Contraceptive Access and Use Among Undergraduate and Graduate Students During COVID-19: Online Survey Study.

BACKGROUND: The COVID-19 pandemic led to widespread college campus closures in the months of March to June 2020, endangering students' access to on-campus health resources, including reproductive health services. OBJECTIVE: To assess contraceptive access and use among undergraduate and graduate students in North Carolina during the COVID-19 pandemic. METHODS: We conducted a cross-sectional web-based survey of undergraduate and graduate students enrolled at degree-granting institutions in North Carolina. Participants were recruited using targeted Instagram advertisements. The survey queried several aspects of participants' sexual behavior, including sex drive, level of sexual experience, number of sexual partners, digital sexual experience, dating patterns, and types of contraception used. Participants were asked to compare many of these behaviors before and after the pandemic. The survey also assessed several sociodemographic factors that we hypothesized would be associated with contraceptive use based on prior data, including educational background, sexual orientation and gender minority status (ie, lesbian, gay, bisexual, transgender, queer), health insurance status, race, ethnicity, degree of sensation seeking, religiosity, and desire to become pregnant. RESULTS: Over 10 days, 2035 Instagram users began our survey, of whom 1002 met eligibility criteria. Of these 1002 eligible participants, 934 completed the survey, for a 93% completion rate. Our respondents were mostly female (665/934, 71%), cisgender (877/934, 94%), heterosexual (592/934, 64%), white (695/934 75%), not Hispanic (835/934, 89%), and enrolled at a 4-year college (618/934, 66%). Over 95% (895/934) of respondents reported that they maintained access to their preferred contraception during the COVID-19 pandemic. In a multivariable analysis, participants who were enrolled in a 4-year college or graduate program were less likely to lose contraceptive access when compared to participants enrolled in a 2-year college (risk ratio [RR] 0.34, 95% CI 0.16-0.71); in addition, when compared to cisgender participants, nonbinary and transgender participants were more likely to lose contraceptive access (RR 2.43, 95% CI 1.01-5.87). Respondents reported that they were more interested in using telehealth to access contraception during the pandemic. The contraceptive methods most commonly used by our participants were, in order, condoms (331/934, 35.4%), oral contraception (303/934, 32.4%), and long-acting reversible contraception (LARC; 221/934, 23.7%). The rate of LARC use among our participants was higher than the national average for this age group (14%). Emergency contraception was uncommonly used (25/934, 2.7%). CONCLUSIONS: Undergraduate and graduate students in North Carolina overwhelmingly reported that they maintained access to their preferred contraceptive methods during the COVID-19 pandemic and through changing patterns of health care access, including telehealth. Gender nonbinary and transgender students and 2-year college students may have been at greater risk of losing access to contraception during the first year of the COVID-19 pandemic.

High throughput screening for drugs that inhibit 3C-like protease in SARS-CoV-2.

The SARS coronavirus 2 (SARS-CoV-2) pandemic remains a major problem in many parts of the world and infection rates remain at extremely high levels. This high prevalence drives the continued emergence of new variants, and possibly ones that are more vaccine-resistant and that can drive infections even in highly vaccinated populations. The high rate of variant evolution makes clear the need for new therapeutics that can be clinically applied to minimize or eliminate the effects of COVID-19. With a hurdle of 10 years, on average, for first in class small molecule therapeutics to achieve FDA approval, the fastest way to identify therapeutics is by drug repurposing. To this end, we developed a high throughput cell-based screen that incorporates the essential viral 3C-like protease and its peptide cleavage site into a luciferase complementation assay to evaluate the efficacy of known drugs encompassing approximately 15,000 clinical-stage or FDA-approved small molecules. Confirmed inhibitors were also tested to determine their cytotoxic properties. Medicinal chemistry efforts to optimize the hits identified Tranilast as a potential lead. Here, we report the rapid screening and identification of potentially relevant drugs that exhibit selective inhibition of the SARS-CoV-2 viral 3C-like protease.

Cross-sectional Survey Examining Patient Attitudes and Preferences for Rescheduling Screening Colonoscopies Canceled due to the COVID-19 Pandemic.

Background. Early in the COVID-19 pandemic colonoscopies for colorectal cancer (CRC) screening were canceled. Patient perceptions of the benefits and risks of routine screening relative to health concerns associated with the COVID-19 pandemic were unknown. Purpose. Assess patient anxiety, worry, and interest in CRC screening during the COVID-19 pandemic. Methods. A random sample of 200 patients aged 45 to 75 y with colonoscopy cancellation due to COVID-19 in March to May 2020 were surveyed. Anxiety, COVID-19 and CRC risk perceptions, COVID-19 and CRC worry, likelihood of following through with colonoscopy in the next month, and interest in alternatives to colonoscopy were assessed. Subsequent screening was tracked for 12 mo. Results. Respondents (N = 127/200, 63.5%) were on average 60 y old, female (59%), college educated (62% college degree or more), and White (91%). A substantial portion of patients (46%) stated they may not follow through with a colonoscopy in the next month. There was greater interest in stool-based testing than in delaying screening (48% v. 26%). Women, older patients, and patients indicating tolerance of uncertainty due to complexity reported they were less likely to follow through with colonoscopy in the next month. Greater interest in stool-based testing was related to lower perceptions of CRC risk. Greater interest in delaying screening was related to less worry about CRC and less tolerance of risk. Over 12 mo, 60% of participants completed screening. Patients who stated they were more likely to screen in the next month were more likely to complete CRC screening (P = 0.01). Conclusions. Respondents who had a colonoscopy canceled during the COVID-19 pandemic varied in interest in rescheduling the procedure. A shared decision-making approach may help patients address varying concerns and select the best approach to screening for them. Highlights: In the wake of the first wave of the COVID-19 pandemic, almost half of patients stated they were not likely to follow through with a colonoscopy in the short term, about half were interested in screening with a stool-based test, and only one-quarter were interested in delaying screening until next year.Patients who perceived themselves at higher risk of colorectal cancer were less interested in stool-based testing, and patients who were more worried about colorectal cancer were less interested in delaying screening.A shared decision-making approach may be necessary to tailor screening discussions for patients during subsequent waves of the pandemic, other occasions where resources are limited and patient preferences vary, or where patients hold conflicting views of screening.

Political polarization drives online conversations about COVID-19 in the United States.

Since the outbreak in China in late 2019, the novel coronavirus (COVID-19) has spread around the world and has come to dominate online conversations. By linking 2.3 million Twitter users to locations within the United States, we study in aggregate how political characteristics of the locations affect the evolution of online discussions about COVID-19. We show that COVID-19 chatter in the United States is largely shaped by political polarization. Partisanship correlates with sentiment toward government measures and the tendency to share health and prevention messaging. Cross-ideological interactions are modulated by user segregation and polarized network structure. We also observe a correlation between user engagement with topics related to public health and the varying impact of the disease outbreak in different U.S. states. These findings may help inform policies both online and offline. Decision-makers may calibrate their use of online platforms to measure the effectiveness of public health campaigns, and to monitor the reception of national and state-level policies, by tracking in real-time discussions in a highly polarized social media ecosystem.

Charting the Information and Misinformation Landscape to Characterize Misinfodemics on Social Media: COVID-19 Infodemiology Study at a Planetary Scale.

BACKGROUND: The novel coronavirus, also known as SARS-CoV-2, has come to define much of our lives since the beginning of 2020. During this time, countries around the world imposed lockdowns and social distancing measures. The physical movements of people ground to a halt, while their online interactions increased as they turned to engaging with each other virtually. As the means of communication shifted online, information consumption also shifted online. Governing authorities and health agencies have intentionally shifted their focus to use social media and online platforms to spread factual and timely information. However, this has also opened the gate for misinformation, contributing to and accelerating the phenomenon of misinfodemics. OBJECTIVE: We carried out an analysis of Twitter discourse on over 1 billion tweets related to COVID-19 over a year to identify and investigate prevalent misinformation narratives and trends. We also aimed to describe the Twitter audience that is more susceptible to health-related misinformation and the network mechanisms driving misinfodemics. METHODS: We leveraged a data set that we collected and made public, which contained over 1 billion tweets related to COVID-19 between January 2020 and April 2021. We created a subset of this larger data set by isolating tweets that included URLs with domains that had been identified by Media Bias/Fact Check as being prone to questionable and misinformation content. By leveraging clustering and topic modeling techniques, we identified major narratives, including health misinformation and conspiracies, which were present within this subset of tweets. RESULTS: Our focus was on a subset of 12,689,165 tweets that we determined were representative of COVID-19 misinformation narratives in our full data set. When analyzing tweets that shared content from domains known to be questionable or that promoted misinformation, we found that a few key misinformation narratives emerged about hydroxychloroquine and alternative medicines, US officials and governing agencies, and COVID-19 prevention measures. We further analyzed the misinformation retweet network and found that users who shared both questionable and conspiracy-related content were clustered more closely in the network than others, supporting the hypothesis that echo chambers can contribute to the spread of health misinfodemics. CONCLUSIONS: We presented a summary and analysis of the major misinformation discourse surrounding COVID-19 and those who promoted and engaged with it. While misinformation is not limited to social media platforms, we hope that our insights, particularly pertaining to health-related emergencies, will help pave the way for computational infodemiology to inform health surveillance and interventions.

Identification of potent small molecule inhibitors of SARS-CoV-2 entry.

The severe acute respiratory syndrome coronavirus 2 responsible for COVID-19 remains a persistent threat to mankind, especially for the immunocompromised and elderly for which the vaccine may have limited effectiveness. Entry of SARS-CoV-2 requires a high affinity interaction of the viral spike protein with the cellular receptor angiotensin-converting enzyme 2. Novel mutations on the spike protein correlate with the high transmissibility of new variants of SARS-CoV-2, highlighting the need for small molecule inhibitors of virus entry into target cells. We report the identification of such inhibitors through a robust high-throughput screen testing 15,000 small molecules from unique libraries. Several leads were validated in a suite of mechanistic assays, including whole cell SARS-CoV-2 infectivity assays. The main lead compound, calpeptin, was further characterized using SARS-CoV-1 and the novel SARS-CoV-2 variant entry assays, SARS-CoV-2 protease assays and molecular docking. This study reveals calpeptin as a potent and specific inhibitor of SARS-CoV-2 and some variants.

Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19.

COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of coronaviruses with no close human analogs. PF-00835231, a 3CL protease inhibitor, has exhibited potent in vitro antiviral activity against SARS-CoV-2 as a single agent. Here we report, the design and characterization of a phosphate prodrug PF-07304814 to enable the delivery and projected sustained systemic exposure in human of PF-00835231 to inhibit coronavirus family 3CL protease activity with selectivity over human host protease targets. Furthermore, we show that PF-00835231 has additive/synergistic activity in combination with remdesivir. We present the ADME, safety, in vitro, and in vivo antiviral activity data that supports the clinical evaluation of PF-07304814 as a potential COVID-19 treatment.

"I'm Being Forced to Make Decisions I Have Never Had to Make Before": Oncologists' Experiences of Caring for Seriously Ill Persons With Poor Prognoses and the Dilemmas Created by COVID-19.

PURPOSE: The COVID-19 pandemic has created a new set of problems for clinicians. This study examines the experiences of oncologists providing care to seriously ill persons near the end of life in the context of the COVID-19 pandemic. METHODS: Between January 2020 and August 2020, we conducted semistructured, in-depth individual interviews with 22 purposefully sampled oncologists from practices enrolled in the Michigan Oncology Quality Consortium. Deidentified transcripts of the interviews were examined using thematic analysis. RESULTS: Our respondents described several novel problems created by the COVID-19 pandemic, including: (1) ethical challenges, (2) the need to manage uncertainty-physically and emotionally-on the part of both patients and oncologists, and (3) the difficulty of integrating technology and communication for seriously ill persons. These problems were made more complex by features of the pandemic: resource scarcity (and the need to fairly allocate poor resources), delays in care, high levels of fear, and the increased importance of advance care planning. Nonabandonment served as a way to cope with increased stress, and the use of telemedicine became an increasingly important medium of communication. CONCLUSION: This study offers an in-depth exploration of the problems faced by oncologists as a result of the COVID-19 pandemic and how they navigated them. Optimal decision making for seriously ill persons with cancer during the COVID-19 pandemic must include open acknowledgment of the ethical challenges involved, the emotions experienced by both patients and their oncologists, and the urgent need to integrate technology with compassionate communication in determining patient preferences.

Political Partisanship and Antiscience Attitudes in Online Discussions About COVID-19: Twitter Content Analysis.

BACKGROUND: The novel coronavirus pandemic continues to ravage communities across the United States. Opinion surveys identified the importance of political ideology in shaping perceptions of the pandemic and compliance with preventive measures. OBJECTIVE: The aim of this study was to measure political partisanship and antiscience attitudes in the discussions about the pandemic on social media, as well as their geographic and temporal distributions. METHODS: We analyzed a large set of tweets from Twitter related to the pandemic, collected between January and May 2020, and developed methods to classify the ideological alignment of users along the moderacy (hardline vs moderate), political (liberal vs conservative), and science (antiscience vs proscience) dimensions. RESULTS: We found a significant correlation in polarized views along the science and political dimensions. Moreover, politically moderate users were more aligned with proscience views, while hardline users were more aligned with antiscience views. Contrary to expectations, we did not find that polarization grew over time; instead, we saw increasing activity by moderate proscience users. We also show that antiscience conservatives in the United States tended to tweet from the southern and northwestern states, while antiscience moderates tended to tweet from the western states. The proportion of antiscience conservatives was found to correlate with COVID-19 cases. CONCLUSIONS: Our findings shed light on the multidimensional nature of polarization and the feasibility of tracking polarized opinions about the pandemic across time and space through social media data.

Drug repurposing screens identify chemical entities for the development of COVID-19 interventions.

The ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. Here, we describe a screening pipeline for the discovery of efficacious SARS-CoV-2 inhibitors. We screen a best-in-class drug repurposing library, ReFRAME, against two high-throughput, high-content imaging infection assays: one using HeLa cells expressing SARS-CoV-2 receptor ACE2 and the other using lung epithelial Calu-3 cells. From nearly 12,000 compounds, we identify 49 (in HeLa-ACE2) and 41 (in Calu-3) compounds capable of selectively inhibiting SARS-CoV-2 replication. Notably, most screen hits are cell-line specific, likely due to different virus entry mechanisms or host cell-specific sensitivities to modulators. Among these promising hits, the antivirals nelfinavir and the parent of prodrug MK-4482 possess desirable in vitro activity, pharmacokinetic and human safety profiles, and both reduce SARS-CoV-2 replication in an orthogonal human differentiated primary cell model. Furthermore, MK-4482 effectively blocks SARS-CoV-2 infection in a hamster model. Overall, we identify direct-acting antivirals as the most promising compounds for drug repurposing, additional compounds that may have value in combination therapies, and tool compounds for identification of viral host cell targets.

High-Throughput Screening for Drugs That Inhibit Papain-Like Protease in SARS-CoV-2.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 has triggered an ongoing global pandemic whereby infection may result in a lethal severe pneumonia-like disease designated as coronavirus disease 2019 (COVID-19). To date, millions of confirmed cases and hundreds of thousands of deaths have been reported worldwide, and there are currently no medical countermeasures available to prevent or treat the disease. The purported development of a vaccine could require at least 1-4 years, while the typical timeline from hit finding to drug registration of an antiviral is >10 years. Thus, repositioning of known drugs can significantly accelerate the development and deployment of therapies for COVID-19. To identify therapeutics that can be repurposed as SARS-CoV-2 antivirals, we developed and initiated a high-throughput cell-based screen that incorporates the essential viral papain-like protease (PLpro) and its peptide cleavage site into a luciferase complementation assay to evaluate the efficacy of known drugs encompassing approximately 15,000 clinical-stage or US Food and Drug Administration (FDA)-approved small molecules. Confirmed inhibitors were also tested to determine their cytotoxic properties. Here, we report the identification of four clinically relevant drugs that exhibit selective inhibition of the SARS-CoV-2 viral PLpro.

#COVID-19: A Public Coronavirus Twitter Dataset Tracking Social Media Discourse about the Pandemic

BACKGROUND: At the time of this writing, the novel coronavirus (COVID-19) pandemic outbreak has already put tremendous strain on many countries' citizens, resources and economies around the world. Social distancing measures, travel bans, self-quarantines, and business closures are changing the very fabric of societies worldwide. With people forced out of public spaces, much conversation about these phenomena now occurs online, e.g., on social media platforms like Twitter. OBJECTIVE: In this paper, we describe a multilingual coronavirus (COVID-19) Twitter dataset that we are making available to the research community via our COVID-19-TweetIDs Github repository. METHODS: We started this ongoing data collection on January 28, 2020, leveraging Twitter's Streaming API and Tweepy to follow certain keywords and accounts that were trending at the time the collection began, and used Twitter's Search API to query for past tweets, resulting in the earliest tweets in our collection dating back to January 21, 2020. RESULTS: Since the inception of our collection, we have actively maintained and updated our Github repository on a weekly basis. We have published over 123 million tweets, with over 60% of the tweets in English. This manuscript also presents basic analysis that shows that Twitter activity responds and reacts to coronavirus-related events. CONCLUSIONS: It is our hope that our contribution will enable the study of online conversation dynamics in the context of a planetary-scale epidemic outbreak of unprecedented proportions and implications. This dataset could also help track scientific coronavirus misinformation and unverified rumors or enable the understanding of fear and panic - and undoubtedly more. CLINICALTRIAL: