Association of systemic adverse reaction patterns with long-term dynamics of humoral and cellular immunity after coronavirus disease 2019 third vaccination.

The objective of this study was to clarify the impact of adverse reactions on immune dynamics. We investigated the pattern of systemic adverse reactions after the second and third coronavirus disease 2019 (COVID-19) vaccinations and their relationship with immunoglobulin G against severe acute respiratory syndrome coronavirus 2 spike 1 protein titers, neutralizing antibody levels, peak cellular responses, and the rate of decrease after the third vaccination in a large-scale community-based cohort in Japan. Participants who received a third vaccination with BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna), had two blood samples, had not had COVID-19, and had information on adverse reactions after the second and third vaccinations (n = 2198) were enrolled. We collected data on sex, age, adverse reactions, comorbidities, and daily medicine using a questionnaire survey. Participants with many systemic adverse reactions after the second and third vaccinations had significantly higher humoral and cellular immunity in the peak phase. Participants with multiple systemic adverse reactions after the third vaccination had small changes in the geometric values of humoral immunity and had the largest geometric mean of cellar immunity in the decay phase. Systemic adverse reactions after the third vaccination helped achieve high peak values and maintain humoral and cellular immunity. This information may help promote uptake of a third vaccination, even among those who hesitate due to adverse reactions.

Varying Cellular Immune Response against SARS-CoV-2 after the Booster Vaccination: A Cohort Study from Fukushima Vaccination Community Survey, Japan.

Booster vaccination reduces the incidence of severe cases and mortality related to COVID-19, with cellular immunity playing an important role. However, little is known about the proportion of the population that has achieved cellular immunity after booster vaccination. Thus, we conducted a Fukushima cohort database and assessed humoral and cellular immunity in 2526 residents and healthcare workers in Fukushima Prefecture in Japan through continuous blood collection every 3 months from September 2021. We identified the proportion of people with induced cellular immunity after booster vaccination using the T-SPOT.COVID test, and analyzed their background characteristics. Among 1089 participants, 64.3% (700/1089) had reactive cellular immunity after booster vaccination. Multivariable analysis revealed the following independent predictors of reactive cellular immunity: age < 40 years (adjusted odds ratio: 1.81; 95% confidence interval: 1.19-2.75; p-value: 0.005) and adverse reactions after vaccination (1.92, 1.19-3.09, 0.007). Notably, despite IgG(S) and neutralizing antibody titers of ≥500 AU/mL, 33.9% (349/1031) and 33.5% (341/1017) of participants, respectively, did not have reactive cellular immunity. In summary, this is the first study to evaluate cellular immunity at the population level after booster vaccination using the T-SPOT.COVID test, albeit with several limitations. Future studies will need to evaluate previously infected subjects and their T-cell subsets.

Colitis with Hypereosinophilia following the Second Dose of the BNT162b2 mRNA COVID-19 Vaccine: A Case Report with a Literature Review.

A 61-year-old man presented with a 7-day history of watery diarrhea and loss of appetite after receiving the second dose of the Pfizer-BioNTech COVID-19 vaccine. Laboratory studies showed significant eosinophilia and an elevated IgE level (white cell count, 18.4×109/L; eosinophil count, 9.5×109/L; and IgE level, 540 IU/L). Symptoms resolved 10 days after vaccination without any steroids or antiallergic medications, and the eosinophil count had also returned to within normal limits 2 months later. Several cases of eosinophilic disorders following receipt of any type of injectable COVID-19 vaccine have been reported, so the etiology should be examined.

Time course of adverse reactions following BNT162b2 vaccination in healthy and allergic disease individuals aged 5-11 years and comparison with individuals aged 12-15 years: an observational and historical cohort study.

We aimed to investigate the type and frequency of adverse events over 7 days following the first and second BNT162b2 vaccination. This observational and historical cohort study included patients aged 5-11 years who received two doses of BNT162b2 and provided consent along with their guardians. We collected data on sex, age, height, weight, blood type, history of Bacille Calmette-Guerin vaccination, allergic disease, medication, history of coronavirus disease 2019 (COVID-19), and adverse reactions 7 days following the first and second BNT162b2 vaccination using a questionnaire. Our results were compared with previously reported results for individuals aged 12-15 years. A total of 421 participants were eligible for this study. Among the 216 patients with allergic disease, 48 (22.2%) had experienced worsening of their chronic diseases, and the frequency of fatigue and dizziness after the second dose was higher than that of healthy individuals. The experience of systemic adverse reactions was associated with asthma. The frequency of headache, diarrhea, fatigue, muscle/joint pain, and fever after the second BNT162b2 vaccination was lower in individuals aged 5-11 years than in those aged 12-15 years. Fever was the only systemic adverse reaction that lasted longer than 5 days (1.0% of participants). CONCLUSIONS: Individuals with allergic diseases, who are potentially susceptible to COVID-19, may experience worsening of their chronic diseases and more frequent adverse reactions after BNT162b2 vaccination than healthy individuals. To ensure that children with allergic diseases receive the vaccine safely, further information needs to be collected. WHAT IS KNOWN: • Adverse reactions after BNT162b2 vaccination among individuals aged 5-11 years are generally nonserious, more common after second vaccination, and substantially less common compared to those observed among individuals aged 12-15 years. WHAT IS NEW: • Individuals with allergic diseases experienced worsening of their chronic diseases and more frequent adverse reactions after BNT162b2 vaccination than healthy individuals. • Systemic adverse reactions were associated with asthma. Fever was the only systemic adverse reaction that lasted longer than 5 days.

Impact of COVID-19 on the endoscopy department since the early phase of the pandemic in 2020: A questionnaire study among patients with canceled examinations at a single Japanese institution.

INTRODUCTION: In early 2020, the Japanese government declared a nationwide state of emergency for the COVID-19 pandemic. We investigated the impact of the emergency declaration on endoscopy adherence and conducted a follow-up study of patients with canceled examinations at a tertiary endoscopy facility in Japan in 2020. METHODS: We compared the number of endoscopies performed, and cancelations at the endoscopy unit between 2019 and 2020 and used the Bayesian structural time series (BSTS) model to estimate the decrease in the number of endoscopies in 2020. We administered a questionnaire to those who had not undergone a scheduled endoscopy. RESULTS: Of 14 146 and 13 338 scheduled examinations, 1233 (8.7%) and 1403 (10.5%) were canceled in 2019 and 2020, respectively. During both years, age < 50 years, age > 80 years, upper endoscopy, and experience of endoscopy in the past 5 years were significantly associated with cancelations. In 2020, cancelations in the 14th-26th week of the year, including the period of state of emergency, increased significantly, and more women canceled. Of the 409 questionnaire-respondents, 174 (42.5%) indicated that COVID-19 had influenced their cancelation, and 315 (77.0%) had not undergone similar endoscopic examinations since then. The BSTS model predicted a decrease of 957 (95% CI -1213 to -708, P = .003) examinations. CONCLUSION: In 2020, despite low numbers of COVID-19 cases in the study site, the number of endoscopies decreased, and cancelation increased. Further research is needed on the future impact of a decrease in the number of endoscopies during a COVID-19 pandemic.

Observational study of financial and non-financial conflicts of interest among the Japanese government advisory board members concerning coronavirus disease 2019.

This cross-sectional analysis aimed to assess the extent of conflicts of interest among the Japanese government coronavirus disease 2019 (COVID-19) advisory board members and elucidate the accuracy of conflicts of interest (COI) disclosure and management strategies. Using the payment data from all 79 pharmaceutical companies in Japan between 2017 and 2019 and direct research grants from the Japanese government between 2019 and 2020, we evaluated the extent of financial and non-financial COI among all 20 Japanese government COVID-19 advisory board members. The Ethic Committee of the Medical Governance Research Institute approved this study. Japanese government COVID-19 advisory board members were predominantly male (75.0%) and physicians (50.0%). Between 2019 and 2020, 2 members (10.0%) received a total of $819,244 in government research funding. Another 5 members (25.0%) received $532,127 in payments, including $276,722 in personal fees, from 31 pharmaceutical companies between 2017 and 2019. The average value of the pharmaceutical payments was $9155 (standard deviation: $12,975). Furthermore, neither the Ministry of Health, Labor, and Welfare nor the Japanese Cabinet Secretariat disclosed financial or non-financial COI with industry. Additionally, the government had no policies for managing COI among advisory board members. This study found that the Japanese government COVID-19 advisory board had financial and non-financial COI with pharmaceutical companies and the government. Furthermore, personal communication received as part of this research indicated that there were no rigorous COI management strategies for the COVID-19 advisory board members. Any government must ensure the independence of scientific advisory boards by implementing more rigorous and transparent management strategies that require the declaration and public disclosure of all COI.

The Trend in Industry Payments During the COVID-19 Pandemic Among Gastroenterologists and Hepatologists in the United States

Background Although the sudden coronavirus disease 2019 (COVID-19) pandemic would have significantly influenced financial relationships between the healthcare industry and gastroenterologists and hepatologists, little is known about the trend in financial relations in the United States. This study, thus, aimed to examine the trends in industry payments made to gastroenterologists and hepatologists during the COVID-19 pandemic. Materials and methods Using the Open Payments Database between 2013 and 2021, we evaluated trends in financial relationships between the healthcare industry and gastroenterologists and hepatologists in the United States. Trends in general payments during the COVID-19 pandemic were evaluated by interrupted time series analysis with monthly and yearly payments at the physician level. Results A total of 16,808 or 89.4% of all active gastroenterologists received general payments totaling $393,823,094 from the pharmaceutical and medical device companies between 2013 and 2021. The payment per gastroenterologist and the number of gastroenterologists receiving payments decreased by 70.9% (95% CI: -73.4% - -68.1%, p<0.001) and by 51.5% (95%CI: -52.2% - -50.7%, p<0.001) due to the onset of the COVID-19 pandemic, respectively. However, both payments and the number of physicians with payments have recovered monthly since the COVID-19 pandemic, with relative monthly change rates of 4.1% (95% CI: 3.5% ‒ 4.7%, p<0.001) and 3.2% (95%CI: 3.1% ‒ 3.2%, p<0.001). Additionally, the general payments per gastroenterologist significantly decreased by 2.5% (95%CI: -3.9% - -1.1%, p<0.001) each year before the COVID-19 pandemic, while there was a very small change in the number of gastroenterologists with payments. Conclusions The industry payments to gastroenterologists and hepatologists significantly decreased due to the COVID-19 pandemic, but the payments have recovered right after the pandemic in the United States.

The Trend in Industry Payments During the COVID-19 Pandemic Among Gastroenterologists and Hepatologists in the United States.

Background Although the sudden coronavirus disease 2019 (COVID-19) pandemic would have significantly influenced financial relationships between the healthcare industry and gastroenterologists and hepatologists, little is known about the trend in financial relations in the United States. This study, thus, aimed to examine the trends in industry payments made to gastroenterologists and hepatologists during the COVID-19 pandemic. Materials and methods Using the Open Payments Database between 2013 and 2021, we evaluated trends in financial relationships between the healthcare industry and gastroenterologists and hepatologists in the United States. Trends in general payments during the COVID-19 pandemic were evaluated by interrupted time series analysis with monthly and yearly payments at the physician level. Results A total of 16,808 or 89.4% of all active gastroenterologists received general payments totaling $393,823,094 from the pharmaceutical and medical device companies between 2013 and 2021. The payment per gastroenterologist and the number of gastroenterologists receiving payments decreased by 70.9% (95% CI: -73.4% - -68.1%, p<0.001) and by 51.5% (95%CI: -52.2% - -50.7%, p<0.001) due to the onset of the COVID-19 pandemic, respectively. However, both payments and the number of physicians with payments have recovered monthly since the COVID-19 pandemic, with relative monthly change rates of 4.1% (95% CI: 3.5% ‒ 4.7%, p<0.001) and 3.2% (95%CI: 3.1% ‒ 3.2%, p<0.001). Additionally, the general payments per gastroenterologist significantly decreased by 2.5% (95%CI: -3.9% - -1.1%, p<0.001) each year before the COVID-19 pandemic, while there was a very small change in the number of gastroenterologists with payments. Conclusions The industry payments to gastroenterologists and hepatologists significantly decreased due to the COVID-19 pandemic, but the payments have recovered right after the pandemic in the United States.

Antibody and T-Cell Responses against SARS-CoV-2 after Booster Vaccination in Patients on Dialysis: A Prospective Observational Study.

Intensive vaccination is recommended for populations more vulnerable to COVID-19 infection, although data regarding the built of immunity after vaccination for dialysis patients are lacking. This prospective, observational cohort study of maintenance hemodialysis patients examined IgG antibody levels against the SARS-CoV-2 spike (S1) protein, neutralizing activity, and interferon gamma levels after the third dose of the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine. Humoral immunity was repeatedly measured for up to two months. The study includes 58 patients on hemodialysis. Median neutralizing antibodies reached a maximum at 56 and 9 days after booster vaccination with BNT162b2 and mRNA-1273, respectively. The median IgG antibody titer reached a maximum of 3104.38 and 7209.13 AU/mL after 16 days of booster dose, and cellular immunity was positive in 61.9% and 100% of patients with BNT162b2 and mRNA-1273 vaccination, respectively. By repeating the measurements over a period of two months, we clarified the chronological aspects of the acquisition of humoral immunity in dialysis patients after a booster COVID-19 vaccination; most dialysis patients acquired not only humoral immunity, but also cellular immunity against SARS-CoV-2. Future research should investigate the continued long-term dynamics of antibody titers and cellular immunity after the third or further vaccinations, evaluating the need for additional vaccinations for hemodialysis patients.

Trends in Industry Payments to Diabetologists and Endocrinologists in the United States During the COVID-19 Pandemic.

Introduction Limited evidence suggests there were substantial amounts of payments from the healthcare industry to diabetologists and endocrinologists in the United States before the coronavirus disease 2019 (COVID-19) pandemic period. However, there is no study on how these industry payments changed during the COVID-19 pandemic. This study aimed to evaluate trends in non-research industry payments to physicians specializing in diabetology and endocrinology in the United States during the COVID-19 pandemic.  Methods Using the open payments database between 2013 and 2021, we examined trends in general payments made to physicians whose primary specialty was diabetology and endocrinology by the healthcare industry in the United States. Trends in industry payments during the COVID-19 pandemic were evaluated by interrupted time series analysis with generalized estimating equation models. Results Of 7965 active endocrinologists and diabetologists, 6991 (87.8%) received one or more general payments from the healthcare industry in the United States between August 2013 and December 2021. Median per-physician payments were $116.68 (interquartile range (IQR): $41.66-$390.00) before the COVID-19 pandemic period and $97.91 (IQR: $32.81-$314.04) during the COVID-19 pandemic period. Monthly per-physician payments, the number of per-physician payments, and the number of physicians receiving payments decreased by 61.0% (95% confidence interval (95% CI): 58.1%-63.7%, p<0.001), 59.2% (95% CI: 57.9%-60.4%, p<0.001), and 39.7% (95% CI: 38.3%-41.0%, p<0.001) at the onset of the COVID-19 pandemic (March 2020), compared to those before pandemic period, respectively.  Conclusion The non-research payments to endocrinologists and diabetologists from the healthcare industry sharply decreased by about 60% in payment amounts due to the COVID-19 pandemic in the United States.

Association between COVID-19 incidence and postponement or cancellation of elective surgeries in Japan until September 2020: a cross-sectional, web-based survey.

OBJECTIVES: This study aimed to examine whether and how the COVID-19 pandemic has affected the postponement or cancellation of elective surgeries in Japan. DESIGN AND SETTING: A cross-sectional, web-based, self-administered survey was conducted nationwide from August 25 to September 30 2020. We used data from the Japan 'COVID-19 and Society' Internet Survey collected by a large internet research agency, Rakuten Insight, which had approximately 2.2 million qualified panellists in 2019. PARTICIPANTS: From a volunteer sample of 28 000 participants, we extracted data from 3678 participants with planned elective surgeries on any postponement or cancellation of elective surgeries. OUTCOME MEASURES: The main outcome measure was any postponement or cancelltion of elective surgeries. In addition, for all respondents, we extracted data on sociodemographic, health-related characteristics, psychological characteristics and prefectural-level residential areas. We used weighted logistic regression approaches to fulfil the study objectives, minimising potential bias relating to web-based surveys. RESULTS: Of the 3678 participants, 431 (11.72%) reported experiencing postponement or cancellation of their elective surgeries. Notably, the participants living in prefectures where the declaration of the state of emergency was made on 7 April 2020 were significantly more likely to experience postponement or cancellation of elective surgeries than those residing in prefectures with the state of emergency beginning on 16 April 2020 (174 (26.02%) vs 153 (12.15%)). CONCLUSIONS: The proportion of patients whose elective surgery had been postponed was limited during Japan's first wave of the COVID-19 pandemic, although the declaration of a state of emergency increased the likelihood of postponement. It is imperative to increase awareness of the secondary health effects related to policy intervention in pandemics and other health crises and to use appropriate countermeasures such as standard infectious control measures and triage of surgical patients.

Trend in industry payments to infectious disease physicians in the United States: a seven-year analysis of nonresearch payments from the Open Payments Database between 2014 and 2020.

OBJECTIVE: To evaluate the trend in nonresearch payments made by the industries to the infectious disease physicians in the United States since the launch of the Open Payments Database and during the COVID-19 pandemic. METHODS: Descriptive analysis was performed for the nonresearch payments made to all infectious disease physicians listed in the Open Payments Database between 2014 and 2020. Using the generalized estimating equation models with panel data of monthly and yearly payment per physician, the payment trend since the inception of the Open Payments Database and during the early stage of the COVID-19 pandemic were evaluated. RESULTS: A total of 7901 (81.5%) infectious disease physicians received $156 837 987 in nonresearch payments between 2014 and 2020. Median annual payments were $197 to $220. Monthly nonresearch per-physician payments and number of physicians with payments rapidly decreased by 58.6% (95% CI: 49.7%‒65.9%, p < 0.001) and by 54.4% (95% CI: 52.7%‒56.1%, p < 0.001) at the beginning of the COVID-19 pandemic, respectively. However, the per-physician payments and number of physicians with payments slightly increased every month right after onset of the pandemic. Both per-physician payments and the number of physicians with payments decreased by 2.6% (95% CI: 0.45‒4.7, p 0.018) and 2.0% (95% CI: 1.6%‒2.4%, p < 0.001) since the inception of the Open Payments Database, respectively. DISCUSSION: The nonresearch payments and number of infectious disease physicians accepting payments had decreased since the inception of the Open Payments Database. Furthermore, the non-research payments to infectious disease physicians suddenly decreased by more than half due to the COVID-19 pandemic.

Impact of the Coronavirus Disease-2019 Pandemic on Pancreaticobiliary Disease Detection and Treatment.

The emergency declaration (ED) associated with the coronavirus disease-2019 (COVID-19) pandemic in Japan had a major effect on the management of gastrointestinal endoscopy. We retrospectively compared the number of pancreaticobiliary endoscopies and newly diagnosed pancreaticobiliary cancers before (1 April 2018 to 6 April 2020), during (7 April to 25 May 2020), and after the ED (26 May to 31 July). Multiple comparisons of the three groups were performed with respect to the presence or absence of symptoms and clinical disease stage. There were no significant differences among the three groups (Before/During/After the ED) in the mean number of diagnoses of pancreatic cancer and biliary cancer per month in each period (8.0/7.5/7.5 cases, p = 0.5, and 4.0/3.5/3.0 cases, p = 0.9, respectively). There were no significant differences among the three groups in the number of pancreaticobiliary endoscopies (EUS: endoscopic ultrasonography/ERCP: endoscopic retrograde cholangiopancreatography) per month (67.8/62.5/69.0 cases, p = 0.7 and 89.8/51.5/86.0 cases, p = 0.06, respectively), whereas the number of EUS cases decreased by 42.7% between before and during the ED. There were no significant differences among the three groups in the presence or absence of symptoms at diagnosis or clinical disease stage. There was no significant reduction in the newly diagnosed pancreaticobiliary cancer, even during the ED. The number of ERCP cases was not significantly reduced as a result of urgent procedures, but the number of EUS cases was significantly reduced.