Cohort Profile: Longitudinal population-based study of COVID-19 in UK adults (COVIDENCE UK)

BackgroundCoronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is estimated to have caused more than 18 million deaths worldwide as of end-May 2022. MethodsCOVIDENCE UK is a longitudinal population-based study that investigates risk factors for, and impacts of, COVID-19 in UK residents aged [≥]16 years. A unique feature is the capacity to support trial-within-cohort studies to evaluate interventions for prevention of COVID-19 and other acute respiratory illnesses. Participants complete a detailed online baseline questionnaire capturing self-reported information relating to their socio-demographic characteristics, occupation, lifestyle, quality of life, weight, height, longstanding medical conditions, medication use, vaccination status, diet and supplemental micronutrient intake. Follow-up on-line questionnaires capturing incident symptoms of COVID-19 and other acute respiratory infections, incident swab test-confirmed COVID-19, doses of SARS-CoV-2 vaccine received, and quality of life are completed at monthly intervals. ResultsThe study was launched on 1st May 2020 and closed to recruitment on 6th October 2021. A total of 19,981 participants enrolled and consented to 5-year follow-up with medical record linkage. Their mean age was 59.1 years (range 16.0 to 94.4 years), 70.2% were female, and 93.7% identified their ethnic origin as White. Analyses conducted to date have provided key insights into risk factors for SARS-CoV-2 infection and COVID-19 disease, determinants of SARS-CoV-2 vaccine immunogenicity and efficacy, and impacts of COVID-19 on health economic outcomes. The cohort has also supported conduct of a Phase 3 randomised trial-within-cohort study (CORONAVIT) evaluating implementation of a test-and-treat approach to correcting sub-optimal vitamin D status on incidence and severity of acute respiratory infections, including COVID-19. ConclusionsThe COVIDENCE UK dataset represents a valuable resource containing granular information on factors influencing susceptibility to, and impacts of, COVID-19 in UK adults. Researchers wishing to access anonymised participant-level data should contacting the corresponding author for further information.

Vitamin D Supplements for Prevention of Covid-19 or other Acute Respiratory Infections: a Phase 3 Randomized Controlled Trial (CORONAVIT)

OBJECTIVESTo determine whether population-level implementation of a test-and- treat approach to correction of sub-optimal vitamin D status (25-hydroxyvitamin D [25(OH)D] <75 nmol/L) influences risk of all-cause acute respiratory infection (ARI) or coronavirus disease 2019 (COVID-19). DESIGNPhase 3 open-label randomised controlled trial (CORONAVIT) utilising trials-within-cohorts (TwiCs) methodology. SETTINGUnited Kingdom. PARTICIPANTS6200 adults aged 16 years or older, who were not already taking vitamin D supplements at baseline. INTERVENTIONSOffer of a postal finger-prick test of blood 25(OH)D concentration with provision of a 6-month supply of higher-dose vitamin D (3200 IU/day, n=1550) or lower-dose vitamin D (800 IU/day, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, vs. no offer of testing or supplementation (n=3100). Follow-up was from 17th December 2020 to 16th June 2021. MAIN OUTCOME MEASURESThe primary outcome was the proportion of participants experiencing at least one doctor- or swab test-confirmed ARI of any cause. Secondary outcomes included the proportion of participants developing swab test-confirmed COVID-19. Logistic regression was used to calculate odds ratios and associated 95% confidence intervals. RESULTSOf 3100 participants offered 25(OH)D testing, 2958 (95.4%) accepted, and 2690 (86.8%) had 25(OH)D <75 nmol/L and were sent vitamin D supplements (1356 higher-dose, 1334 lower-dose). 76 (5.0%) vs. 87 (5.7%) vs. 136 (4.6%) participants in higher-dose vs. lower-dose vs. no offer groups experienced at least one ARI of any cause (odds ratio [OR] for higher-dose vs. no offer 1.09, 95% CI 0.82-1.46; lower-dose vs. no offer 1.26, 0.96-1.66). 45 (3.0%) vs. 55 (3.6%) vs. 78 (2.6%) participants in higher-dose vs. lower-dose vs. no offer groups developed COVID-19 (OR for higher-dose vs. no offer 1.13, 0.78-1.63; lower-dose vs. no offer 1.39, 0.98-1.97). CONCLUSIONSAmong adults with a high baseline prevalence of sub-optimal vitamin D status, implementation of a population-level test-and-treat approach to vitamin D replacement did not reduce risk of all-cause ARI or COVID-19. TRIAL REGISTRATIONClinicalTrials.gov no. NCT04579640 SUMMARY BOXO_ST_ABSWhat is already known on this topic?C_ST_ABSVitamin D metabolites support innate immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory pathogens. Sub-optimal vitamin D status (25-hydroxyvitamin D <75 nmol/L) associates with increased susceptibility to all-cause acute respiratory infections (ARI) and coronavirus disease 2019 (COVID-19). Phase 3 randomised controlled trials of vitamin D to prevent COVID-19 have not yet reported. What this study addsThis phase 3 randomised controlled trial, including 6200 participants, shows that implementation of a population-level test-and-treat approach to oral vitamin D replacement at a dose of 800 IU or 3200 IU per day did not reduce risk of all-cause ARI or COVID-19 among adults with a high baseline prevalence of sub-optimal vitamin D status.

Partial external mitral annuloplasty in dogs with myxomatous mitral valve degeneration and congestive heart failure: outcome in 9 cases.

OBJECTIVE: To report the outcome of partial external mitral annuloplasty in dogs with congestive heart failure (CHF) due to mitral regurgitation caused by myxomatous mitral valve degeneration (MMVD). ANIMALS, MATERIALS AND METHODS: Nine client-owned dogs with CHF due to mitral regurgitation caused by MMVD. Surgery consisted of a double row of pledget-butressed continuous suture lines placed into the left ventricle parallel and just ventral to the atrioventricular groove between the subsinuosal branch of the left circumflex coronary artery and the paraconal branch of the left coronary artery. RESULTS: Two dogs died during surgery because of severe hemorrhage. Two dogs died 12 and 36 h after surgery because of acute myocardial infarction. Three dogs were euthanized 2 and 4 weeks after surgery because of progression of CHF, 1 was euthanized 30 days after surgery for non-cardiac disease, and 1 survived for 48 months. In the 5 dogs that survived to discharge there was no significant change in the left atrium to aortic ratio with surgery (3.6 ± 0.56 before surgery; 3.1 ± 0.4 after surgery; p = 0.182), and no significant change in mitral regurgitant fraction in 4 dogs in which this measurement was made (78.7 ± 2.0% before surgery; 68.7 ± 7.5% after surgery; p = 0.09). CONCLUSIONS: Partial external mitral annuloplasty in dogs with CHF due to MMVD was associated with high perioperative mortality and most dogs that survived to discharge failed to show clinically relevant palliation from this procedure. Consequently, partial external mitral annuloplasty is not a viable option for dogs with mitral regurgitation due to MMVD that has progressed to the stage of CHF.

Immunoproteomic identification of bovine pericardium xenoantigens.

Bovine pericardium is an important biomaterial with current application in glutaraldehyde-fixed bioprosthetic heart valves and possible future application as an unfixed biological scaffold for tissue engineering. The importance of both humoral and cell-mediated rejection responses toward fixed and unfixed xenogeneic tissues has become increasingly apparent. However, the full scope and specific identities of bovine pericardium proteins that can elicit an immune response remain largely unknown. In this study, an immunoproteomic approach was used to survey bovine pericardium proteins for their ability to elicit a humoral immune response in rabbits. A two-stage protein extraction protocol was used to separate bovine pericardium proteins into water- and lipid-soluble fractions. Two-dimensional (2-D) gel electrophoresis was performed to separate the proteins from each fraction. Western blots were generated from 2-D gels of both bovine pericardium protein fractions. These blots were probed with serum from rabbits immunized with bovine pericardium and a secondary antibody was used to assess for IgG positivity. Western blots were compared to duplicate 2-D gels and proteins in matched spots were identified by tandem mass spectrometry. Thirty-one putative protein antigens were identified, eight of which are known to be antigenic from previous studies. All of the putative antigens demonstrated progressive staining intensity with increasing days of post-exposure serum. Identified antigenic proteins represented a variety of functional and structural protein types, and included both cellular and matrix proteins. The results of this study have implications for the use of bovine pericardium as a biomaterial in bioprostheses and tissue engineering applications, as well as xenotransplantation in general.