Acute coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is characterized by diverse clinical presentations, ranging from asymptomatic infection to fatal respiratory failure, and often associated with varied longer-term sequelae. Over the past 18 months, it has become apparent that inappropriate immune responses contribute to the pathogenesis of severe COVID-19. Researchers working at the intersection of COVID-19 and autoimmunity recently gathered at an American Autoimmune Related Disease Association (AARDA) Noel R. Rose Colloquium to address the current state of knowledge regarding two important questions: Does established autoimmunity predispose to severe COVID-19? And, at the same time, can SARS-CoV-2 infection trigger de novo autoimmunity? Indeed, work to date has demonstrated that 10 to 15% of patients with critical COVID-19 pneumonia exhibit autoantibodies against type I interferons, suggesting that preexisting autoimmunity underlies severe disease in some patients. Other studies have identified functional autoantibodies following infection with SARS-CoV-2, such as those that promote thrombosis or antagonize cytokine signaling. These autoantibodies may arise from a predominantly extrafollicular B cell response that is more prone to generating autoantibody-secreting B cells. This review highlights the current understanding, evolving concepts, and unanswered questions provided by this unique opportunity to determine mechanisms by which a viral infection can be exacerbated by, and even trigger, autoimmunity. The potential role of autoimmunity in post-acute sequelae of COVID-19 is also discussed.

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The intersection of COVID-19 and autoimmunity.

https://academic.oup.com/jamia/advance-article-pdf/doi/10.1093/jamia/ocab264/41364439/ocab264.pdf

The Mass General Brigham Biobank Portal: an i2b2-based data repository linking disparate and high-dimensional patient data to support multimodal analytics.

Central nervous system outcomes of COVID-19.

Introduction Our community-based participatory research partnership aims to expand understanding of the social, ethical and behavioural implications of COVID-19 testing and vaccination to inform the development of an integrated intervention that harnesses community-based peer navigation and mHealth strategies to improve COVID-19 testing and vaccination; test the intervention; and develop and disseminate practice, research and policy recommendations to further increase COVID-19 testing and vaccination among Spanish-speaking Latine communities in the USA. Methods and analysis We will conduct 50 individual in-depth interviews with health providers, who have conducted COVID-19 testing and/or vaccination activities within Spanish-speaking communities, and with representatives from Latine-serving community-based organisations. We will also conduct six focus groups with 8–12 Spanish-speaking Latine community member participants each for a total number of about 60 focus group participants. Next, we will develop the Nuestra Comunidad Saludable intervention based on findings from interviews and focus groups and use a longitudinal group-randomised trial design with two arms (intervention and delayed intervention) to evaluate the impact of the intervention. We will recruit, enrol and collect baseline data from 20 community-based peer navigators (Navegantes) and their social network members (n=8 unique social network members per Navegante). Navegantes (coupled with their social networks) will be randomised to intervention or delayed intervention groups (10 Navegantes and 80 social network members per group). Ethics and dissemination Ethical approval for data collection was granted by the Wake Forest University School of Medicine Institutional Review Board. Following the description of study procedures, we will obtain consent from all study participants. Study findings will be disseminated through an empowerment theory-based community forum, peer-reviewed publications and presentations at scientific meetings, and reports and briefs for lay, community and practitioner audiences. Trial registration number NCT05302908.

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Increasing COVID-19 testing and vaccination among Spanish speakers in the USA: protocol for the development and evaluation of the Nuestra Comunidad Saludable intervention using a group-randomised trial design

The coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus has affected over 170 million people, and caused over 3.5 million deaths throughout the world as of May 2021. Although over 150 million people around the world have recovered from this disease, the long term effects of the disease are still under study. A year after the start of the pandemic, data from COVID-19 recovered patients shows multiple organs affected with a broad spectrum of manifestations. Long term effects of SARS-CoV-2 infection includes fatigue, chest pain, cellular damage, and robust innate immune response with inflammatory cytokine production. More clinical studies and clinical trials are needed to not only document, but also to understand and determine the factors that predispose certain people to the long term side effects of his infection. In this manuscript, our goal was to explore the multidimensional landscape of infected lung tissue microenvironment to better understand complex interactions between SARS-CoV-2 viral infection, immune response and the lungs microbiome of COVID-19 patients. Each sample was analyzed with several machine learning tools allowing simultaneous detection and quantification of viral RNA amount at genome and gene level; human gene expression and fractions of major types of immune cells, as well as metagenomic analysis of bacterial and viral abundance. To contrast and compare specific viral response to SARS-COV-2 we have analyzed deep sequencing data from additional cohort of patients infected with NL63 strain of corona virus. Our correlation analysis of three types of measurements in patients i.e. fraction of viral RNA (at genome and gene level), Human RNA (transcripts and gene level) and bacterial RNA (metagenomic analysis), showed significant correlation between viral load as well as level of specific viral gene expression with the fractions of immune cells present in lung lavage as well as with abundance of major fractions of lung microbiome in COVID-19 patients. Our exploratory study has provided novel insights into complex regulatory signaling interactions and correlative patterns between the viral infection, inhibition of innate and adaptive immune response as well as microbiome landscape of the lung tissue. These initial findings could provide better understanding of the diverse dynamics of immune response and the side effects of the SARS-CoV-2 infection.

https://www.biorxiv.org/content/biorxiv/early/2021/05/30/2021.05.28.446250.full.pdf

Computational genomic analysis of the lung tissue microenvironment in COVID-19 patients

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.

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Alyssa Asaro

Papers

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design