The Influence of the Rapid Increase in the Number of Adverse Event Reports for COVID-19 Vaccine on the Disproportionality Analysis Using JADER.

BACKGROUND/AIM: The COVID-19 prophylactic vaccine for the prevention of coronavirus infection was approved in Japan on February 14, 2021. Adverse event reports for the vaccine were collected from the Japan Adverse Drug Event Relief (JADER) database, similar to those for drugs. Reported odds ratios (RORs) and proportional reporting ratios (PRRs) are commonly used in disproportionality analysis to detect safety signals. Therefore, adverse event reports from the vaccinated population may affect the detection of safety signals for the registered drugs. This study determined the impact of adverse event reports on the detection of safety signals for a COVID-19 prophylactic vaccine by analyzing the JADER database using disproportionality analysis. PATIENTS AND METHODS: We extracted data from the JADER dataset, in which the COVID-19 vaccine was reported as a suspected drug, and selected the top 10 adverse events in terms of the number of reports. We then extracted the top 30 drugs by the amount of information in the selected 10 adverse events and compared the changes in the number of signal detections with and without the COVID-19 vaccine report data. RESULTS: The total number of adverse events reported in the JADER database during the study period was 2,002,564. Of the total number of reports, 85,489 (4.3%) reported adverse events related to the COVID-19 vaccine. Of the top 30 drugs reported in the 10 selected adverse events, the ROR and PRR were found to be lower with the inclusion of COVID-19 vaccine data than without. Detection by ROR excluded 23 out of 245 drugs, and detection by PRR excluded 34 out of 204 drugs. CONCLUSION: The rapid increase in the number of adverse event reports for the COVID-19 vaccine in JADER may affect the detection of safety signals by disproportionality analysis.

Associations Between Gastrointestinal Symptoms and COVID-19 Severity Outcomes Based on a Propensity Score-Weighted Analysis of a Nationwide Cohort.

Background and Aims: Gastrointestinal (GI) symptoms are well-recognized manifestations of coronavirus disease 2019 (COVID-19). Our primary objective was to evaluate the association between GI symptoms and COVID-19 severity. Methods: In this nationwide cohort of US veterans, we evaluated GI symptoms (nausea/vomiting/diarrhea) reported 30 days before and including the date of positive SARS-CoV-2 testing (March 1, 2020, to February 20, 2021). All patients had ≥1 year of prior baseline data and ≥60 days follow-up relative to the test date. We used propensity score (PS)-weighting to balance covariates in patients with vs without GI symptoms. The primary composite outcome was severe COVID-19, defined as hospital admission, intensive care unit admission, mechanical ventilation, or death within 60 days of positive testing. Results: Of 218,045 SARS-CoV-2 positive patients, 29,257 (13.4%) had GI symptoms. After PS weighting, all covariates were balanced. In the PS-weighted cohort, patients with vs without GI symptoms had severe COVID-19 more often (29.0% vs 17.1%; P < .001). When restricted to hospitalized patients (14.9%; n=32,430), patients with GI symptoms had similar frequencies of intensive care unit admission and mechanical ventilation compared with patients without symptoms. There was a significant age interaction; among hospitalized patients aged ≥70 years, lower COVID-19-associated mortality was observed in patients with vs without GI symptoms, even after accounting for COVID-19-specific medical treatments. Conclusion: In the largest integrated US health care system, SARS-CoV-2-positive patients with GI symptoms experienced severe COVID-19 outcomes more often than those without symptoms. Additional research on COVID-19-associated GI symptoms may inform preventive efforts and interventions to reduce severe COVID-19.

Excess deaths by sex and Age Group in the first two years of the COVID-19 pandemic in the United States.

The COVID-19 pandemic hastened hundreds of thousands of deaths in the United States. Many of these excess deaths are directly attributed to COVID-19, but others stem from the pandemic's social, economic, and health care system disruptions. This study compares provisional mortality data for age and sex subgroups across different time windows, with and without COVID-19 deaths, and assesses whether mortality risks are returning to pre-pandemic levels. Using provisional mortality reports from the CDC, we compute mortality risks for 22 age and sex subgroups in 2021 and compare against 2015-2019 using odds ratios. We repeat this comparison for the first twelve full months of the COVID-19 pandemic in the United States (April 2020-March 2021) against the next twelve full months (April 2021-March 2022). Mortality risks for most subgroups were significantly higher in 2021 than in 2015-2019, both with and without deaths involving COVID-19. For ages 25-54, Year 2 (April 2021-March 2022) was more fatal than Year 1 (April 2020-March 2021), whereas total mortality risks for the 65 + age groups declined. Given so many displaced deaths in the first two years of the COVID-19 pandemic, mortality risks in the next few years may fall below pre-pandemic levels. Provisional mortality data suggest this is already happening for the 75 + age groups when excluding COVID-19 deaths.

How reliable are the multiple comparison methods for odds ratio?

The homogeneity tests of odds ratios are used in clinical trials and epidemiological investigations as a preliminary step of meta-analysis. In recent studies, the severity or mortality of COVID-19 in relation to demographic characteristics, comorbidities, and other conditions has been popularly discussed by interpreting odds ratios and using meta-analysis. According to the homogeneity test results, a common odds ratio summarizes all of the odds ratios in a series of studies. If the aim is not to find a common odds ratio, but to find which of the sub-characteristics/groups is different from the others or is under risk, then the implementation of a multiple comparison procedure is required. In this article, the focus is placed on the accuracy and reliability of the homogeneity of odds ratio tests for multiple comparisons when the odds ratios are heterogeneous at the omnibus level. Three recently proposed multiple comparison tests and four homogeneity of odds ratios tests with six adjustment methods to control the type-I error rate are considered. The reliability and accuracy of the methods are discussed in relation to COVID-19 severity data associated with diabetes on a country-by-country basis, and a simulation study to assess the powers and type-I error rates of the tests is conducted.

Trichodynia and telogen effluvium in COVID-19 patients: Results of an international expert opinion survey on diagnosis and management.

BACKGROUND: The cutaneous manifestations of COVID-19 may be useful disease markers and prognostic indicators. Recently, postinfectious telogen effluvium and trichodynia have also been reported. OBJECTIVE: To evaluate the presence of trichodynia and telogen effluvium in patients with COVID-19 and describe their characteristics in relation to the other signs and symptoms of the disease. METHODS: Patients with a history of COVID-19 presenting to the clinics of a group of hair experts because of telogen effluvium and/or scalp symptoms were questioned about their hair signs and symptoms in relation to the severity of COVID-19 and associated symptoms. RESULTS: Data from 128 patients were collected. Telogen effluvium was observed in 66.3% of the patients and trichodynia in 58.4%. Trichodynia was associated with telogen effluvium in 42.4% of the cases and anosmia and ageusia in 66.1% and 44.1% of the cases, respectively. In majority (62.5%) of the patients, the hair signs and symptoms started within the first month after COVID-19 diagnosis, and in 47.8% of the patients, these started after 12 weeks or more. LIMITATIONS: The recruitment of patients in specialized hair clinics, lack of a control group, and lack of recording of patient comorbidities. CONCLUSION: The severity of postviral telogen effluvium observed in patients with a history of COVID-19 infection may be influenced by COVID-19 severity. We identified early-onset (<4 weeks) and late-onset (>12 weeks) telogen effluvium.

Beyond COVID-19 deaths during the COVID-19 pandemic in the United States.

COVID-19 has disrupted society and health care systems, creating a fertile environment for deaths beyond the virus. The year 2020 will prove to be the most deadly year on record in the United States. Direct deaths due to COVID-19 have been well documented and reported. Older people (those over 65) have been hardest hit, with over 80% of the COVID-19 deaths in this age group. What has been less clear is the impact on those under 65 years old, particularly those under 44 years old. This study considers both COVID-19 deaths and non-COVID-19 deaths during a 39 weeks period beginning 1 March in both 2020 and averaged over the five years from 2015 to 2019. Across 22 age and gender cohorts, death risks are compared using odds ratios. The results indicate that younger people (those under 15 years old) have experienced the same or a reduction in death risk between 2020 and the average from 2015 to 2019, suggesting that societal changes were protective for some of them. With all COVID-19 deaths removed from the 2020 death counts, 15-64 year olds experienced increased death risk between 2020 and the 2015 to 2019 average. For example, 15-44 year old males experienced a significant increase in their death risk, even though the absolute number of COVID-19 deaths for this cohort is small. The key take away from this study is that COVID-19 resulted in a large number of additional deaths in 2020 compared to the average from 2015 to 2019, both directly from the virus and indirectly due to societal responses to the virus.

Age-Related Changes in Clinical Presentation of Covid-19: the EPICOVID19 Web-Based Survey.

BACKGROUND: The influence of aging and multimorbidity on Covid-19 clinical presentation is still unclear. OBJECTIVES: We investigated whether the association between symptoms (or cluster of symptoms) and positive SARS-CoV-2 nasopharyngeal swab (NPS) was different according to patients' age and presence of multimorbidity. METHODS: The study included 6680 participants in the EPICOVID19 web-based survey, who reported information about symptoms from February to June 2020 and who underwent at least one NPS. Symptom clusters were identified through hierarchical cluster analysis. The associations between symptoms (and clusters of symptoms) and positive NPS were investigated through multivariable binary logistic regression in the sample stratified by age (<65 vs ≥65 years) and number of chronic diseases (0 vs 1 vs ≥2). RESULTS: The direct association between taste/smell disorders and positive NPS was weaker in older and multimorbid patients than in their younger and healthier counterparts. Having reported no symptoms reduced the chance of positive NPS by 86% in younger (95%CI: 0.11-0.18), and by 46% in older participants (95%CI: 0.37-0.79). Of the four symptom clusters identified (asymptomatic, generic, flu-like, and combined generic and flu-like symptoms), those associated with a higher probability of SARS-CoV-2 infection were the flu-like for older people, and the combined generic and flu-like for the younger ones. CONCLUSIONS: Older age and pre-existing chronic diseases may influence the clinical presentation of Covid-19. Symptoms at disease onset tend to aggregate differently by age. New diagnostic algorithms considering age and chronic conditions may ease Covid-19 diagnosis and optimize health resources allocation. TRIAL REGISTRATION: NCT04471701 (ClinicalTrials.gov).