REACTOGENICITY AMONG PEOPLE LIVING WITH HIV AFTER mRNA-1273 VACCINE IN UBUNTU STUDY

Background: The tolerability of mRNA COVID-19 vaccines among people living with HIV (PLWH) has been understudied in vaccine trials. CoVPN 3008 (Ubuntu) is the largest multicenter Phase 3 efficacy trial of mRNA vaccines in sub-Saharan Africa. Method(s): We enrolled adults age >=18 years living with HIV or another comorbidity associated with severe COVID-19. Previously vaccinated individuals were excluded. Baseline testing included HIV, CD4 count and HIV viral load (VL) (if HIV+), anti-SARS-CoV-2 antibodies, and nasal swab SARS-CoV-2 nucleic acid amplification test (NAAT). All participants receive vaccinations at months 0 and 6, and SARS-CoV-2 seronegative individuals also receive vaccination at month 1. This analysis includes mRNA-1273 vaccinations at months 0 and 1. Reactogenicity (solicited adverse events [AEs]) was assessed among a representative subset of participants (Safety Subset, SS) for 7 days post-vaccination. Baseline characteristics associated with moderate/severe reactogenicity events were assessed by univariate and multivariate logistic regression. Result(s): 14002 participants were enrolled in the trial (1510 into the SS) at 46 sites from 2 Dec 2021 to 9 Sep 2022. At baseline in the SS, 71% (1065) were female, median age 38 years (IQR 32-46), and median BMI 25.0 (IQR 20.7-30.2). 73% (1108) were SARS-CoV-2 seropositive, and 8.7% (131) had a positive nasal NAAT swab. 16% (197) had a history of tuberculosis. 84% (1267) were PLWH, with median CD4 count of 614 cells/muL (IQR 414-861);7.8% had CD4 count < 200. 21% (238) had detectable HIV VL (>=50 copies/mL), with median VL 1660 (IQR 182-23932). 14% (172/1262) and 12% (64/542) of PLWH reported moderate/severe reactogenicity after the 1st and 2nd vaccination (Figure), with no hospitalizations. Female PLWH and CD4 count >500 had 35% (p=0.03) and 44% (p=0.04) increased odds of moderate/severe reactogenicity, respectively. Other baseline characteristics were not associated with the odds of reporting moderate/severe reactogenicity among PLWH after 1st vaccination. Similar trends were seen after the 2nd vaccination, but none reached statistical significance. In multivariate models, female sex remained associated with increased odds of moderate/severe reactogenicity after the 2nd vaccination. Conclusion(s): Similar to observations in HIV-negative populations, mRNA-1273 was well tolerated by PLWH with more reactogenicity in females. Impaired inflammatory responses among participants with CD4 counts < 500 cell/muL may explain less moderate/severe reactions.

Hiv Outcomes after Extended 12-Month Scripts for Art during Covid-19 in South Africa

Background: There is an urgent need for more efficient models of differentiated anti-retroviral therapy (ART) delivery, with the World Health Organization and PEPFAR calling for evidence to guide whether 12-monthly ART prescriptions and clinic review (12M scripts) should be recommended in global guidelines. We assessed the association between 12M scripts (allowed temporarily during the COVID-19 pandemic) and clinical outcomes in South Africa. Method(s): We performed a retrospective cohort study using routine, deidentified data from 59 public clinics in KwaZulu-Natal. We included PLHIV aged >18 years with a recent suppressed viral load (VL), and who had been referred from their clinic into a community ART delivery programme with a standard 6-month prescription and clinic review (6M script) or a 12M script. In the community ART programme, PLHIV collected ART every two months at external pick-up points, before returning to the clinic after 6 or 12 months for a new script. We used multivariable modified Poisson regression, accounting for clinic clustering, to compare 12-month retention-in-care (not >90 days late for any visit) and viral suppression (< 50 copies/mL) between 6M and 12M script groups. Result(s): Among 27,148 PLHIV referred for community ART between Jun-Dec 2020, 42.6% received 6M scripts and 57.4% 12M scripts. The median age was 39 years (interquartile range [IQR] 33-46) and 69.4% were women. Age, gender, prior community ART use and time on ART were similar in the two groups (Table). However, a larger proportion of the 12M script group had a dolutegravirbased regimen (60.0% versus 46.3%). The median (IQR) number of clinic visits in the 12 months of follow-up was 1(1-1) in the 12M group and 2(2-3) in the 6M group. Retention at 12 months was 94.6% (95% confidence interval [CI] 94.2%- 94.9%) among those receiving 12M scripts and 91.8% (95% CI 91.3%-92.3%) among those with 6M scripts. 16.8% and 16.7% of clients in the 12M and 6M groups were missing follow-up VL data, respectively. Among those with VLs, 90.4% (95% CI 89.9%-91.0%) in the 12M group and 88.9% (95% CI 88.3%- 89.5%) in the 6M group were suppressed. After adjusting for age, gender, ART regimen, time on ART and prior community ART use, retention (adjusted risk ratio [aRR]: 1.03, 95% CI 1.01-1.04) and suppression (aRR: 1.02(1.01-1.03) were higher with 12M scripts. Conclusion(s): COVID-19 led to temporary introduction of 12M scripts in South Africa. Wider use could reduce clinic visits without negative impacts on shortterm clinical outcomes.

SAFETY OF HETEROLOGOUS mRNA-1273 BOOST AFTER Ad26.COV2.S PRIME IN SOUTH AFRICA

Background: Given the paucity of data on safety and effectiveness of mRNA COVID-19 booster vaccinations in lower income settings with high HIV prevalence, we evaluated a heterologous mRNA-1273 (Moderna) boost after priming with 1 or 2 doses of Ad26.COV2.S (Janssen, Johnson & Johnson) vaccine among health care workers (HCWs) in South Africa. Method(s): SHERPA is an open-label, phase 3 mRNA-1273 booster study, nested in the Sisonke Phase 3b implementation trial, that vaccinated ~500000 HCWs with 1 or 2 doses of Ad26.COV2.S from Feb and Dec 2021. Sisonke participants were offered mRNA-1273 boosters between 23 May and 12 Nov 2022 (median 17 and 8 months after 1 and 2 Ad26.COV2.S, respectively), with data cut-off on 12 Dec 2022. Reactogenicity and adverse events (AEs) were self-reported via an online data entry link shared by SMS with participants 1, 7 and 28 days after boosting. Using national databases analyses are underway to compare effectiveness against COVID-19 infections and severe disease with Sisonke participants who did not receive the booster. Result(s): 12188 HCWs (79.5% female, 28.6% with self-reported previous COVID-19 diagnosis) received a mRNA-1273 booster, of whom 44.6% and 55.4% had received 1 and 2 prior Ad26.COV2.S vaccines in Sisonke, respectively. 3056 (25.2%) reported being HIV positive, more among those receiving only 1 previous Ad26.COV2.S (26.8% vs 23.9%), and 1.4% reported not being on antiretroviral therapy. 17.0% of participants reported hypertension and 6.4% diabetes mellitus. 262 participants (2.1% of women, 2.5% of men) reported 234 reactogenicity events and 95 AEs post-vaccination, with more reported by those with prior COVID-19 infection (3.5% vs 1.6%), HIV negative status (2.5% vs 1.2%) and those who received 2 prior doses of Ad26.COV2.S (2.4% vs 1.8%) (Table). Among 159 (1.3%) reporting injection site reactions the commonest were pain (59.7%), swelling (42.1%) and induration (20.1%). Of 177 (1.5%) systemic reactogenicity events (all grade 1 or 2 severity), the commonest were myalgia (69.5%), headache (67.8%) and fever (37.9%). 14 participants had AEs of special interest or serious AEs, of which 4 (all AESIs of ageusia or anosmia) were deemed related to the booster. 13 COVID-19 infections occurred a median of 125 days post booster vaccination (IQR 90-154) after 3477 person-years of follow up. Conclusion(s): A mRNA-1273 booster administered after 1 or 2 doses of Ad26. COV2.S was well tolerated regardless of HIV status, other chronic conditions or prior COVID-19 infection.

SAFETY and EFFECTIVENESS of the Ad26.COV2.S VACCINE in SOUTH AFRICA

Background: The Sisonke Phase IIIB open-label implementation study vaccinated health care workers (HCWs) with the single dose Ad26.COV2.S vaccine during two phases of the South African Covid-19 epidemic, dominated first by the Beta followed by the Delta variant of concern. Methods: HCWs were vaccinated over 3 months (17 February-17 May 2021). Safety was monitored by self-reporting, facility reporting and linkage to national databases. Vaccine effectiveness (VE) against Covid-19 related hospitalisation, hospitalisation requiring critical or intensive care and death, ascertained 28 days or more post vaccination was assessed up until 17 July 2021. Nested sub-cohorts (A and B) from two national medical schemes were evaluated to assess VE using a matched retrospective cohort design. Results: Over the 3-month period, 477234 HCWs were vaccinated in 122 vaccination sites across South Africa. VE derived from the sub-cohorts comprising 215 813 HCWs was 83% (95% CI 75-89) to prevent Covid-19 deaths, 75% (95% CI 69-82) to prevent hospital admissions requiring critical or intensive care and 67% (95% CI 62-71) to prevent Covid-19 related hospitalisations. The VE was maintained in older HCWs and those with comorbidities including HIV infection. VE remained consistent throughout the Beta and Delta dominant phases of the study. 10279 adverse events were reported and 139 (1.4%) were serious, including two cases of thrombosis with thrombocytopenia syndrome and four cases of Guillain-Barré syndrome who recovered. Conclusion: The single dose Ad26.COV2.S was safe and effective against severe Covid-19 disease and death post-vaccination, and against both Beta and Delta variants providing real-world evidence for its use globally.

Increased Lengths of Stay, ICU, and Ventilator Days in Trauma Patients with Asymptomatic COVID-19 Infection.

BACKGROUND: The SARS-Cov-2 coronavirus has varying clinical effects-from asymptomatic patients to life-threatening illness and death. At the only Level 1 Trauma Center in a rural state, outcomes appeared worse in trauma patients who tested positive for COVID despite these patients presumably being asymptomatic or only mildly affected before their traumatic event. This study compares all trauma admissions that were COVID-positive to those who were not. METHODS: The institutional database was queried for all level 1 and 2 trauma activations from March 2020-July 2021. The analysis consisted of a multivariate regression between COVID-negative and the COVID-positive group controlling for age, injury severity score (ISS), and Glasgow Coma Score (GCS). Outcomes compared were hospital length-of-stay (LOS), ICU LOS, ventilator days, days to discharge to a facility, and in-hospital mortality. RESULTS: Hospital LOS was 2.7 days longer in the COVID-positive group (P < .0005). ICU LOS was 2.9 days longer for patients admitted to the ICU in the COVID positive-group (P = .017). Ventilator days were 4.7 days longer for patients requiring mechanical ventilation in the COVID-positive group (P = .002). Discharge to a post-acute facility required 6.1 more days in the COVID-positive group (P = .005). CONCLUSION: Trauma patients presenting positive for COVID-19 are presumed to be asymptomatic before their traumatic event. Despite this, the physiologic toll of trauma combined with the COVID infection causes significantly worse clinical outcomes, including increasing hospital days in this patient population, which continues to tax the already burdened healthcare system.

Sisonke phase 3B open-label study: Lessons learnt for national and global vaccination scale-up during epidemics

Sisonke is a multicentre, open-label, single-arm phase 3B vaccine implementation study of healthcare workers (HCWs) in South Africa, with prospective surveillance for 2 years. The primary endpoint is the rate of severe COVID-19, including hospitalisations and deaths. The Sisonke study enrolled and vaccinated participants nationally at potential vaccination roll-out sites between 17 February and 26 May 2021. After May 2021, additional HCWs were vaccinated as part of a sub-study at selected clinical research sites. We discuss 10 lessons learnt to strengthen national and global vaccination strategies: (i) consistently advocate for vaccination to reduce public hesitancy;(ii) an electronic vaccination data system (EVDS) is critical;(iii) facilitate access to a choice of vaccination sites, such as religious and community centres, schools, shopping malls and drive-through centres;(iv) let digitally literate people help elderly and marginalised people to register for vaccination;(v) develop clear 'how to' guides for vaccine storage, pharmacy staff and vaccinators;(vi) leverage instant messaging platforms, such as WhatsApp, for quick communication among staff at vaccination centres;(vii) safety is paramount - rapid health assessments are needed at vaccination centres to identify people at high risk of serious adverse events, including anaphylaxis or thrombosis with thrombocytopenia syndrome. Be transparent about adverse events and contextualise vaccination benefits, while acknowledging the small risks;(viii) provide real-time, responsive support to vaccinees post vaccination and implement an accessible national vaccine adverse events surveillance system;(ix) develop efficient systems to monitor and investigate COVID-19 breakthrough infections;and (x) flexibility and teamwork are essential in vaccination centres across national, provincial and district levels and between public and private sectors.

Sisonke phase 3B open-label study: Lessons learnt for national and global vaccination scale-up during epidemics.

Sisonke is a multicentre, open-label, single-arm phase 3B vaccine implementation study of healthcare workers (HCWs) in South Africa, with prospective surveillance for 2 years. The primary endpoint is the rate of severe COVID­19, including hospitalisations and deaths. The  Sisonke study enrolled and vaccinated participants nationally at potential vaccination roll-out sites between 17 February and 26 May 2021. After May 2021, additional HCWs were vaccinated as part of a sub-study at selected clinical research sites. We discuss 10 lessons learnt to strengthen national and global vaccination strategies:(i) consistently advocate for vaccination to reduce public hesitancy; (ii) an electronic vaccination data system (EVDS) is critical; (iii) facilitate access to a choice of vaccination sites, such as religious and community centres, schools, shopping malls and drive-through centres; (iv) let digitally literate people help elderly and marginalised people to register for vaccination; (v) develop clear 'how to' guides for vaccine storage, pharmacy staff and vaccinators; (vi) leverage instant messaging platforms, such as WhatsApp, for quick communication among staff at vaccination centres; (vii) safety is paramount - rapid health assessments are needed at vaccination centres to identify people at high risk of serious adverse events, including anaphylaxis or thrombosis with thrombocytopenia syndrome. Be transparent about adverse events and contextualise vaccination benefits, while acknowledging the small risks; (viii) provide real-time, responsive support to vaccinees post vaccination and implement an accessible national vaccine adverse events surveillance system; (ix) develop efficient systems to monitor and investigate COVID­19 breakthrough infections; and (x) flexibility and teamwork are essential in vaccination centres across national, provincial and district levels and between public and private sectors.

What Really Matters: Experiences of Emergency Remote Teaching in University Teaching and Learning During the COVID-19 Pandemic

The COVID-19 pandemic and related lock downs have accelerated the need for online and remote teaching within university settings. However, due to the abrupt nature of the pandemic, many academic staff were not prepared for this forced transition. This study aimed to understand how the pandemic affected academics at a New Zealand university, with regards to their transition to emergency remote teaching. Specifically, it explores the challenges as well as benefits academics experienced during this transition. Recommendations for future online learning are also made. Academic staff (N = 67) at a New Zealand University completed an anonymous online survey. Quantitative data were analyzed statistically using descriptive and inferential statistics, while qualitative data were analyzed thematically. Major challenges experienced included miscommunication from the university, concerns about student access to technology, finding a quiet space to work, lack of digital competence skills, too much screen-time, managing work hours, and work/life balance. Benefits included enhanced flexibility, enhanced teacher creativity, increasing autonomy of learners, and reduced commute time. Looking forward, academic staff desired future teaching to include blended learning and virtual immersion. New strategies of working remotely are being explored to facilitate teaching and learning while catering to the preferences and skills of both educators and students. Our findings honor the considerable agility of academic staff who sought to sustain and enhance excellence in remote education. At an institutional level our findings point to the need for staff to be supported by their institutions as they further refine their work within new-found spaces.

Increases in Violence and Changes in Trauma Admissions During the COVID Quarantine.

BACKGROUND: The COVID-19 pandemic caused an abrupt change to societal norms. We anecdotally noticed an increase in penetrating and violent trauma during the period of stay-at-home orders. Studying these changes will allow trauma centers to better prepare for future waves of COVID-19 or other global catastrophes. METHODS: We queried our institutional database for all level 1 and 2 trauma activations presenting from the scene within our local county from March 18 to May 21, 2020 and matched time periods from 2016 to 2019. Primary outcomes were overall trauma volume, rates of penetrating trauma, rates of violent trauma, and transfusion requirements. RESULTS: The number of penetrating and violent traumas at our trauma center during the period of societal quarantine for the COVID-19 pandemic was more than any historical total. During the COVID-19 time period, we saw 39 penetrating traumas, while the mean value for the same time period from 2016 to 2019 was 26 (P = .03). We saw 45 violent traumas during COVID; the mean value from 2016 to 2019 was 32 (P = .05). There was also a higher rate of trauma patients requiring transfusion in the COVID cohort (6.7% vs 12.2%). DISCUSSION: Societal quarantine increased the number of penetrating and violent traumas, with a concurrent increased percentage of patients transfused. Despite this, there was no change in outcomes. Given the continuation of the COVID-19 pandemic, quarantine measures could be re-implemented. Data from this study can help guide expectations and utilization of hospital resources in the future.

The impact of coronavirus 2019 on general surgery residency: A national survey of program directors.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has had a widespread impact on graduate medical education. This survey aims to assess how general surgery residency programs adapted to the initial wave of the COVID-19 pandemic in the United States (US). MATERIALS AND METHODS: General surgery program directors (PDs) in the US were invited to partake in a 16-question survey between April 17 and May 1, 2020. The survey included questions about basic program information, clinical practice changes, changes to education structure, surgery resident clinical duties, and perceived impact on resident operative experience and future career choices. RESULTS: Forty-eight PDs completed the survey in the designated two-week period. Almost all (44/48, 91.7%) programs changed their didactic education to an online video conference-based format. Thirteen programs (27.1%) decreased the amount/frequency of formal education, and 13 (27.1%) reported canceling didactic education for some period of time. The majority of PDs (26/48, 54.2%) felt these changes had no impact on resident didactic participation, 14 (29.2%) reported an increase in participation, and 8 (16.7%) reported decreased participation. Ten programs (20.8%) redeployed residents to non-surgical services at the time of this survey, 30 (62.5%) have not redeployed residents but plan to if needed, and 8 (16.7%) did not have any plans to redeploy residents. CONCLUSIONS: The outbreak of COVID-19 has required general surgery residency PDs to change numerous aspects of resident education and clinical roles. Future inquiry is needed to assess if these changes lead to appreciable differences in resident preparedness and career selection.

The impact of COVID-19 on thoracic surgery residency programs in the US: A program director survey.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) has altered how the current generation of thoracic surgery residents are being trained. The aim of this survey was to determine how thoracic surgery program directors (PDs) are adapting to educating residents during the COVID-19 pandemic. METHODS: Thoracic surgery PDs of integrated, traditional (2 or 3 year), and combined 4 + 3 general/thoracic surgery training programs in the United States were surveyed between 17th April and 1st May 2020 during the peak of the COVID-19 pandemic in much of the United States. The 15-question electronic survey queried program status, changes to the baseline surgical practice, changes to didactic education, deployment/scheduling of residents, and effect of the pandemic on case logs and preparedness for resident graduation. RESULTS: All 23 institutions responding had ceased elective procedures, and most had switched to telemedicine clinic visits. Online virtual didactic sessions were implemented by 91% of programs, with most (69.6%) observing same or increased attendance. PDs reported that 82.7% of residents were on a non-standard schedule, with most being deployed in a 1 to 2 week on, 1 to 2 week off block schedule. Case volumes were affected for both junior and graduating trainees, but a majority of PDs report that graduating residents will graduate on time without perceived negative effect on first career/fellowship position. CONCLUSIONS: The COVID-19 pandemic has radically changed the educational approach of thoracic surgery programs. PDs are adapting educational delivery to optimize training and safety during the pandemic. Long-term effects remain uncertain and require additional study.