Early infection risk in patients with systemic lupus erythematosus treated with rituximab or belimumab from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR): a prospective longitudinal study

Background: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. Method(s): The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. Finding(s): Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002.7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117.7 (95% CI 98.3-141.0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1.68 [0.60-4.68]) and belimumab groups (1.01 [0.21-4.80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg;2.38 [95%CI 1.47-3.84]), hypogammaglobulinaemia (<6 g/L;2.16 [1.38-3.37]), and multimorbidity (1.45 [1.17-1.80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0.60 [0.41-0.90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. Interpretation(s): In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. Funding(s): None.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Suddenly moving large classes online: Illuminating the experience of the teaching staff in one university

In early 2020, the transition of large classes from the face-to-face to the online context occurred overnight and at scale at a time when the crisis was being faced at all levels of society, nationally and internationally. This paper is based on research which examined the impact of this sudden transition on large classes in Dublin City University with a view to illuminating the experience to inform future practice (Authors., in press). A rapid, systemised review of literature was carried out with the aim of contextualising data gathered through surveys with staff and students in relation to our experience of moving large classes online in the early stages of the Covid-19 pandemic. While the study examined the impact from the perspectives of teaching staff and students, this paper reports on the perspectives of teaching staff only. Large class teachers found this experience challenging, reporting a sense of isolation and worry. However, it would seem that opportunity was seen in the face of adversity, whereby staff have identified potential for better ways of doing things going forward as a result of their experiences between March and May 2020

Longitudinal serologic and viral testing post-SARS-CoV-2 infection and post-receipt of mRNA COVID-19 vaccine in a nursing home cohort-Georgia, October 2020‒April 2021.

There are limited data describing SARS-CoV-2-specific immune responses and their durability following infection and vaccination in nursing home residents. We conducted a prospective longitudinal evaluation of 11 consenting SARS-CoV-2-positive nursing home residents to evaluate the quantitative titers and durability of binding antibodies detected after SARS-CoV-2 infection and subsequent COVID-19 vaccination. The evaluation included nine visits over 150 days from October 25, 2020, through April 1, 2021. Visits included questionnaire administration, blood collection for serology, and paired anterior nasal specimen collection for testing by BinaxNOW™ COVID-19 Ag Card (BinaxNOW), reverse transcription polymerase chain reaction (RT-PCR), and viral culture. We evaluated quantitative titers of binding SARS-CoV-2 antibodies post-infection and post-vaccination (beginning after the first dose of the primary series). The median age among participants was 74 years; one participant was immunocompromised. Of 10 participants with post-infection serology results, 9 (90%) had detectable Pan-Ig, IgG, and IgA antibodies, and 8 (80%) had detectable IgM antibodies. At first antibody detection post-infection, two-thirds (6/9, 67%) of participants were RT-PCR-positive, but none were culture- positive. Ten participants received vaccination; all had detectable Pan-Ig, IgG, and IgA antibodies through their final observation ≤90 days post-first dose. Post-vaccination geometric means of IgG titers were 10-200-fold higher than post-infection. Nursing home residents in this cohort mounted robust immune responses to SARS-CoV-2 post-infection and post-vaccination. The augmented antibody responses post-vaccination are potential indicators of enhanced protection that vaccination may confer on previously infected nursing home residents.

Unmotivated, Depressed, Anxious: Impact of the COVID-19 Emergency Transition to Remote Learning on Undergraduates' Math Anxiety

In summer 2020, we invited the 6761 undergraduate students who took a Spring 2020 math course at the University of Arizona to participate in a survey, with 13% responding. We asked about their experience with the emergency transition to remote learning and measured their math anxiety before and after the transition using the well-established Abbreviated Math Anxiety Scale (AMAS). "Unmotivated, depressed, anxious" are the words one undergraduate used to describe their emergency transition to remote learning. Our results indicate that limited access to quality technology and inadequate communication with an instructor were the two greatest predictors for an increase in math anxiety after the emergency transition to remote learning. These results may encourage instructors to foster community with their students, especially during emergency remote learning.

Evaluating the Presence of Replication-Competent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From Nursing Home Residents With Persistently Positive Reverse Transcription Polymerase Chain Reaction (RT-PCR) Results.

Replication-competent virus has not been detected in individuals with mild to moderate coronavirus disease 2019 (COVID-19) more than 10 days after symptom onset. It is unknown whether these findings apply to nursing home residents. Of 273 specimens collected from nursing home residents >10 days from the initial positive test, none were culture positive.

Repeated antigen testing among severe acute respiratory coronavirus virus 2 (SARS-CoV-2)-positive nursing home residents.

Repeated antigen testing of 12 severe acute respiratory coronavirus virus 2 (SARS-CoV-2)-positive nursing home residents using Abbott BinaxNOW identified 9 of 9 (100%) culture-positive specimens up to 6 days after initial positive test. Antigen positivity lasted 2-24 days. Antigen positivity might last beyond the infectious period, but it was reliable in residents with evidence of early infection.

Depression Symptoms, Mattering, and Anti-mattering: Longitudinal Associations in Young Adulthood

We examined the dynamic interplay of depression symptoms, mattering (i.e., self-evaluation of importance or significance to others), and anti-mattering across four years of development in young adulthood (age 20-23;N = 452) using a cross-lagged panel model (CLPM). Support for a transactional model between anti-mattering and depression symptoms was found. Specifically, anti-mattering positively predicted later depression symptoms and depression symptoms consistently predicted later anti-mattering. Depression symptoms also shared a negative association with later mattering but not the reverse, supporting a symptoms-driven model of depression symptoms and mattering. Auto-regressive paths, residual covariances, and cross-lagged paths were invariant over time. Accounting for gender, household income, parental education, and fear of COVID-19 as covariates did not change the results. The stability of mattering and anti-mattering suggest careful consideration of how to effectively change these patterns. The implications for assessment and intervention on mattering or anti-mattering in the prevention and treatment of depression are discussed.

Longitudinal serologic and viral testing post-SARS-CoV-2 infection and post-receipt of mRNA COVID-19 vaccine in a nursing home cohort--Georgia, October 2020-April 2021 (preprint)

Importance: There are limited data describing SARS-CoV-2-specific immune responses and their durability following infection and vaccination in nursing home residents. Objective: To evaluate the quantitative titers and durability of binding antibodies detected after SARS-CoV-2 infection and subsequent COVID-19 vaccination. Design: A prospective longitudinal evaluation included nine visits over 150 days; visits included questionnaire administration, blood collection for serology, and paired anterior nasal specimen collection for testing by BinaxNOW COVID-19 Ag Card (BinaxNOW), reverse transcription polymerase chain reaction (RT-PCR), and viral culture. Setting: A nursing home during and after a SARS-CoV-2 outbreak. Participants: 11 consenting SARS-CoV-2-positive nursing home residents. Main Outcomes and Measures: SARS-CoV-2 testing (BinaxNOW, RT-PCR, viral culture); quantitative titers of binding SARS-CoV-2 antibodies post-infection and post-vaccination (beginning after the first dose of the primary series). Results: Of 10 participants with post-infection serology results, 9 (90%) had detectable Pan-Ig, IgG, and IgA antibodies and 8 (80%) had detectable IgM antibodies. At first antibody detection post-infection, two-thirds (6/9, 67%) of participants were RT-PCR-positive but none were culture positive. Ten participants received vaccination; all had detectable Pan-Ig, IgG, and IgA antibodies through their final observation [≤]90 days post-first dose. Post-vaccination geometric means of IgG titers were 10-200-fold higher than post-infection. Conclusions and Relevance: Nursing home residents in this cohort mounted robust immune responses to SARS-CoV-2 post-infection and post-vaccination. The augmented antibody responses post-vaccination are potential indicators of enhanced protection that vaccination may confer on previously infected nursing home residents.

Occupational exposures and mitigation strategies among homeless shelter workers at risk of COVID-19.

OBJECTIVE: To describe the work environment and COVID-19 mitigation measures for homeless shelter workers and assess occupational risk factors for COVID-19. METHODS: Between June 9-August 10, 2020, we conducted a self-administered survey among homeless shelter workers in Washington, Massachusetts, Utah, Maryland, and Georgia. We calculated frequencies for work environment, personal protective equipment use, and SARS-CoV-2 testing history. We used generalized linear models to produce unadjusted prevalence ratios (PR) to assess risk factors for SARS-CoV-2 infection. RESULTS: Of the 106 respondents, 43.4% reported frequent close contact with clients; 75% were worried about work-related SARS-CoV-2 infections; 15% reported testing positive. Close contact with clients was associated with testing positive for SARS-CoV-2 (PR 3.97, 95%CI 1.06, 14.93). CONCLUSIONS: Homeless shelter workers may be at risk of being exposed to individuals with COVID-19 during the course of their work. Frequent close contact with clients was associated with SARS-CoV-2 infection. Protecting these critical essential workers by implementing mitigation measures and prioritizing for COVID-19 vaccination is imperative during the pandemic.

Atypical head and neck infections as a precursor to MIS-C

Introduction: Multisystem inflammatory syndrome in children (MIS-C) is a rare, life-threatening sequela of COVID-19 infection in pediatric patients. We review the literature and describe a novel presentation of severe head and neck manifestations in 2 MIS-C patients. Method: A case report and PubMed literature search were conducted. Results: Two adolescent patients were evaluated at a tertiary care children's hospital for headache, fever, and neck pain. Examination demonstrated massive cervical lymphadenopathy (LAD), neck cellulitis, and tonsillopharyngitis. Laboratory findings demonstrated C-reactive protein elevation and negative COVID-19 polymerase chain reaction (PCR) testing. Computed tomography (CT) imaging demonstrated extensive multicompartment head and neck phlegmonous fluid collections. Steroids and broad-spectrum antibiotics were initiated. Rapid resolution of neck pain and fever occurred but was succeeded by the development of cardiogenic shock requiring critical care transfer and initiation of vasopressors. Positive COVID-19 immunoglobulin G testing was followed by the initiation of intravenous immunoglobulin and normalization of cardiac function in both patients with subsequent discharge home in stable condition. PubMed reviews for articles highlighting MIS-C presentations and head and neck manifestations were included. The defining presenting characteristics are typically prolonged fever, abdominal pain, and cardiac involvement without any signs of pneumonia on chest CT. Cervical LAD and sore throat are rare presenting symptoms of MIS-C but common in the general pediatric population. Otolaryngologists are frequently engaged to help manage patients with complications such as severe tonsillitis or deep neck fluid collections. A negative COVID-19 polymerase chain reaction may falsely lower the threshold of suspicion of a SARS-CoV-2-related illness;however, awareness of unusual head and neck manifestations as a presentation of MIS-C may help the early recognition and treatment of this potentially fatal syndrome. Conclusion: COVID-19 should be considered in the differential for atypical head and neck infection in the pediatric patient, as this may serve as a precursor to MIS-C.

Performance Evaluation of Serial SARS-CoV-2 Rapid Antigen Testing During a Nursing Home Outbreak.

BACKGROUND: To address high COVID-19 burden in U.S. nursing homes, rapid SARS-CoV-2 antigen tests have been widely distributed in those facilities. However, performance data are lacking, especially in asymptomatic people. OBJECTIVE: To evaluate the performance of SARS-CoV-2 antigen testing when used for facility-wide testing during a nursing home outbreak. DESIGN: A prospective evaluation involving 3 facility-wide rounds of testing where paired respiratory specimens were collected to evaluate the performance of the BinaxNOW antigen test compared with virus culture and real-time reverse transcription polymerase chain reaction (RT-PCR). Early and late infection were defined using changes in RT-PCR cycle threshold values and prior test results. SETTING: A nursing home with an ongoing SARS-CoV-2 outbreak. PARTICIPANTS: 532 paired specimens collected from 234 available residents and staff. MEASUREMENTS: Percentage of positive agreement (PPA) and percentage of negative agreement (PNA) for BinaxNOW compared with RT-PCR and virus culture. RESULTS: BinaxNOW PPA with virus culture, used for detection of replication-competent virus, was 95%. However, the overall PPA of antigen testing with RT-PCR was 69%, and PNA was 98%. When only the first positive test result was analyzed for each participant, PPA of antigen testing with RT-PCR was 82% among 45 symptomatic people and 52% among 343 asymptomatic people. Compared with RT-PCR and virus culture, the BinaxNOW test performed well in early infection (86% and 95%, respectively) and poorly in late infection (51% and no recovered virus, respectively). LIMITATION: Accurate symptom ascertainment was challenging in nursing home residents; test performance may not be representative of testing done by nonlaboratory staff. CONCLUSION: Despite lower positive agreement compared with RT-PCR, antigen test positivity had higher agreement with shedding of replication-competent virus. These results suggest that antigen testing could be a useful tool to rapidly identify contagious people at risk for transmitting SARS-CoV-2 during nascent outbreaks and help reduce COVID-19 burden in nursing homes. PRIMARY FUNDING SOURCE: None.

Learning from student experience: large, higher education classes transitioning online

In March 2020, Irish universities closed their doors and teaching, learning and assessment moved online, due to the Covid-19 pandemic. This paper arises from a Dublin City University (DCU) research study with a three-fold purpose: Examine the sudden transition of large classes (100+ students) from face-to-face teaching and learning to remote online provision from the perspectives of staff and students. Contextualise these perspectives by reviewing relevant literature. Inform the work of teaching large classes in future online teaching and learning spaces. Presented here, are findings informed by;a rapid, systematised literature review;analysis of student and staff survey responses who experienced the swift move online;and academic support data mined by the Teaching Enhancement Unit (TEU) between March and June 2020. This paper will contribute to prompt, timely reflection on the lived student experience of engagement and isolation during the sudden pivot for large class cohorts. These reflections and analysis will add to the growing body of literature on large class teaching and online pedagogy, specifically in the context of the Covid-19 pandemic. The authors provide conceptualised solutions as we move out of the emergency pivot and into more considered, planned approaches to better engage students in online, hybrid and face-to-face contexts. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Coronavirus Disease 2019 (COVID-19) in Americans Aboard the Diamond Princess Cruise Ship.

BACKGROUND: The Diamond Princess cruise ship was the site of a large outbreak of coronavirus disease 2019 (COVID-19). Of 437 Americans and their travel companions on the ship, 114 (26%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We interviewed 229 American passengers and crew after disembarkation following a ship-based quarantine to identify risk factors for infection and characterize transmission onboard the ship. RESULTS: The attack rate for passengers in single-person cabins or without infected cabinmates was 18% (58/329), compared with 63% (27/43) for those sharing a cabin with an asymptomatic infected cabinmate, and 81% (25/31) for those with a symptomatic infected cabinmate. Whole genome sequences from specimens from passengers who shared cabins clustered together. Of 66 SARS-CoV-2-positive American travelers with complete symptom information, 14 (21%) were asymptomatic while on the ship. Among SARS-CoV-2-positive Americans, 10 (9%) required intensive care, of whom 7 were ≥70 years. CONCLUSIONS: Our findings highlight the high risk of SARS-CoV-2 transmission on cruise ships. High rates of SARS-CoV-2 positivity in cabinmates of individuals with asymptomatic infections suggest that triage by symptom status in shared quarters is insufficient to halt transmission. A high rate of intensive care unit admission among older individuals complicates the prospect of future cruise travel during the pandemic, given typical cruise passenger demographics. The magnitude and severe outcomes of this outbreak were major factors contributing to the Centers for Disease Control and Prevention's decision to halt cruise ship travel in US waters in March 2020.

Silver lining of a very dark cloud: Telehealth virtually perfect in the COVID-19 era

Background and Aim: Public hospital outpatient departments are a critical interface between acute and specialist hospital services and primary care. Failure of patients to attend is an expensive and persistent issue worldwide, with reported did-not-attend (DNA) rates of up to 30% in some centers. Non-attendance is influenced by many factors, such as logistics in getting to the hospital, work commitments, financial hardship, transportation access, and competing health interests. Telehealth has been available for some years, but its implementation and uptake have been limited. Telehealth is defined as “information and communications technologies to deliver health and transmit health information over both long and short distances,”1 and it can be conducted via videoconferencing or telephone. It represents an attractive model to increase outpatient clinic appointments, which is important given the long waiting times for many clinics. Telehealth also provides avenues to continue critical outpatient management during the coronavirus disease 2019 (COVID-19) pandemic and for ongoing clinical management for furloughed or isolated staff who can still be engaged in outpatient care. At our institution, the COVID-19 pandemic stimulated the immediate and almost universal implementation of the telehealth model of care for outpatient appointments. We aimed to evaluate the experience of the telehealth model in the first 3 months of the COVID-19 pandemic in Victoria, focusing on the impact of telehealth on the number of scheduled appointments and clinic DNA rates. Methods: Over a 9-week period during the first COVID-19 lockdown in Melbourne, scheduled appointment numbers and patient attendance rates at 13 gastroenterology and hepatology outpatient clinics at a single tertiary hospital were evaluated through the hospital's online patient administration system, following rapid implementation of the telehealth model of outpatient care. Appointment numbers and attendance were compared with the average attendance rate over the same period in the preceding 5 years. Data collected included patient DNA rates for every scheduled clinic and appointment type (videoconferencing, telephone, or face-to-face consultation). Results: A total of 2626 outpatient clinic appointments were scheduled during the first 9-week COVID-19 lockdown, with 2237 appointments (85%) attended and 389 DNAs (15%), an improvement of 2.2% in attendance rate compared with the average attendance rate during the same 9-week period in the preceding 5 years (P = 0.035). Of the 2626 appointments, 1319 (50%) were video consultations, and 1307 (50%) were telephone consultations. In the preceding 5 years, an average of 2304 outpatient clinic appointments (322 fewer appointments) were scheduled during the same 9-week period, with 1912 appointments (83%) attended and 392 (17%) not attended. Of these 2304 appointments, 2271 (99%) were face-to-face consultations and only 33 (1%) were video consultations. Attendance rates differed according to clinic type. Compared with previous years, outpatient clinics with significantly lower DNA rates during COVID-19 included combined general gastroenterology (15% vs 20%, P = 0.014), satellite inflammatory bowel disease (2% vs 10%, P = 0.033), satellite liver clinic (20% vs 28%, P = 0.198), and privatized liver clinic (13% vs 18%, P = 0.051). Clinics with higher numerical DNA rates included hepatoma (18% vs 12%, P = 0.731) and weight management (20% vs 15%, P = 0.343). When evaluating the appointment type, we found that consultations carried out by telephone resulted in a significantly lower DNA rate, compared with video consultations (9% vs 21%;P < 0.001). Furthermore, an additional 37 clinic lists occurred during this 9-week period, equivalent to four additional lists per week, compared with the average number in the preceding 5 years. Conclusion: Despite the upheaval of clinical services during the COVID-19 pandemic, the major and rapid systems change to overhaul outpatient clinics to an almost exclusively telehealth model was highly succes ful. A total of 1319 video consultations occurred during the 9-week period, compared with just 43 in the preceding year, demonstrating the rapid and widespread implementation of telehealth. Importantly, there was a significant overall reduction in DNA rates, by 2.2%, using the telehealth model. Phone calls were particularly effective for clinic consultations, with DNA rates of only 9.0%. Telehealth has the potential to improve outpatient clinic attendance and efficiency, and our data strongly advocate for ongoing support for telehealth models, including both video and telephone consultation, beyond the COVID-19 era.

Signs, Symptoms, and Comorbidities Associated With Onset and Prognosis of COVID-19 in a Nursing Home.

BACKGROUND: Effective halting of outbreaks in skilled nursing facilities (SNFs) depends on the earliest recognition of cases. We assessed confirmed COVID-19 cases at an SNF impacted by COVID-19 in the United States to identify early indications of COVID-19 infection. METHODS: We performed retrospective reviews of electronic health records for residents with laboratory-confirmed SARS-CoV-2 during February 28-March 16, 2020. Records were abstracted for comorbidities, signs and symptoms, and illness outcomes during the 2 weeks before and after the date of positive specimen collection. Relative risks (RRs) of hospitalization and death were calculated. RESULTS: Of the 118 residents tested among approximately 130 residents from Facility A during February 28-March 16, 2020, 101 (86%) were found to test positive for SARS-CoV-2. At initial presentation, about two-thirds of SARS-CoV-2-positive residents had an abnormal vital sign or change in oxygen status. Most (90.2%) symptomatic residents had elevated temperature, change in mental status, lethargy, change in oxygen status, or cough; 9 (11.0%) did not have fever, cough, or shortness of breath during their clinical course. Those with change in oxygen status had an increased relative risk (RR) of 30-day mortality [51.1% vs 29.7%, RR 1.7, 95% confidence interval (CI) 1.0-3.0]. RR of hospitalization was higher for residents with underlying hepatic disease (1.6, 95% CI 1.1-2.2) or obesity (1.5, 95% CI 1.1-2.1); RR of death was not statistically significant. CONCLUSIONS AND IMPLICATIONS: Our findings reinforce the critical role that monitoring of signs and symptoms can have in identifying COVID-19 cases early. SNFs should ensure they have a systematic approach for responding to abnormal vital signs and oxygen saturation and consider ensuring common signs and symptoms identified in Facility A are among those they monitor.