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

Abstract

T he 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][2][3][4][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 . 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. Letter to the Editor

Patient‐reported outcomes after Tixagevimab and Cilgavimab pre‐exposure prophylaxis among solid organ transplant recipients: Safety, effectiveness, and perceptions of risk

“…Overall, breakthrough COVID‐19 occurred in 8.9% of this population over 3 months of follow‐up that predominately overlapped a period of BA.2 and BA.4/5 sublineage predominance in the United States. These rates are similar to post‐vaccination breakthrough rates previously reported in our cohort during the BA.1 wave among those who did not receive T + C, albeit more frequent than rates observed during Alpha and Delta predominance 13 . Recent work by Al Jurdi et al.…”

“…As demonstrated, another consideration in interpreting breakthrough rates is potential changes in risk behavior following T + C, which may have led to increased exposure to SARS‐CoV‐2 and infections among those receiving PrEP (i.e., downward bias in drug effectiveness during follow‐up versus maintenance of “standard” behavior patterns). This, and the lack of a formal control group, and the fact that our parent cohort includes vaccinated SOTRs may limit the generalizability of reported breakthrough incidence rates to non‐recipients of T + C and unvaccinated SOTRs, although we were able to reference breakthrough rates among fully vaccinated SOTRs within the parent cohort during Omicron predominance who had not received T + C prophylaxis, and SARS‐CoV‐2 vaccination is universally accepted and recommended by transplant centers in the United States 13 . In our T + C population, 99% of SOTRs had received three or more SARS‐CoV‐2 vaccines prior to T + C, and 70% were seropositive for antibodies against the spike protein prior to receiving T + C, which is generally reflective of the target population (SOTRs) for whom T + C is recommended.…”

“…These rates are similar to post-vaccination breakthrough rates previously reported in our cohort during the BA.1 wave among those who did not receive T + C, albeit more frequent than rates observed during Alpha and Delta predominance. 13 Recent work by Al Jurdi et al…”

mRNA Vaccination Decreases COVID-19-Associated Morbidity and Mortality Among Organ Transplant Recipients: A Contemporary Cohort Study

“…Moreover, these observations may not correlate with clinical outcomes, given confounding from the increased transmissibility but attenuated virulence of Omicron strains [ 22 ]. For example, one study of vaccinated OTRs during the Omicron surge showed that seronegativity was not associated with risk of breakthrough SARS-CoV-2 infection, which, nonetheless, decreased with increasing antispike antibody titers [ 23 ]. Importantly, most of the aforementioned studies spanned earlier phases of the pandemic [ 2 , 4 , 6 , 9 , 11 ], with different circulating variants and potentially standards of care, which can affect base mortality rates [ 24 , 25 ].…”

Relationship Between Immune Response to Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines and Development of Breakthrough Infection in Solid Organ Transplant Recipients: The CONTRAST Cohort

“…In a multicenter longitudinal cohort study of 1467 SOT recipients from United States, 150 (10.2%) reported a BI during the Omicron wave, with 11 (7.3%) hospitalizations and 2 (1.3%) deaths [ 10 ]. Among SOT recipients with serological available data, 96 of 666 (14.4%) were seronegative, 24% had medium-level AbR (anti-RBD, 250–2500 U/mL), and 47% had high-level AbR (anti-RBD, >2500 U/mL).…”