Translating IL-6 biology into effective treatments.

In 1973, IL-6 was identified as a soluble factor that is secreted by T cells and is important for antibody production by B cells. Since its discovery more than 40 years ago, the IL-6 pathway has emerged as a pivotal pathway involved in immune regulation in health and dysregulation in many diseases. Targeting of the IL-6 pathway has led to innovative therapeutic approaches for various rheumatic diseases, such as rheumatoid arthritis, juvenile idiopathic arthritis, adult-onset Still's disease, giant cell arteritis and Takayasu arteritis, as well as other conditions such as Castleman disease and cytokine release syndrome. Targeting this pathway has also identified avenues for potential expansion into several other indications, such as uveitis, neuromyelitis optica and, most recently, COVID-19 pneumonia. To mark the tenth anniversary of anti-IL-6 receptor therapy worldwide, we discuss the history of research into IL-6 biology and the development of therapies that target IL-6 signalling, including the successes and challenges and with an emphasis on rheumatic diseases.

Household Transmission of Influenza A Viruses in 2021-2022.

Importance: Influenza virus infections declined globally during the COVID-19 pandemic. Loss of natural immunity from lower rates of influenza infection and documented antigenic changes in circulating viruses may have resulted in increased susceptibility to influenza virus infection during the 2021-2022 influenza season. Objective: To compare the risk of influenza virus infection among household contacts of patients with influenza during the 2021-2022 influenza season with risk of influenza virus infection among household contacts during influenza seasons before the COVID-19 pandemic in the US. Design, Setting, and Participants: This prospective study of influenza transmission enrolled households in 2 states before the COVID-19 pandemic (2017-2020) and in 4 US states during the 2021-2022 influenza season. Primary cases were individuals with the earliest laboratory-confirmed influenza A(H3N2) virus infection in a household. Household contacts were people living with the primary cases who self-collected nasal swabs daily for influenza molecular testing and completed symptom diaries daily for 5 to 10 days after enrollment. Exposures: Household contacts living with a primary case. Main Outcomes and Measures: Relative risk of laboratory-confirmed influenza A(H3N2) virus infection in household contacts during the 2021-2022 season compared with prepandemic seasons. Risk estimates were adjusted for age, vaccination status, frequency of interaction with the primary case, and household density. Subgroup analyses by age, vaccination status, and frequency of interaction with the primary case were also conducted. Results: During the prepandemic seasons, 152 primary cases (median age, 13 years; 3.9% Black; 52.0% female) and 353 household contacts (median age, 33 years; 2.8% Black; 54.1% female) were included and during the 2021-2022 influenza season, 84 primary cases (median age, 10 years; 13.1% Black; 52.4% female) and 186 household contacts (median age, 28.5 years; 14.0% Black; 63.4% female) were included in the analysis. During the prepandemic influenza seasons, 20.1% (71/353) of household contacts were infected with influenza A(H3N2) viruses compared with 50.0% (93/186) of household contacts in 2021-2022. The adjusted relative risk of A(H3N2) virus infection in 2021-2022 was 2.31 (95% CI, 1.86-2.86) compared with prepandemic seasons. Conclusions and Relevance: Among cohorts in 5 US states, there was a significantly increased risk of household transmission of influenza A(H3N2) in 2021-2022 compared with prepandemic seasons. Additional research is needed to understand reasons for this association.

Stroke Mortality Among Black and White Adults Aged ≥35 Years Before and During the COVID-19 Pandemic - United States, 2015-2021.

Stroke is the fifth leading cause of death and a leading cause of long-term disability in the United States (1). Although stroke death rates have declined since the 1950s, age-adjusted rates remained higher among non-Hispanic Black or African American (Black) adults than among non-Hispanic White (White) adults (1,2). Despite intervention efforts to reduce racial disparities in stroke prevention and treatment through reducing stroke risk factors, increasing awareness of stroke symptoms, and improving access to treatment and care for stroke (1,3), Black adults were 45% more likely than were White adults to die from stroke in 2018.* In 2019, age-adjusted stroke death rates (AASDRs) (stroke deaths per 100,000 population) were 101.6 among Black adults and 69.1 among White adults aged ≥35 years. Stroke deaths increased during the early phase of the COVID-19 pandemic (March-August 2020), and minority populations experienced a disproportionate increase (4). The current study examined disparities in stroke mortality between Black and White adults before and during the COVID-19 pandemic. Analysts used National Vital Statistics System (NVSS) mortality data accessed via CDC WONDER† to calculate AASDRs among Black and White adults aged ≥35 years prepandemic (2015-2019) and during the pandemic (2020-2021). Compared with that during the prepandemic period, the absolute difference in AASDR between Black and White adults during the pandemic was 21.7% higher (31.3 per 100,000 versus 38.0). During the pandemic period, an estimated 3,835 excess stroke deaths occurred among Black adults (9.4% more than expected) and 15,125 among White adults (6.9% more than expected). These findings underscore the importance of identifying the major factors contributing to the widened disparities; implementing prevention efforts, including the management and control of hypertension, high blood cholesterol, and diabetes; and developing tailored interventions to reduce disparities and advance health equity in stroke mortality between Black and White adults. Stroke is a serious medical condition that requires emergency care. Warning signs of a stroke include sudden face drooping, arm weakness, and speech difficulty. Immediate notification of Emergency Medical Services by calling 9-1-1 is critical upon recognition of stroke signs and symptoms.

Potential impact of seasonal forcing on a SARS-CoV-2 pandemic.

A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 100,000 confirmed infections and 4000 fatalities (as of 10 March 2020). The outbreak has been declared a pandemic by the WHO on Mar 11, 2020. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterise our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures, and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.

Maternal and perinatal outcomes with COVID-19: A systematic review of 108 pregnancies.

INTRODUCTION: The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has exposed vulnerable populations to an unprecedented global health crisis. The knowledge gained from previous human coronavirus outbreaks suggests that pregnant women and their fetuses are particularly susceptible to poor outcomes. The objective of this study was to summarize the clinical manifestations and maternal and perinatal outcomes of COVID-19 during pregnancy. MATERIAL AND METHODS: We searched databases for all case reports and series from 12 February to 4 April 2020. Multiple terms and combinations were used including COVID-19, pregnancy, maternal mortality, maternal morbidity, complications, clinical manifestations, neonatal morbidity, intrauterine fetal death, neonatal mortality and SARS-CoV-2. Eligibility criteria included peer-reviewed publications written in English or Chinese and quantitative real-time polymerase chain reaction (PCR) or dual fluorescence PCR-confirmed SARS-CoV-2 infection. Unpublished reports, unspecified date and location of the study or suspicion of duplicate reporting, cases with suspected COVID-19 that were not confirmed by a laboratory test, and unreported maternal or perinatal outcomes were excluded. Data on clinical manifestations, maternal and perinatal outcomes including vertical transmission were extracted and analyzed. RESULTS: Eighteen articles reporting data from 108 pregnancies between 8 December 2019 and 1 April 2020 were included in the current study. Most reports described women presenting in the third trimester with fever (68%) and coughing (34%). Lymphocytopenia (59%) with elevated C-reactive protein (70%) was observed and 91% of the women were delivered by cesarean section. Three maternal intensive care unit admissions were noted but no maternal deaths. One neonatal death and one intrauterine death were also reported. CONCLUSIONS: Although the majority of mothers were discharged without any major complications, severe maternal morbidity as a result of COVID-19 and perinatal deaths were reported. Vertical transmission of the COVID-19 could not be ruled out. Careful monitoring of pregnancies with COVID-19 and measures to prevent neonatal infection are warranted.

Assessing the impact of non-pharmaceutical interventions on SARS-CoV-2 transmission in Switzerland.

Following the rapid dissemination of COVID-19 cases in Switzerland, large-scale non-pharmaceutical interventions (NPIs) were implemented by the cantons and the federal government between 28 February and 20 March 2020. Estimates of the impact of these interventions on SARS-CoV-2 transmission are critical for decision making in this and future outbreaks. We here aim to assess the impact of these NPIs on disease transmission by estimating changes in the basic reproduction number (R0) at national and cantonal levels in relation to the timing of these NPIs. We estimated the time-varying R0 nationally and in eleven cantons by fitting a stochastic transmission model explicitly simulating within-hospital dynamics. We used individual-level data from more than 1000 hospitalised patients in Switzerland and public daily reports of hospitalisations and deaths. We estimated the national R0 to be 2.8 (95% confidence interval 2.1–3.8) at the beginning of the epidemic. Starting from around 7 March, we found a strong reduction in time-varying R0 with a 86% median decrease (95% quantile range [QR] 79–90%) to a value of 0.40 (95% QR 0.3–0.58) in the period of 29 March to 5 April. At the cantonal level, R0 decreased over the course of the epidemic between 53% and 92%. Reductions in time-varying R0 were synchronous with changes in mobility patterns as estimated through smartphone activity, which started before the official implementation of NPIs. We inferred that most of the reduction of transmission is attributable to behavioural changes as opposed to natural immunity, the latter accounting for only about 4% of the total reduction in effective transmission. As Switzerland considers relaxing some of the restrictions of social mixing, current estimates of time-varying R0 well below one are promising. However, as of 24 April 2020, at least 96% (95% QR 95.7–96.4%) of the Swiss population remains susceptible to SARS-CoV-2. These results warrant a cautious relaxation of social distance practices and close monitoring of changes in both the basic and effective reproduction numbers.

Covid-19 Surveillance Testing and Resident Outcomes in Nursing Homes.

BACKGROUND: Despite widespread adoption of surveillance testing for coronavirus disease 2019 (Covid-19) among staff members in skilled nursing facilities, evidence is limited regarding its relationship with outcomes among facility residents. METHODS: Using data obtained from 2020 to 2022, we performed a retrospective cohort study of testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among staff members in 13,424 skilled nursing facilities during three pandemic periods: before vaccine approval, before the B.1.1.529 (omicron) variant wave, and during the omicron wave. We assessed staff testing volumes during weeks without Covid-19 cases relative to other skilled nursing facilities in the same county, along with Covid-19 cases and deaths among residents during potential outbreaks (defined as the occurrence of a case after 2 weeks with no cases). We reported adjusted differences in outcomes between high-testing facilities (90th percentile of test volume) and low-testing facilities (10th percentile). The two primary outcomes were the weekly cumulative number of Covid-19 cases and related deaths among residents during potential outbreaks. RESULTS: During the overall study period, 519.7 cases of Covid-19 per 100 potential outbreaks were reported among residents of high-testing facilities as compared with 591.2 cases among residents of low-testing facilities (adjusted difference, -71.5; 95% confidence interval [CI], -91.3 to -51.6). During the same period, 42.7 deaths per 100 potential outbreaks occurred in high-testing facilities as compared with 49.8 deaths in low-testing facilities (adjusted difference, -7.1; 95% CI, -11.0 to -3.2). Before vaccine availability, high- and low-testing facilities had 759.9 cases and 1060.2 cases, respectively, per 100 potential outbreaks (adjusted difference, -300.3; 95% CI, -377.1 to -223.5), along with 125.2 and 166.8 deaths (adjusted difference, -41.6; 95% CI, -57.8 to -25.5). Before the omicron wave, the numbers of cases and deaths were similar in high- and low-testing facilities; during the omicron wave, high-testing facilities had fewer cases among residents, but deaths were similar in the two groups. CONCLUSIONS: Greater surveillance testing of staff members at skilled nursing facilities was associated with clinically meaningful reductions in Covid-19 cases and deaths among residents, particularly before vaccine availability.

COVID-19 in the homeless population: a scoping review and meta-analysis examining differences in prevalence, presentation, vaccine hesitancy and government response in the first year of the pandemic.

AIMS: People experiencing homelessness (PEH) have been identified as being increasingly susceptible to Coronavirus disease (COVID-19), with policies enacted to test, isolate, increase hygiene practices and prioritise vaccines among this population. Here, we conduct a scoping review of the current evidence-base pertaining to the prevalence and presentation of COVID-19 in PEH, COVID-vaccine hesitancy rates and government interventions enacted within the first year of the pandemic for PEH. MATERIALS AND METHODS: A systematic search was conducted on Pubmed, Cochrane, Embase and MedRxiv databases for studies reporting primary data on COVID-19 prevalence and clinical characteristics in PEH, vaccine uptake for PEH and policies enacted targeting PEH. Study qualities were assessed with The National Heart, Lung and Blood Institute's set of Study Quality. RESULTS: Eighty-three studies were included in our final analysis. The overall prevalence of symptomatic COVID-19 infection in PEH is estimated at 35%. The most common symptoms found were cough and shortness of breath, followed by fever. Concerns regarding vaccine hesitancy amongst PEH related to thoroughness of COVID-19 vaccine clinical trials, side effects and mistrust of the government. The main strategies implemented by governments were mass testing, adaption of healthcare service provision, provision of alternative housing, encouraging personal hygiene (hand sanitation and mask wearing), and inter-organisational communication. DISCUSSION: In our meta-analysis, 35% of PEH with a COVID-19 infection presented symptomatically; the low prevalence of symptomatic COVID-19 infection suggests widespread testing following outbreaks would be beneficial for this group of individuals. Temporary recuperation units and measures for housing stability in the pandemic, namely provision of alternative housing and stopping evictions, were found to be highly effective. High rates of vaccine hesitancy means that education and encouragement towards vaccination would be beneficial for this vulnerable population, where comorbidities are common. Finally increased focus in research should be placed on the mental health burden of COVID-19 and the pandemic on PEH moving forwards.

Stress load of Chinese nurses in Fangcang Shelter Hospitals during the COVID-19 pandemic: A latent profile analysis.

The Omicron wave of the COVID-19 pandemic significantly affected Shanghai, China, from March to June 2022. Numbers of Fangcang Shelter Hospitals (FSHs) were conversed from stadiums and exhibition centers to tackle the pandemic. This study aimed to identify the stress load profiles of nurses working in FSHs and explore the characteristics and factors influencing stress load profiles. Totally, 609 out of 700 FSH nurses (with an effective response rate of 87%) participated in an online survey investigating their socio-demographic information, work-related stressors, and stress load. Results of the latent profile analysis identified four classes of stress load, which were labeled as the low (Class 1), mild (Class 2), moderate (Class 3), and high (Class 4) stress load class. Maternity status and self-perceived health condition were significantly different between the four stress load classes by comparisons using the Chi-square test and the Kruskal-Wallis test. The contributors to the stress load profiles were determined by the multinomial logistic regression analysis, including age, education, maternity status, self-perceived health condition, working time in FSHs, and the four dimensions of work-related stressors. Participants who were less healthy (OR = 0.045, 95% CI:0.012,0.171), worked longer time in FSHs (OR = 40.483, 95% CI: 12.103,135.410), faced with more workload (OR = 3.664, 95% CI: 1.047,12.815), and worse working environment (OR = 12.274, 95% CI: 3.029,49.729) were more likely to be classified to the high stress load class. The task arrangement and working environment for FSH nurses should be optimized, and psychological training should be conducted routinely.

icumonitoring.ch: a platform for short-term forecasting of intensive care unit occupancy during the COVID-19 epidemic in Switzerland.

In Switzerland, the COVID-19 epidemic is progressively slowing down owing to “social distancing” measures introduced by the Federal Council on 16 March 2020. However, the gradual ease of these measures may initiate a second epidemic wave, the length and intensity of which are difficult to anticipate. In this context, hospitals must prepare for a potential increase in intensive care unit (ICU) admissions of patients with acute respiratory distress syndrome. Here, we introduce icumonitoring.ch, a platform providing hospital-level projections for ICU occupancy. We combined current data on the number of beds and ventilators with canton-level projections of COVID-19 cases from two S-E-I-R models. We disaggregated epidemic projection in each hospital in Switzerland for the number of COVID-19 cases, hospitalisations, hospitalisations in ICU, and ventilators in use. The platform is updated every 3-4 days and can incorporate projections from other modelling teams to inform decision makers with a range of epidemic scenarios for future hospital occupancy.

Real and/or potential impacts of the Covid-19 pandemic on the mental health in older adults / Impactos reais e/ou potenciais da pandemia de Covid-19 na saúde mental de idosos / Impactos reales y/o potenciales de la pandemia de Covid-19 en la salud mental de los ancianos

A pandemia de COVID-19 e as medidas de controle para conter a disseminação do vírus, como o distanciamento social, trouxeram mudanças à rotina das pessoas, mundialmente. Esse contexto pode gerar impactos adversos para a saúde mental dos indivíduos, especialmente, àqueles em maior vulnerabilidade, os idosos. O objetivo desse estudo foi analisar na literatura os impactos reais e/ou potenciais da pandemia de COVID-19 na saúde mental de idosos. Trata-se de uma revisão integrativa de literatura com buscas realizadas na Biblioteca Virtual em Saúde, que utilizou a seguinte estratégia de busca: (Coronavírus OR "Infecções por Coronavirus" OR "Coronavirus Infections" OR COVID-19) AND (idoso OR elderly OR aged) AND ("Saúde Mental" OR "Mental Health"). Foram critérios de inclusão: artigos acessados na íntegra, sem distinção de ano e idioma, indexados até o dia 11 de novembro de 2020; e os critérios de exclusão: artigos com fuga do escopo da pesquisa, revisões de literatura, arquivos multimídia e duplicados. Foram encontrados 241 registros, e após a aplicação dos critérios de elegibilidade estabelecidos restaram 27 artigos para discussão. Dentre os impactos reais/potenciais da pandemia de COVID-19 na saúde mental dos idosos, abordados nos estudos, destaca-se a ansiedade, depressão, solidão, estresse, sensação de medo ou pânico, tristeza, suicídio/ideação suicida e insônia. Apesar disso, considera-se que há uma quantidade ainda escassa de estudos voltados especificamente para a população idosa que permitam aprofundar as discussões sobre esse tema.

The COVID-19 pandemic and control measures to contain the spread of the virus, such as social detachment, have brought changes to people's routine, worldwide. This context can generate adverse impacts on the mental health of individuals, especially those most vulnerable, the older adults. The aim of this study was to analyze in the literature the real and / or potential impacts of the COVID-19 pandemic on the mental health of the older adults. It is an integrative literature review with searches performed in the Virtual Health Library, which used the following search strategy: (Coronavírus OR "Infecções por Coronavirus" OR "Coronavirus Infections" OR COVID- 19) AND (idoso OR elderly OR aged) AND ("Saúde Mental" OR "Mental Health"). Inclusion criteria were: articles accessed in full, without distinction of year and language, indexed until November 11, 2020; and exclusion criteria: articles with escape the scope of the research, literature reviews, multimedia and duplicate files, 241 records were found, and after applying the established eligibility criteria, 27 articles remained for discussion, among the actual / potential impacts of the COVID-19 pandemic on older people, addressed in the studies, anxiety, depression, loneliness, stress, feeling of fear or panic, sadness, suicide / suicidal ideation and insomnia stand out. Despite this, there is still a small amount studies specifically aimed at the older population that allow further discussions on this topic.

La pandemia de covid-19 y las medidas de control para contener la propagación del virus, como el distanciamiento social, han supuesto cambios en la rutina de las personas en todo el mundo. Este contexto puede generar impactos adversos a la salud mental de los individuos, especialmente a los más vulnerables, los ancianos. El objetivo de este estudio fue analizar en la literatura los impactos reales y/o potenciales de la pandemia de COVID-19 en la salud mental de los ancianos. Se trata de una revisión bibliográfica integradora con búsquedas realizadas en la Biblioteca Virtual de Salud, que utilizó la siguiente estrategia de búsqueda: (Coronavirus OR "Coronavirus Infections" OR "Coronavirus Infections" OR COVID-19) AND (elderly OR aged) AND ("Mental Health" OR "Mental Health"). Los criterios de inclusión fueron: artículos accedidos en su totalidad, independientemente del año y el idioma, indexados hasta el 11 de noviembre de 2020; y los criterios de exclusión: artículos que estuvieran fuera del ámbito de la investigación, revisiones bibliográficas, archivos multimedia y duplicados. Se encontraron un total de 241 registros, y tras aplicar los criterios de elegibilidad establecidos, quedaron 27 artículos para su discusión. Entre los impactos reales/potenciales de la pandemia de COVID-19 en la salud mental de los ancianos, abordados en los estudios, destacan la ansiedad, la depresión, la soledad, el estrés, la sensación de miedo o pánico, la tristeza, la ideación suicida/suicida y el insomnio. A pesar de ello, se considera que todavía hay una escasa cantidad de estudios dirigidos específicamente a la población de edad avanzada que permitan profundizar en las discusiones sobre este tema.

Telework and telerehabilitation programs for workers with a stroke during the COVID-19 pandemic: A commentary.

BACKGROUND: Due to the coronavirus disease 2019 (COVID-19) pandemic, rehabilitation facilities have become less accessible for patients with a stroke. Lack of early, intensive rehabilitation misses the opportunity for recovery during the critical time window of endogenous plasticity and improvement post-stroke. OBJECTIVES: The purpose of this commentary was to highlighting the benefits of telework and telerehabilitation programs for workers with a stroke during the COVID-19 pandemic. METHODS: Relevant publications regarding the management of individuals with a stroke, telerehabilitation and teleworking in the setting of COVID-19 were reviewed. RESULTS: Previous studies showed that telerehabilitation can effectively provide an alternate method of promoting recovery for patients with a stroke. With the physical distancing precautions in place for mitigating viral spread, teleworking can also provide a method for long term recovery and improvements in quality of life after a stroke. CONCLUSIONS: Overall, this commentary addresses the benefits of physically distant, safe and effective alternatives to support individuals who live with a stroke during COVID-19 pandemic.

Severe Acute Respiratory Syndrome Coronavirus 2, COVID-19, and the Renin-Angiotensin System: Pressing Needs and Best Research Practices.

The coronavirus disease 2019 (COVID-19) pandemic is associated with significant morbidity and mortality throughout the world, predominantly due to lung and cardiovascular injury. The virus responsible for COVID-19-severe acute respiratory syndrome coronavirus 2-gains entry into host cells via ACE2 (angiotensin-converting enzyme 2). ACE2 is a primary enzyme within the key counter-regulatory pathway of the renin-angiotensin system (RAS), which acts to oppose the actions of Ang (angiotensin) II by generating Ang-(1-7) to reduce inflammation and fibrosis and mitigate end organ damage. As COVID-19 spans multiple organ systems linked to the cardiovascular system, it is imperative to understand clearly how severe acute respiratory syndrome coronavirus 2 may affect the multifaceted RAS. In addition, recognition of the role of ACE2 and the RAS in COVID-19 has renewed interest in its role in the pathophysiology of cardiovascular disease in general. We provide researchers with a framework of best practices in basic and clinical research to interrogate the RAS using appropriate methodology, especially those who are relatively new to the field. This is crucial, as there are many limitations inherent in investigating the RAS in experimental models and in humans. We discuss sound methodological approaches to quantifying enzyme content and activity (ACE, ACE2), peptides (Ang II, Ang-[1-7]), and receptors (types 1 and 2 Ang II receptors, Mas receptor). Our goal is to ensure appropriate research methodology for investigations of the RAS in patients with severe acute respiratory syndrome coronavirus 2 and COVID-19 to ensure optimal rigor and reproducibility and appropriate interpretation of results from these investigations.