Analysis of participant-reported adverse events following the first dose of inactivated SARS-Cov-2 vaccine (TURKOVAC™) through telephone survey in Türkiye.

BACKGROUND/OBJECTIVE(S)/INTRODUCTION: TURKOVAC™ is a whole-virion inactivated COVID-19 vaccine, which was developed and recently granted emergency use authorization (conditional marketing authorization) in Türkiye. The objective of this study is to assess the spectrum and the distribution of adverse events reported following the administration of the first 150,000 doses as primary and booster vaccine doses in 22 state hospitals of 17 provinces in Türkiye. PATIENTS/MATERIALS AND METHODS: In this cohort study, a verbal survey was conducted via telephone calls between 10 January and 17 January 2022, utilizing a structured questionnaire algorithm on a sample group of 20,000 persons on the third- and seventh-days following vaccination. The algorithm consisted of two parts focusing on both systemic and local adverse effects. Other adverse events reported by the participants were also recorded. 6023 people and 5345 people agreed to participate in the telephone survey on the 3rd- and 7th- days of having received the first dose of the vaccine, respectively. RESULTS: Thirty-six-point-six percent of the participants on the 3rd day and 22.5% of the participants on the 7th day reported any adverse event following the first dose of the vaccine. On both follow-up days, the most commonly reported (29.7% for Day 3 and 13.1% for Day 7) adverse events were on the injection site. Among the local adverse events, the most frequently reported one was the pain on the injection site (27.9% for Day 3 and 12.4% for Day 7), induration (4.8% for Day 3 and 2.7% for Day 7) and swelling (3.5% for Day 3 and 2.0% for Day 7). Fatigue/weakness (9.6% for Day 3 and 8.3% for Day 7) and headache (7.9% for Day 3 and 8.0% for Day 7) were the most frequent systemic adverse events. Younger age, vaccine dose, and female sex were associated with having any adverse event and pain (on the injection site). Female sex was associated with more swelling (on the injection site), induration (on the injection site), fever, and a higher impact on daily living. CONCLUSION(S): In this study, we conducted a rapid assessment of adverse events following the first dose of the TURKOVAC vaccine. The vaccine appears to have a good safety profile in the first 7 days following vaccination. Younger age, vaccine dose, and female sex are associated with any adverse event and pain (on the injection site). These results present valuable information for the community and may contribute to increasing vaccine confidence.KEY MESSAGESAs a whole-virion inactivated SARS-CoV-2 vaccine, the TURKOVAC™ vaccine, which has a favorable safety profile, can be an alternative to other COVID-19 vaccines including mRNA and viral vector vaccines.

Self-Reported Allergic Adverse Events Following Inactivated SARS-CoV-2 Vaccine (TURKOVAC™) among General and High-Risk Population.

TURKOVAC™ is a whole-virion inactivated COVID-19 vaccine which was developed and granted emergency use and conditional marketing authorization in December 2021 in Türkiye. The objective of this study is to assess the distribution and the severity of allergic adverse events following the administration of the vaccine as the primary or the booster dose in 15 provinces in Türkiye. In this cohort study, between February and May 2022, in the selected 15 provinces having an adequate number of health care personnel in the community health centers to conduct the study, 32,300 people having the first, the second, or the booster dose of the vaccine were invited to the survey. A total of 29,584 people voluntarily agreed to participate to the survey and were given a structured questionnaire after a minimum of 10 days following the vaccination. In our study, only 0.5% of the participants (142 persons) reported to experience any allergic reaction, and 12 of them (8.5%) reported to be given medical treatment in a health center. Male predominance (55.6%) was observed among participants reported to experience any allergic reaction. No hospitalization was recorded. Of the participants, 4.4% (1315 people) reported to have a history of allergy. The most reported allergens were drugs. Among the participants without a known history of allergy (n = 28,269), 0.4% of them (110 people) reported to experience an allergic reaction following the vaccination, and 5.4% of the allergic reactions (six people) were reported to be treated in a health center. The percentage of the participants given any medical treatment among the participants without a known history of allergy is 0.02%. No immediate or anaphylactic reaction was reported. Among the participants with a known history of allergy (n = 1315), 32 people (2.4% of them) reported to experience an allergic reaction following the vaccination, and 18.7% of the allergic reactions (six people) were reported to be prescribed a medical treatment. The percentage of the participants given any medical treatment among the participants with a known history of allergy is 0.4%. A known history of allergy increased the risk of having an allergic experience by approximately six times following vaccination. As a whole-virion inactivated SARS-CoV-2 vaccine, the TURKOVAC™ vaccine, with a low allergic reaction-related adverse event profile, can be an alternative to other COVID-19 vaccines.

Safety and immunogenicity of an inactivated whole virion SARS-CoV-2 vaccine, TURKOVAC, in healthy adults: Interim results from randomised, double-blind, placebo-controlled phase 1 and 2 trials.

BACKGROUND: Development of safe and effective vaccine options is crucial to the success of fight against COVID-19 pandemic. Herein, we report interim safety and immunogenicity findings of the phase 1&2 trials of ERUCoV-VAC, an inactivated whole virion SARS-CoV-2 vaccine. METHODS: Double-blind, randomised, single centre, phase 1 and 2 trials included SARS-CoV-2 seronegative healthy adults aged 18-55 years (18-64 in phase 2). All participants, except the first 4 in phase 1 who received ERUCoV-VAC 3 µg or 6 µg unblinded and monitored for 7 days for safety purposes, were assigned to receive two intramuscular doses of ERUCoV-VAC 3 µg or 6 µg (an inactivated vaccine containing alhydrogel as adjuvant) or placebo 21 days apart (28 days in phase 2) according to computer-generated randomisation schemes. Both trials are registered at ClinicalTrials.gov (phase 1, NCT04691947 and phase 2, NCT04824391). RESULTS: Forty-four participants (3 µg [n:17], 6 µg [n:17], placebo [n:10]) in phase 1 and 250 (3 µg [n:100], 6 µg [n:100], placebo [n:50]) in phase 2 received ≥1 dose. In phase 1 trial, 25 adverse events AEs (80 % mild) occured in 15 participants (34.1 %) until day 43. There was no dose-response relationship noted in safety events in ERUCoV-VAC recipients (p = 0.4905). Pain at injection site was the most common AE (9/44;20.5 %). Both doses of ERUCoV-VAC 3 µg and 6 µg groups were comparable in inducing SARS-CoV-2 wild-type neutralising antibody (MNT50): GMTs (95 %CI) were 8.3 (6.4-10.3) vs. 8.6 (7.0-10.2) at day 43 (p = 0.7357) and 9.7 (6.0-13.4) vs. 10.8 (8.8-12.8) at day 60 (p = 0.8644), respectively. FRNT50 confirmed MNT50 results: SARS-CoV-2 wild-type neutralising antibody GMTs (95 %CI) were 8.4 (6.3-10.5) vs. 9.0 (7.2-10.8) at day 43 (p = 0.5393) and 11.0 (7.0-14.9) vs. 12.3 (10.3-14.5) at day 60 (p = 0.8578). Neutralising antibody seroconversion rates (95 %CI) were 86.7 % (59.5-98.3) vs 94.1 % (71.3-99.8) at day 43 (p = 0.8727) and 92.8 % (66.1-99.8) vs. 100 % (79.4-100.0) at day 60 (p = 0.8873), in ERUCoV-VAC 3 µg and 6 µg groups, respectively. In phase 2 trial, 268 AEs, (67.2 % moderate in severity) occured in 153 (61.2 %) participants. The most common local and systemic AEs were pain at injection site (23 events in 21 [8.4 %] subjects) and headache (56 events in 47 [18.8 %] subjects), respectively. Pain at injection site was the only AE with a significantly higher frequency in the ERUCoV-VAC groups than in the placebo arm in the phase 2 study (p = 0.0322). ERUCoV-VAC groups were comparable in frequency of AEs (p = 0.4587). ERUCoV-VAC 3 µg and 6 µg groups were comparable neutralising antibody (MNT50): GMTs (95 %CI) were 30.0 (37.9-22.0) vs. 34.9 (47.6-22.1) at day 43 (p = 0.0666) and 34.2 (23.8-44.5) and 39.6 (22.7-58.0) at day 60, (p = 0.2166), respectively. FRNT50 confirmed MNT50 results: SARS-CoV-2 wildtype neutralising antibody GMTs were 28.9 (20.0-37.7) and 30.1 (18.5-41.6) at day 43 (p = 0.3366) and 34.2 (23.8-44.5) and 39.6 (22.7-58.0) at day 60 (p = 0.8777). Neutralising antibody seroconversion rates (95 %CI) were 95.7 % (91.4-99.8) vs. 98.9 % (96.9-100.0) at day 43 (p = 0.8710) and 96.6 % (92.8-100.0) vs 98.9 % (96.7-100.0) at day 60 (p = 0.9129) in ERUCoV-VAC 3 µg and 6 µg groups, respectively. CONCLUSIONS: Two-dose regimens of ERUCoV-VAC 3 µg and 6 µg 28 days both had an acceptable safety and tolerability profile and elicited comparable neutralising antibody responses and seroconversion rates exceeding 95 % at day 43 and 60 after the first vaccination. Data availability Data will be made available on request.

Safety and immunogenicity of inactive vaccines as booster doses for COVID-19 in Türkiye: A randomized trial.

Protective neutralizing antibody titers reduce in time after COVID-19 vaccinations, as in individuals who have had COVID-19. This study aimed to evaluate the safety and immunogenicity of CoronaVac and TURKOVAC vaccines used as a booster dose after CoronaVac primary vaccination. This double-blind, randomized, controlled, phase II, multicenter study included healthy male and female adults (18-60 years) who were vaccinated with two doses of CoronaVac vaccine and did not exceed the duration of at least 90 days and a maximum of 270 days from the second dose of vaccination. Among 236 eligible volunteers, 222 were recruited for randomization between July 12, 2021 and September 10, 2021; 108 and 114 were randomized to the TURKOVAC and CoronaVac arms, respectively. The primary endpoint was adverse events (AEs) (ClinicalTrials.gov; Identifier: NCT04979949). On day 28, at the neutralizing antibody threshold of 1/6, the positivity rate reached 100% from 46.2% to 98.2% from 52.6% in the TURKOVAC and CoronaVac arms, respectively, against the Wuhan variant and the positivity rate reached 80.6% from 8.7% in the TURKOVAC arm vs. 71.9% from 14.0% in the CoronaVac arm against the Delta variant. IgG spike antibody positivity rate increased from 57.3% to 98.1% and from 57.9% to 97.4% in the TURKOVAC and CoronaVac arms, respectively. The TURKOVAC and CoronaVac arms were comparable regarding the frequency of overall AEs. Both vaccines administered as booster yielded higher antibody titers with acceptable safety profiles.

What is the context? The timing of the primary and booster doses for each vaccine differs.We aimed to evaluate the safety and immunogenicity of CoronaVac and TURKOVAC vaccines used as homologous booster dose after CoronaVac primary vaccination.What is new? The neutralizing antibody titers against the Wuhan variant decreased below 1/6- the seropositivity threshold value- in more than 55% of the participants 4 months after administration of two doses of CoronaVac vaccine.Immunogenicity was re-stimulated and the neutralizing antibody titers increased rapidly and markedly with the administration of the CoronaVac or TURKOVAC as a booster dose 4 months after the second dose.While the increase in neutralizing antibodies against the Wuhan variant was similar with both CoronaVac and TURKOVAC, more antibodies developed against the Delta variant with TURKOVAC.What is the impact? With the Hybrid COV-RAPEL TR study, after the primary vaccination consisting of two doses of inactivated vaccine, antibody titers decreased in the long term; however, higher antibody titers are achieved than the primary vaccination after the booster dose administered after 4­6 month interval.Booster application with TURKOVAC provides antibodies at least as much as the CoronaVac booster dose, with an acceptable safety profile.

Questions on Immunization and Vaccination and Short Answers: Journal of Pediatric Infection

The antibody response to the vaccine is considered protective after day 14. [...]it should be remembered that protection against influenza begins as of the 14th day of vaccination. Following their meeting on November 3rd, 2021, the COVID-19 Scientific Advisory Board recommended three primary doses for people who "received a solid organ transplant or bone marrow transplant, have active cancer, HIV infection with a CD4 count below 200, are on hemodialysis, or are severely immunosuppressed with high-dose steroids or biological agents." Antibody response after a third dose of the mRNA-1273 SARS-CoV-2 vaccine in kidney transplant recipients with minimal serologic response to 2 doses.

Multisystem inflammatory syndrome in children

As the COVID-19 pandemic continues, children can be infected with the virus that causes COVID-19. Clinical symptoms of children with COVID from China, where the disease was first reported, generally were less severe than adults. However, at the end of April 2020 in Europe, it was observed that some children with SARS-CoV-2 infection developed fever, abdominal pain, shock, myocardial insufficiency and they needed to be taken care of in intensive care unit. This new disease has been called multisystem inflammatory syndrome in children (MIS-C). Although the pathogenesis of MIS-C is unclear, it progresses with signs of multiorgan involvement as a result of uncontrolled inflammation of the immune system and even causes death. Therefore, the diagnosis and treatment of patients with MIS-C should be managed quickly. In this review, the pathophysiology, clinical and laboratory findings, diagnostic methods, and treatment regimens of MIS-C were discussed.

Comparison of SARS-CoV-2 Antibodies and Six Immunoassays in Pediatric and Adult Patients 12 Weeks After COVID-19.

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific humoral immune persistence has been proposed to be affected by patients' characteristics. Moreover, available conflicting assay results are needed to be settled through comparative research with defined clinical specimens. Methods This prospective study investigated SARS-CoV-2-specific antibodies among 43 adults and 34 children at a mean of 12 weeks after the onset of COVID-19 symptoms using six serological assays and compared their performance. We used two Euroimmun (Euroimmun, Luebeck, Germany), two automated Roche Elecsys (Basel, Switzerland), and two rapid immuno-chromatographic Ecotest (Matrix Diagnostics, Assure Tech. (Hangzhou) Co., L, China) assays to investigate SARS-CoV-2 antibodies. Results The findings showed that the Roche Elecsys anti-S total test yielded the best positivity/sensitivity (children 94.1% and adults 93.0%; p = 0.877) while five immunoglobulin IgG targeting assays had similar positivity/sensitivity between children (88.2% to 94.1%) and adults (88.4% to 93.0%) (p > 0.05). Although IgM positivity was relatively low (p < 0.001), it was found in the majority of our pediatric and adult patients (67.6% and 86.0%, respectively; p = 0.098). SARS-CoV-2 S IgG titers were found to be higher among males in pediatric and adult groups compared to females (p = 0.027 and p = 0.041, respectively). Furthermore, we observed significantly higher antibody titers among pneumonia patients (p = 0.001). Conclusion Overall, we concluded SARS-CoV-2 antibody persistence over an average of 12 weeks after the onset of COVID-19 symptoms. While automated Roche Elecsys total antibody assays yielded the best sensitivity (> 90%) and five assays targeting IgG had acceptable performance. Patients with pneumonia and males have higher antibody titers. The effect of antibody persistence on re-infections should be monitored in longitudinal studies.

Nine-month course of SARS-CoV-2 antibodies in individuals with COVID-19 infection.

BACKGROUND: The continual course of the pandemic points to the importance of studies on the rate and durability of protective immunity after infection or vaccination. AIMS: In this study, we aimed to monitor anti-nucleocapsid (N) and anti-spike (S) antibodies against SARS-CoV-2 nearly 9 months duration after infection. METHODS: Anti-nucleocapsid (N) (at 11-15-20-29-38 weeks) and anti-spike antibodies (at 11 and 38 weeks) against SARS-CoV-2 were monitored during 38 weeks after the initial symptoms of COVID-19. RESULTS: Of 37 cases between 18 and 57 years old, 54% were women. The findings showed that anti-N antibodies decreased significantly after the 15th week (between 15 and 20 weeks, p = 0.016; 20-29 weeks, p = 0.0009; and 29-38 weeks, p = 0.049). At the 38th week, mean antibody levels decreased 35% compared to the 11th week, and 8% of the cases turned negative results. Anti-N antibody average level was 56.48 on the 11th week (the cut-off index threshold ≥ 1). It was estimated statistically that it would decrease to an average of 20.48 in weeks 53-62. In females, average antibody levels of all measurements were lower than males (p > 0.05). Anti-S antibody levels 14% increased at 38th week compared to 11th week (quantitative positivity threshold ≥ 0.8 U/ml), and no cases were negative at 38th week. CONCLUSIONS: Patients had ≥ 90% positivity after at least 9 months of symptoms, both anti-N and anti-S antibodies. In all samples, both anti-N and anti-S antibody levels were lower in females. The findings suggest that the quantitative values of anti-S antibodies remained high for at least 9 months and could provide protection.

Bağışıklama ve Aşı ile Ílgili Sorular ve Kısa Cevaplar: Journal of Pediatric Infection

Bu durum bazı koşullar için tanı konulmasında güçlüǧe neden olabilir ya da uygulanan aşı ile istenilen korunma düzeyinin elde edilmediǧi koşullar için de geçerli olabilir. American Academy of Pediatrics. 2019 Novel Coronavirus COVID-19 Infections. Available from: https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/ [CrossRef] 3. American Academy of Pediatrics. 2019 Novel Coronavirus COVID-19 Infections: Guidance on Provididng Pediatric Well Care During COVID-19. Available from: https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/guidance-on-providing-pediatric-well-care-during-covid-19/ [CrossRef]

Alteration in vaccination rates and an evaluation of physicians' perceptions of the possible impact of the SARS-CoV-2 pandemic on childhood vaccinations in Ankara, Turkey.

Vaccination is the most effective and cost-efficient approach to protect both individual and community health. Decreased vaccination rates have been reported in many countries during the COVID-19 pandemic. In this study, we compared the vaccination rates of the current year with those of the same period of 2019 in Ankara and presented the physicians' thoughts about effects of COVID-19 pandemic on vaccinations in Turkey. An online survey was sent to family practitioners, pediatricians, and pediatric infectious disease specialists to ascertain their thoughts on vaccination during the pandemic. A majority of family practitioners stated that, despite hesitations, families brought their children for vaccination. They noted that vaccination should be emphasized, physicians should be supported by health authorities, and all related media and social media channels should be used to promote maintaining vaccinations. In contrast, pediatricians and pediatric infectious disease specialists were of the opinion that families were expressing greater hesitation and would not bring their children for vaccination. Vaccination rates in Ankara have decreased 2-5% during the pandemic, and the greatest decrease was observed for vaccines administered after 18 months of age. Outbreaks of vaccine-preventable diseases can threaten community health worldwide. Thus, vaccinations must continue, and effective regulations and recommendations need to be implemented by healthcare authorities to promote it.

Bağışıklama ve Aşı ile Ílgili Sorular ve Kısa Cevaplar: Journal of Pediatric Infection

Bugüne kadar ülkemizde rutin olarak ilköğretim birinci sınıfta, okullarda yapılan difteri-tetanos-aselüler boğmaca ve inaktif polio (DaBT-IPA) hatırlatma aşı dozu ile kızamık-kızamıkçık-kabakulak hatırlatma aşı dozu, aile hekimliğinde ve 48. ayda uygulanacak. Çok kısa bir cevap ile, bağışıklama hizmetleri;rutin aşı takvimimizin uygulanması, gebe aşılaması, yetişkin aşılaması-risk grubu aşılaması, koruyucu hizmetlerin temelidir ve salgın döneminde de aksatılmadan devam etmesi sağlanmalıdır. Yazışma Adresi/Correspondence Address Ateş Kara Hacettepe Üniversitesi Tıp Fakültesi, Çocuk Sağlığı ve Hastalıkları Anabilim Dalı, Çocuk Enfeksiyon Hastalıkları Bilim Dalı, Ankara, Türkiye E-mail: ateskara@hacettepe.edu.tr Geliş Tarihi: 29.06.2020 Kabul Tarihi: 30.06.2020 Çevrimiçi Yayın Tarihi: 04.08.2020 ©Telif Hakkı 2020 Çocuk Enfeksiyon Hastalıkları ve Bağışıklama Derneği.

Global surveillance, travel, and trade during a pandemic

Pandemics have had very important consequences in human history. Lots of people lost their lives and countries have been intensively affected in terms of socioeconomic problems. Unfortunately, avoidance of pandemics and limiting the spread are still currently not always possible. Maybe the most important factor for this is the increasing frequency of traveling. Increasing airline traveling rate also increases the rate of spread. Global organizations like the World Health Organization and United Nations are trying to play a supreme role over the countries. Pandemics do not have borders; therefore, efforts should be given globally, definition of pandemic should be established as soon as possible, and protective measures should be shared with countries. If these are not done, severe health consequences and serious economic problems are inevitable.