Safety, efficacy, and immunogenicity of the NVX-CoV2373 vaccine.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in significant morbidity and mortality worldwide. As SARS-CoV-2 moves into endemic status, vaccination remains a key element in protecting the health of individuals, societies, and economies worldwide. AREAS COVERED: NVX-CoV2373 (Novavax, Gaithersburg, MD) is a recombinant protein vaccine composed of SARS-CoV-2 spike trimer nanoparticles formulated with saponin-based Matrix-M™ adjuvant (Novavax, Gaithersburg, MD). NVX-CoV2373 is authorized for emergency use in adults and adolescents aged ≥12 years in the United States and numerous other countries. EXPERT OPINION: In clinical trials, NVX-CoV2373 showed tolerable reactogenicity and favorable safety profiles characterized by mostly mild-to-moderate adverse events of short duration and by low rates of severe and serious adverse events comparable to those seen with placebo. The two-dose primary vaccination series resulted in robust increases in anti-spike protein immunoglobulin G, neutralizing antibody titers, and cellular immune responses. NVX-CoV2373 vaccination was associated with complete protection against severe disease and a high (90%) rate of protection against symptomatic disease in adults, including symptomatic disease caused by SARS-CoV-2 variants. Additionally, the NVX-CoV2373 adjuvanted recombinant protein platform offers a means to address issues of COVID-19 vaccination hesitancy and global vaccine equity.

Safety of the NVX-CoV2373 COVID-19 vaccine in randomized placebo-controlled clinical trials.

BACKGROUND: NVX-CoV2373 (Nuvaxovid™ or the Novavax COVID-19 Vaccine, Adjuvanted), the first protein-based COVID-19 vaccine, received emergency use authorization (EUA) as a primary series/booster and is available globally. NVX-CoV2373 primary series demonstrated efficacy rates of 89.7-90.4 % and an acceptable safety profile. This article summarizes safety in adult recipients (aged ≥ 18 years) of primary series NVX-CoV2373 in four randomized placebo-controlled trials. METHODS: All participants who received NVX-CoV2373 primary series or placebo (pre-crossover) were included according to actual received treatment. The safety period was from Day 0 (first vaccination) to unblinding/receipt of EUA-approved/crossover vaccine, end of each study (EOS), or last visit date/cutoff date minus 14 days. The analysis reviewed local and systemic solicited adverse events (AEs) within 7 days after NVX-CoV2373 or placebo; unsolicited AEs from after Dose 1 to 28 days after Dose 2; serious AEs (SAEs), deaths, AEs of special interest, and vaccine-related medically attended AEs from Day 0 through end of follow-up (incidence rate per 100 person-years). FINDINGS: Pooled data from 49,950 participants (NVX-CoV2373, n = 30,058; placebo, n = 19,892) were included. Solicited reactions after any dose were more frequent in NVX-CoV2373 recipients (local, 76 %/systemic, 70 %) than placebo recipients (local, 29 %/systemic, 47 %), and were mostly of mild-to-moderate severity. Grade 3+ reactions were infrequent, with greater frequency in NVX-CoV2373 recipients (local, 6.28 %/systemic, 11.36 %) than placebo recipients (local, 0.48 %/systemic, 3.58 %). SAEs and deaths occurred with similarly low frequency in NVX-CoV2373 (SAEs: 0.91 %, deaths: 0.07 %) and placebo recipients (SAEs: 1.0 %, deaths: 0.06 %). INTERPRETATION: To date, NVX-CoV2373 has displayed an acceptable safety profile in healthy adults. FUNDING: Supported by Novavax, Inc.

A study protocol to explore and implement community-based point-of-care COVID-19 testing for women who use drugs in Baltimore, Maryland: The CARE study.

Women who use drugs (WWUD) experience structural vulnerabilities (e.g., housing, food insecurities) and comorbidities that elevate their susceptibility to more severe COVID-19 symptoms or fatality compared to similarly-aged women who do not use illicit drugs. Testing is a cornerstone of effective COVID prevention, however, entrenched barriers to healthcare utilization means that WWUD may have diminished accessing to COVID testing. The CARE (COVID Action Research Engagement) study first examines predisposing and enabling factors that predict COVID testing uptake over six months (baseline, 3-, and 6-month follow-up) among a cohort of WWUD (N = 250) in Baltimore, Maryland, providing a nuanced and holistic understanding of how to meaningfully engage WWUD in COVID testing. Then, point-of-care COVID testing will be implemented on a mobile outreach van affiliated with a local community-based organization primarily serving WWUD; anonymous surveys of mobile outreach guests (N = 100) will assess feasibility and acceptability of this integrated testing. The study is grounded in the Behavioral Model for Vulnerable Populations and the Theoretical Framework of Acceptability. We hypothesize that point-of-care COVID testing integrated into a low-barrier harm reduction service, such as a mobile outreach program, will be an enabling environment for COVID testing uptake in part by reducing structural impediments to testing and will be highly feasible and acceptable to participants. Strengths, limitations, and plans for results dissemination are discussed.

IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2.

Humoral immunity to SARS-CoV-2 can be supplemented with polyclonal sera from convalescent donors or an engineered monoclonal antibody (mAb) product. While pentameric IgM antibodies are responsible for much of convalescent sera's neutralizing capacity, all available mAbs are based on the monomeric IgG antibody subtype. We now show that IgM mAbs derived from immune memory B cell receptors are potent neutralizers of SARS-CoV-2. IgM mAbs outperformed clonally identical IgG antibodies across a range of affinities and SARS-CoV-2 receptor-binding domain epitopes. Strikingly, efficacy against SARS-CoV-2 viral variants was retained for IgM but not for clonally identical IgG. To investigate the biological role for IgM memory in SARS-CoV-2, we also generated IgM mAbs from antigen-experienced IgM+ memory B cells in convalescent donors, identifying a potent neutralizing antibody. Our results highlight the therapeutic potential of IgM mAbs and inform our understanding of the role for IgM memory against a rapidly mutating pathogen.

Exploring the impact of the COVID-19 pandemic on syringe services programs in rural Kentucky.

BACKGROUND: The coronavirus pandemic (COVID-19) exacerbated risks for adverse health consequences among people who inject drugs by reducing access to sterile injection equipment, HIV testing, and syringe services programs (SSPs). Several decades of research demonstrate the public health benefits of SSP implementation; however, existing evidence primarily reflects studies conducted in metropolitan areas and before the COVID-19 pandemic. OBJECTIVES: We aim to explore how the COVID-19 pandemic affected SSP operations in rural Kentucky counties. METHODS: In late 2020, we conducted eighteen in-depth, semi-structured interviews with persons (10 women, 8 men) involved in SSP implementation in rural Kentucky counties. The interview guide broadly explored the barriers and facilitators to SSP implementation in rural communities; participants were also asked to describe how COVID-19 affected SSP operations. RESULTS: Participants emphasized the need to continue providing SSP-related services throughout the pandemic. COVID-19 mitigation strategies (e.g., masking, social distancing, pre-packing sterile injection equipment) limited relationship building between staff and clients and, more broadly, the pandemic adversely affected overall program expansion, momentum building, and coalition building. However, participants offered multiple examples of innovative solutions to the myriad of obstacles the pandemic presented. CONCLUSION: The COVID-19 pandemic impacted SSP operations throughout rural Kentucky. Despite challenges, participants reported that providing SSP services remained paramount. Diverse adaptative strategies were employed to ensure continuation of essential SSP services, demonstrating the commitment and ingenuity of program staff. Given that SSPs are essential for preventing adverse injection drug use-associated health consequences, further resources should be invested in SSP operations to ensure service delivery is not negatively affected by co-occurring crises.

Contextualizing Engagement With Health Information on Facebook: Using the Social Media Content and Context Elicitation Method.

BACKGROUND: Most of what is known regarding health information engagement on social media stems from quantitative methodologies. Public health literature often quantifies engagement by measuring likes, comments, and/or shares of posts within health organizations' Facebook pages. However, this content may not represent the health information (and misinformation) generally available to and consumed by platform users. Furthermore, some individuals may prefer to engage with information without leaving quantifiable digital traces. Mixed methods approaches may provide a way of surpassing the constraints of assessing engagement with health information by using only currently available social media metrics. OBJECTIVE: This study aims to discuss the limitations of current approaches in assessing health information engagement on Facebook and presents the social media content and context elicitation method, a qualitatively driven, mixed methods approach to understanding engagement with health information and how engagement may lead to subsequent actions. METHODS: Data collection, management, and analysis using the social media content and context elicitation method are presented. This method was developed for a broader study exploring how and why US Latinos and Latinas engage with cancer prevention and screening information on Facebook. The study included 20 participants aged between 40 and 75 years without cancer who participated in semistructured, in-depth interviews to discuss their Facebook use and engagement with cancer information on the platform. Participants accessed their Facebook account alongside the researcher, typed cancer in the search bar, and discussed cancer-related posts they engaged with during the previous 12 months. Engagement was defined as liking, commenting, and/or sharing a post; clicking on a post link; reading an article in a post; and/or watching a video within a post. Content engagement prompted questions regarding the reasons for engagement and whether engagement triggered further action. Data were managed using MAXQDA (VERBI GmbH) and analyzed using thematic and content analyses. RESULTS: Data emerging from the social media content and context elicitation method demonstrated that participants mainly engaged with cancer prevention and screening information by viewing and/or reading content (48/66, 73%) without liking, commenting, or sharing it. This method provided rich content regarding how US Latinos and Latinas engage with and act upon cancer prevention and screening information on Facebook. We present 2 emblematic cases from the main study to exemplify the additional information and context elicited from this methodology, which is currently lacking from quantitative approaches. CONCLUSIONS: The social media content and context elicitation method allows a better representation and deeper contextualization of how people engage with and act upon health information and misinformation encountered on social media. This method may be applied to future studies regarding how to best communicate health information on social media, including how these affect assessments of message credibility and accuracy, which can influence health outcomes.

Mental health prior to and during the COVID-19 pandemic in individuals with bipolar disorder: Insights from prospective longitudinal data.

OBJECTIVES: Many studies have examined the impact of COVID-19 on the mental health of the public, but few have focused on individuals with existing severe mental illness with longitudinal data before and during the pandemic. AIMS: To investigate the impact of the COVID-19 pandemic on the mental health of people with bipolar disorder (BD). METHODS: In an ongoing study of people with BD who used an online mood monitoring tool, True Colours, 356 participants provided weekly data on their mental health. Symptoms of depression, mania, insomnia, and suicidal thoughts were compared in 2019 and 2020. From May 2020, participants also provided weekly data on the effect of the COVID-19 pandemic on anxiety, coping strategies, access to care, and medications. RESULTS: On average, symptoms of depression, mania, insomnia, and suicidal thoughts did not significantly differ in 2020 compared to 2019, but there was evidence of heterogeneity. There were high rates of anxiety about the pandemic and its impact on coping strategies, which increased to over 70% of responders in January 2021. A significant proportion of participants reported difficulty accessing routine care (27%) and medications (21%). CONCLUSIONS: Although mood symptoms did not significantly increase during the pandemic overall, we observed heterogeneity among our BD sample and other impacted areas. Individuals' unique histories and psychosocial circumstances are key and should be explored in future qualitative studies. The significant impacts of the pandemic may take time to manifest, particularly among those who are socioeconomically disadvantaged, highlighting the need for further long-term prospective studies.

Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico.

BACKGROUND: NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b-3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America. METHODS: We conducted a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults (≥18 years of age) who had not had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants were randomly assigned in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary objective was to determine vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction-confirmed Covid-19 occurring at least 7 days after the second dose. Vaccine efficacy against moderate-to-severe disease and against different variants was also assessed. RESULTS: Of the 29,949 participants who underwent randomization between December 27, 2020, and February 18, 2021, a total of 29,582 (median age, 47 years; 12.6% ≥65 years of age) received at least one dose: 19,714 received vaccine and 9868 placebo. Over a period of 3 months, 77 cases of Covid-19 were noted - 14 among vaccine recipients and 63 among placebo recipients (vaccine efficacy, 90.4%; 95% confidence interval [CI], 82.9 to 94.6; P<0.001). Ten moderate and 4 severe cases occurred, all in placebo recipients, yielding vaccine efficacy against moderate-to-severe disease of 100% (95% CI, 87.0 to 100). Most sequenced viral genomes (48 of 61, 79%) were variants of concern or interest - largely B.1.1.7 (alpha) (31 of the 35 genomes for variants of concern, 89%). Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7). Reactogenicity was mostly mild to moderate and transient but was more frequent among NVX-CoV2373 recipients than among placebo recipients and was more frequent after the second dose than after the first dose. CONCLUSIONS: NVX-CoV2373 was safe and effective for the prevention of Covid-19. Most breakthrough cases were caused by contemporary variant strains. (Funded by Novavax and others; PREVENT-19 ClinicalTrials.gov number, NCT04611802.).

Under the spotlight: understanding the role of the Chief Medical Officer in a pandemic.

As the COVID-19 pandemic took hold in 2020, Chief Medical Officers (CMOs) entered the public spotlight like never before. Amidst this increased visibility, the role is deeply contested. Much of the disagreement concerns whether CMOs should act independently of the government: while some argue CMOs should act as independent voices who work to shape government policy to protect public health, others stress that CMOs are civil servants whose job is to support the government. The scope and diversity of debates about the CMO role can be explained by its inherently contradictory nature, which requires incumbents to balance their commitments as physicians with their mandates as civil servants who advise and speak on the government's behalf. The long-haul COVID-19 pandemic has further tested the CMO role and has shone light on its varying remits and expectations across different jurisdictions, institutions and contexts. It is perhaps unsurprising, then, that calls to amend the CMO role have emerged in some jurisdictions during the pandemic. However, any discussions about changing the CMO role need a stronger understanding of how different institutional and individual approaches impact what incumbents feel able to do, say and achieve. Based on an ongoing comparative analysis of the position across five countries with Westminster-style political systems, we provide an overview of the CMO role, explain its prominence in a pandemic, examine some debates surrounding the role and discuss a few unanswered empirical questions before describing our ongoing study in greater detail.

Are Huddles the Missing PEACE of the Puzzle in Implementing Clinical Innovation for the Eating Disorder and Autism Comorbidity?

Huddles are brief, time-limited, focused meetings to help organize and support clinical teams. Huddles have demonstrated their value and transferable benefits across a range of settings. Based on their transferable nature, their potential could be unacknowledged as a clinical implementation technique, particularly in specific subgroups of patients with anorexia who need a higher level of care. An innovative clinical pathway aimed at supporting autistic patients with eating disorders (PEACE Pathway) evaluated the use of weekly PEACE huddles for the multidisciplinary team as part of the implementation process across a 12-months period. A total of 283 responses evaluated the huddle as useful on average 84/100. Using content analysis, several perceived benefits were found of the huddles which were in line with the underpinnings of traditional huddles, suggesting that huddles are transferable as implementation techniques, as evidence by a team providing higher-level care for eating disorders.

Drastic times need drastic measures: COVID-19 and widening access to medicine.

In response to COVID-19, schools, colleges and universities across the world have closed or shifted to online/remote or blended teaching, learning and assessment. These changed ways of working pose challenges to students and will likely exacerbate existing educational attainment gaps between different societal groups. Our focus is the potential impact of COVID-19 on widening access to medicine. We provide an account of the process, in the form of comparative cases, of applying for medical school for two applicants from differing backgrounds. Three challenges were identified: family circumstances and support (financial security and parental educational support); staying connected (access to educational material, technology and Wifi); getting the grades and meeting other entry criteria (predicting grades and work experience). We propose that medical schools adopt drastic measures to protect widening access including increasing the use of aptitude tests, contextualised admissions, online multiple mini interviews (MMIs), creative outreach and promotion of alternative means of gaining relevant experience.