Decentralized study of COVID Vaccine Antibody Response (STOPCoV): Results of a participant satisfaction survey.

The Covid-19 pandemic required many clinical trials to adopt a decentralized framework to continue research activities during lock down restrictions. The STOPCoV study was designed to assess the safety and efficacy of Covid-19 vaccines in those aged 70 and above compared to those aged 30-50 years of age. In this sub-study we aimed to determine participant satisfaction for the decentralized processes, accessing the study website and collecting and submitting study specimens. The satisfaction survey was based on a Likert scale developed by a team of three investigators. Overall, there were 42 questions for respondents to answer. The invitation to participate with a link to the survey was emailed to 1253 active participants near the mid-way point of the main STOPCoV trial (April 2022). The results were collated and answers were compared between the two age cohorts. Overall, 70% (83% older, 54% younger cohort, no difference by sex) responded to the survey. The overall feedback was positive with over 90% of respondents answering that the website was easy to use. Despite the age gap, both the older cohort and younger cohort reported ease of performing study activities through a personal electronic device. Only 30% of the participants had previously participated in a clinical trial, however over 90% agreed that they would be willing to participate in future clinical research. Some difficulties were noted in refreshing the browser whenever updates to the website were made. The feedback attained will be used to improve current processes and procedures of the STOPCoV trial as well as share learning experiences to inform future fully decentralized research studies.

COVID-19 vaccine antibody responses in community-dwelling adults to 48 weeks post primary vaccine series.

We report a decentralized prospective cohort study of self-reported adverse events and antibody responses to COVID vaccines derived from dried blood spots. Data are presented for 911 older (aged >70 years) and 375 younger (30-50 years) recruits to 48 weeks after the primary vaccine series. After a single vaccine, 83% younger and 45% older participants had overall seropositivity (p < 0.0001) increasing to 100/98% with the second dose, respectively (p = 0.084). A cancer diagnosis (p = 0.009), no mRNA-1273 vaccine doses (p <0 .0001), and older age (p <0 .0001) predicted lower responses. Antibody levels declined in both cohorts at 12 and 24 weeks increasing with booster doses. At 48 weeks, for participants with 3 vaccine doses, the median antibody levels were higher in the older cohort (p = 0.04) with any dose of mRNA-1273 (p <0 .0001) and with COVID infection (p <0 .001). The vaccines were well tolerated. Breakthrough COVID infections were uncommon (16% older cohort, 29% younger cohort; p < 0.0001) and mild.

COVID-19 Vaccine Antibody Responses in Community Dwelling Adults to 48 weeks Post Primary Vaccine Series

We report a decentralized prospective cohort study of self-reported adverse events and antibody responses to COVID vaccines derived from dried blood spots. Data is presented for 911 older (aged >70 years) and 375 younger (30-50 years) recruits to 48 weeks after the primary vaccine series. After a single vaccine, 83% younger and 45% older participants had overall seropositivity (p<0.0001) increasing to 100/98% with the second dose respectively (p=0.084). A cancer diagnosis (p=.009), no mRNA1273 vaccine doses (p<.0001) and older age (p <.0001) predicted lower responses. Antibody levels declined in both cohorts at 12 and 24 weeks increasing with booster doses. At 48 weeks, for participants with 3 vaccine doses, the median antibody levels were higher in the older cohort (p=.04) with any dose of mRNA-1273 (p<.0001) and with COVID infection (p<.001). The vaccines were well tolerated. Breakthrough COVID infections were uncommon (16% older cohort, 29% younger cohort;p<0.0001) and mild. Graphical abstract

BEING: Bone Health in Aging Women with HIV: Impact of Switching Antiretroviral Therapy on Bone Mineral Density During the Perimenopausal Period.

Menopause is a high-risk period for osteoporosis, which may be exacerbated by HIV and/or antiretroviral therapy (ART). Our goal was to study the impact of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on bone mineral density (BMD) in peri- and early postmenopausal women living with HIV. This is a randomized international multicenter study of an early versus delayed (48-week) switch. BMD was measured by dual energy X-ray absorptiometry scan. Thirty-four women were enrolled: 19 in the immediate and 15 in the delayed switch arm from September 2017 to April 2019; 30 completed the 96-week protocol. The study closed for futility during the COVID-19 pandemic. The median (intraquartile range [IQR]) age was 51 years (47, 53), with a median (IQR) of 16.5 years (14, 23) since HIV diagnosis, median (IQR) 14 years (11, 20) of ART, and mean 8.6 years TDF. At enrollment, TDF was used in combination with a boosted protease inhibitor (n = 7), a non-nucleoside reverse transcriptase inhibitor (n = 13), an integrase inhibitor (n = 11), or more than one ART class (n = 3). The median (95% confidence interval [CI]) percentage change in BMD at the lumbar spine from 0 to 48 weeks in the immediate switch group was 1.97% (-1.15 to 5.49) compared with a median (95% CI) decrease of 2.32% (-5.11 to 0.19) in the delayed arm. The median (95% CI) percentage change in BMD from 0 to 96 weeks was 2.33% (0-4.51) in the immediate arm compared with 0.70% (-3.19 to 2.47) in the delayed arm. We demonstrated a trend to increased BMD at the lumbar spine after a switch from TDF to TAF in peri- and early postmenopausal women living with HIV. Clinical Trials.gov: NCT02815566.

COVID-19 breakthrough infections in vaccinated participants of the Safety and Efficacy of Preventative COVID Vaccines sub-study.

BACKGROUND: The rate of breakthrough infection in vaccinated Ontarians during the Omicron wave is unknown. METHODS: Active participants of the Safety and Efficacy of Preventative COVID Vaccines (STOPCoV) study (892 ≥age 70 years and 369 aged 30-50 years) were invited to participate in a sub-study evaluating breakthrough COVID-19 infection. Self-administered rapid antigen tests (RAT) were reported twice weekly and symptom questionnaires weekly for 6 weeks. The primary outcome was the proportion reporting a positive RAT. RESULTS: A total of 806 e-consented, and 727 (90%) completed ≥1 RAT, with total 7,116 RATs completed between January 28 and March 29, 2022. Twenty out of twenty-five participants with a positive RAT had a booster vaccine prior to the positive test. All cases were mild, none requiring hospitalization. Nineteen had positive dried blood spot analysis for IgG antibody to the receptor binding domain (RBD) prior to the positive RAT. The mean normalized IgG ratio to RBD was 1.22 (SD 0.29) for younger and 0.98 (SD 0.44) for older participants, values similar to corresponding ratios for those without positive RATs and those in the main cohort. One hundred and five participants reported one and 96 reported ≥2 possible COVID-19 symptoms despite negative RATs. The false negative RAT was low (4% to 6.6 %) compared with subsequent positive nucleoprotein antibody. CONCLUSIONS: Positive RAT for COVID-19 was infrequent (3.4%). We were unable to determine a protective antibody level against breakthrough infection. Our findings can inform public health COVID-19 restrictions guidelines. Our decentralized study provides a model for rapid institution of new questions during a pandemic.

HISTORIQUE: On ne connaît pas le taux d'infections postvaccinales pendant la vague Omicron chez les Ontariens vaccinés. MÉTHODOLOGIE: Les participants actifs de l'étude Safety and Efficacy of Preventative COVID Vaccines (STOPCoV; 892 de 79 ans ou plus et 369 de 30 à 50 ans) ont été invités à prendre part à une sous-étude évaluant les infections postvaccinales causées par la COVID-19. Les résultats des tests d'antigène rapides (TAR) autoadministrés ont été transmis deux fois par semaine et le questionnaire sur les symptômes, toutes les semaines pendant six semaines. Les résultats primaires correspondaient à la proportion ayant déclaré des TAR positifs. RÉSULTATS: Au total, 806 ont consenti par voie électronique et 727 (90 %) ont effectué au moins un TAR, pour un total de 7 116 TAR effectués entre le 28 janvier et le 29 mars 2022. Ainsi, 21 des 25 participants ayant obtenu un résultat positif au TAR avaient reçu une dose de rappel auparavant. Tous les cas étaient légers, et aucun n'a dû être hospitalisé. Dix-neuf ont obtenu une analyse des gouttes de sang séché positives aux anticorps des IgG du domaine de liaison des récepteurs (RBD) avant le résultat positif du TAR. L'écart-type moyen du ratio d'IgG normalisé au RBD était de 1,22 (ÉT = 0,29) pour les participants plus jeunes, et de 0,98 (ÉT = 0,44) chez les participants plus âgés, les valeurs étaient semblables aux ratios correspondants pour ceux dont le TAR n'était pas positif et ceux de la cohorte principale. Au total, 105 participants ont déclaré un symptôme possible de COVID-19 et 96 en ont déclaré au moins deux, malgré des résultats négatifs au TAR. Le taux de TAR faussement négatifs était faible (4 % à 6,6 %) par rapport à l'anticorps nucléoprotéique positif subséquent. CONCLUSIONS: Les résultats positifs des TAR à la COVID-19 étaient peu courants (3,4 %). Les chercheurs n'ont pas été en mesure de déterminer le taux d'anticorps protecteurs contre l'infection postvaccinale. Ces résultats peuvent éclairer les directives sur les restrictions sanitaires liées à la COVID-19. La présente étude décentralisée fournit un modèle pour l'adoption rapide de nouvelles questions pendant une pandémie.

Protecting Frontline Health Care Workers from COVID-19 with Hydroxychloroquine Pre-exposure Prophylaxis: A structured summary of a study protocol for a randomised placebo-controlled multisite trial in Toronto, Canada.

OBJECTIVES: Primary Objective: To determine if pre-exposure prophylaxis (PrEP) with 400mg hydroxychloroquine (HCQ), taken orally once daily reduces microbiologically confirmed COVID-19 among front line health care workers at high risk for SARS-CoV-2 exposure. Secondary Objectives: To compare the following between study arms: adverse events; symptomatic COVID-19; duration of symptomatic COVID-19; days hospitalized attributed to COVID-19; respiratory failure attributable to COVID-19 requiring i) non-invasive ventilation or ii) intubation/mechanical ventilation; mortality attributed to COVID-19, number of days unable to work attributed to COVID-19, seroconversion (COVID-19 negative to COVID-19 positive over the study period); ability of participant plasma to neutralize SARS-CoV-2 virus in vitro; To describe short-term psychological distress associated with risk of COVID-19 exposure at 1, 60, 120 days of the study. To explore laboratory markers within participants with confirmed COVID-19: including circulating markers of host immune and endothelial activation in participant plasma and their correlation with disease severity and outcome TRIAL DESIGN: The HEROS study is a two-arm, parallel-group, individually randomized (1:1 allocation ratio), placebo controlled, participant and investigator-blinded, multi-site superiority trial of oral HCQ 400 mg taken once daily for 90 days as PrEP to prevent COVID-19 in health care workers at high risk of SARS-CoV-2 exposure. At 90 days, there is an open label extension wherein all participants are offered a one-month course of HCQ 400mg once daily for PrEP of COVID-19. PARTICIPANTS: Frontline HCWs aged 18 years of age or older, at high risk of SARS-CoV-2 exposure (including staff of emergency departments, intensive care units, intubation teams, COVID-wards, and staff deployed to Long Term Care facilities) of five academic hospitals in downtown Toronto, Canada. Exclusion criteria include: currently pregnant, planning to become pregnant during the study period, and/or breast feeding; known hypersensitivity/allergy to hydroxychloroquine or to 4-aminoquinoline compounds; current use of hydroxychloroquine; known prolonged QT syndrome and/or baseline resting ECG with QTc>450 ms and/or concomitant medications which simultaneously may prolong the QTc that cannot be temporarily suspended/replaced; known pre-existing retinopathy, G6PD deficiency, porphyria, liver disease including cirrhosis, encephalopathy, hepatitis or alcoholism, diabetes on oral hypoglycemics or insulin, or renal insufficiency/failure; disclosure of self-administered use of hydroxychloroquine or chloroquine within 12 weeks prior to study; confirmed symptomatic COVID-19 at time of enrollment. INTERVENTION AND COMPARATOR: Intervention: hydroxychloroquine, 400mg (2 tablets) orally per day. Comparator: placebo, two tablets visually identical to the intervention, orally per day MAIN OUTCOMES: The primary outcome is microbiologically confirmed COVID-19 (i.e. SARS-CoV-2 infection). This is a composite endpoint which includes positive results from any validated SARS-CoV-2 diagnostic assay including detection of viral RNA, and/or seroconversion. Participants will be assessed at baseline, and then undergo monthly follow-up at day 30, 60, and 90, 120. At each visit, participants will provide an oropharyngeal sample, blood sample, and will undergo electrocardiogram monitoring of the QTc interval. Secondary outcome measures include: adverse events; symptom duration of COVID-19; days of hospitalization attributed to COVID-19; respiratory failure requiring ventilator support attributed to COVID-19; mortality attributed to COVID-19; total days off work attributed to COVID-19; seropositivity (reactive serology by day 120); and short term psychological impact of exposure to SARS-CoV-2 at day 1, 60, 120 days using the K10, a validated measure of non-specific psychological distress. RANDOMISATION: Within each site, participants will be individually randomized to either the intervention arm with HCQ or the placebo arm using a fixed 1:1 allocation ratio using an interactive web-based response system to ensure concealment of allocation. Randomization schedules will be computer-generated and blocked using variable block sizes. BLINDING (MASKING): All participants, research coordinators, technicians, clinicians and investigators will be blinded to the participant allocation group. Numbers to be randomised (sample size) N=988, randomised into two groups of 494 patients. TRIAL STATUS: This summary describes protocol version No. 1.6, May 15, 2020. Recruitment is ongoing - started April 20, 2020 and anticipated end date is July 30, 2021 TRIAL REGISTRATION: ISRCTN.com Identifier: ISRCTN14326006, registered April 14, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).