Gravité de la COVID-19 chez les receveurs d'une transplantation d'organe plein au Canada, 2020­2021 : étude de cohorte prospective multicentrique.

CONTEXTE: La forme grave de COVID-19 semble affecter de manière disproportionnée les gens immunovulnérables, même si les données canadiennes dans ce contexte sont limitées. Nous avons voulu déterminer quels facteurs sont associés aux paramètres de la forme grave de COVID-19 chez les receveurs de transplantations au Canada. MÉTHODES: Nous avons procédé à une étude de cohorte multicentrique prospective regroupant tous les receveurs d'une transplantation d'organe plein ayant reçu un diagnostic de COVID-19 suivis dans 9 programmes de transplantation au Canada entre mars 2020 et novembre 2021. Les données ont été analysées afin de dégager les facteurs de risque à l'égard du recours à l'oxygénothérapie et autres critères de la gravité de la maladie. Nous avons comparé les paramètres selon le type d'organe transplanté et suivi l'évolution des paramètres au fil du temps. Nous avons procédé à une analyse multivariée pour déterminer quelles variables sont associées au recours à l'oxygénothérapie. RÉSULTATS: En tout, 509 patients ayant reçu une transplantation d'organe plein ont contracté la COVID-19 durant la période de l'étude. Les facteurs de risque associés au recours à l'oxygénothérapie (n = 190) ou non (n = 319) incluaient l'âge (âge médian 62,6 ans, intervalle interquartile [II] 52,5­69,5 ans c. âge médian 55,5 ans, II 47,5­66,5; p < 0,001) et le nombre de comorbidités (nombre médian 3, II 2­3 c. nombre médian 2, II 1­3; p < 0,001), de même que les paramètres concernant l'immunosuppression. Les receveurs d'une transplantation pulmonaire (n = 48) étaient plus susceptibles de souffrir d'une forme grave de la maladie, avec un taux de mortalité élevé (n = 15, 31,3 %) comparativement aux receveurs d'autres organes, y compris le rein (n = 48, 14,8 %), le cœur (n = 1, 4,4 %), le foie (n = 9, 11,4 %) et le rein­pancréas (n = 3, 12,0 %) (p = 0,02). Les facteurs protecteurs contre le recours à l'oxygénothérapie incluaient le fait d'avoir subi une transplantation hépatique et de recevoir de l'azathioprine. Le fait d'avoir reçu 2 doses de vaccin anti-SRAS-CoV-2 n'a pas eu d'influence appréciable sur le recours à l'oxygénothérapie. L'analyse multivariée a montré que l'âge avancé (rapport des cotes [RC] 1,04, intervalle de confiance [IC] de 95 % 1,02­1,07) et le nombre de comorbidités (RC 1,63, IC de 95 % 1,30­2,04), entre autres facteurs, étaient associés au recours à l'oxygénothérapie. La gravité de la maladie n'a pas considérablement diminué au fil du temps. INTERPRÉTATION : Malgré les progrès thérapeutiques et la vaccination des receveurs d'une transplantation d'organe plein, les signes de gravité accrue de la COVID-19, en particulier chez les receveurs d'une transplantation pulmonaire, justifient le maintien des mesures de santé publique pour protéger ces personnes à risque, et l'utilisation hâtive de traitements contre la COVID-19 chez les receveurs d'une transplantation d'organe plein.

Severity of COVID-19 among solid organ transplant recipients in Canada, 2020-2021: a prospective, multicentre cohort study.

BACKGROUND: Severe COVID-19 appears to disproportionately affect people who are immunocompromised, although Canadian data in this context are limited. We sought to determine factors associated with severe COVID-19 outcomes among recipients of organ transplants across Canada. METHODS: We performed a multicentre, prospective cohort study of all recipients of solid organ transplants from 9 transplant programs in Canada who received a diagnosis of COVID-19 from March 2020 to November 2021. Data were analyzed to determine risk factors for oxygen requirement and other metrics of disease severity. We compared outcomes by organ transplant type and examined changes in outcomes over time. We performed a multivariable analysis to determine variables associated with need for supplemental oxygen. RESULTS: A total of 509 patients with solid organ transplants had confirmed COVID-19 during the study period. Risk factors associated with needing (n = 190), compared with not needing (n = 319), supplemental oxygen included age (median 62.6 yr, interquartile range [IQR] 52.5-69.5 yr v. median 55.5 yr, IQR 47.5-66.5; p < 0.001) and number of comorbidities (median 3, IQR 2-3 v. median 2, IQR 1-3; p < 0.001), as well as parameters associated with immunosuppression. Recipients of lung transplants (n = 48) were more likely to have severe disease with a high mortality rate (n = 15, 31.3%) compared with recipients of other organ transplants, including kidney (n = 48, 14.8%), heart (n = 1, 4.4%), liver (n = 9, 11.4%) and kidney-pancreas (n = 3, 12.0%) transplants (p = 0.02). Protective factors against needing supplemental oxygen included having had a liver transplant and receiving azathioprine. Having had 2 doses of SARS-CoV-2 vaccine did not have an appreciable influence on oxygen requirement. Multivariable analysis showed that older age (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.07) and number of comorbidities (OR 1.63, 95% CI 1.30-2.04), among other factors, were associated with the need for supplemental oxygen. Over time, disease severity did not decline significantly. INTERPRETATION: Despite therapeutic advances and vaccination of recipients of solid organ transplants, evidence of increased severity of COVID-19, in particular among those with lung transplants, supports ongoing public health measures to protect these at-risk people, and early use of COVID-19 therapies for recipients of solid organ transplants.

Outcomes of SARS-CoV-2 Infection in Unvaccinated Compared With Vaccinated Solid Organ Transplant Recipients: A Propensity Matched Cohort Study.

BACKGROUND: Solid organ transplant (SOT) recipients are at high risk for complications from coronavirus disease 2019 (COVID-19). Vaccination may mitigate this risk; however, immunogenicity appears to be significantly impaired, with reports of increased risk of breakthrough infection. It is unknown if vaccine breakthrough infections are milder or as severe as infections in unvaccinated patients. METHODS: We performed a multicenter matched cohort study between March 2020 and September 2021 to assess influence of COVID-19 vaccination on outcomes of COVID-19 infection. Treatment characteristics and disease severity outcomes were compared on the basis of vaccine status; breakthrough infections versus unvaccinated infections. Variable ratio propensity score matching based on age, sex, transplant type, and number of comorbidities, was used to develop the analytic cohort. Logistic regression was used to assess the influence of vaccination status on the selected outcomes. RESULTS: From a cohort of 511 SOT patients with COVID-19, we matched 77 partially or fully vaccinated patients with 220 unvaccinated patients. Treatment characteristics including use of dexamethasone, remdesivir, and antibiotics did not differ. Vaccinated participants were more likely to receive tocilizumab, 15 of 77 (19.5%) versus 5 of 220 (2.3%), P < 0.001. Disease severity outcomes including oxygen requirement, mechanical ventilation, and mortality were similar among medically attended vaccine breakthroughs compared with unvaccinated patients. CONCLUSIONS: SOT recipients who develop medically attended COVID-19 following 1- or 2-dose vaccination seem to have similar disease severity to unvaccinated patients who develop infection. This is consistent with the requirement that SOT recipients need 3 or more vaccine doses and emphasizes the importance of alternate strategies for this population.