Clinical Outcomes Among Kidney Transplant Recipients During Omicron XBB Contrasted Against Preceding BA.1, BA.2, and BA.4/5 Pandemic Waves

Kidney transplant recipients (KTRs) are at higher risk of poorer outcomes post–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although vaccination and antispike monoclonal antibodies (mAbs) may have mitigated risk, the emergence of more immune-evasive Omicron subvariants (eg, Omicron XBB/BQ.1.1) has raised concern. Failure of mAbs to neutralize XBB/BQ.1.1 has been reported.1 Additionally, sera of KTRs vaccinated with monovalent messenger RNA vaccines could not neutralize Omicron in vitro.2 We describe outcomes in a vaccinated single-center cohort of KTRs over 1 y (January 1–December 28, 2022) during which successive Omicron subvariants predominated community transmission, including Omicron XBB. Demographic and clinical data were extracted from the electronic medical record, including information on vaccination and therapeutics. Antivirals were offered to all eligible patients unless contraindicated; remdesivir was initially offered for 3 d, with extension based on physician discretion. Patients with undetectable SARS-CoV-2 immunoglobulin G response were offered mAbs. Study outcomes were progression to severe coronavirus disease 2019 (COVID-19), acute kidney injury (AKI), and COVID-19–related readmission. Readmission within 30 d of symptom onset was defined as COVID-19 related if readmission (after initial hospitalization) was related to symptom persistence, disease progression, or relapse. KTRs who notified transplant coordinators of infection within a week of onset were recalled for clinical assessment and triaged based on severity/home isolation suitability to either initial hospitalization in our isolation ward or in a home-based virtual ward where remote monitoring via telemedicine and home visits by family physicians were conducted for clinical review/treatment. This allowed measurement of antispike antibody titer at symptom onset and determination of variant via a polymerase chain reaction. The cohort was initially stratified by infection period (BA.1/2/4/5/XBB) based on local surveillance data.3 Omicron XBB predominated (≥50% of circulating strains) from October 2022.3 During transitions between predominant strains, spike gene target failure on polymerase chain reaction was used to distinguish variants. Undetectable SARS-CoV-2 immunoglobulin G was defined as <50 AU/mL. Multivariate logistic regression was used to identify factors independently associated with AKI/severe COVID-19/readmission. Institutional review board approval was obtained (CIRB:2021/2823). Overall, 427 cases were included, of which 74 (17.3%) were attributed to Omicron XBB (Table S1, SDC,https://links.lww.com/TP/C811); 92.3% of cases (393/427) received ≥3 messenger RNA vaccine doses; one-third (32.9%; 135/410) had undetectable anti-spike antibodies. In the Omicron era, only 2.6% of cases (11/427) progressed to severe COVID-19, 10.8% (46/427) sustained AKI, and 3.5% (15/427) were readmitted. However, 66.0% of cases (282/427) received treatment. There was no difference in outcomes (Table S1, SDC,https://links.lww.com/TP/C811) during Omicron XBB and preceding variant periods on univariate analysis (AKI: 10.8% versus 10.8%; odds ratio [OR] = 1.00; 95% confidence interval [CI], 0.45-2.25; readmission: 4.2% versus 3.4%, OR = 1.20, 95% CI = 0.33-4.37; severe COVID-19: 0.0% versus 3.1%, P = 0.224) possibly because of increased booster uptake, residual immunity from prior infection, and higher antiviral usage during the XBB period (Table S1, SDC,https://links.lww.com/TP/C811). On multivariate analysis, undetectable anti-spike antibodies were independently associated with anti-spike readmission (Table 1). In the subset with undetectable anti-spike antibodies who received treatment before XBB emergence (N = 119), treatment with mAbs was associated with lower odds of severe COVID-19 (adjusted OR = 0.11; 95% CI, 0.02-0.62; P = 0.013; Table 1). Rates of severe COVID-19 ranging from 6.3% to 22.2% were reported in various KTR cohorts during the Omicron era,4,5 albeit during waves driven by earlier variants (Table S2, SDC,https://links.lww.com/TP/C811). Association of mAbs with reduced severity among serological nonresponders before Omicron XBB emergence highlights the need for updated therapeutics. TABLE 1. - Multivariate regression analysis of association of clinical characteristics and infection-related parameters on outcomes after COVID-19 transplant recipients in the Omicron era (N = 427) Main cohort (N = 427)a Subset of study population infected before Omicron XBB emergence, with nonreactive spike antibody (<50 AU/mL), who received treatment (N = 119)b AKIc Dependent variable aOR 95% CI P Dependent variable aOR 95% CI P Baseline eGFR ≤30 mL/min/1.73 m2 5.14 2.55-10.37 <0.001 Baseline eGFR ≤30 mL/min/1.73 m2 4.25 1.56-11.60 0.005 Nonreactive spike antibody (<50 AU/mL) 2.13 1.09-4.22 0.030 ISARIC-4C score at admission ≥9 4.27 1.41-12.99 0.010 Severe COVID-19d Dependent variable aOR 95% CI P Dependent variable aOR 95% CI P Nonreactive spike antibody (<50 AU/mL) 3.29 0.79-13.77 0.103 Received a monoclonal 0.11 0.02-0.62 0.013 ISARIC-4C score at admission ≥9 10.55 2.84-39.19 <0.001 ISARIC-4C score at admission ≥9 6.94 1.39-34.74 0.018 COVID-19–related readmission within 30 d of symptom onsete Dependent variable aOR 95% CI P Dependent variable aOR 95% CI P CCMI score ≥5 4.05 1.07-15.40 0.040 CCMI score ≥5 6.40 0.75-54.37 0.089 Chinese ethnicity 0.31 0.10-0.95 0.040 Chinese ethnicity 0.18 0.45-0.95 0.030 Nonreactive spike antibody (<50 AU/mL) 4.90 1.50-16.01 0.008 – – – – Bold values indicate a P <0.05.aBinary logistic multivariable regression analysis was performed to determine the association of independent variables on the outcomes of AKI, severe COVID-19 disease, and COVID-19–related readmission within 30 d of symptom onset, in the entire cohort (N = 427). Independent variables were included in the multivariable analysis if a P value was <0.1 on univariate analysis. On univariate analysis, baseline eGFR of ≤30 mL/min/1.73 m2 was associated with AKI (OR = 6.12; 95% CI, 3.17-11.80; P < 0.001); CCMI score of ≥5 was associated with readmission (OR = 4.04; 95% CI, 1.12-14.52; P = 0.032), and nonreactive spike antibody (<50 AU/mL) was significantly associated with all outcomes on univariate analysis (OR = 3.21; 95% CI, 1.71-6.05; P < 0.001 for AKI; OR = 5.71; 95% CI, 1.49-21.89; P = 0.007 for severe COVID-19; and OR = 6.01; 95% CI, 1.87-19.25; P = 0.001 for readmission). ISARIC-4C score at admission of ≥9 was associated with severe COVID-19 on univariate analysis (OR = 16.01; 95% CI, 4.61-55.64; P < 0.001). Chinese ethnicity showed a trend toward lower odds of readmission on univariate analysis (OR = 0.40; 95% CI, 0.14-1.14; P = 0.10).bBinary logistic multivariable regression analysis was performed to determine the association of independent variables on the outcomes of AKI, severe COVID-19 disease, and COVID-19–related readmission within 30 d of symptom onset, in the subset of the study population infected during the Omicron BA.1/2/4/5 period before Omicron XBB emergence, with nonreactive spike antibody (<50 IU/mL), and who received treatment. Independent variables were included in the multivariable analysis if a P value was <0.1 on univariate analysis. On univariate analysis, baseline eGFR of ≤30 mL/min/1.73 m2 was associated with AKI (OR = 5.67; 95% CI, 2.19-14.73; P < 0.001); ISARIC-4C score at admission of ≥9 was associated with AKI (OR = 6.07; 95% CI, 2.14-17.23; P = 0.001) and severe COVID-19 on univariate analysis (OR = 5.94; 95% CI, 1.35-26.18; P = 0.027). Receipt of a monoclonal antibody was associated with lower odds of severe COVID-19 (OR = 0.13; 95% CI, 0.03-0.64; P = 0.025) on univariate analysis. CCMI score of ≥5 (OR = 1.12; 95% CI = 1.04-1.21; P = 0.02) and Chinese ethnicity were associated with lower odds of readmission on univariate analysis (OR = 0.23; 95% CI, 0.05-0.99; P = 0.05).cAKI was defined by an increase in serum creatinine by at least ≥0.3 mg/dL or an increase by ≥150% to 200% of baseline values.dSevere COVID-19 disease was defined as requiring oxygen supplementation, intensive care unit admission, or death.eA readmission within 30 d of symptom onset was defined as COVID-19 related if the reason for readmission was related to the persistence of COVID-19–related symptoms, progression of COVID-19 disease (eg, from URTI to pneumonia), or a relapse of COVID-19, where relapse was defined as a new clinical episode of symptoms consistent with acute COVID-19, accompanied by repositive/persisting PCR or RATs in respiratory samples.AKI, acute kidney injury; aOR, adjusted odds ratio; CCMI, Charlson comorbidity index; CI, confidence interval; COVID-19, coronavirus disease 2019; eGFR, estimated glomerular filtration rate; PCR, polymerase chain reaction; RAT, rapid antigen test; URTI, upper respiratory tract infection.