COVID-19 Therapies and Outcomes in Solid Organ Transplants

In This Article

Abstract and Introduction

Abstract

Treatment outcomes associated with the use of novel COVID-19 therapeutics in solid organ transplant recipients (SOTR) are not well described in the literature. The objective of this analysis was to characterize 30-day hospitalization and other key secondary endpoints experienced by outpatient SOTR with mild–moderate COVID-19 treated with nirmatrelvir/ritonavir (NR), sotrovimab, or no SARS-CoV-2 specific treatment. This IRB-approved, retrospective study included 154 SOTR with a documented positive SARS-CoV-2 infection between December 16, 2021 and January 19, 2022 (a predominant Omicron BA.1 period in New York City). Patients who received NR (N = 28) or sotrovimab (N = 51) experienced a lower rate of 30-day hospitalization or death as compared to those who received no specific treatment (N = 75) (p = .009). A total of three deaths occurred, all among patients who initially received no specific treatment prior to hospitalization. These results suggest a role for SARS-CoV-2 specific agents in the treatment of SOTR with COVID-19, and that there does not appear to be any difference in effectiveness when comparing NR versus sotrovimab.

Introduction

Solid organ transplant recipients (SOTR) are at high risk for morbidity due to COVID-19.^[1,2] The risk of hospitalization or death among SOTR who develop COVID-19 has been reported to be upwards of four-times greater than that of the immunocompetent population.^[3]

Multiple therapeutic options have been authorized by the United States Food and Drug Administration (FDA) for use in patients with mild–moderate COVID-19 who are at high risk for progression to severe disease. Sotrovimab, a monoclonal antibody that binds to and neutralizes the SARS-CoV-2 spike protein, was evaluated in a randomized, placebo-controlled clinical trial.^[4] Compared to placebo, sotrovimab reduced the risk of hospitalization or death from any cause through day 29 by 82%. Nirmatrelvir/ritonavir (NR), an orally available viral protease inhibitor, was also evaluated in a population of at-risk patients with mild–moderate COVID-19.^[5] Compared to placebo, NR reduced the risk of hospitalization or death from any cause through day 28 by 89%.

However, neither of the aforementioned clinical studies enrolled SOTR. As such, it is not yet known if these agents are safe or effective in this particularly at-risk population. Case series describing outcomes of SOTR treated with either sotrovimab or NR have been published, though they are limited by small sample sizes and do not include comparator populations.^[6–8]

The objective of this analysis was to evaluate outcomes in a heterogeneous population of outpatient SOTR infected with COVID-19 during an Omicron BA.1-dominated period in New York City who received either NR or sotrovimab, compared to those who received no SARS-CoV-2 specific treatment.

Table 1. Baseline characteristics
	Nirmatrelvir/ritonavir (N = 28)	Sotrovimab (N = 51)	No treatment (N = 75)	p-value
Age at time of COVID-19 symptom onset (years)	57.6 (44.3–68.6)	53.3 (45–61.6)	53.3 (37.6–64.6)	.513
Male sex	11 (39.3)	21 (41.2)	32 (42.7)	.976
Organ transplant
Kidney	4 (14.3)	18 (35.3)	43 (57.3)	<.001
Liver	2 (7.1)	0 (0)	6 (8)
Heart	11 (39.3)	19 (37.3)	14 (18.7)
Lung	11 (39.3)	4 (9.8)	9 (12)
Kidney/pancreas	0 (0)	1 (2)	1 (1.3)
Dual organ	0 (0)	8 (15.7)	2 (2.7)
BMI (kg/m²)	25.3 (22.3–30)	24.6 (21.5–30.2)	27 (23.3–29.5)	.707
History of previous COVID-19 infection	4 (14.3)	5 (9.8)	7 (9.3)	.730
SCr prior to COVID-19 symptom onset (mg/dL)	1.2 (0.9–1.6)	1.4 (1.1–1.9)	1.7 (1.2–2.2)	.033
Time from transplant to COVID-19 symptom onset (years)	3.9 (1.8–10.6)	3.4 (0.8–10.7)	4 (2.3–8.1)	.52
COVID-19 symptom severity^a
Asymptomatic	2 (7.1)	3 (5.9)	8 (10.7)	.657
Mild	25 (89.3)	45 (88.2)	59 (78.7)
Moderate	1 (3.6)	3 (5.9)	8 (10.7)
mRNA vaccine
1 dose	1 (3.6)	2 (3.9)	3 (4)	1.000
2 doses	8 (28.6)	14 (27.5)	22 (29.3)
3 doses	15 (53.6)	27 (52.9)	39 (52)
Adenovirus vector	1 (3.6)	2 (3.9)	4 (5.3)	1.000
Immunosuppressive agents administered within 6 months prior to COVID-19 symptom onset
Lymphocyte depleting agent	2 (7.1)	5 (9.8)	3 (4)	.419
High dose steroids^b	5 (17.9)	10 (19.6)	5 (6.7)	.074
Rituximab	1 (3.6)	0 (0)	1 (1.3)	.44
Bortezomib	0 (0)	0 (0)	0 (0)	—
Maintenance immunosuppressive agents prior to COVID-19 symptom onset
Tacrolimus (ng/ml)	8.6 (6.4–13.8)	7.8 (5.6–10.7)	6.8 (5.1–8)	.01
Cyclosporine (ng/ml)	75.9 (73.1–79.3)	174.3 (107.8–254.7)	144.9 (103–152.8)	.148
Everolimus (ng/ml)	4.1 (3.6–4.5)	4 (3.1–6.4)	4.1 (3.9–4.3)	.997
MMF equivalents (mg/day)	2000 (1000–2000)	1750 (1000–2000)	1000 (1000–2000)	.003
Azathioprine (mg/day)	—	100 (100–150)	100 (100–100)	.524
Prednisone (mg/day)	5 (5–5)	5 (3–5)	5 (5–5)	.349
Belatacept	3 (10.7)	5 (9.8)	20 (27)	.027

Note: Continuous variables reported as median (IQR), categorical variables reported as n (%).
Abbreviations: BMI, body mass index; MMF, mycophenolate mofetil; SCr, serum creatinine.
^aCOVID-19 symptom severity defined by the National Institutes of Health.
^bDefined as at least 1 mg/kg prednisone equivalents (associated with treatment of allograft rejection).

Table 2. Secondary outcomes through day 30
	Nirmatrelvir/ritonavir (N = 28)	Sotrovimab (N = 51)	No treatment (N = 75)	p-value
Time from symptom onset to hospitalization (days)	17.5 (6–28)	13.5 (12–21)	10 (7–12)	.217
AKI^a
No AKI	27 (96.4)	44 (89.8)	54 (72)	.017
Stage 1	1 (3.6)	1 (2)	14 (18.7)
Stage 2	0 (0)	2 (4.1)	2 (2.7)
Stage 3	0 (0)	2 (4.1)	5 (6.7)
Oxygen requirement
No oxygen requirement	26 (92.9)	49 (96.1)	62 (82.7)	.172
Supplemental oxygen	2 (7.1)	2 (3.9)	9 (12)
Mechanical ventilation	0 (0)	0 (0)	4 (5.3)
Other COVID-19 agents used
Remdesivir	2 (7.1)	2 (3.9)	16 (21.6)	.011
Dexamethasone	2 (7.1)	2 (3.9)	16 (21.6)	.011
Tocilizumab/baricitinib	0 (0)	0 (0)	1 (1.3)	1.000
Acute rejection episode^b	0 (0)	0 (0)	1 (1.3)	1.000

Note: All variables as reported as n (%).
Abbreviation: AKI, acute kidney injury.
^aAcute kidney injury defined according to the Acute Kidney Injury Network classification.
^bSuspected rejection episode, not biopsy-confirmed.