ARTICLE: Incident COVID-19 and Hospitalizations by Variant Era Among Vaccinated Solid Organ Transplant Recipients
AUTHORS: Teresa Po-Yu Chiang, Aura T Abedon, Jennifer L Alejo, Dorry L Segev, Allan B Massie, William A Werbel
JOURNAL: JAMA Netw Open. 2023 Aug 1;6(8):e2329736. doi: 10.1001/jamanetworkopen.2023.29736.
Introduction: Solid organ transplant recipients experienced severe COVID-19 outcomes before vaccination and high breakthrough rates despite primary vaccine series.1,2 Infection risks among transplant recipients amid shifting immunity landscape and Omicron subvariant waves are not well described. Understanding longitudinal COVID-19 outcomes on a population scale has implications for future counseling and risk prediction; thus, we quantified changes in COVID-19 burden among transplant recipients, hypothesizing reduced disease severity in recent variant eras among SARS-CoV-2 vaccine uptake.
Methods: Transplant recipients reporting 1 or more SARS-CoV-2 vaccination within a national prospective cohort were surveyed following immunoprophylaxis events to ascertain incident COVID-19 (self-reported positive molecular or antigen test result) and hospitalizations between January 2021 and December 2022, with additional cohortwide surveys in January and June 2022 and unsolicited reporting (eMethods in Supplement 1). Follow-up time accrued from first vaccination through last survey. This cohort study followed the STROBE reporting guideline and was approved by Johns Hopkins University, with waiver of documentation of informed consent because of no more than minimal risk intervention.
Cohort characteristics, COVID-19 incidence rate, and hospitalization ratio were reported by variant era: pre-Delta (January to May 2021), Delta (June to December 2021), and Omicron BA.1 (January to March 2022), BA.2 (April to June 2022), and BA.4-BA.5-BQ.1 (July to December 2022). Monthly transplant recipient COVID-19 incidence rate was plotted against US population case counts.3 Post hoc, COVID-19 hospitalization ratio and serious COVID-19 disease (hospitalizations plus deaths) were compared between post-BA.1 and pre-Delta, Delta, and BA.1 waves using Poisson regression. Two-sided P < .05 was significant. Stata/SE, version 17 was used for analysis.
Results: Of 2461 participants, 2356 (95.7%) responded to 1 or more survey. Vaccinations increased over time (Table). COVID-19 survey response rate was 76.1% (13 483 of 17 726; median responses/participant, 5 [IQR, 3-7]); 464 of 2356 participants (19.7%) reported SARS-CoV-2 infection (15 reinfections). Among 936 330 person-days across all eras, COVID-19 incidence (per 1 000 000 person-days) was 90 for pre-Delta; 304, Delta; 1292, BA.1; 1051, BA.2; and 1066, BA.4-BA.5-BQ.1. Overall incidence was lower among participants 60 years or older vs younger than 60 years (420.2 vs 605.0; P < .001) and similar if less than 2 years vs 2 years or more from transplant (599.6 vs 485.7; P = .06) and in lung vs nonlung recipients (572.8 vs 500.4; P = .37). Transplant recipient COVID-19 incidence paralleled US population case counts (Figure, A), peaking during the BA.1 wave, albeit with greater relative decreases in US cases in later eras.
There were 37 COVID-19-related hospitalizations among 35 of 464 participants (7.5%). Hospitalized participants more often reported stronger immunosuppression (eg, 3-drug regimens: 56.8% vs 36.5%; P = .02) and lung transplant (24.3% vs 9.5%; P = .01). Hospitalization ratios (per 100 incident infections) were 14.1 for pre-Delta; 11.8, Delta; 9.2; BA.1; 2.3, BA.2; and 3.5, BA.4-BA.5-BQ.1 (Figure, B). Overall hospitalization ratio was similar among participants 60 years or older vs younger than 60 years (8.3 vs 7.4; P = .75) and less than 2 years vs 2 years or more from transplant (8.6 vs 7.6; P = .74) yet higher in lung vs nonlung recipients (18.4 vs 6.6; P = .007).
Hospitalization ratio comparing post-BA.1 vs pre-Delta, Delta, and BA.1 was 0.27 (95% CI, 0.11-0.69; P = .006), with a similar ratio of serious COVID-19 disease (0.29; 95% CI, 0.12-0.69; P = .005). Of 16 reported deaths, 5 were COVID-19 related (1 post-BA.1); 6, non-COVID-19 related (3 post-BA.1); and 5, unknown cause (4 post-BA.1).
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