Outcomes of Solid Organ Transplant Recipients Treated With Antispike Monoclonal Antibodies for Coronavirus Disease 2019 Across Variant Epochs: Impact of Comorbidities and Vaccination : Transplantation

Journal Logo

Letters to the Editor

Outcomes of Solid Organ Transplant Recipients Treated With Antispike Monoclonal Antibodies for Coronavirus Disease 2019 Across Variant Epochs: Impact of Comorbidities and Vaccination

Yetmar, Zachary A. MD1; O’Horo, John C. MD, MPH1,2; Seville, Maria Teresa MD3; Speicher, Leigh L. MD, MPH4; Ganesh, Ravindra MBBS, MD5; Razonable, Raymund R. MD1,6

Author Information
doi: 10.1097/TP.0000000000004325
  • Free

Solid organ transplant recipients (SOTRs) are at high risk of poor outcomes from coronavirus disease 2019 (COVID-19), with high rates of hospitalization and mortality.1 Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has been shown to reduce the risk of severe infection, SOTRs have a blunted immune response to vaccination, and breakthrough infection remains a significant issue in this population.2 Several therapies have been developed to reduce progression to severe COVID-19, including antispike neutralizing monoclonal antibodies.3 However, data regarding outcomes of antispike monoclonal antibody therapies in SOTRs across variant eras are limited.

We conducted a multicenter retrospective study analyzing adult SOTRs with mild-to-moderate COVID-19 who received antispike monoclonal antibody treatment at our centers in Arizona, Florida, Minnesota, and Wisconsin. We aimed to determine if there are differences in clinical outcomes across epochs dominated by different SARS-CoV-2 variants (as defined by Centers for Disease Control surveillance data) and assess for factors associated with the risk of progression to severe infection despite treatment with antispike monoclonal antibodies. The primary outcome was progression to severe COVID-19, defined as an oxygen saturation ≤94% on room air or hospitalization for COVID-19 by day 30 after diagnosis. This study was reviewed by our institutional review board and granted an exempt status (no. 20-012919).

Between November 19, 2020, and February 28, 2022, 657 SOTRs were treated with an antispike monoclonal antibody for mild-to-moderate COVID-19 (Table 1). Progression to severe COVID-19 occurred in 65 patients (9.9%), with 57 (8.7%) requiring hospital admission and 16 (2.4%) admission to an intensive care unit. Three patients (0.5%) died within 30 d of diagnosis, and 5 patients (0.8%) died within 90 d; 2 of the deaths were due to progressive COVID-19 pneumonia. Rates of severe COVID-19 were lowest in the Omicron era (5%) compared with pre-Delta (12%) and Delta (12%). Lung recipients had the highest rate of severe infection (20%).

TABLE 1. - Characteristics of 657 solid organ transplant recipients with COVID-19 treated with an antispike monoclonal antibody, stratified by progression to severe COVID-19
Variables Mild-moderate (N = 592) Severe (N = 65) Total (N = 657) P
Age, mean (SD), y 56.7 (13.7) 62.8 (12.5) 57.3 (13.7) <0.001
Male sex 369 (62.3) 41 (63.1) 410 (62.4) 0.906
Race 0.145
 American Indian or Alaska Native 7 (1.2) 1 (1.5) 8 (1.2)
 Asian 10 (1.7) 3 (4.6) 13 (2.0)
 Black or African American 53 (9.0) 3 (4.6) 56 (8.5)
 Native Hawaiian or other Pacific Islander 3 (0.5) 0 (0.0) 3 (0.5)
 Other 15 (2.5) 1 (1.5) 16 (2.4)
 White 501 (84.6) 55 (84.6) 556 (84.6)
 Unknown 3 (0.5) 2 (3.1) 5 (0.8)
Ethnicity 0.999
 Hispanic or Latino 72 (12.2) 8 (12.3) 80 (12.2)
 Not Hispanic or Latino 511 (86.3) 56 (86.2) 567 (86.3)
 Unknown 9 (1.5) 1 (1.5) 10 (1.5)
BMI, mean (SD), kg/m2 29.3 (6.1) 28.0 (5.7) 29.1 (6.1) 0.096
Diabetes 208 (35.1) 24 (36.9) 232 (35.3) 0.775
Charlson comorbidity index, median (IQR) 2.0 (1.0–4.0) 2.0 (1.0–4.0) 2.0 (1.0–4.0) 0.353
MASS, median (IQR) 7.0 (6.0–10.0) 10.0 (7.0–12.0) 8.0 (6.0–10.0) <0.001
Transplant type 0.196
 Kidney 290 (49.0) 37 (56.9) 327 (49.8)
 Heart 93 (15.7) 9 (13.8) 102 (15.5)
 Lung 20 (3.4) 5 (7.7) 25 (3.8)
 Liver 114 (19.3) 7 (10.8) 121 (18.4)
 Pancreas 12 (2.0) 0 (0.0) 12 (1.8)
 Multiorgan 63 (10.6) 7 (10.8) 70 (10.7)
Subsequent transplant 87 (14.7) 12 (18.5) 99 (15.1) 0.420
Time from first transplant, median (IQR), y 4.6 (1.7–10.6) 4.5 (1.6–13.0) 4.5 (1.7–10.9) 0.769
Vaccination status 0.025
 Unvaccinated 189 (31.9) 29 (44.6) 218 (33.2)
 Partially vaccinated 168 (28.4) 21 (32.3) 189 (28.8)
 Fully vaccinated 235 (39.7) 15 (23.1) 250 (38.1)
Booster vaccine dose 15 (2.5) 0 (0.0) 15 (2.3) 0.194
Vaccine manufacturer (N = 439) 0.804
 Johnson & Johnson 19 (4.7) 2 (5.6) 21 (4.8)
 Moderna 168 (41.7) 13 (36.1) 181 (41.2)
 Pfizer-BioNTech 216 (53.6) 21 (58.3) 237 (54.0)
Time from last vaccine dose, median (IQR), d (N = 439) 129.0 (70.5–162.0) 129.5 (52.0–194.0) 129.0 (68.0–162.5) 0.900
VOC era (N = 624) a 0.011
 Pre-Delta 100 (17.7) 14 (23.7) 114 (18.3)
 Delta 237 (41.9) 33 (55.9) 270 (43.3)
 Omicron 228 (40.4) 12 (20.3) 240 (38.5)
Antispike monoclonal antibody 0.090
 Bamlanivimab 66 (11.1) 11 (16.9) 77 (11.7)
 Bamlanivimab-etesevimab 24 (4.1) 4 (6.2) 28 (4.3)
 Casirivimab-imdevimab 246 (41.6) 32 (49.2) 278 (42.3)
 Sotrovimab 256 (43.2) 18 (27.7) 274 (41.7)
Time from diagnosis to infusion, median (IQR), d 2.0 (1.0–3.0) 2.0 (1.0–3.0) 2.0 (1.0–3.0) 0.786
Data are n (%) unless otherwise specified.
aThe period before June 2021 was classified as pre-Delta epoch, July through December 15, 2021, as Delta epoch, and January 1, 2022, through February 28, 2022, as Omicron epoch. The periods of June 2021 and December 16 to 31, 2021, were transitional periods in predominant variant, and those diagnosed in these transition periods were excluded from VOC-specific analyses.
BMI, body mass index; COVID-19, coronavirus disease 2019; IQR, interquartile range; MASS, Monoclonal Antibody Screening Score; VOC, variant of concern.

After adjusting for time to monoclonal antibody infusion, multivariable logistic regression found SARS-CoV-2 vaccination (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.25-0.97) and higher Monoclonal Antibody Screening Score (OR, 1.26 per unit; 95% CI, 1.15-1.39) to be significantly associated with severe COVID-19. Compared with the pre-Delta era, diagnosis in the Omicron epoch had a nonsignificant decreased odds (OR, 0.67; 95% CI, 0.25-1.75), whereas Delta epoch had a nonsignificant increased odds (OR, 1.50; 95% CI, 0.68-3.38) of severe COVID-19.

This study demonstrates a lower rate of severe COVID-19 among SOTRs treated with antispike monoclonal antibody during the Omicron epoch in unadjusted analysis. However, after multivariable adjustment, diagnosis in the Omicron epoch was not significant, and improved outcomes appear to be attributable to higher rates of vaccination instead.4,5 No patients who had received a booster vaccine dose developed severe infection, although the over all number of these patients was small. A higher number of comorbidities increases risk of poor outcomes in SOTRs. Our study highlights the importance of a layered approach to COVID-19 management in SOTRs. Vaccination provides primary protection against severe COVID-19, even in SOTRs who receive early therapy with antispike monoclonal antibodies.

REFERENCES

1. Heldman MR, Kates OS, Safa K, et al.; UW Covid-19 SOT Study Team. Delayed mortality among solid organ transplant recipients hospitalized for COVID-19. Clin Infect Dis. [Online ahead of print. February 25, 2022]. doi:10.1093/cid/ciac159
2. Qin CX, Moore LW, Anjan S, et al. Risk of breakthrough SARS-CoV-2 infections in adult transplant recipients. Transplantation. 2021;105:e265–e266.
3. Yetmar ZA, Beam E, O’Horo JC, et al. Monoclonal antibody therapy for COVID-19 in solid organ transplant recipients. Open Forum Infect Dis. 2021;8:ofab255.
4. Solera JT, Arbol BG, Alshahrani A, et al. Impact of vaccination and early monoclonal antibody therapy on Covid-19 outcomes in organ transplant recipients during the omicron wave. Clin Infect Dis. [Online ahead of print. April 21, 2022]. doi:10.1093/cid/ciac324
5. Nyberg T, Ferguson NM, Nash SG, et al.; COVID-19 Genomics UK (COG-UK) consortium. Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study. Lancet. 2022;399:1303–1312.
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.