A longitudinal prospective cohort study of health-related quality of life assessment in outpatient adults with post-COVID-19 conditions.

Background: Few studies have reported the long-term effects of post-COVID-19 condition (PCC) on health-related quality of life (HRQoL). We aim to assess HRQoL in outpatient adults with PCC over a 2-year period. Methods: This prospective longitudinal cohort study compared 413 PCC participants (cases) to 520 COVID-19-positive participants who recovered (controls). HRQoL was assessed with the EuroQol 5-Dimension 5-Level preference-based questionnaire (EQ-5D-5L) and fitness and frailty with the Clinical Frailty Scale (CFS) at each visit for up to 24 months. Results: Among a total of 933 participants, 413 (42.3%) met the definition of PCC (cases) and 520 (55.7%) did not (controls). Overall, there was a significant difference in EQ-5D-5L index score from 3 months post-infection up to 18 months between cases and controls (p < 0.001). This score continued to decline up to 18 months in the PCC group only. Most impaired EQ-5D-5L dimensions at 12 months in the PCC group included pain/discomfort, anxiety/depression, and usual activities. Conclusions: This is one of the first studies to report 2-year alterations of HRQoL in outpatients with PCC. Our study highlights the need for continued monitoring for PCC long-term consequences. Given the high proportion of PCC participants experiencing anxiety/depression problems, further studies are needed to specifically address mental health in this population.

Historique: Peu d'études traitent des effets à long terme de l'affection post-COVID-19 (APC) sur la qualité de vie liée à la santé (QVLS). Les chercheurs ont évalué la QVLS des adultes ambulatoires atteints d'une APC sur une période de deux ans. Méthodologie: Dans la présente étude de cohorte longitudinale prospective, les chercheurs ont comparé 413 participants atteints d'une APC (les cas) à 520 participants ayant obtenu un résultat positif à la COVID-19 qui se sont rétablis (les sujets témoins). Ils ont évalué la QVLS à l'aide du questionnaire EQ-5D-5L, de même que la condition physique et la fragilité à l'aide de l'échelle de fragilité clinique (CFS) lors de chaque rendez-vous sur une période maximale de 24 mois. Résultats: Sur un total de 933 participants, 413 (42,3 %) respectaient la définition d'APC (les cas) et 520 (55,7 %) ne la respectaient pas (sujets témoins). Dans l'ensemble, les chercheurs ont constaté une différence significative du score de l'indice EQ-5D-5L entre trois mois et un maximum de 18 mois suivant l'infection entre les cas et les sujets témoins (p < 0,001). C'est seulement au sein du groupe atteint d'une APC que ce score a continué de baisser pendant une période maximale de 18 mois. La douleur et les malaises, l'anxiété et la dépression et les activités habituelles étaient les dimensions de l'EQ-5D-5L les plus touchées au bout de 12 mois dans le groupe atteint d'une. APC Conclusions: La présente étude est l'une des premières à rendre compte des transformations de la QVLS chez les patients ambulatoires atteints d'une APC sur deux ans. Elle démontre la nécessité d'une surveillance continue des conséquences à long terme de l'APC. Étant donné la forte proportion de participants atteints d'une APC qui éprouvent des troubles d'anxiété et de dépression, d'autres études s'imposent pour évaluer expressément les problèmes de santé mentale au sein de cette population.

SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition.

Background: Following SARS-CoV-2 infection a significant proportion of convalescent individuals develop the post-COVID condition (PCC) that is characterized by wide spectrum of symptoms encompassing various organs. Even though the underlying pathophysiology of PCC is not known, detection of viral transcripts and antigens in tissues other than lungs raise the possibility that PCC may be a consequence of aberrant immune response to the viral antigens. To test this hypothesis, we evaluated B cell and antibody responses to the SARS-CoV-2 antigens in PCC patients who experienced mild COVID-19 disease during the pre-vaccination period of COVID-19 pandemic. Methods: The study subjects included unvaccinated male and female subjects who developed PCC or not (No-PCC) after clearing RT-PCR confirmed mild COVID-19 infection. SARS-CoV-2 D614G and omicron RBD specific B cell subsets in peripheral circulation were assessed by flow cytometry. IgG, IgG3 and IgA antibody titers toward RBD, spike and nucleocapsid antigens in the plasma were evaluated by ELISA. Results: The frequency of the B cells specific to D614G-RBD were comparable in convalescent groups with and without PCC in both males and females. Notably, in females with PCC, the anti-D614G RBD specific double negative (IgD-CD27-) B cells showed significant correlation with the number of symptoms at acute of infection. Anti-spike antibody responses were also higher at 3 months post-infection in females who developed PCC, but not in the male PCC group. On the other hand, the male PCC group also showed consistently high anti-RBD IgG responses compared to all other groups. Conclusions: The antibody responses to the spike protein, but not the anti-RBD B cell responses diverge between convalescent males and females who develop PCC. Our findings also suggest that sex-related factors may also be involved in the development of PCC via modulating antibody responses to the SARS-CoV-2 antigens.

SARS-CoV-2 infection outcomes associated with the Delta variant: A prospective cohort study.

Background: It is well established that fully vaccinated (≥2 doses) individuals may develop COVID-19. However, little is known about the specific prevalence of post-COVID-19 conditions associated with the Delta variant or the effect of vaccination on post-acute outcomes of COVID-19. In addition, how Delta variant infection severity compares in fully vaccinated individuals versus in those unvaccinated is unknown. Methods: This prospective single-centre observational cohort study assessed adults with SARS-CoV-2 proven infection from August 1 to November 1, 2021. Study participants were enrolled in the Biobanque Québécoise de la COVID-19. Data on demographics, comorbidities, and severity of COVID-19 were collected. Simple and multiple logistic regressions were used to identify risk factors for post-COVID-19 conditions. Results: Among the 395 individuals who were interviewed by phone, 138 (39.4%) agreed to participate. Of the 138 participants, 62.8% were Delta-associated breakthrough infections that occurred in fully vaccinated individuals and 37.1% in unvaccinated individuals. The majority (93.5%) had a history of mild COVID-19 illness. The prevalence of Delta-variant-associated post-COVID-19 conditions was similar in both vaccinated (61.4%) and unvaccinated (51.4%) groups (p = 0.347). The number of symptoms during acute infection was an independent risk factor for post-COVID-19 conditions. Conclusions: This study is the first to describe the incidence of Delta-associated post-COVID-19 condition. In this study, COVID-19 vaccination was not associated with decreased post-COVID-19 conditions in patients with breakthrough Delta infection. These findings have important implications for provincial services planning and underscore the need to develop alternative strategies to prevent post-COVID-19 conditions.

Historique: Il est bien établi que les personnes pleinement vaccinées (au moins deux doses) peuvent contracter la COVID-19. Cependant, on sait peu de choses sur la prévalence exacte des affections post-COVID-19 associées au variant Delta et sur l'effet de la vaccination sur les résultats post-aigus de la COVID-19. Par ailleurs, on ne sait pas quelle est la gravité de l'infection par le variant Delta chez les personnes pleinement vaccinées par rapport à celles qui ne le sont pas. Méthodologie: La présente étude de cohorte observationnelle unicentrique et prospective visait à évaluer des adultes atteints d'une infection démontrée par le SRAS-CoV-2 entre le 1er aoÛt et le 1er novembre 2021. Les participants à l'étude étaient inscrits à la Biobanque québécoise de la COVID-19. Les chercheurs ont recueilli les données sur les caractéristiques démographiques, les affections connexes et la gravité de la COVID-19. Ils ont utilisé la régression logistique simple et multiple pour déterminer les facteurs de risque d'affections post-COVID-19. Résultats: Des 395 personnes interviewées par téléphone, 138 (39,4%) ont accepté de participer. De ce nombre, 62,8% étaient des personnes pleinement vaccinées qui avaient souffert d'une infection postvaccinale par le variant Delta et 37,1%, des personnes non vaccinées. La majorité (93,5%) avait une histoire de COVID-19 légère. La prévalence d'affections post-COVID-19 liées au variant Delta était semblable dans les groupes vaccinés (61,4% [48,4%­73%]) et non vaccinés (51,4% [35,6%­67%]; p = 0,347. Le nombre de symptômes pendant l'infection aiguë était un facteur de risque indépendant d'affections post-COVID-19. Conclusions: La présente étude est la première à décrire l'incidence d'affections post-COVID-19 liées au variant Delta. La vaccination contre la COVID-19 n'était pas liée à une diminution d'affections post-COVID-19 chez les patients atteints d'une infection postvaccinale par le variant Delta. Ces observations ont des conséquences importantes pour la planification des services provinciaux et font ressortir la nécessité de trouver d'autres stratégies pour éviter les affections post-COVID-19.

Prevalence of persistent symptoms at least 1 month after SARS-CoV-2 Omicron infection in adults.

Background: Persistent post-COVID-19 symptoms pose an important health care burden. The Omicron variant has rapidly spread across the world and infected millions of people, largely exceeding previous variants. The potential for many of these people to develop persistent symptoms is a major public health concern. The aim of this study was to determine the prevalence and risk factors of post-COVID-19 symptoms associated with Omicron. Methods: We conducted a single-centre prospective observational study in Quebec, Canada, between December 2021 and April 2022. Participants were adults enrolled in the Biobanque Québécoise de la COVID-19 (BQC19). Cases were considered Omicron cases as more than 85% were estimated to be attributable to Omicron variant during that period. Adults with polymerase chain reaction (PCR)-confirmed COVID-19 were recruited at least 4 weeks after the onset of infection. Results: Of 1,338 individuals contacted, 290 (21.7%) participants were recruited in BQC19 during that period. Median duration between the initial PCR test and follow-up was 44 days (IQR 31-56 d). A total of 137 (47.2%) participants reported symptoms at least 1-month post-infection. The majority (98.6%) had a history of mild COVID-19 illness. Most common persistent symptoms included fatigue (48.2%), shortness of breath (32.6%), and cough (24.1%). Number of symptoms during acute COVID-19 was identified as a risk factor for post-COVID-19 symptoms (OR 1.07 [95% CI 1.03% to 1.10%] p = 0.009). Conclusions: This is the first study reporting the prevalence of post-COVID-19 symptoms associated with Omicron in Canada. These findings will have important implications for provincial services planning.

Historique: Les symptômes post-COVID-19 persistants représentent un fardeau important pour la santé. Le variant Omicron s'est propagé rapidement dans le monde et a infecté des milliers de personnes, un nombre largement supérieur aux variants qui l'avaient précédé. Le risque que bon nombre d'entre elles acquièrent des symptômes persistants est un problème sanitaire majeur. La présente étude visait à déterminer la prévalence et les facteurs de risques de symptômes post-COVID-19 liés au variant Omicron. Méthodologie: Les chercheurs ont réalisé une étude observationnelle monocentrique à Québec, au Canada, entre décembre 2021 et avril 2022. Les participants étaient des adultes inscrits à la Biobanque québécoise de la COVID-19 (BQC19). Les cas étaient considérés comme découler du variant Omicron parce que plus de 85% étaient estimés y être attribuables pendant cette période. Les adultes atteints d'une COVID-19 confirmée par un test d'amplification en chaîne par polymérase (PCR) ont été recrutés au moins quatre semaines après l'apparition de l'infection. Résultats: Des 1 338 personnes contactées, 290 (21,7%) ont été recrutées dans la BQC19 pendant cette période. La période moyenne entre le test PCR initial et le suivi était de 44 jours (ÉIQ: de 31 à 56 jours). Au total, 137 participants (47,2%) ont déclaré des symptômes au moins un mois après l'infection. La majorité avait été atteinte d'une COVID-19 légère. Les symptômes les plus persistants étaient la fatigue (48,2%), l'essoufflement (32,6%) et la toux (24,1%). Il a été établi que le nombre de symptômes pendant la COVID-19 aiguë (rapport de cotes: 1,07, IC à 95% 1,03% à 1,10%; p = 0,009) était un facteur de risque de symptômes post-COVID-19. Conclusions: La présente étude est la première à rendre compte de la prévalence de symptômes post-COVID-19 associés au variant Omicron au Canada. Ces observations auront des conséquences importantes pour la planification des services provinciaux.

Kinetics of 13C-DHA before and during fish-oil supplementation in healthy older individuals.

BACKGROUND: Docosahexaenoic acid (DHA) kinetics appear to change with intake, which is an effect that we studied in an older population by using uniformly carbon-13-labeled DHA ((13)C-DHA). OBJECTIVE: We evaluated the influence of a fish-oil supplement over 5 mo on the kinetics of (13)C-DHA in older persons. DESIGN: Thirty-four healthy, cognitively normal participants (12 men, 22 women) aged between 52 and 90 y were recruited. Two identical kinetic studies were performed, each with the use of a single oral dose of 40 mg (13)C-DHA. The first kinetic study was performed before participants started taking a 5-mo supplementation that provided 1.4 g DHA/d plus 1.8 g eicosapentaenoic acid (EPA)/d (baseline); the second study was performed during the final month of supplementation (supplement). In both kinetic studies, blood and breath samples were collected ≤8 h and weekly over 4 wk to analyze (13)C enrichment. RESULTS: The time × supplement interaction for (13)C-DHA in the plasma was not significant, but there were separate time and supplement effects (P < 0.0001). The area under the curve for plasma (13)C-DHA was 60% lower while subjects were taking the supplement than at baseline (P < 0.0001). The uniformly carbon-13-labeled EPA concentration was 2.6 times as high 1 d posttracer while patients were taking the supplement as it was at baseline. The mean (±SEM) plasma (13)C-DHA half-life was 4.5 ± 0.4 d at baseline compared with 3.0 ± 0.2 d while taking the supplement (P < 0.0001). Compared with baseline, the mean whole-body half-life was 61% lower while subjects were taking the supplement. The loss of (13)C-DHA through ß-oxidation to carbon dioxide labeled with carbon-13 increased from 0.085% of dose/h at baseline to 0.208% of dose/h while subjects were taking the supplement. CONCLUSIONS: In older persons, a supplement of 3.2 g EPA + DHA/d increased ß-oxidation of (13)C-DHA and shortened the plasma (13)C-DHA half-life. Therefore, when circulating concentrations of EPA and DHA are increased, more DHA is available for ß-oxidation. This trial was registered at clinicaltrials.gov as NCT01577004.

Reduction in DHA transport to the brain of mice expressing human APOE4 compared to APOE2.

Benefits on cognition from docosahexaenoic acid (DHA, 22 : 6 n-3) intake are absent in humans carrying apolipoprotein E ε4 allele (APOE4), the most important genetic risk factor for Alzheimer's disease (AD). To test the hypothesis that carrying APOE4 impairs DHA distribution, we evaluated plasma and brain fatty acid profiles and uptake of [(14) C]-DHA using in situ cerebral perfusion through the blood-brain barrier in 4- and 13-month-old male and female APOE-targeted replacement mice (APOE2, APOE3, and APOE4), fed with a DHA-depleted diet. Cortical and plasma DHA were 9% lower and 34% higher in APOE4 compared to APOE2 mice, respectively. Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. A significant relationship was established between DHA and apoE concentrations in the cortex of mice (r(2) = 0.21) and AD patients (r(2) = 0.32). Altogether, our results suggest that lower brain uptake of DHA in APOE4 than in APOE2 mice may limit the accumulation of DHA in cerebral tissues. These data provide a mechanistic explanation for the lack of benefit of DHA in APOE4 carriers on cognitive function and the risk of AD. Using human APOE2, 3, and 4 isoform-specific transgenic mice, we found a lower brain uptake of docosahexaenoic acid (DHA) in APOE4 than in APOE2 mice that may limit the biodistribution of DHA in cerebral tissues. These data provide a mechanistic explanation for the lack of benefit of DHA in APOE4 carriers on cognitive function and the risk of Alzheimer's disease (AD).