (ARDS) who received tocilizumab and favipiravir treatments together before vaccination were investigated.Material-Methods The data of patients who were followed up and treated between 1 July 2020 and 5 October 2020 were retrospectively analyzed. Demographic data of the patients (age, gender), oro-nasopharyngeal swab RT-PCR and classification of ARDS, respiratory support treatments, all medical treatments, and ICU outcomes were recorded.Results Totally, 60 patients with a median age of 69.8 [24–87], 25 females and 35 males were included in the study. Mean APACHE II score was 18.9 ± 8.0; and SOFA score was 4.5 ± 2.0. Thirty-four (56.7%) patients were intubated during follow-up. Tocilizumab was given on average of 2.5th day (± 2.0 days). On the day of tocilizumab administration, 1 (1.7%) patient had mild ARDS, 30 (50.0%) had moderate ARDS, 29 (48.3%) had severe ARDS. PaO2/FIO2 on the day of tocilizumab administration was 96.7 ± 36.6 mmHg. Forty (66.7%) patients died, while 20 (33.3%) patients transferred to the service. The mean length of stay in the ICU was 11.4 ± 5.5 days. Advanced age [Hazard ratio (HR) 1.8; 95% confidense interval (CI) 0.88–0.93; p < 0.001), higher APACHE II score (HR 0.81, 95% CI 0.74–0.98; p = 0.001), higher SOFA score on the day of tocilizumab administration (HR 1.47, 95% CI 0.39–0.79; p = 0.001), and lower PaO2/FIO2 ratio (HR 2.54, 95% CI 2.33–3.79; p < 0.001) were determined as independent risk factors for mortality.Conclusion Patients who were administered tocilizumab and favipiravir together in our intensive care unit were mostly patients with severe ARDS and had higher inflammatory markers. High mortality was attributed to the use of tocilizumab as an add-on treatment, not as a routine treatment.

Early Report of BCG Group Against COVID-19: Initial Results of the Volunteer BCG Vaccination (preprint)

Objective: This article aimed to report the potential protective effect of BCG vaccine against COVID-19 by presenting the follow-up report of individuals who voluntarily receive BCG vaccination (BCG group). In this direction, preliminary data from BCG group regarding participants’ SARS-CoV-2 infection status, and the side effects with complications of BCG vaccination is reported. Method: A total of 84 health professionals and their relatives who voluntarily received BCG vaccine included in the study. Participants completed an online questionnaire that consists of 14 questions regarding their characteristics, SARS-CoV-2 infection status, and effects of BCG. Results: 63 participants were healthcare workers, and 21 participants were relatives of a healthcare worker. 81(96.4%) participants stated that they consider themselves in the high-risk group for getting infected with SARS-CoV-2. 69(82.1%) participants declared that they had been in the same environment and contacted with a COVID-19 patient. 82(97.6%) participants had at least one BCG scar from childhood. 21(25%) participants declared one complication after BCG vaccination. As a complication, 8(38.1%) participants had local non-permanent sterile abscess, and 13(61.9%) of them had weakness, joint pain, and subfebrile fever. 31(36.9%) participants had a PCR test for COVID-19 at least 4 weeks after BCG revaccination, and the results of all 31 participants were negative. 82(97.6%) participants declared that they felt more protected against COVID-19 after BCG vaccination. Conclusion: Results from this study suggest that it is beneficial to administer BCG vaccine to protect the high-risk group against COVID-19 with no side effects and risks.

What We Learned From COVID 19? Trying to find best approach from pathophysiology to treatment. (preprint)

Introduction: The outbreak of the novel coronavirus 2019 (COVID-19) caused a pandemic that led to death of more than 3 million people globally. COVID-19 may yield a variety of clinical pictures, differing from pneumonitis to Acute Respiratory Distress Syndrome (ARDS) along with vascular damage in the lung tissue, which is named as endotheliitis, To date, no specific treatment was approved by any authority for the prevention or treatment of COVID-19. Materials and Methods: Here, we presented our experience on COVID-19 with evaluating 11,190 COVID-19 patients by presenting the manifestations of endotheliitis in skin, lung, and brain tissues according to different phases of COVID-19. In our perspective, distinctive manifestations in each COVID-19 patient, including non-respiratory conditions in the acute phase and the emerging risk of long-lasting complications, suggest that COVID-19 has an endotheliitis-centred thrombo-inflammatory pathophysiology. Accordingly, our treatment strategy was adopted to prevent both respiratory and vascular distresses, which are categorized according to extent of endotheliitis. (Group A: no or mild pulmonary involvement, Group B: moderate pulmonary involvement with clinical risk of deterioration, Group C: severe pulmonary involvement and respiratory failure). Potential pathophysiological mechanisms contributing to endotheliitis includes cytokine storm and toxic plasma, thromboinflammation and systemic microangiopathy. Results: A total of 11.190 COVID-19 patients that were diagnosed and treated in Samsun VM Medicalpark Hospital, Turkey, between March 2020 and April 2021 were retrospectively evaluated. The mean age was 59.2 years and male to female ratio was 5507/5683. Among these patients, 1896 (16.9%) individuals were hospitalized. While 1220 (64.3%) of the inpatients were hospitalized within the first 10 days after the diagnosis, 676 (35.7%) of them were hospitalized 10 days after their diagnosis. The number of patients who did not respond to group A and B treatments and developed hypoxemic respiratory failure (Group C) was 520 (27.4%). Among hospitalized patients, 146 (7.7%) individuals needed ventilator support (non-invasive/invasive mechanical ventilation) and were followed in the intensive care unit, and 43 (2.2%) patients died. In conclusion; Endotheliitis can also explain the mechanism behind the respiratory failure in COVID-19, and the difference of COVID-19 related ARDS from ARDS seen in other critical conditions. Hence, daily evaluation of momentary changes in clinical, laboratory and radiological findings of patients and deciding appropriate pathophysiological treatment would help to reduce the mortality rate of COVID-19.

The Characteristics of Health Care Workers with COVID-19 and Relationship Between COVID-19 Mortality and BCG/Tuberculosis History: a multi-center study (preprint)

Background: Today, COVID-19 pandemic has brought countries' health services into sharp focus. Despite the low incidence of cases(1.2%) and high mortality rate(2.4%) among Turkish population, the low mortality rate(0.3%) despite the high incidence(11.5%) declared in healthcare workers drew our group's attention. Therefore, we aimed to report the characteristics of infected health-care workers and investigate the relationship between BCG vaccine and tuberculosis history with COVID-19 mortality in infected health-care worker population. Method: This study was conducted in three hospitals to assess the clinical presentations, disease severity and correlation with BCG vaccine and tuberculous history in COVID-19 positive health-care workers by an online questionnaire platform. The relationship between characteristics and tuberculosis history were investigated according to hospitalization status of the patients. Result: Total of 465 infected healthcare workers included in the study. The rate of history of direct care and contact to tuberculosis patient, presence of previous tuberculosis treatment and BCG scar, presence of radiological infiltrations was significantly higher in hospitalized healthcare workers. The ratio of direct care and direct contact to the patient with tuberculosis, and presence of family history of tuberculosis were statistically significantly higher in patients with radiological infiltrations. Conclusion: Although COVID-19 risk and incidence are higher among healthcare workers compared to the normal population due to higher virus load, we think that the lower mortality rate seen in infected healthcare workers results from healthcare workers' frequent exposure to tuberculosis bacillus and the mortality-reducing effects of BCG vaccine, despite the higher hospitalization rate and radiological infiltrations due to over-triggered immune system.

Alternative or Complementary Role of Serological Rapid Antibody Test in the Management of Possible COVID-19 Cases (preprint)

Background: Although the gold diagnostic method for COVID-19 is accepted as the detection of viral particles by reverse transcription polymerase chain reaction (RT-PCR), serology testing for SARS-CoV-2 is at increased demand. A primary aim for utilization of serological tests are to better quantify the number of COVID-19 cases including those RT-PCR samples were negative but showing clinical and radiological signs of COVID-19. In this study, we aimed to report the features of the patients that were diagnosed and treated as possible COVID-19 cases whose multiple nasopharyngeal swab samples were negative by RT-PCR but serological IgM/IgG antibody against SARS-CoV-2 were detected by rapid antibody test. Method: We retrospectively analyzed eighty suspected COVID-19 cases that have at least two negative consecutive COVID-19 PCR test and were subjected to serological rapid antibody test. Result: The specific antibodies against SARS-CoV-2 were detected as positive in twenty-two patients. The mean age of patient group was 63.2+-13.1 years old with male /female ratio 11/11. Cough was the most common symptom with 90.9%. Most common presenting chest CT findings were bilateral ground glass opacities (77.2%) and alveolar consolidations (50.09%). The mean duration from symptom initiation to hospital admission, to hospitalization, to treatment initiation and to detection of antibody positivity were 8.6 +- 7.2, 11.2 +- 5.4, 7.9 +- 3.2 and 24 +- 17 days, respectively. Conclusion: Our study demonstrated the feasibility of COVID-19 diagnosis based on rapid antibody test in the cases of patients whose RT-PCR samples were negative. We suggest that the detection of antibodies against SARS-CoV-2 with rapid antibody test should be included in the diagnostic algorithm in suspected COVID-19 patients.

Trying to Find the Answer for Two Questions in Patients with COVID-19:1. Are pulmonary infiltrates of COVID-19 infective or inflammatory in nature (Pneumonia of Pneumonitis)?2. Is Hydroxychloroquine plus Azithromycin or Favipiravir plus Dexamethasone more effective in the COVID-19 treatment? (preprint)

Background: During the current pandemic, a great effort is made to understand the COVID-19 and find an effective treatment. As of 17 August 2020, there is no specific drug or biologic agent which have been approved by the FDA for the prevention or treatment of COVID-19. Methods: We retrospectively analyzed the clinical and radiological findings of 211 COVID-19 in-patients that were treated between March - August 2020. Confirmation of a COVID-19 diagnosis was made according to a positive RT-PCR result with a consistent high-resolution-CT (HRCT) finding. Radiological images and the rate of clinical response of patients were investigated. Result: While 128 patients (58.7) did not develop pneumonia, the mild, moderate and severe pneumonia ratios were 28(13.2%), 31(18.7%) and 27(22.9%). 72 patients (34.1%) whose PCR tests were positive did not show any symptom and they were followed in isolation without treatment. 52 patients (24.6%) received hydroxychloroquine plus azithyromycine, 57 patients (27%) received favipiravir and 30 patients (14.2%) received favipiravir plus dexamethosone as the first line of treatment. 63.1% of pneumonia patients who received hydroxychloroquine plus azithyromycine, 28.3% of patients who received favipravir and 10% of patients who received favipravir plus dexamethasone showed a failure of treatment. Conclusion: The pulmonary infiltrates of COVID-19 are not infective; therefore, the characteristic of the disease should be described as COVID-19 pneumonitis instead of pneumonia. The favipiravir plus dexamethasone seems to be the only drug combination to achieve the improvement of radiological presentation and clinical symptoms in COVID-19 pneumonia patients.