Case definitions for onchocerciasis-associated epilepsy and nodding syndrome: A focused review.

Onchocerciasis-associated epilepsy (OAE) is an important but neglected public health problem in onchocerciasis-endemic areas with insufficient or inadequate onchocerciasis control. Hence, there is a need for an internationally accepted, easy-to-use epidemiological case definition of OAE to identify areas of high Onchocerca volvulus transmission and disease burden requiring treatment and prevention interventions. By including OAE as a manifestation of onchocerciasis, we will considerably improve the accuracy of the overall onchocerciasis disease burden, which is currently underestimated. Hopefully, this will lead to increased interest and funding for onchocerciasis research and control interventions, notably the implementation of more effective elimination measures and treatment and support for affected individuals and their families.

Biases in COVID-19 Case and Death Definitions: Potential Causes and Consequences.

This paper investigates three controversies involving potential causes and consequences of information bias in case and death definitions during the coronavirus disease (COVID-19) pandemic. First, evidence suggests China's surveillance data were biased and misinterpreted by the World Health Organization (WHO), prompting the WHO to advise nations to copy China's lockdowns. China appeared to use narrow diagnostic definitions that undercounted cases and deaths. Second, novel genomic data disseminated during the pandemic without adequate guidance from rigorous epidemiologic studies biased infection control policies in many countries. A novel genomic sequence of a virus is insufficient to declare new cases of a novel disease. Third, media reports of COVID-19 surveillance data in many nations appeared to be biased. Broadened surveillance definitions captured additional information, but unadjusted surveillance data disseminated to the public are not true cases and deaths. Recommendations include clarification of the proper use of diagnostic and surveillance case and death definitions to avoid information bias.

Anaphylaxis: Revision of the Brighton collaboration case definition.

The Brighton Collaboration (BC) has formulated a number of case definitions which have primarily been applied to adverse events of special interest in the context of vaccine safety surveillance. This is a revision of the 2007 BC case definition for anaphylaxis. Recently, the BC definition has been widely used for evaluating reports of suspected anaphylaxis following COVID-19 vaccination. This has led to debate about the performance of the BC definition in comparison with those from the US National Institute of Allergy and Infectious Disease/Food Allergy Anaphylaxis Network (NIAID/FAAN) and the World Allergy Organization (WAO). BC convened an expert working group to revise the case definition based on their usual process of literature review and expert consensus. This manuscript presents the outcome of this process and proposes a revised case definition for anaphylaxis. Major and minor criteria have been re-evaluated with an emphasis on the reporting of observable clinical signs, rather than subjective symptoms, and a clearer approach to the ascertainment of levels of certainty is provided. The BC case definition has also been aligned with other contemporary and international case definitions for anaphylaxis.

ME/CFS and Post-Exertional Malaise among Patients with Long COVID.

This study sought to ascertain the prevalence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) among a sample of 465 patients with Long COVID. The participants completed three questionnaires: (1) a new questionnaire measuring both the frequency and severity of 38 common symptoms of COVID and Long COVID, (2) a validated short form questionnaire assessing ME/CFS, and (3) a validated questionnaire measuring post-exertional malaise. The population was predominantly white, female, and living in North America. The mean duration since the onset of COVID-19 symptoms was 70.5 weeks. Among the 465 participants, 58% met a ME/CFS case definition. Of respondents who reported that they had ME/CFS only 71% met criteria for ME/CFS and of those who did not report they had ME/CFS, 40% nevertheless did meet criteria for the disease: both over-diagnosis and under-diagnosis were evident on self-report. This study supports prior findings that ME/CFS occurs with high prevalence among those who have persistent COVID-19 symptoms.

Anosmia: Brighton Collaboration case definition and guidelines for data collection, analysis, and presentation of immunization safety data.

This is a Brighton Collaboration case definition of anosmia to be used in the evaluation of adverse events following immunization, and for epidemiologic studies for the assessment of background incidence or hypothesis testing. The case definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of SARS-CoV-2 vaccines. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by two expert reviewers prior to submission.

Thrombosis and thromboembolism: Brighton collaboration case definition and guidelines for data collection, analysis, and presentation of immunization safety data.

This is a Brighton Collaboration case definition of thrombosis and thromboembolism to be used in the evaluation of adverse events following immunization, and for epidemiologic studies for the assessment of background incidence or hypothesis testing. The case definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of SARS-CoV-2 vaccines. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected expert reviewers prior to submission.

Using EHR data to identify coronavirus infections in hospitalized patients: Impact of case definitions on disease surveillance.

PURPOSE: To evaluate the number, characteristics, and outcomes of patients identified hospitalized with coronavirus disease 2019 (COVID-19) using two different case definitions. PROCEDURES: Electronic Health Record data were evaluated from patients hospitalized with COVID-19 through May 2020 at 52 health systems across the United States. Characteristics of inpatients with positive laboratory tests for SARS-CoV-2 were compared with those with clinical diagnosis of COVID-19 but without a confirmatory lab result. FINDINGS: Of 14,371 inpatients with COVID-19, 6623 (46.1 %) had a positive laboratory result, and n = 7748 (52.9 %) had only a clinical diagnosis of COVID-19. Compared with clinically diagnosed cases, those with laboratory-confirmed COVID were similar in age and sex, but differed by race, ethnicity, and insurance status. Laboratory-confirmed cases were more likely to receive certain COVID-19 therapies including hydroxychloroquine, anti-IL6 agents and antivirals (p < 0.001). Those with laboratory-confirmed COVID-19 had lower rates of most complications such as myocardial infarction, but higher overall mortality (p < 0.001). CONCLUSION: We observed a two-fold difference in the number of patients hospitalized with COVID-19 depending on whether the case definition required laboratory confirmation. Variations in case definitions also led to differences in cohort characteristics, treatments, and outcomes.

Data innovation in response to COVID-19 in Somalia: application of a syndromic case definition and rapid mortality assessment method.

BACKGROUND: During the COVID-19 pandemic, the importance of reliable public health data has been highlighted, as well as the multiple challenges in collecting it, especially in low income and conflict-affected countries. Somalia reported its first confirmed case of COVID-19 on 16 March 2020 and has experienced fluctuating infection levels since then. OBJECTIVES: To monitor the impact of COVID-19 on beneficiaries of a long-term cash transfer programme in Somalia and assess the utility of a syndromic score case definition and rapid mortality surveillance tool. METHODS: Five rounds of telephone interviews were conducted from June 2020 - April 2021 with 1,046-1,565 households participating in a cash transfer programme. The incidence of COVID-19 symptoms and all-cause mortality were recorded. Carers of the deceased were interviewed a second time using a rapid verbal autopsy questionnaire to determine symptoms preceding death. Data were recorded on mobile devices and analysed using COVID Rapid Mortality Surveillance (CRMS) software and R. RESULTS: The syndromic score case definition identified suspected symptomatic cases that were initially confined to urban areas but then spread widely throughout Somalia. During the first wave, the peak syndromic case rate (311 cases/million people/day) was 159 times higher than the average laboratory confirmed case rate reported by WHO for the same period. Suspected COVID-19 deaths peaked at 14.3 deaths/million people/day, several weeks after the syndromic case rate. Crude and under-five death rates did not cross the respective emergency humanitarian thresholds (1 and 2 deaths/10,000 people/day). CONCLUSION: Use of telephone interviews to collect data on the evolution of COVID-19 outbreaks is a useful additional approach that can complement laboratory testing and mortality data from the health system. Further work to validate the syndromic score case definition and CRMS is justified.

Myocarditis and pericarditis: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data.

Myocarditis and/or pericarditis (also known as myopericarditis) are inflammatory diseases involving the myocardium (with non-ischemic myocyte necrosis) and/or the pericardial sac. Myocarditis/pericarditis (MPC) may present with variable clinical signs, symptoms, etiologies and outcomes, including acute heart failure, sudden death, and chronic dilated cardiomyopathy. Possible undiagnosed and/or subclinical acute myocarditis, with undefined potential for delayed manifestations, presents further challenges for diagnosing an acute disease and may go undetected in the setting of infection as well as adverse drug/vaccine reactions. The most common causes of MPC are viral, with non-infectious, drug/vaccine associated hypersensitivity and/or autoimmune causes being less well defined and with potentially different inflammatory mechanisms and treatment responses. Potential cardiac adverse events following immunization (AEFIs) encompass a larger scope of diagnoses such as triggering or exacerbating ischemic cardiac events, cardiomyopathy with potential heart failure, arrhythmias and sudden death. The current published experience does not support a potential causal association with vaccines based on epidemiologic evidence of relative risk increases compared with background unvaccinated incidence. The only evidence supporting a possible causal association of MPC with a vaccine comes from case reports. Hypersensitivity MPC as a drug/vaccine induced cardiac adverse event has long been a concern for post-licensure safety surveillance, as well as safety data submission for licensure. Other cardiac adverse events, such as dilated cardiomyopathy, were also defined in the CDC definitions for adverse events after smallpox vaccination in 2006. In addition, several groups have attempted to develop and improve the definition and adjudication of post-vaccination cardiovascular events. We developed the current case definitions for myocarditis and pericarditis as an AEFI building on experience and lessons learnt, as well as a comprehensive literature review. Considerations of other etiologies and causal relationships are outside the scope of this document.

Reports of anaphylaxis after coronavirus disease 2019 vaccination, South Korea, 26 February to 30 April 2021.

The South Korea mass vaccination programme administered 3.8 million doses of COVID-19 vaccinations between 26 February and 30 April 2021. After 173 suspected anaphylaxis reports to the nationwide monitoring system for adverse events following immunisation, 44 anaphylaxis cases were confirmed using Brighton Collaboration case definitions. The rates per million doses were 18.2 cases and 6.2 cases for Vaxzevria and Comirnaty, respectively. Median time of onset was 14 min after vaccination and most cases had recovered at the time of review.

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study.

BACKGROUND: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. METHODS: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. RESULTS: 'Typical' symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. INTERPRETATION: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men.

Multisystem inflammatory syndrome in children and adults (MIS-C/A): Case definition & guidelines for data collection, analysis, and presentation of immunization safety data.

This is a Brighton Collaboration Case Definition of the term "Multisystem Inflammatory Syndrome in Children and Adults (MIS-C/A)" to be utilized in the evaluation of adverse events following immunization. The case definition was developed by topic experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2. The format of the Brighton Collaboration was followed, including an exhaustive review of the literature, to develop a consensus definition and defined levels of certainty. The document underwent peer review by the Brighton Collaboration Network and by selected expert external reviewers prior to submission. The comments of the reviewers were taken into consideration and edits incorporated into this final manuscript.

Vaccine-associated enhanced disease: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data.

This is a Brighton Collaboration Case Definition of the term "Vaccine Associated Enhanced Disease" to be utilized in the evaluation of adverse events following immunization. The Case Definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2 vaccines and other emerging pathogens. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected Expert Reviewers prior to submission.

Acute respiratory distress syndrome (ARDS) as an adverse event following immunization: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data.

This is a Brighton Collaboration Case Definition of the term "Acute Respiratory Distress Syndrome - ARDS" to be utilized in the evaluation of adverse events following immunization. The Case Definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2 vaccines and other emerging pathogens. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected Expert Reviewers prior to submission. The comments of the reviewers were taken into consideration and edits incorporated in this final manuscript.

Asymptomatic SARS Coronavirus 2 infection: Invisible yet invincible.

While successful containment measures of COVID-19 in China and many European countries have led to flattened curves, case numbers are rising dramatically in other countries, with the emergence of a second wave expected. Asymptomatic individuals carrying SARS-CoV-2 are hidden drivers of the pandemic, and infectivity studies confirm the existence of transmission by asymptomatic individuals. The data addressed here show that characteristics of asymptomatic and presymptomatic infection are not identical. Younger age correlates strongly with asymptomatic and mild infections and children as hidden drivers. The estimated proportion of asymptomatic infections ranges from 18% to 81%. The current perception of asymptomatic infections does not provide clear guidance for public-health measures. Asymptomatic infections will be a key contributor in the spread of COVID-19. Asymptomatic cases should be reported in official COVID-19 statistics.

COVID-19 symptoms at hospital admission vary with age and sex: ISARIC multinational study.

BACKGROUND: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. METHODS: International, prospective observational study of 60,109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. RESULTS: 'Typical' symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80%, 79%, 69%; at least one 95%). They were reported less frequently in children (≤18 years: 69%, 48%, 23%; 85%), older adults (≥70 years: 61%, 62%, 65%; 90%), and women (66%, 66%, 64%; 90%; vs men 71%, 70%, 67%; 93%). The most common atypical presentation under 60 years of age was nausea and vomiting, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. INTERPRETATION: Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men.

Serological survey following SARS-COV-2 outbreaks at long-term care facilities in metro Vancouver, British Columbia: Implications for outbreak management and infection control policies.

A cross-sectional serological survey was carried out in two long-term care facilities that experienced COVID-19 outbreaks in order to evaluate current clinical COVID-19 case definitions. Among individuals with a negative or no previous COVID-19 diagnostic test, myalgias, headache, and loss of appetite were associated with serological reactivity. The US CDC probable case definition was also associated with seropositivity. Public health and infection control practitioners should consider these findings for case exclusion in outbreak settings.

Death tolls of COVID-19: Where come the fallacies and ways to make them more accurate.

The death toll of the coronavirus disease 2019 (COVID-19) sparked much controversy since its advent in December 2019. Underestimation because of under testing and deaths happening outside the hospitals were important causes. Bold revisions of the diagnostic criteria leading to dramatic changes in death tolls by different governments were observed in attempts to generate more accurate estimates. On the other hand, the influence, censorship and manipulation on case and death data from top political leaders of some countries could create important impacts on the death toll. Baseline mortality data of previous years may help make more accurate estimates of the actual death toll. The pitfalls and strategies during such processes could become valuable lessons to leaders and policymakers worldwide as more accurate statistics serve to navigate policies to combat this pandemic in the days and months to come.

COVID-19, Australia: Epidemiology Report 9 (Reporting week to 23:59 AEDT 29 March 2020).

This is the ninth epidemiological report for coronavirus disease 2019 (COVID-19), reported in Australia as at 23:59 Australian Eastern Daylight Time [AEDT] 29 March 2020. It includes data on COVID-19 cases diagnosed in Australia, the international situation and a review of current evidence.