Project description:Vulnerability to coronavirus disease (COVID)-19 varies due to differences in interferon gamma (IFNγ) immunity. We investigated whether a key modifiable interferon precursor, interleukin-18, was related to COVID-19, overall and by severity, using Mendelian randomisation. We used four established genome-wide significant genetic predictors of interleukin-18 applied to the most recent genome-wide association study of COVID-19 (June 2021) to obtain Mendelian randomisation inverse variance weighted estimates by severity, i.e. any (cases = 112 612, non-cases = 2 474 079), hospitalised (cases = 24 274, non-cases = 2 061 529) and very severe (cases = 8779, non-cases = 1 001 875) COVID-19. To be comprehensive, we also conducted an exploratory analysis for IFNγ and two related cytokines with less well-established genetic predictors, i.e. interleukin-12 and interleukin-23. Genetically predicted interleukin-18 was associated with lower risk of any COVID-19 (odds ratio (OR) 0.96 per standard deviation, 95% confidence interval (0.94-0.99, P-value 0.004)) and of very severe COVID-19 (OR 0.88, 95% CI 0.78-0.999, P-value 0.048). Sensitivity analysis and a more liberal genetic instrument selection gave largely similar results. Few genome-wide significant genetic predictors were available for IFNγ, interleukin-12 or interleukin-23, and no associations with COVID-19 were evident. Interleukin-18 could be a modifiable target to prevent COVID-19 and should be further explored in an experimental design.
Project description:Seven years after the Middle East respiratory syndrome (MERS) outbreak, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) made its first appearance in a food market in Wuhan, China, drawing an entirely new course to our lives. As the virus belongs to the same genus of MERS and SARS, researchers have been trying to draw lessons from previous outbreaks to find a potential cure. Although there were five Phase I human vaccine trials against SARS and MERS, the lack of data in humans provided us with limited benchmarks that could help us design a new vaccine for Coronavirus disease 2019 (COVID-19). In this review, we showcase the similarities in structures of virus components between SARS-CoV, MERS-CoV, and SARS-CoV-2 in areas relevant to vaccine design. Using the ClinicalTrials.gov and World Health Organization (WHO) databases, we shed light on the 16 current approved clinical trials worldwide in search for a COVID-19 vaccine. The different vaccine platforms being tested are Bacillus Calmette-Guérin (BCG) vaccines, DNA and RNA-based vaccines, inactivated vaccines, protein subunits, and viral vectors. By thoroughly analyzing different trials and platforms, we also discuss the advantages and disadvantages of using each type of vaccine and how they can contribute to the design of an adequate vaccine for COVID-19. Studying past efforts invested in conducting vaccine trials for MERS and SARS will provide vital insights regarding the best approach to designing an effective vaccine against COVID-19.
Project description:The outbreak of a novel coronavirus (SARS-CoV-2) in Wuhan, China in December 2019 has now become a pandemic with no approved therapeutic agent. At the moment, the genomic structure, characteristics, and pathogenic mechanisms of SARS-CoV-2 have been reported. Based upon this information, several drugs including the directly acting antivirals have been proposed to treat people with coronavirus disease 2019 (COVID-19). This rapid review aims to describe the directly acting antivirals that have been examined for use in the management of COVID-19. Searches were conducted in three electronic databases, supplemented with a search on arXiv, bioRxiv, medRxiv, ChinaXiv, ClinicalTrials.gov, and Chinese Clinical Trial Registry for studies examining the use of antivirals in COVID-19 to identify for case reports, case series, observational studies, and randomized controlled studies describing the use of antivirals in COVID-19. Data were extracted independently and presented narratively. A total of 98 studies were included, comprising of 38 published studies and 60 registered clinical trials. These drugs include the broad spectrum antivirals such as umifenovir, protease inhibitors such as lopinavir/ritonavir as well as the RNA-dependent RNA polymerase inhibitors, remdesivir, and favipiravir. Other drugs that have been used include the nucleosidase inhibitors and polymerase acidic endonuclease inhibitors which are currently approved for prevention of influenza infections. While some of the drugs appear promising in small case series and reports, more clinical trials currently in progress are required to provide higher quality evidence.
Project description:IntroductionThe Coronavirus disease (COVID-19) pandemic has significantly altered the provision of rehabilitation services, especially pulmonary rehabilitation (PR). Our objective was to assess the provision of PR services in Latin America 18 months after the COVID-19 pandemic was declared.MethodsA cross-sectional study that included professionals dedicated to PR in centres in Latin America was applied. Responses to an online questionnaire were collected from May to September 2021. The following data were included for the analysis: demographic data, evaluation strategies, program structure, PR intervention in post-COVID-19 patients, and perception of strategies therapies for the care of post-COVID-19 patients. The questionnaire was distributed in Spanish and Portuguese languages.ResultsResponses were received from 196 PR centres. Exercise tolerance was predominantly measured with the six-minute walk test. Less than 50% of the institutions evaluate quality of life, physical qualities, symptoms, and lung function. Most of the programmes have physiotherapists (90.8%), as well as pulmonologists (60%), and psychologists (35%), among other professionals.ConclusionPR services in Latin America have adapted in their way to the requirements of the pandemic, and most continued to provide face-to-face services. It was identified that the application of the programs is heterogeneous both in evaluations and interventions.
Project description:The impact of COVID-19 anxiety on mental health and its association with preventive measures is well-established. We aimed to study how COVID-19 anxiety and its dimensions vary over time (16 months) in a sample of individuals (N = 2717) suffering from mental distress in the pandemic context that participated in a randomized clinical trial testing psychosocial interventions in Brazil. Results showed that pandemic anxiety reduced over time. COVID-19 influences fear of others being infected and concerns about mental health being affected by COVID-19 were more significant than the fear of being infected or the physical health influenced by COVID-19. A similar temporal effect was not found for burnout, and this effect was not correlated with the number of COVID-related deaths. Habituation to pandemic anxiety or higher intolerance of uncertainty at the beginning of the pandemic is putative mechanisms for the patterns observed in the data. They might have implications for mental health interventions in the pandemic scenario and motivational strategies for prevention. TRIAL REGISTRATION NUMBER: Plataforma Basil (CAAE: 30608420.5.0000.5327), ClinicalTrials.gov (NCT04632082; November 17, 2020).