JHU COVID-19 Publications
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Item US Consumer Experiences with Food Access During Covid-19(NFACT (National Food Access & COVID Research Team), 2020) Robinson, Joelle; Bertmann, Farryl; Harper, Kaitlyn; Biehl, Erin; Neff, RoniItem Experiences of households with new and persistent food insecurity during the first four months of the COVID-19 pandemic(NFACT (National Food Access & COVID Research Team), 2020) Harper, Kaitlyn; Acciai, Francesco; Josephson, Anna; Ohri-Vachaspati, Punam; Belarmino, Emily H.; Niles, Meredith; Robinson, Joelle; Neff, Roni; Bertmann, FarrylItem Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is blocked by factor D inhibition(American Society of Hematology)Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious respiratory virus that can lead to venous/arterial thrombosis, stroke, renal failure, myocardial infarction, thrombocytopenia, and other end-organ damage. Animal models demonstrating end-organ protection in C3-deficient mice and evidence of complement activation in humans have led to the hypothesis that SARS-CoV-2 triggers complement-mediated endothelial damage, but the mechanism is unclear. Here, we demonstrate that the SARS-CoV-2 spike protein (subunit 1 and 2), but not the N protein, directly activates the alternative pathway of complement (APC). Complement-dependent killing using the modified Ham test is blocked by either C5 or factor D inhibition. C3 fragments and C5b-9 are deposited on TF1PIGAnull target cells, and complement factor Bb is increased in the supernatant from spike protein–treated cells. C5 inhibition prevents the accumulation of C5b-9 on cells, but not C3c; however, factor D inhibition prevents both C3c and C5b-9 accumulation. Addition of factor H mitigates the complement attack. In conclusion, SARS-CoV-2 spike proteins convert nonactivator surfaces to activator surfaces by preventing the inactivation of the cell-surface APC convertase. APC activation may explain many of the clinical manifestations (microangiopathy, thrombocytopenia, renal injury, and thrombophilia) of COVID-19 that are also observed in other complement-driven diseases such as atypical hemolytic uremic syndrome and catastrophic antiphospholipid antibody syndrome. C5 inhibition prevents accumulation of C5b-9 in vitro but does not prevent upstream complement activation in response to SARS-CoV-2 spike proteins.Item Characteristics of registered clinical trials assessing treatments for COVID-19: a cross-sectional analysis(BMJ)Objectives -- The coronavirus disease 2019 (COVID-19) pandemic has prompted many initiatives to identify safe and efficacious treatments, yet little is known regarding where early efforts have focused. We aimed to characterise registered clinical trials assessing drugs or plasma treatments for COVID-19. Design, setting and participants Cross-sectional analysis of clinical trials for the treatment of COVID-19 that were registered in the USA or in countries contributing to the WHO’s International Clinical Trials Registry Platform. Relevant trial entries of drugs or plasma were downloaded on 26 March 2020, deduplicated, verified with reviews of major medical journals and WHO websites and independently analysed by two reviewers. Main outcome(s) -- Trial intervention, sponsorship, critical design elements and specified outcomes Results -- Overall, 201 clinical trials were registered for testing the therapeutic benefits of 92 drugs or plasma, including 64 in monotherapy and 28 different combinations. Only eight (8.7%) products or combinations involved new molecular entities. The other test therapies had a wide range of prior medical uses, including as antivirals, antimalarials, immunosuppressants and oncology treatments. In 152 trials (75.7%), patients were randomised to treatment or comparator, including 55 trials with some form of blinding and 97 open-label studies. The 49 (24.4%) of trials without a randomised design included 29 single armed studies and 20 trials with some comparison group. Most trial designs featured multiple endpoints. Clinical endpoints were identified in 134 (66.7%) of trials and included COVID-19 symptoms, death, recovery, required intensive care and hospital discharge. Clinical scales were being used in 33 (16.4%) trials, most often measures of oxygenation and critical illness. Surrogate endpoints or biomarkers were studied in 88 (42.3%) of trials, primarily assays of viral load. Although the trials were initiated in more than 17 countries or regions, 100 (49.8%) were registered in China and 78 (37.8%) in the USA. Registered trials increased rapidly, with the number of registered trials doubling from 1 March to 26 March 2020. Conclusions -- While accelerating morbidity and mortality from the COVID-19 pandemic has been paralleled by early and rapid clinical investigation, many trials lack features to optimise their scientific value. Global coordination and increased funding of high-quality research may help to maximise scientific progress in rapidly discovering safe and effective treatments.Item Use and Content of Primary Care Office-Based vs Telemedicine Care Visits During the COVID-19 Pandemic in the US(American Medical Association (AMA))Importance Little is known about the association between the coronavirus disease 2019 (COVID-19) pandemic and the level and content of primary care delivery in the US. Objective To quantify national changes in the volume, type, and content of primary care delivered during the COVID-19 pandemic, especially with regard to office-based vs telemedicine encounters. Design, Setting, and Participants Analysis of serial cross-sectional data from the IQVIA National Disease and Therapeutic Index, a 2-stage, stratified nationally representative audit of outpatient care in the US from the first calendar quarter (Q1) of 2018 to the second calendar quarter (Q2) of 2020. Main Outcomes and Measures Visit type (office-based or telemedicine), overall and stratified by patient population and geographic region; assessment of blood pressure or cholesterol measurement; and initiation or continuation of prescription medications. Results In the 8 calendar quarters between January 1, 2018, and December 31, 2019, between 122.4 million (95% CI, 117.3-127.5 million) and 130.3 million (95% CI, 124.7-135.9 million) quarterly primary care visits occurred in the US (mean, 125.8 million; 95% CI, 121.7-129.9 million), most of which were office-based (92.9%). In 2020, the total number of encounters decreased to 117.9 million (95% CI, 112.6-123.2 million) in Q1 and 99.3 million (95% CI, 94.9-103.8 million) in Q2, a decrease of 21.4% (27.0 million visits) from the average of Q2 levels during 2018 and 2019. Office-based visits decreased 50.2% (59.1 million visits) in Q2 of 2020 compared with Q2 2018-2019, while telemedicine visits increased from 1.1% of total Q2 2018-2019 visits (1.4 million quarterly visits) to 4.1% in Q1 of 2020 (4.8 million visits) and 35.3% in Q2 of 2020 (35.0 million visits). Decreases occurred in blood pressure level assessment (50.1% decrease, 44.4 million visits) and cholesterol level assessment (36.9% decrease, 10.2 million visits) in Q2 of 2020 compared with Q2 2018-2019 levels, and assessment was less common during telemedicine than during office-based visits (9.6% vs 69.7% for blood pressure; P < .001; 13.5% vs 21.6% for cholesterol; P < .001). New medication visits in Q2 of 2020 decreased by 26.0% (14.1 million visits) from Q2 2018-2019 levels. Telemedicine adoption occurred at similar rates among White individuals and Black individuals (19.3% vs 20.5% of patient visits, respectively, in Q1/Q2 of 2020), varied by region (low of 15.1% of visits [East North Central region], high of 26.8% of visits [Pacific region]), and was not correlated with regional COVID-19 burden. Conclusions and Relevance The COVID-19 pandemic has been associated with changes in the structure of primary care delivery, with the content of telemedicine visits differing from that of office-based encounters.Item Ensuring Access to Medications in the US During the COVID-19 Pandemic(American Medical Association (AMA))Item The United States Postal Service: an Essential Public Health Agency?(Springer Science and Business Media LLC)Item Kidney diseases in the time of COVID-19: major challenges to patient care(American Society for Clinical Investigation)Item The Urgency and Challenge of Opening K-12 Schools in the Fall of 2020(American Medical Association (AMA))Item An Ethics Framework for the COVID-19 Reopening Process(2020-05-27) Bernstein, Justin; Hutler, Brian; Rieder, Travis N.; Faden, Ruth; Han, Hahrie; Barnhill, AnneAs some political leaders are fond of saying, reopening society after months of social distancing is not like flipping a switch. Reopening is a process. It will extend over many, many months. Policy makers will need to continuously re-evaluate whether the guidance they have set for the next stage of reopening still makes sense. Also, for each stage, they will have to decide not only the when, but the how of each reopening decision. When public schools open in the fall, for example, how exactly should that happen? And, at any stage of the reopening process, if cases or hospitalizations exceed a concerning benchmark, decision makers will have to decide which social distancing policies should be re-imposed. This document presents a framework for ethically evaluating the cascade of policy decisions that define the COVID-19 reopening process. These decisions will not and should not be made based on the science alone. Nor should they be driven by the economics alone. Rather, these decisions are best understood as a series of tradeoffs that reflect many shared values in our society, including not only our shared interests in health and economic flourishing, but also our shared interest in other aspects of well-being, and in liberty and justice. These values, and how to think about them in concert, are the subject of ethics. The framework developed here is specifically designed to aid government decision-makers at the state and local levels. Aspects of the framework may also be useful for decision-makers in a variety of private-sector institutions, including manufacturers, retailers, houses of worship, and private schools and universities.