Incidence and Severity of COVID-19 Among Vaccinated Solid Organ Transplant Recipients During the Omicron Wave

Abstract

The Omicron variant has caused an unprecedented surge in SARS-CoV-2 infections among vaccinated people in the United States, owing to high transmissibility, immune evasion, and higher circulating antibodies required to achieve neutralization. Vaccine-derived protection is suboptimal among solid organ transplant recipients (SOTRs).1-5 We studied frequency and severity of COVID-19 breakthrough during the US Omicron wave (December 25, 2021–March 1, 2022) in vaccinated SOTRs, focusing on the effect of preceding antispike antibody level. A total of 1801 >3×-vaccinated SOTRs from our national observational cohort were surveyed about incident COVID-19 during the Omicron wave, of whom 1467 (81%) responded. A subgroup (n = 666) was tested for antispike antibodies on 1 of 2 clinical assays correlated with neutralizing capacity: the Roche Elecsys anti–receptor binding domain (RBD) or Euroimmun antispike (S1) clinical assay. We used the most recent preinfection titer (measured between November 26, 2021, and March 7, 2022) for those reporting incident COVID-19 and titers measured between November 26, 2021, and December 25, 2021, for those reporting no incident COVID-19. Exclusion criteria included receiving monoclonal antibodies within the last 6 mo (n = 82), skipped key survey questions (n = 334), not having a recent titer (n = 654), and previously having COVID-19 (n = 65). This study was approved by the Johns Hopkins Institutional Review Board; participants provided informed consent electronically. A total of 150 of 1467 (10%) reported a positive PCR or home SARS-CoV-2 antigen test (“confirmed”) at a median (interquartile range) 134 (109–146) d since receiving their last vaccine, 25 of 1467 (2%) reported COVID-19 symptoms/suspicion but did not test positive (“suspected”), and 1292 of 1467 (88%) reported no confirmed or suspected COVID-19 during the follow-up period. Two deaths were reported during the follow-up period (both secondary to COVID-19) by family members. Eleven of 173 (6%) SOTRs with confirmed or suspected COVID-19 reported hospitalization for COVID-19. Sixty-four of 173 (37%) reported moderate symptoms (significant fever or shortness of breath), 97 of 173(56%) reported mild cold-like symptoms, and 9 of 173(5%) were asymptomatic (2 did not respond). The most common symptoms were nasal congestion (71%), cough (61%), malaise (58%), headache (57%), and sore throat (57%). There was a greater proportion of lung transplant recipients (24% versus 8%, P < 0.001) and those taking calcineurin-inhibitors (100% versus 86%, P = 0.015) in the COVID-19–confirmed group (Table 1). A sensitivity analysis was performed excluding those with suspected/unconfirmed COVID-19, and inferences were unchanged, so they were included in the no–COVID-19 group. TABLE 1. - Population characteristics of solid organ transplant recipients who underwent serologic antibody testing during the Omicron wave, stratified by test-confirmed COVID-19 infection status Characteristic Suspected/unconfirmed or no COVID-19 Test-confirmed COVID-19 P N 629 37 Age, median (IQR) 62 (51–69) 58 (44–66) 0.066 Female 357 (56.8%) 22 (59.5%) 0.76 Non-White race 65 (10.4%) 6 (16.2%) 0.26 Organ transplanted 0.026 Kidney only 334 (53.1%) 17 (45.9%) Liver only 126 (20.0%) 5 (13.5%) Pancreas only 5 (0.8%) 1 (2.7%) Lung only 43 (6.8%) 8 (21.6%) Heart only 70 (11.1%) 3 (8.1%) Multiorgan 51 (8.1%) 3 (8.1%) Lung transplant 50 (7.9%) 9 (24.3%) <0.001 Time since transplant at dose 1, median (IQR) 6 (3–14) 5 (2–9) 0.083 Number of medications, median (IQR) 2 (2–3) 3 (2–3) 0.039 Mycophenolate 439 (69.8%) 26 (70.3%) 0.95 Tacrolimus 483 (76.8%) 34 (91.9%) 0.032 Belatacept 21 (3.3%) 0 (0.0%) 0.62 Antimetabolite 467 (74.2%) 29 (78.4%) 0.58 Calcineurin-inhibitors 542 (86.2%) 37 (100.0%) 0.015 mTOR inhibitors 97 (15.4%) 2 (5.4%) 0.096 Steroids 355 (56.4%) 28 (75.7%) 0.021 Triple immunosuppression 224 (35.6%) 18 (48.6%) 0.11 Dose 1 vaccine type (n = 665) BNT162b2 359 (57.2%) 20 (54.1%) 0.84 mRNA-1273 260 (41.4%) 17 (45.9%) Ad.26.COV2.S 9 (1.4%) 0 (0.0%) Dose 2 vaccine type (n = 663) BNT162b2 365 (58.2%) 20 (55.6%) 0.86 mRNA-1273 262 (41.8%) 16 (44.4%) Dose 3 vaccine type (n = 666) BNT162b2 313 (49.8%) 18 (48.6%) 0.76 mRNA-1273 280 (44.5%) 16 (43.2%) Ad.26.COV2.S 36 (5.7%) 3 (8.1%) Dose 4 vaccine type (n = 123) BNT162b2 44 (38.3%) 1 (12.5%) 0.18 mRNA-1273 65 (56.5%) 6 (75.0%) Ad.26.COV2.S 6 (5.2%) 1 (12.5%) Dose 5 vaccine type (n = 22) BNT162b2 5 (25.0%) 0 (0.0%) >0.99 mRNA-1273 15 (75.0%) 2 (100.0%) Antibody testing Negative (anti-RBD <0.8 U/mL or anti-S1 <1.1) 88 (14.0%) 8 (21.6%) 0.007 Positive (anti-RBD >0.8 U/mL or anti-S1 >1.1 AU) 541 (86.0%) 29 (78.4%) Anti-RBD 0.8–250 U/mL or anti-S1 1.1–4 AU 87 (14.0%) 12 (32.4%) Anti-RBD 250–2500 U/mL or anti-S1 4–8 AU 151 (24.0%) 6 (16.2%) Anti-RBD >2500 U/mL or anti-S1 >8 AU 303 (48.2%) 11 (29.7%) Time from last vaccine dose to antibody testing median (IQR) d a 103 (91–156) 96 (80–107) 0.021 an = 137.χ2 for negative/positive antibody response by Omicron category: 1.734, P = 0.1879; χ2 for titer cutoff anti-RBD >250 U/mL or anti-S1 >4 AU: 11.613, P = 0.000655; χ2 for titer cutoff anti-RBD >2500 U/mL or anti-S1 > 8 AU: 4.770, P = 0.0290; χ2 for titer categories: negative/[anti-RBD 0.8–250 U/mL or anti-S1 1.1–4 AU]/[anti-RBD 250–2500 U/mL or anti-S1 4–8 AU]/[anti-RBD >2500 U/mL or anti-S1>8 AU]: 12.9658, P = 0.005.IQR, interquartile range; RBD, receptor binding domain; S1, Euroimmun antispike. A total of 96 of 666 (14%) SOTRs were seronegative for antispike antibodies immediately pre-Omicron wave. One hundred fifty-seven of 666 (24%) had anti-RBD (250–2500) U/mL or anti-S1 (4–8) AU, and 314 of 666 (47%) had anti-RBD >2500 U/mL or anti-S1 >8 AU. A chi-square test of independence showed no significant association between seronegative status and confirmed infection (χ2 = 1.7, P = 0.19); however, there was a statistically significant relationship between increasing titer categories and proportion with confirmed infection (Wilcoxon rank-sum, P = 0.0056). Limitations of this study include the nature of convenience sampling, which relied on participant self-report, and the fact that antinucleocapsid testing was not available to ascertain antecedent or incident subclinical COVID-19. In this longitudinal cohort study, 10% of vaccinated SOTRs reported incident COVID-19 during the Omicron wave. Seronegativity alone was not associated with breakthrough COVID-19, but incremental increases in titers were associated with decreasing likelihood of reporting breakthrough infection. These findings support antibody titers as a potential clinical correlate of protection and suggest their utility in risk assessment during the Omicron era. ACKNOWLEDGMENTS We thank the participants of the Johns Hopkins COVID-19 Transplant Vaccine Study, without whom this research could not be possible. We also thank the members of the study team, including Brian J. Boyarsky, MD, PhD; Aura T. Abedon, BS; Alexa Jefferis, BS; Nicole Fortune Hernandez, BS; Letitia Thomas; Chunyi Xia; Kim Hall; Mary Sears; Alex Alex; Jonathan Susilo; Andrew Lea, BS; and Evelyn Leland, BS. We also thank Andrew H. Karaba, MD, PhD, and Ms Yolanda Eby for project support and guidance.

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