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Background: Solid organ transplant recipients face an increased risk of severe coronavirus disease 2019 (COVID-19) and are vulnerable to repeat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. In nonimmunocompromised individuals, SARS-CoV-2 reinfections are milder likely because of cross-protective immunity. We sought to determine whether SARS-CoV-2 reinfection exhibits milder manifestations than primary infection in transplant recipients., Methods: Using a large, prospective cohort of adult transplant patients with COVID-19, we identified patients with SARS-CoV-2 reinfections. We performed a 1:1 nearest neighbor propensity score matching to control potential confounders, including the COVID-19 variant. We compared outcomes including oxygen requirement, hospitalization, and intensive care unit admission within 30 d after diagnosis between patients with reinfection and those with the first episode of COVID-19., Results: Between 2020 and 2023, 103 reinfections were identified in a cohort of 1869 transplant recipients infected with SARS-CoV-2 (incidence of 2.7% per year). These included 50 kidney (48.5%), 27 lung (26.2%), 7 heart (6.8%), 6 liver (5.8%), and 13 multiorgan (12.6%) transplants. The median age was 54.5 y (interquartile range [IQR], 40.5-65.5) and the median time from transplant to first infection was 6.6 y (IQR, 2.8-11.2). The time between the primary COVID-19 and reinfection was 326 d (IQR, 226-434). Three doses or more of SARS-CoV-2 vaccine are received by 87.4% of patients. After propensity score matching, reinfections were associated with significantly lower hospitalization (5.8% versus 19.4%; risk ratio, 0.3; 95% CI, 0.12-0.71) and oxygen requirement (3.9% versus 13.6%; risk ratio, 0.29; 95% CI, 0.10-0.84). In a within-patient analysis only in the reinfection group, the second infection was milder than the first (3.9% required oxygen versus 19.4%, P  < 0.0001), and severe first COVID-19 was the only predictor of severe reinfection., Conclusions: Transplant recipients with COVID-19 reinfection present better outcomes than those with the first infection, providing clinical evidence for the development of cross-protective immunity., Competing Interests: D.K. has received clinical trials grants from GSK and Roche and consultancy fees from GSK, Roche, Merck, Takeda, and Exevir. A.H. has received clinical trials grants from Merck and consultancy fees from Merck and Takeda. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Patients with cancer demonstrate an increased vulnerability for infection and severe disease by SARS-CoV-2, the causative agent of COVID-19. Risk factors for severe COVID-19 include comorbidities, uncontrolled disease, and current line of treatment. Although COVID-19 vaccines have afforded some level of protection against infection and severe disease among patients with solid tumors and hematologic malignancies, decreased immunogenicity and real-world effectiveness have been observed among this population compared with healthy individuals. Characterizing and understanding the immune response to increasing doses or differing schedules of COVID-19 vaccines among patients with cancer is important to inform clinical and public health practices. In this article, we review SARS-CoV-2 susceptibility and immune responses to COVID-19 vaccination in patients with solid tumors, hematologic malignancies, and those receiving hematopoietic stem cell transplant or chimeric-antigen receptor T-cell therapy., Competing Interests: Potential conflicts of interest. V. G. H. is supported by a National Health and Medical Research Council postgraduate PhD scholarship (Number 2014210). B. W. T. has participated on advisory boards for Moderna, CSL-Behring, and Takeda, and received grants from Seqirus and MSD, honoraria from Pfizer, Alexion, and Janssen, and is supported by the Australian Government Medical Research Future Fund Fellowship. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: In solid organ transplant (SOT) recipients, the primary vaccination series against Coronavirus Disease 2019 is 3 doses followed by boosters. We determined whether a fourth dose booster induced Omicron BA.4/5 neutralizing antibodies (nAbs) and T cells in a large multicenter cohort study., Methods: Serum was collected 4-6 weeks post-third and post-fourth doses of messenger RNA vaccine in 222 SOT recipients. nAbs were measured using a pseudovirus neutralization assay that targeted the Omicron BA.4/5 spike protein. A subset underwent T-cell testing., Results: The median age of the cohort was 63 years (interquartile range [IQR], 50-68) with 61.7% men. BA.4/5 nAb detection increased from 26.6% (59 of 222) post-third dose to 53.6% (119 of 222) post-fourth dose (P < .0001). In patients with breakthrough infection prior to the fourth dose (n = 27), nAbs were detected in 77.8% and median nAb titers were significantly higher compared with those with 4 vaccine doses alone (P < .0001). Factors associated with a low BA.4/5 neutralization response after the fourth dose were older age (odds ratio [OR], 0.96; 95% confidence interval [CI], .94-.99), mycophenolate use (OR, 0.39; 95% CI, .20-.77) and prednisone use (OR, 0.34; 95% CI, .18-.63), and vaccine type (OR, 0.72; 95% CI, .51-.99), while breakthrough infection prior to the fourth dose (OR, 3.6; 95% CI, 1.3-9.9) was associated with a greater nAb response. Polyfunctional BA.4/5-specific CD4+ T cells significantly increased after 4 doses and were identified in 76.9% of patients at a median frequency of 213/106 cells (IQR, 98-650)., Conclusions: In summary, a booster significantly increases BA.4/5-specific neutralization and polyfunctional CD4+ T-cell responses, suggesting protection from severe disease even with new Omicron variants. However, SOT recipients who are older and on mycophenolate and prednisone need additional preventative strategies., Competing Interests: Potential conflicts of interest. D. Kumar reports research grants from Roche and GSK and consulting fees from Roche, GSK, Merck, and Medscape. D. Kabbani reports a clinical trials grant from Pulmocide, a research grant from AVIR pharma, an educational grant from GSK, and honoraria for lectures from GSK and AVIR pharma. A. H. reports research grants and consulting fees from Merck. A.-C. G. reports receipt of funds from a research contract with Providence Therapeutics Holdings, Inc (unrelated to this work); co-PI/collab in grants from CIHR and the Ontario Research Fund on SARS-CoV-2; and unpaid roles as chair of the CIHR Institute of Genetics Advisory Board, former chair and current member of the National Research Council of Canada (NRC) HHT division, member of working parties for the COVID-19 Immunity Task Force, and pillar lead on functional genomics and structure-function at CoVaRR-Net. S. B. reports a team grant from the Vancouver Coastal Health Research Institute and the Transplant Research Foundation of British Columbia (paid to institution); consulting fees from AstraZeneca and GSK; and payment or honoraria from Merck for speaking engagements or presentations. M.-J. H. reports roles as a chairperson for the Governing Council at the Canadian Institutes of Health Research, as a Mila board member at the Institute of Artificial Intelligence, and as a board member of Hopital Ste-Justine in Quebec, Canada. V. H. F. reports grants or contracts (paid to the author’s institution) from the Canadian Institutes of Health Research, the COVID-19 Immunity Task Force, the University Health Network–Transplant Program Strategic Clinical Project Fund, and the Mount Sinai Hospital University Health Network Academic Medical Organization COVID19 Innovation Fund Project. V. G. H. reports a research stipend from the National Health Medical Research Council post graduate PhD scholarship (unrelated to this work). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: Competing interests: Geneviève Huard reports payment from Gilead and AbbVie, and participation on a data safety monitoring board with Paladin. Ruth Sapir-Pichhadze reports grants from the Canadian Institutes of Health Research, Fonds de recherche du Québec, Genome Canada and Kidney Foundation of Canada, as well as speaker fees from the Korean Society of Nephrology. Atul Humar reports fees from Roche, Astellas and Merck. Deepali Kumar reports grants from Roche, GSK, Takeda, Qiagen, Amplyx and Atara Biotherapeutics, as well as fees from Roche, GSK, Takeda, Exevir, Astellas and Meducom. Deepali Kumar is the 2022–2023 president of the American Society of Transplantation. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Immunocompromised patients are predisposed to severe COVID-19. Here we compare homotypic and heterotypic humoral and cellular immune responses to Omicron BA.1 in organ transplant patients across a diverse clinical spectrum. We perform variant-specific pseudovirus neutralization assays for D614G, and Omicron-BA.1, -BA.2, and Delta variants. We also measure poly-and monofunctional T-cell responses to BA.1 and ancestral SARS-CoV-2 peptide pools. We identify that partially or fully-vaccinated transplant recipients after infection with Omicron BA.1 have the greatest BA.1 neutralizing antibody and BA.1-specific polyfunctional CD4 + and CD8 + T-cell responses, with potent cross-neutralization against BA.2. In these patients, the magnitude of the BA.1-directed response is comparable to immunocompetent triple-vaccinated controls. A subset of patients with pre-Omicron infection have heterotypic responses to BA.1 and BA.2, whereas uninfected transplant patients with three doses of vaccine demonstrate the weakest comparative responses. These results have implications for risk of infection, re-infection, and disease severity among immune compromised hosts with Omicron infection., (© 2022. The Author(s).)

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., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The SARS-CoV-2 virus Omicron variant has now supplanted wild-type virus as the dominant circulating strain globally. Three doses of mRNA COVID-19 vaccine are recommended for transplant recipients as their primary vaccine series. However, the immunogenicity of mRNA vaccines as they specifically relate to the Omicron variant are not well studied. We analyzed Omicron-specific neutralization in transplant recipients after three-doses of mRNA-1273 vaccine. Neutralization was determined using a SARS-CoV-2 spike pseudotyped lentivirus assay with constructs for Omicron and Delta variants. A total of 60 transplant patients (kidney, kidney-pancreas, lung, heart, liver) were analyzed 1 month and 3 months after completion of three doses of mRNA-1273. At 1 month, 11/60 (18.3%) patients had detectable neutralizing antibody responses to Omicron (log 10 ID50 of 2.38 [range 1.34-3.57]). At 3 months, 8/51 (15.7%) were positive (median log 10 ID50 [1.68; range 1.12-3.61; approximate fivefold reduction over time]). The proportion of positive patients was lower for Omicron versus wild-type, and Omicron vs. Delta (p < .001). No demographic variables were found to be significantly associated with Omicron response. Many patients with a positive anti-RBD response still had undetectable Omicron-specific neutralizing antibody. In conclusion, three doses of mRNA vaccine results in poor neutralizing responses against the Omicron variant in transplant patients., (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Delayed dosing intervals are a strategy to immunize a greater proportion of the population. In an observational study, we compared humoral and cellular responses in health care workers receiving two doses of BNT162b2 (Pfizer-BioNTech) vaccine at standard (3- to 6-week) and delayed (8- to 16-week) intervals. In the delayed-interval group, anti-receptor-binding domain antibody titers were significantly enhanced compared to the standard-interval group. The 50% plaque reduction neutralization test (PRNT50) and PRNT90 titers against wild-type (ancestral) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Alpha, Beta and Delta variants were higher in the delayed-interval group. Spike-specific polyfunctional CD4 + and CD8 + T cells expressing interferon-γ and interleukin-2 were comparable between the two groups. Here, we show that the strategy of delaying second doses of mRNA vaccination may lead to enhanced humoral immune responses, including improved virus neutralization against wild-type and variant SARS-CoV-2 viruses. This finding has potentially important implications as vaccine implementation continues across a greater proportion of the global population., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: COVID-19 is more severe in transplant recipients. Variants of concern have supplanted wild-type virus. In transplant recipients, data are limited on 2-dose or 3-dose vaccine immunogenicity against variant viruses., Objective: To assess neutralizing antibody responses against SARS-CoV-2 variants in transplant recipients after 2 and 3 vaccine doses., Design: Secondary analysis of a randomized, double-blind, controlled trial of a third dose of mRNA-1273 vaccine versus placebo. (ClinicalTrials.gov: NCT04885907)., Setting: Single-center transplant program., Patients: Organ transplant recipients., Intervention: Third dose of mRNA-1273 vaccine versus placebo., Measurements: Sera were analyzed for neutralization against wild-type virus and the Alpha, Beta, and Delta variants using a surrogate virus neutralization assay and a spike-pseudotyped lentivirus assay., Results: A total of 117 transplant recipients were analyzed (60 in the mRNA-1273 group and 57 in the placebo group). Sera were obtained before and 4 to 6 weeks after the third dose. After 2 doses, the proportion of patients with positive neutralization for all 3 variants was small compared with wild-type virus. After the third dose of mRNA-1273 vaccine, the proportion with a positive neutralization response versus placebo was improved for all 3 variants as measured by both assays. Based on the pseudovirus neutralization assay against the Delta variant, 33 of 60 (55%) patients were positive in the mRNA-1273 group versus 10 of 57 (18%) in the placebo group (difference, 37 [95% CI, 19 to 53] percentage points). The differences were 36 (CI, 17 to 51) percentage points for the Alpha variant and 31 (CI, 15 to 46) percentage points for the Beta variant. In the mRNA-1273 group, lower neutralization values were observed for variants compared with wild-type virus, especially the Beta variant., Limitations: There is no clear correlate of protection for neutralizing antibody. This was a secondary analysis., Conclusion: In organ transplant recipients, a third dose of mRNA vaccine increases neutralizing antibody response against SARS-CoV-2 variants compared with placebo., Primary Funding Source: Ajmera Transplant Centre.

Solid organ transplant recipients are at high risk of severe disease from COVID-19. We assessed the immunogenicity of mRNA-1273 vaccine using a combination of antibody testing, surrogate neutralization assays, and T cell assays. Patients were immunized with two doses of vaccine and immunogenicity assessed after each dose using the above tests. CD4+ and CD8+ T cell responses were assessed in a subset using flow-cytometry. A total of 127 patients were enrolled of which 110 provided serum at all time points. A positive anti-RBD antibody was seen in 5.0% after one dose and 34.5% after two doses. Neutralizing antibody was present in 26.9%. Of note, 28.5% of patients with anti-RBD did not have neutralizing antibody. T cell responses in a sub-cohort of 48 patients showed a positive CD4+ T cell response in 47.9%. Of note, in this sub-cohort, 46.2% of patients with a negative anti-RBD, still had a positive CD4+ T cell response. The vaccine was safe and well-tolerated. In summary, immunogenicity of mRNA-1273 COVID-19 vaccine was modest, but a subset of patients still develop neutralizing antibody and CD4+T- cell responses. Importantly polyfunctional CD4+T cell responses were observed in a significant portion who were antibody negative, further highlighting the importance of vaccination in this patient population. IRB Statement: This study was approved by the University Health Network Research Ethics Board (CAPCR ID 20-6069)., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The optimal management of immunosuppression in transplant patients infected with COVID-19 is unknown. We performed an in vitro study to determine the effect of individual immunosuppressive agents on SARS-CoV-2-specific T-cell cytokine expression. Convalescent peripheral blood mononuclear cells from eleven non-immunosuppressed patients with COVID-19 were preincubated with clinically relevant concentrations of immunosuppressive drugs (tacrolimus, mycophenolate, sirolimus, prednisone) and then stimulated with a SARS-CoV-2 peptide pool. Supernatants were analyzed by 14-plex high sensitivity T-cell cytokine array. With increasing concentrations of tacrolimus, there was a trend to reduction in the release of IL-2 (p = .0137), and IFN-γ (p = .0147) in response to peptide stimulation. There was also a subsequent trend toward a Th2 phenotype, indicated by lower IFN-γ:IL-13 ratio (p = .0663) and IFNγ:IL-4 ratio (p = .0176). Sirolimus appeared to be associated with a proinflammatory cytokine release, including TNF-α (p = .0027) and IL-1β (p = .0016), in response to SARS-CoV-2 peptides. In contrast, mycophenolate and prednisone did not influence the SARS-CoV-2-specific cytokine response. These are preliminary findings only, with larger studies required to inform clinical recommendations., (© 2021 Wiley Periodicals LLC.)

T-cell immunity associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination in solid organ transplant recipients (SOTRs) is poorly understood. To address this, we measured T-cell responses in 50 SOTRs with prior SARS-CoV-2 infection. The majority of patients mounted SARS-CoV-2-specific CD4+ T-cell responses against spike (S), nucleocapsid, and membrane proteins; CD8+ T-cell responses were generated to a lesser extent. CD4+ T-cell responses correlated with antibody levels. Severity of disease and mycophenolate dose were moderately associated with lower proportions of antigen-specific T cells. Relative to nontransplant controls, SOTRs had perturbations in both total and antigen-specific T cells, including higher frequencies of total PD-1+ CD4+ T cells. Vaccinated SOTRs (n = 55) mounted significantly lower proportions of S-specific polyfunctional CD4+ T cells after 2 doses, relative to unvaccinated SOTRs with prior coronavirus disease 2019. Together, these results suggest that SOTRs generate robust T-cell responses following natural infection that correlate with disease severity but generate comparatively lower T-cell responses following mRNA vaccination., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Revaccination after receipt of a hematopoietic cell transplant (HCT) or cellular therapies is a pillar of patient supportive care, with the potential to reduce morbidity and mortality linked to vaccine‐preventable infections. This review synthesizes national, international, and expert consensus vaccination schedules post‐HCT and presents evidence regarding the efficacy of newer vaccine formulations for pneumococcus, recombinant zoster vaccine, and coronavirus disease 2019 in patients with hematological malignancy. Revaccination post‐cellular therapies are less well defined. This review highlights important considerations around poor vaccine response, seroprevalence preservation after cellular therapies, and the optimal timing of revaccination. Future research should assess the immunogenicity and real‐world effectiveness of new vaccine formulations and/or vaccine schedules in patients post‐HCT and cellular therapy, including analysis of vaccine response that relates to the target of cellular therapies. [ABSTRACT FROM AUTHOR]

Background In-depth immunogenicity studies of tixagevimab-cilgavimab (T-C) are lacking, including following breakthrough coronavirus disease 2019 (COVID-19) in vaccinated patients with hematologic malignancy (HM) receiving T-C as pre-exposure prophylaxis. Methods We performed a prospective, observational cohort study and detailed immunological analyses of 93 patients with HM who received T-C from May 2022, with and without breakthrough infection, during a follow-up period of 6 months and dominant Omicron BA.5 variant. Results In 93 patients who received T-C, there was an increase in Omicron BA.4/5 receptor-binding domain (RBD) immunoglobulin G (IgG) antibody titers that persisted for 6 months and was equivalent to 3-dose-vaccinated uninfected healthy controls at 1 month postinjection. Omicron BA.4/5 neutralizing antibody was lower in patients receiving B-cell–depleting therapy within 12 months despite receipt of T-C. COVID-19 vaccination during T-C treatment did not incrementally improve RBD or neutralizing antibody levels. In 16 patients with predominantly mild breakthrough infection, no change in serum neutralization of Omicron BA.4/5 postinfection was detected. Activation-induced marker assay revealed an increase in CD4+ (but not CD8+) T cells post infection, comparable to previously infected healthy controls. Conclusions Our study provides proof-of-principle for a pre-exposure prophylaxis strategy and highlights the importance of humoral and cellular immunity post–breakthrough COVID-19 in vaccinated patients with HM. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]