Dual neutralization of influenza virus hemagglutinin and neuraminidase by a bispecific antibody leads to improved antiviral activity.

Targeting multiple viral proteins is pivotal for sustained suppression of highly mutable viruses. In recent years, broadly neutralizing antibodies that target the influenza virus hemagglutinin and neuraminidase glycoproteins have been developed, and antibody monotherapy has been tested in preclinical and clinical studies to treat or prevent influenza virus infection. However, the impact of dual neutralization of the hemagglutinin and neuraminidase on the course of infection, as well as its therapeutic potential, has not been thoroughly tested. For this purpose, we generated a bispecific antibody that neutralizes both the hemagglutinin and the neuraminidase of influenza viruses. We demonstrated that this bispecific antibody has a dual-antiviral activity as it blocks infection and prevents the release of progeny viruses from the infected cells. We show that dual neutralization of the hemagglutinin and the neuraminidase by a bispecific antibody is advantageous over monoclonal antibody combination as it resulted an improved neutralization capacity and augmented the antibody effector functions. Notably, the bispecific antibody showed enhanced antiviral activity in influenza virus-infected mice, reduced mice mortality, and limited the virus mutation profile upon antibody administration. Thus, dual neutralization of the hemagglutinin and neuraminidase could be effective in controlling influenza virus infection.

SARS-CoV-2 variants with reduced infectivity and varied sensitivity to the BNT162b2 vaccine are developed during the course of infection.

In-depth analysis of SARS-CoV-2 quasispecies is pivotal for a thorough understating of its evolution during infection. The recent deployment of COVID-19 vaccines, which elicit protective anti-spike neutralizing antibodies, has stressed the importance of uncovering and characterizing SARS-CoV-2 variants with mutated spike proteins. Sequencing databases have allowed to follow the spread of SARS-CoV-2 variants that are circulating in the human population, and several experimental platforms were developed to study these variants. However, less is known about the SARS-CoV-2 variants that are developed in the respiratory system of the infected individual. To gain further insight on SARS-CoV-2 mutagenesis during natural infection, we preformed single-genome sequencing of SARS-CoV-2 isolated from nose-throat swabs of infected individuals. Interestingly, intra-host SARS-CoV-2 variants with mutated S genes or N genes were detected in all individuals who were analyzed. These intra-host variants were present in low frequencies in the swab samples and were rarely documented in current sequencing databases. Further examination of representative spike variants identified by our analysis showed that these variants have impaired infectivity capacity and that the mutated variants showed varied sensitivity to neutralization by convalescent plasma and to plasma from vaccinated individuals. Notably, analysis of the plasma neutralization activity against these variants showed that the L1197I mutation at the S2 subunit of the spike can affect the plasma neutralization activity. Together, these results suggest that SARS-CoV-2 intra-host variants should be further analyzed for a more thorough characterization of potential circulating variants.

Rheumatoid arthritis patients treated with Janus kinase inhibitors show reduced humoral immune responses following BNT162b2 vaccination.

OBJECTIVES: The mRNA-based COVID-19 vaccines are now employed globally and have shown high efficacy in preventing SARS-CoV-2 infection. However, less is known about the vaccine efficacy in immune-suppressed individuals. This study sought to explore whether humoral immunity to the COVID-19 vaccine BNT162b2 is altered in RA patients treated with Janus kinase inhibitors by analysing their antibodies titre, neutralization activity and B cell responses. METHODS: We collected plasma samples from 12 RA patients who were treated with Janus kinase inhibitors and received two doses of the BNT162b2 vaccine, as well as 26 healthy individuals who were vaccinated with the same vaccine. We analysed the quantity of the anti-spike IgG and IgA antibodies that were elicited following the BNT162b2 vaccination, the plasma neutralization capacity and the responsiveness of the B-lymphocytes. We used ELISA to quantify the antibody titres, and a plasma neutralization assay was used to determine the virus neutralization capacity. Alteration in expression of the genes that are associated with B cell activation and the germinal centre response were analysed by quantitative PCR. RESULTS: Reduced levels of anti-spike IgG antibodies and neutralization capacity were seen in the RA patients who were treated with JAK inhibitors in comparison with healthy individuals. Furthermore, B cell responsiveness to the SARS-CoV-2 spike protein was reduced in the RA patients. CONCLUSION: RA patients who are treated with JAK inhibitors show a suppressed humoral response following BNT162b2 vaccination, as revealed by the quantity and quality of the anti-spike antibodies.

Understanding the "Social" in "Social Media". An Analysis of Twitter Engagement of Pulmonary and Critical Care Fellowship Programs.

Background: Social media is ubiquitous as a tool for collaboration, networking, and dissemination. However, little is known about use of social media platforms by pulmonary and critical care medicine fellowship programs.Objective: We identify and characterize pulmonary and critical care fellowship programs using Twitter and Instagram, as well as the posting behaviors of their social media accounts.Methods: We identified all adult and pediatric pulmonary, critical care medicine (CCM), and combined pulmonary and critical care medicine (PCCM) programs in the United States using the Electronic Residency Application Service. We searched for Twitter profiles for each program between January 1, 2018, and September 30, 2018. Tweets and Twitter interactions were classified into the following three types: social, clinical, or medical education (MedEd) related. We collected data about content enhancements of tweets, including the use of pictures, graphics interchange format or videos, hashtags, links, and tagging other accounts. The types of tweets, content enhancement characteristics, and measures of engagement were analyzed for association with number of followers.Results: We assessed 341 programs, including 163 PCCM, 36 adult CCM, 20 adult pulmonary, 67 pediatric CCM, and 55 pediatric pulmonary programs. Thirty-three (10%) programs had Twitter accounts. Of 1,903 tweets by 33 of the 341 programs with Twitter accounts, 476 (25%) were MedEd related, 733 (39%) were clinical, and 694 (36%) were social. The median rate of tweets per month was 1.65 (interquartile range [IQR], 0.4-6.65), with 55% programs tweeting more than monthly. Accounts tweeting more often had significantly more followers than those tweeting less frequently (median, 240 followers; 25-75% IQR, 164-388 vs. median, 107 followers; 25-75% IQR, 13-188; P = 0.006). Higher engagement with clinical and social Twitter interactions (tweets, retweets, likes, and comments) was associated with more followers but not for the MedEd-related Twitter interactions. All types of content enhancements (pictures, graphics interchange format/videos, links, and tagging) were associated with a higher number of followers, except for hashtags.Conclusion: Despite the steadily increasing use of social media in medicine, only 10% of the pulmonary and critical care fellowship programs in the United States have Twitter accounts. Social and clinical content appears to gain traction online; however, additional evaluation is needed on how to effectively engage audiences with MedEd content.

Comparing the Digital Footprint of Pulmonary and Critical Care Conferences on Twitter.

Background: Pulmonary and critical care societies, including the American Thoracic Society, the American College of Chest Physicians, and the Society of Critical Care Medicine have large memberships that gather at academic conference events, attracting thousands of attendees. Objective: With the growth of social media use among pulmonary and critical care clinicians, our goal was to examine the Twitter presence and digital footprint of these three major medical society conferences. Methods: We used Symplur Signals (Symplur, LLC) to track the tweets and most active participants of the 2017-2019 annual conferences of American Thoracic Society, American College of Chest Physicians, and the Society of Critical Care Medicine. Attendance records of participants were obtained from each society. Results: During the study period, there was growth in the number of tweets, participants, and impressions for all three society conferences. Across all conferences, the amount of original content generated was less than the retweets, which comprised 50-72% of all tweets. Individuals physically attending each conference were more likely to post original content than those not in attendance (53-68% vs. 32-47%). For each society and at each meeting, clinicians made up the largest group of participants (44-60%), and most (59-82%) were physicians. A small cohort of participants was responsible for a large share of the tweets, with more than half of the participants at each conference for each society tweeting only once and only between 5-8% of participants tweeting more than 10 times. Seventy-eight individuals tweeted more than 100 times at one or more of the conferences. There was significant overlap in this group, with 32 of these individual participants tweeting more than 100 times at two or more of these conferences. Conclusion: Growth in conference digital footprints is largely due to increased activity by a small group of prolific participants that attend conferences by multiple academic societies. Original content makes up the smallest proportion of posts, suggesting that amplification of content is more prevalent than posting of original content. In a postpandemic environment, engagement of users producing original content may be even more important for medical societies.

Medical Education During the COVID-19 Pandemic.

All aspects of medical education were affected by the COVID-19 pandemic. Several challenges were experienced by trainees and programs alike, including economic repercussions of the pandemic; social distancing affecting the delivery of medical education, testing, and interviewing; the surge of patients affecting redeployment of personnel and potential compromises in core training; and the overall impact on the wellness and mental health of trainees and educators. The ability of medical teams and researchers to peer review, conduct clinical research, and keep up with literature was similarly challenged by the rapid growth in peer-reviewed and preprint literature. This article reviews these challenges and shares strategies that institutions, educators, and learners adopted, adapted, and developed to provide quality education during these unprecedented times.

A Qualitative Study of Pulmonary and Palliative Care Clinician Perspectives on Early Palliative Care in Chronic Obstructive Pulmonary Disease.

Background: Guidelines recommend that pulmonary clinicians involve palliative care in chronic obstructive pulmonary disease (COPD); however, integration before advanced stage, that is, early palliative care, is rare. Objective: To explore and compare pulmonary and palliative care clinician perspectives on barriers, facilitators, and potential referral criteria for early palliative care in COPD. Design: Qualitative descriptive formative evaluation study. Setting/Subjects: Pulmonary and palliative care clinicians at a tertiary academic medical center. Measurements: Transcribed interviews were thematically analyzed by specialty to identify within- and across-specialty perspectives on barriers, facilitators, and referral criteria. Results: Twelve clinicians (n = 6 pulmonary, n = 6 palliative care) participated. Clinicians from both specialties agreed that early palliative care could add value to disease-focused COPD care. Perspectives on many barriers and facilitators were shared between specialties along broad educational, clinical, and operational categories. Pulmonary and palliative care clinicians shared concerns about the misconception that palliative care was synonymous to end-of-life care. Pulmonologists were particularly concerned about the potential risks of opioids and benzodiazepines in COPD. Both specialties stressed the need for clearly defined roles, consensus referral criteria, and novel delivery models. Although no single referral criterion was discussed by all, frequent hospitalizations and emotional symptoms were raised by most across disciplines. Multimorbidity and poor prognosis were discussed only by palliative care clinicians, whereas medication adherence was discussed only by pulmonary clinicians. Conclusions: Pulmonary and palliative care clinicians supported early palliative care in COPD. Continued needs include addressing pulmonologists' misconceptions of palliative care, establishing consensus referral criteria, and implementing novel early palliative care models.

Oral Tuberculosis: A Rare Manifestation of Disseminated Disease in a Patient with Dermatomyositis on Chronic Corticosteroids.

Tuberculosis remains one of the leading causes of death around the world despite advancements in diagnostic testing and medical therapies. It commonly affects the lungs, but isolated extra pulmonary clinical manifestations have been reported. Tuberculosis of the oral cavity is exceedingly rare. We present a case of a patient with dermatomyositis on chronic steroid therapy, who presented with tuberculosis involving the tongue as the only clinical manifestation of disseminated disease. Physicians must be aware of extra pulmonary manifestations of tuberculosis in patients at risk, in order to avoid delays in diagnosis and treatment and to prevent further contagion.