Efficacy, Immunogenicity, and Safety of the Two-Dose Schedules of TURKOVAC versus CoronaVac in Healthy Subjects: A Randomized, Observer-Blinded, Non-Inferiority Phase III Trial.

We present the interim results of the efficacy, immunogenicity, and safety of the two-dose schedules of TURKOVAC versus CoronaVac. This was a randomized, observer-blinded, non-inferiority trial (NCT04942405). Volunteers were 18-55 years old and randomized at a 1:1 ratio to receive either TURKOVAC or CoronaVac at Day 0 and Day 28, both of which are 3 µg/0.5 mL of inactivated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) adsorbed to aluminum hydroxide. The primary efficacy outcome was the prevention of polymerase chain reaction (PCR)-confirmed symptomatic coronavirus disease 2019 (COVID-19) at least 14 days after the second dose in the modified per-protocol (mPP) group. Safety analyses were performed in the modified intention-to-treat (mITT) group. Between 22 June 2021 and 7 January 2022, 1290 participants were randomized. The mITT group consisted of 915 participants, and the mPP group consisted of 732 participants. During a median follow-up of 90 (IQR 86-90) days, the relative risk reduction with TURKOVAC compared to CoronaVac was 41.03% (95% CI 12.95-60.06) for preventing PCR-confirmed symptomatic COVID-19. The incidences of adverse events (AEs) overall were 58.8% in TURKOVAC and 49.7% in CoronaVac arms (p = 0.006), with no fatalities or grade four AEs. TURKOVAC was non-inferior to CoronaVac in terms of efficacy and demonstrated a good safety and tolerability profile.

Independent predictors of in-hospital mortality and the need for intensive care in hospitalized non-critical COVID-19 patients: a prospective cohort study.

One of the most helpful strategies to deal with ongoing coronavirus pandemics is to use some prudence when treating patients infected with SARS-CoV-2. We aimed to evaluate the clinical, demographic, and laboratory parameters that might have predictive value for in-hospital mortality and the need for intensive care and build a model based on them. This study was a prospective, observational, single-center study including non-critical patients admitted to COVID-19 wards. Besides classical clinic-demographic features, basic laboratory parameters obtained on admission were tested, and then new models for each outcome were developed built on the most significant variables. Receiver operating characteristics (ROC) analyses were performed by calculating each model's probability. A total of 368 non-critical hospitalized patients were recruited, the need for ICU care was observed in 70 patients (19%). The total number of patients who died in either ICU or wards was 39 (10.6%). The first two models (based on clinical features and demographics) were developed to predict ICU and death, respectively; older age, male sex, active cancer, and low baseline saturation were noted to be independent predictors. The area under the curve values of the first two models were noted 0.878 and 0.882 (p < .001; confidence interval [CI] 95% [0.837-0.919], p < .001; CI 95% [0.844-0.922]). Following two models, the third and fourth were based on laboratory parameters with clinic-demographic features. Initial lower sodium and lower albumin levels were determined as independent factors in predicting the need for ICU care; higher blood urea nitrogen and lower albumin were independent factors in predicting in-hospital mortality. The area under the curve values of the third and fourth model was noted 0.938 and 0.929, respectively (p < .001; CI 95% [0.912-0.965], p < .001; CI 95% [0.895-962]). By integrating the widely available blood tests results with simple clinic demographic data, non-critical patients can be stratified according to their risk level. Such stratification is essential to filter the patients' non-critical underlying diseases and conditions that can obfuscate the physician's predictive capacity.

Relative Vaccine Effectiveness of the Third Dose of CoronaVac or BNT162b2 Following a Two-Dose CoronaVac Regimen: A Prospective Observational Cohort Study from an Adult Vaccine Center in Turkey.

Coronavirus disease 2019 (COVID-19) continues to pose a threat to public health with the potential for the emergence of new variants. Vaccines are the milestones to control and slow down the damage of the pandemic. As of January 2021, a two-dose regimen with CoronaVac was authorized in Turkey. Due to the waning seroprevalence rate of SARS-CoV-2 over time, BNT162b2 or CoronaVac has been administered as the third dose following a two-dose CoronaVac regimen as a national vaccination policy. As of 14 January 2021, 5243 volunteers who received two doses of the CoronaVac vaccine at Hacettepe University Adult Vaccine Center were followed prospectively. In our study, relative vaccine effectiveness (VEff) for the third dose of the CoronaVac was 58.24% and 87.27% for BNT162b2 in preventing symptomatic COVID-19 cases. There were no hospitalizations, intensive care unit admissions, or deaths in third-dose booster groups with either BNT162b2 or CoronaVac, yielding 100% effectiveness. Both homologous or heterologous third-dose boosters provided further protection against severe COVID-19 and should be prioritized as an effective strategy to combat the COVID-19 pandemic.

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.

'Anxiety is still ongoing!' Evaluation of the effect of the COVID-19 pandemic on anxiety severity of physicians working in the internal medicine department after 1 year: a collaborative cross-sectional study.

The COVID-19 pandemic has increased anxiety in society and particularly in healthcare workers, as shown with a questionnaire in our centre at the beginning of the pandemic. In this collaborative study, we aimed to evaluate the effects of the pandemic on anxiety 1 year later by applying the same questionnaire to the physicians working in the same department. A total of 77 participants consented to the study. The median age was 28 (interquartile range = 4) years and 55.8% were male. As in the first survey, female gender, having family members over 65 years of age, and having family members with chronic diseases were significantly associated with high anxiety scores and levels. There were no statistically significant differences between the first and second survey participants in any of the anxiety scales, which means anxiety persists.

"COVID-19: The final nail in the coffin for physical examination" Evaluation of the effects of COVID-19 pandemic on physical examination habits of residents in a university hospital: A cross-sectional survey.

AIMS: It is evident that the COVID-19 pandemic has affected the medical practice and training of residents. In this study, we evaluated the physical examination (PE) habits of residents working in a university hospital and how their PE practices did change during the pandemic. METHODS: This single-centre, non-interventional, cross-sectional descriptive study was conducted in a university hospital using an online survey questionnaire between 5 and 20 October 2020. RESULTS: Of the 308 residents who participated in the study, 172 of them (55.8%) were female and the median age was 27 (IQR (3) = Q1 (29)-Q3 (26)). Amongst all, 263 participants (85.4%) declared that they have worked in the areas where suspected/confirmed COVID-19 patients were being served. A total of 262 (85%) residents stated that PE habits have changed generally during the pandemic. There was a significant difference with regards to the change in PE habits between those residents who have worked in the COVID-19 areas (n = 230, 87.5%) and those who have not (n = 32, 71.1%) (P = .004). PE habits of Internal Medicine Residents were changed more than others (P < .001). The main reason for the change in PE habits in general (77.9%) and during the examination of suspected/confirmed COVID-19 patients (89.7%) were "self-protection." Independent factors for limited PE in suspected/confirmed COVID-19 patients were found as "Avoiding performing physical examination to be exposed less/to protect (adjusted ORs = 13.067)," "relying on laboratory and radiological investigations during practice (adjusted ORs = 4.358)," and "not having a thought that reduced physical examination will render the diagnosis and course of COVID-19 (adjusted ORs = 2.244)." CONCLUSIONS: This study clearly demonstrated that the COVID-19 pandemic has had a serious impact on the PE habits of the residents while examining patients in general and with COVID-19.

Characteristics and management of asymptomatic SARS-CoV-2 infections.

The coronavirus disease 2019 (COVID-19) pandemic has caused and is still causing tremendous morbidity, mortality, and damage to our societies. The disease course of COVID-19 can be unpredictable ranging from asymptomatic infections to multi-organ failure and death. Transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from an asymptomatic infected individual to others has been observed early in the pandemic. Asymptomatic individuals have been shown to have quantitative SARS-CoV-2 viral loads, there may or may not be radiological and/or laboratory abnormalities. No antiviral therapy has been approved for the treatment of asymptomatic SARS-CoV2- infection. The management of asymptomatic individuals at home requires that the person can be monitored for any signs and symptoms of deterioration and that the requirements for infection prevention and control measures can be fulfilled. It is crucial to properly diagnose and manage asymptomatic COVID-19 cases with effective testing, contact tracing, quarantine, and isolation strategies. Preventing asymptomatic SARS-CoV-2 infections that have a major role in the unhindered transmission of the virus is a milestone to take control of the pandemic. Vaccination has been proven to be the crucial pillar for preventing asymptomatic infections and real-life data will continue to exhibit the effects of community vaccination in breaking the transmission chain of SARS-CoV-2 infections.

Influenza or other respiratory viruses: does it matter as the cause of acute respiratory failure in the critically-ill patients?

INTRODUCTION: Respiratory virus infections may cause serious respiratory failure requiring intensive care unit (ICU) admission. The objective of this study was to evaluate the clinical features and the outcome in patients with acute respiratory failure (ARF) due to viral infections comparing etiological agents. MATERIALS AND METHODS: ARF patients with positive viral serology were retrospectively recruited. Cohort was evaluated with regard to subgroups as influenza and other respiratory viruses (ORV), as well as survivors and nonsurvivors. RESULT: Out of 938 admitted patients, 319 were followed as ARF and only 149 patients had viral respiratory panel results. In 49 patients with ARF, 52 positive viral results were detected and 47 patients with single positive viral isolates of either influenza or ORV were included. Among them, 62% had ORV with quite similar characteristics with influenza group apart from diabetes mellitus which was encountered more in influenza group (p= 0.02). Overall ICU mortality was 32% and there was no difference between the two groups (p= 0.42). Acute Physiology and Chronic Health Evaluation (APACHE) II score was independently associated with ICU mortality (OR: 1.25; 95% CI: 1.04-1.51; p= 0.02). CONCLUSIONS: This study emphasizes to consider the possibility of other respiratory viruses for the cause of ARF with similar characteristics and mortality as influenza species.

Thirty-day readmission rate of COVID-19 patients discharged from a tertiary care university hospital in Turkey: an observational, single-center study.

BACKGROUND: The 30-day readmission rate is an important indicator of patient safety and hospital's quality performance. In this study, we aimed to find out the 30-day readmission rate of mild and moderate severity coronavirus disease of 2019 (COVID-19) patients discharged from a tertiary care university hospital and to demonstrate the possible factors associated with readmission. METHODS: This is an observational, single-center study. Epidemiological and clinical data of patients who were hospitalized with a diagnosis of COVID-19 were retrieved from a research database where patient information was recorded prospectively. Readmission data were sought from the hospital information management system and the National Health Information System to detect if the patients were readmitted to any hospital within 30 days of discharge. Adult patients (≥18 years old) hospitalized in COVID-19 wards with a diagnosis of mild or moderate COVID-19 between 20 March 2020 (when the first case was admitted to our hospital) and 26 April 2020 were included. RESULTS: From 26 March to 1 May, there were 154 mild or moderate severity (non-critical) COVID-19 patients discharged from COVID-19 wards, of which 11 (7.1%) were readmitted. The median time of readmission was 8.1 days (interquartile range [IQR] = 5.2). Two patients (18.1%) were categorized to have mild disease and the remaining 9 (81.9%) as moderate disease. Two patients who were over 65 years of age and had metastatic cancers and hypertension developed sepsis and died in the hospital during the readmission episode. Malignancy (18.7% vs. 2.1%, P = 0.04) and hypertension (45.5% vs. 14%, P = 0.02) were more common in those who were readmitted. CONCLUSIONS: This is one of the first studies to report on 30-day readmission rate of COVID-19 in the literature. More comprehensive studies are needed to reveal the causes and predictors of COVID-19 readmissions.

Evaluation of the effect of COVID-19 pandemic on anxiety severity of physicians working in the internal medicine department of a tertiary care hospital: a cross-sectional survey.

BACKGROUND: Internists who have an important role in the global response to the COVID-19 pandemic are under both physical and psychological pressures. AIMS: To assess the anxiety among physicians working in the internal medicine department of a tertiary care hospital who are on the frontline of the COVID-19 pandemic. METHODS: This single-centre, non-intervention, cross-sectional descriptive study was conducted using an online survey questionnaire from 1 April to 14 April 2020. Physicians of the Department of Internal Medicine were invited to participate with a self-administered questionnaire. The degree of symptoms of anxiety was assessed by the Turkish versions of the 7-item Generalised Anxiety Disorder scale and Beck Anxiety Inventory, respectively. RESULTS: A total of 113 participants consented for the study and completed the questionnaire. The median age was 29 (IQR = 5) years and 53.1% were male. A total of 72 internists (63.7%) worked as 'frontline' healthcare workers directly engaged in diagnosing, treating or caring for patients with or suspected to have COVID-19. Female gender was significantly associated with high scores and levels in all scales compared to the male gender (P < 0.005). Having family members over 65 years old and with chronic diseases were significantly associated with high anxiety scores and levels (P < 0.005). CONCLUSIONS: In this survey of internists in a university hospital equipped with clinics, wards and intensive care unit for patients with COVID-19, female gender and having family members over 65 years old and with chronic diseases were associated with increased anxiety levels.