Impact of pharmacist-led educational intervention on pneumococcal vaccination rates in cancer patients: a randomized controlled study.

PURPOSE: This study aimed to evaluate clinical pharmacist's contribution to the pneumococcal vaccination rate by providing education to cancer patients in hospital settings. METHODS: This study was conducted in 2 tertiary-care hospitals' medical oncology outpatient clinics. Patients over 18 years of age and diagnosed with cancer for less than 2 years, in remission stage, and have not previously received the pneumococcal vaccine were included. Patients were randomized to intervention and control groups. The intervention group was provided vaccination education and recommended to receive the PCV13 vaccine. The control group received routine care. Patients' knowledge about pneumonia/pneumococcal vaccine, Vaccine Attitude Examination Scale (VAX) score, and vaccination rates were evaluated at baseline and 3 months after the education. RESULTS: A total of 235 patients (intervention: 117, control: 118) were included. The mean age ± SD was 57.86 ± 11.88 years in the control and 60.68 ± 11.18 years in the intervention groups. The numbers of correct answers about pneumonia/pneumococcal vaccine (p = 0.482) and VAX scores (p = 0.244) of the groups were similar at baseline. After the intervention, the median (IQR) number of correct answers in intervention group [10(3)] was higher than control group [8(4)] (p < 0.001). After the education, the total VAX score (mean ± SD) was less in intervention group (33.09 ± 7.018) than the control group (36.07 ± 6.548) (p = 0.007). Three months after the education, 20.2% of the patients in the intervention and 6.1% in the control groups were vaccinated with pneumococcal vaccine (p = 0.003). CONCLUSIONS: The pneumococcal vaccination rate in cancer patients has increased significantly by the education provided by a clinical pharmacist in hospital settings.

Human memory T cell dynamics after aluminum-adjuvanted inactivated whole-virion SARS-CoV-2 vaccination.

This study evaluates the functional capacity of CD4+ and CD8+ terminally-differentiated effector (TEMRA), central memory (TCM), and effector memory (TEM) cells obtained from the volunteers vaccinated with an aluminum-adjuvanted inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac). The volunteers were followed for T cell immune responses following the termination of a randomized phase III clinical trial. Seven days and four months after the second dose of the vaccine, the memory T cell subsets were collected and stimulated by autologous monocyte-derived dendritic cells (mDCs) loaded with SARS-CoV-2 spike glycoprotein S1. Compared to the placebo group, memory T cells from the vaccinated individuals significantly proliferated in response to S1-loaded mDCs. CD4+ and CD8+ memory T cell proliferation was detected in 86% and 78% of the vaccinated individuals, respectively. More than 73% (after a short-term) and 62% (after an intermediate-term) of the vaccinated individuals harbored TCM and/or TEM cells that responded to S1-loaded mDCs by secreting IFN-γ. The expression of CD25, CD38, 4-1BB, PD-1, and CD107a indicated a modulation in the memory T cell subsets. Especially on day 120, PD-1 was upregulated on CD4+ TEMRA and TCM, and on CD8+ TEM and TCM cells; accordingly, proliferation and IFN-γ secretion capacities tended to decline after 4 months. In conclusion, the combination of inactivated whole-virion particles with aluminum adjuvants possesses capacities to induce functional T cell responses.

Knowledge and Attitudes of Turkish Physicians towards Human Monkeypox Disease and Related Vaccination: A Cross-Sectional Study.

Background: In May 2022, the monkeypox virus outbreak in multiple countries on various continents marked a potential resurgence of the disease as a global health issue. Considering the crucial role of physicians in mitigating the monkeypox outbreak, we sought to evaluate physicians' knowledge, attitude, concerns, and vaccine acceptance for monkeypox, in the shadow of the COVID-19 pandemic. Methods: A large-scale, cross-sectional survey was conducted among 283 physicians between 20 August−2 September 2022, in Turkey. The participants' sociodemographic characteristics, knowledge, attitudes, concerns, and vaccine acceptance toward monkeypox infection were collected via a questionnaire. Results: Our study revealed that 32.5% of physicians achieved a good level of knowledge; similarly, 31.4% of the physicians planned to have the monkeypox vaccine. Multivariate binary logistic regression analysis showed that female physicians (p = 0.031) and older people (≥30 vs. <30) were more likely to be knowledgeable about monkeypox (p = 0.007). We found that participants from divisions of internal medicine (p = 0.033) who knew about the monkeypox disease during medical school or residency (p = 0.005) and were previously exposed to COVID-19 disease (p = 0.005) were more likely to have a good knowledge score of monkeypox. We also found that physicians with a good knowledge score were more worried about monkeypox compared to COVID-19 (AOR: 2.22; 95% CI:1.13−4.33; p = 0.019). Additionally, those who had information on monkeypox during medical education (AOR = 2.16, 95% CI = 1.10−4.21; p = 0.024) were more likely to receive the smallpox vaccine to prevent monkeypox viral infection when available. Conclusions: The present study pointed out that physicians in Turkey have unsatisfactory levels of knowledge about the emerging monkeypox. This study results can impede attempts to detect and manage cases of monkeypox and should be addressed through appropriate and timely awareness and educational programs, alerts, and seminars. These might serve as the basis for policymakers' decisions about promoting national monkeypox vaccination strategies and addressing potential vaccine hesitancy and misinformation when needed.

Prevalence of Common Human Coronaviruses (NL63, 229E, and OC43) in Adults Before The COVID-19 Pandemic between 2015 and 2020: A Single-Center Study from Turkey.

Common Human Coronaviruses (HCoVs) (NL63, HKU1, 229E, and OC43) circulate worldwide and cause respiratory tract infections. Epidemiologic study of HCoVs paramount importance since the disease burden and its trajectory in years has not been well addressed in adults. Here, we aimed to describe the burden of HCoVs in a hospital setting over five years before the COVID-19 pandemic. This is a retrospective study among patients (>18 years) between Jan 1, 2015, and Jan 1, 2020, whose respiratory specimens were tested by multiplex RT-PCR. In total, 7861 respiratory samples (4540 patients) were included; 38% tested positive for any respiratory viruses. Of these, 212 (12.2%) samples were positive for HCoVs, and their co-infection with other respiratory viruses was 30.6%. Rhinovirus (RV) (27.6%) was the most common co-infection for all three HCoVs. The overall prevalence of HCoVs tended to be the highest in the winter (40.9%). Patients aged ≥60 years had the highest prevalence of overall HCoVs (39.7%). Given the duration and the large sample size, this study from Turkey is one of the largest to date among adults in the literature. These epidemiological data and molecular surveillance HCoVs have important implications for the control and prevention of respiratory infection.

Immunogenicity of two doses of inactive COVID-19 vaccine and third booster dose mRNA vaccine in patients with cancer receiving active systemic therapy.

We aimed to evaluate the seroconversion rates after two doses of inactive COVID-19 vaccine (CoronaVac) and the benefit of a third dose mRNA vaccine booster in patients with cancer receiving active treatment. Patients with solid tumors receiving active treatment (n = 101) and patients with no-cancer (n = 48) as the control group were included in the study. All the patients and controls had received two doses of CoronaVac and a third booster dose of the mRNA vaccine (Bnt162b2). Anti-SARS-CoV-2 Spike Receptor Binding Domain IgG antibody levels after the second and third dose were measured with quantitative ELISA. The median age of the patients was 66 (IQR 60-71). 79% of the patients were receiving chemotherapy, and 21% were receiving immunotherapy at the time of vaccination. Antibody levels measured after two doses of CoronaVac were significantly lower in patients with cancer than in the control group (median 0 µg/ml [IQR 0-1.17 µg/ml] vs median 0.91 µg/ml [IQR 0-2.24 µg/ml], respectively, P = .002). Seropositivity rates were 46.5% in patients with cancer and 72.9% in the control group (P = .002). Antibody measurement was performed in 26 patients after the third dose. Seroconversion rate increased from 46.5% to 88.5% (P < .001), and the antibody titers significantly increased with the third-dose booster (median 0 µg/ml [IQR 0-1.17 µg/ml] after two doses vs 12.6 µg/ml [IQR 1.8-69.1 µg/ml] after third booster dose, P < .001). Immunogenicity of CoronaVac is low in patients with cancer receiving active treatment, and administering a third dose of an mRNA vaccine is effective in terms of improving seroconversion rates.

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. METHODS: Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. RESULTS: Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49-69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI - 0.1% [- 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (- 3.2% [- 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. CONCLUSION: This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 ).

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.

The impact of COVID-19 pandemic on nosocomial multidrug-resistant bacterial bloodstream infections and antibiotic consumption in a tertiary care hospital.

We investigated the change in the epidemiology of nosocomial bloodstream infections (BSIs) caused by multidrug-resistant bacteria during Coronavirus Disease (COVID-19) and antibiotic consumption rates at a pandemic hospital and at the Oncology Hospital which operated as COVID-19-free on the same university campus. Significant increases in the infection density rate (IDRs) of BSIs caused by carbapenem-resistant Acinetobacter baumannii (CRAB) and ampicillin-resistant Enterococcus faecium (ARE) were detected at the pandemic hospital, whereas carbapenem-resistant Klebsiella pneumoniae BSIs were increased at the non-pandemic Oncology Hospital. Pulsed field gel electrophoresis showed a polyclonal outbreak of CRAB in COVID-19 intensive care units. Antibiotic consumption rates were increased for almost all antibiotics, and was most significant for meropenem at both of the hospitals. Increased IDRs of CRAB and ARE BSIs as well as an increased consumption rate of broad-spectrum antibiotics emphasize the importance of a multimodal infection prevention strategy combined with an active antibiotic stewardship program.

Country data on AMR in Türkiye in the context of community-acquired respiratory tract infections: links between antibiotic susceptibility, local and international antibiotic prescribing guidelines, access to medicine and clinical outcome.

BACKGROUND: Antimicrobial resistance (AMR) is one of the biggest threats to global public health. Selection of resistant bacteria is driven by inappropriate use of antibiotics, amongst other factors. COVID-19 may have exacerbated AMR due to unnecessary antibiotic prescribing. Country-level knowledge is needed to understand options for action. OBJECTIVES: To review AMR in Türkiye and initiatives addressing it. Identifying any areas where more information is required will provide a call to action to minimize any further rise in AMR within Türkiye and to improve patient outcomes. METHODS: National AMR initiatives, antibiotic use and prescribing, and availability of susceptibility data, particularly for the key community-acquired respiratory tract infection (CA-RTI) pathogens Streptococcus pneumoniae and Haemophilus influenzae, were identified. National and international antibiotic prescribing guidelines commonly used locally for specific CA-RTIs (community-acquired pneumonia, acute otitis media, acute bacterial rhinosinusitis) were also reviewed, plus local antibiotic availability. Insights from both a local clinician and local clinical microbiologist were sought to contextualize this information. CONCLUSIONS: Türkiye developed an antibiotic stewardship programme, The Rational Drug Use National Action Plan 2014-2017, prioritizing appropriate antibiotic prescription in the community. Public campaigns discouraging inappropriate antibiotic use were also initiated. Türkiye has a high level of antibiotic resistance and a high level of consumption, however, in 2015 over-the-counter antibiotic sales were prohibited, resulting in a declining trend in overall consumption. There is still a need for physician education on current developments in antibiotic use. Several ongoing global surveillance studies provide antibiotic susceptibility data in Türkiye. Clinicians in Türkiye use several country-specific guidelines for common CA-RTIs plus a range of international guidelines. A more standardized inclusive approach in developing local guidelines, using up-to-date surveillance data on isolates from community-acquired infections in Türkiye, could make guideline use more relevant for clinicians. This would pave the way for a higher level of appropriate antibiotic prescribing and improved adherence. This would, in turn, potentially limit AMR development and improve patient outcome.

Remdesivir treatment for patients with moderate to severe COVID-19.

BACKGROUND: Remdesivir, which was first developed for the treatment of Ebola disease but failed to meet expectations, has become hope in the fight against the COVID-19 pandemic. This study aimed to evaluate risk factors for mortality and prognosis of adult moderate/severe COVID-19 patients treated with remdesivir, and safety and tolerability of 5 days of remdesivir treatment. METHODS: This multicenter prospective observational study was conducted in 14 centers in Turkey. Pregnancy or breastfeeding, multiorgan failure, or usage of vasopressors for septic shock, ALT > 5 × the upper limit of the normal range, or eGRF <30 mL/min or dialysis and receiving favipiravir were the exclusion criteria of the study. RESULTS: Among 500 patients, 494 patients were included in the study. On admission, 392 (79.3%) patients had moderate and 102 (20.6%) patients had severe COVID-19. The 28-day mortality was 10.1%. The median of the scores of the seven-category ordinal scale assessed on days 0, 3, 5, 7 were 4 and 3 on day 14. When the survival status of the patients was evaluated according to the time between the remdesivir start date and the end date of the symptoms, no statistically significant difference was found between the medians of the groups (p = 0.404). In multivariable analysis, age (OR, 1.05; 95%CI, 1.02-1.08; p = 0.003), SpO2 level on admission (OR, 3.03; 95%CI, 1.35-6.81; p = 0.007), heart rate (OR, 2.48; 95%CI, 1.01-6.07; p = 0.047), follow-up site at the hospital (clinic/ICU) (OR, 26.4; 95%CI, 11.6-60.17; p < 0.001) were independently associated with increased mortality. Grade 3 adverse event (AE) was observed in 4 (0.8%) patients. None of the patients experienced grade 4 or 5 AEs. DISCUSSION: Remdesivir is a safe and well-tolerated drug and older age, low SpO2 level on admission, tachycardia, and ICU admission are independently associated with increased mortality among patients with moderate/severe COVID-19 receiving remdesivir treatment.

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.

Antibody response with SARS-CoV-2 inactivated vaccine (CoronaVac) in Turkish geriatric population.

BACKGROUND: Sars-CoV-2 infection influences older individuals at the forefront, and there is still limited data on the COVID-19 vaccine response in the geriatric population. This study aimed to assess antibody response after vaccination with SARS-CoV-2 inactivated vaccine and examine possible factors affecting this response in a geriatric population. METHODS: individuals who have been on at least the 28th day after the second dose of the COVID-19 vaccine were included. Comprehensive geriatric assessment tools and the Clinical Frailty Scale were performed. SARS-CoV-2 spike-specific IgG antibodies were detected and, levels ≥1 U/ml were defined as seropositive, <1 U/ml were defined as seronegative. RESULTS: a total of 497 patients were included and divided into three groups according to the days past after the second dose of the vaccine (Group 1: 28-59 days, Group 2: 60-89 days and Group 3: 90 days and more). Groups included 188, 148 and 171 patients, respectively. Seropositivity rate in each group was 80.9,73.2 and 57.3%, respectively. In Groups 1 and 2, Charlson Comorbidity Index score was higher in the seronegative group (P = 0.023 and P = 0.011, respectively). In Group 3, the prevalence of frailty was significantly higher in the seronegative group (P = 0.002). CONCLUSION: to the best of our knowledge, this is the first study assessing the antibody response after vaccination with Sars-CoV 2 inactivated vaccine in the Turkish geriatric population. Moreover, this is the first study revealing the relationship between antibody response and frailty. Larger studies are needed to confirm the antibody response duration and the association between frailty and COVID-19 vaccine response.

RNA-Based COVID-19 vaccine candidates with clinical phase trials in progress

Due to the COVID-19 infection, which was recognized as a global pandemic by the WHO on March 11, 2020, the number of cases and disease-related deaths increases day by day globally. For this reason, antiviral agents used in treatment and vaccines, the most effective weapon in prevention, continue to be the most popular topic of the plan. Several situations are expected to affect the course of the pandemic. The loss of the ability of the virus to mutate and cause disease, the fact that those who become immunized by having the disease in the society reach a critical rate and create social immunity (herd immunity), and the provision of social immunity with effective vaccination can be counted as some of these situations. Candidate vaccines in the clinical phase among RNA-based vaccines: This review aimed to examine COVID-19 vaccine candidates using RNA technology and compile its current data. We used PubMed, Google Scholar, and World Health Organization (WHO) databases. Also, we followed up on the latest news and developments on vaccine companies' websites. Conclusion: Vaccination trials, which started due to the seriousness and urgency of the situation that we are in, continue exceptionally quickly and effectively. As per the WHO>s data on July 9, 2021, there have been 291 vaccine trials, 107 of which are in the clinical phase, and 18 (16%) of the vaccine candidates in the clinical phase are RNA-based vaccines. Also, the number of RNA-based vaccines with ongoing preclinical trials is 2

Knowledge, Attitudes, and Perception towards COVID-19 Vaccination among the Adult Population: A Cross-Sectional Study in Turkey.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to wreak havoc on lives and ravage the world. Several vaccines have been approved for use against COVID-19; however, there may be hesitancy and negative perceptions towards vaccination, which may reduce the willingness to be vaccinated. Further, studies assessing the current perception toward COVID-19 vaccination are scarce. This study aimed to assess community knowledge, attitudes, and perceptions regarding COVID-19 vaccines among the general population of Turkey. METHODS: A cross-sectional survey was carried out among 1009 adult participants from the 13-20 April 2021. Demographic data were collected, and attitudes and perceptions toward COVID-19 vaccines were evaluated. A multivariable regression analysis was performed to identify the factors predicting perception towards COVID-19 vaccinations. RESULTS: Just over half of participants were male (52.6%) and the majority of respondents were aged between 30 and 39 years (33.8%). Our study revealed that 62.7% of participants had positive perceptions of COVID-19 vaccines. Logistic regression analysis results showed that older people (≥30 vs. <30) were less likely to have a positive perception towards COVID-19 vaccines (OR = 0.70, 95% CI = 0.51-0.94). We also found participants who had a previous history of influenza vaccines (OR = 2.01, 95% CI = 1.43-2.84), bachelor's degrees or above (OR = 1.47, 95% CI = 1.12-1.91), and a personal history of COVID-19 (OR = 1.58, 95% CI = 1.10-2.26) were more likely to have a positive perception regarding COVID-19 vaccines. CONCLUSION: The proportion of the general population in Turkey who believe in COVID-19 vaccine effectiveness is not inferior to that of other countries. However, the low positive perception even among the population applying for vaccination indicates that understanding the perception of the general population and its influencing factors may contribute to developing a strategy for improving vaccination rates by addressing these factors.

Seroprevalence of SARS-CoV-2 Antibodies and Associated Factors in Healthcare Workers before the Era of Vaccination at a Tertiary Care Hospital in Turkey.

Healthcare workers (HCWs), as frontliners, are assumed to be among the highest risk groups for COVID-19 infection, especially HCWs directly involved in patient care. However, the data on the COVID-19 infection and seroprevalence rates are limited in HCWs. Therefore, we aimed to evaluate the seroprevalence rates in HCWs according to risk groups for COVID-19 contraction in a large cross-sectional study from a tertiary care hospital in Turkey. We enrolled 1974 HCWs before the vaccination programs. In two separate semi-quantitative ELISAs, either IgA or IgG antibodies against SARS-CoV-2 spike protein subunit 1 (S1) were measured. The proportion of positive test results for IgG, IgA, or both against SARS-CoV-2 of study subjects was 19% (375/1974). Frontline HCWs who had contact with patients (21.7%, RR 2.1 [1.51-2.92]) and HCWs in working in the COVID-19 units, intensive care units, or emergency department (19.7%, RR 1.61 [1.12-2.32]) had a notably higher Anti-SARS-CoV-2 IgG compared to the rest of HCWs who has no daily patient contacts ([11.1%]; p < 0.0001). HCWs who care for regular patients in the medium-risk group have also experienced a sustained higher risk of exposure to SARS-CoV-2. We should enhance the precaution against COVID-19 to protect HCW's safety through challenging times.

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.

Pretreatment serum uric acid level is not a surrogate marker for the outcome of favipiravir treatment in COVID-19 patients.

BACKGROUND: To the editor, Favipiravir (FVP) was developed against the influenza virus infection and licensed for the treatment of influenza in Japan [1]. In addition to influenza viruses, FVP demonstrates a broad-spectrum activity against many RNA viruses including Ebola, Lassa, rabies, and severe fever with thrombocytopenia [2]. FVP exhibited a comparable in vitro efficacy against SARS-CoV-2 with remdesivir in a cell culture model [3]. DISCUSSION: The authors would like to acknowledge the contributions of numerous physicians, nurses, and healthcare personnel of Hacettepe University's COVID-19 response team for their selfless efforts in follow-up and care of the patients. Authors declare that there is no conflict of interest.

The effect of gestational age at the time of diagnosis on adverse pregnancy outcomes in women with COVID-19.

OBJECTIVE: We aimed to investigate the incidence of adverse pregnancy outcomes including preterm birth, preeclampsia (PE), and fetal growth restriction (FGR) in pregnant women with COVID-19 according to the gestational age. METHODS: This retrospective study included 167 pregnant women who were hospitalized with confirmed COVID-19. The patients were divided into three groups according to the time of diagnosis as follows: <12 weeks of gestation (first trimester, n = 10), 12-24 weeks of gestation (n = 28), and >24 weeks of gestation (n = 129). Medical records of the patients were reviewed retrospectively and adverse pregnancy outcomes were analyzed. RESULTS: A total of 49 (29.3%) patients had an active COVID-19 infection at the time of delivery, while 118 (70.7%) gave birth after the infection was cleared. Twenty-three patients had preterm birth and the gestational age was <34 weeks in only four of these patients. There was no significant difference in the preterm birth, PE, FGR, HELLP syndrome, and gestational diabetes mellitus among the three gestation groups (p = 0.271, 0.394, 0.403, 0.763, and 0.664, respectively). Four (2.39%) patients required intensive care unit stay. Maternal death was seen in only one (0.59%) patient. CONCLUSION: Our study showed no significant correlation between the gestational age at the time of COVID-19 infection and the frequency of adverse pregnancy outcomes such as preterm birth, PE, FGR, and gestational diabetes mellitus. However, further studies are needed to draw a firm conclusion on this topic.