Rapid resolution of cytokine release syndrome and favorable clinical course of severe COVID-19 in a kidney transplant recipient treated with tocilizumab

To the editor:

Immunomodulatory drugs, such as tocilizumab, hold promise for the management of cytokine release syndrome in coronavirus disease 2019 (COVID-19).^{1 , 2} However, its clinical utility in immunosuppressed patients is still lacking.^{3 , 4} Here, we describe the successful use of tocilizumab in a kidney transplant recipient with severe COVID-19.

A 69-year-old man received a kidney transplant in 2005 because of end-stage renal disease due to membranoproliferative glomerulonephritis complicated by chronic allograft nephropathy. Comorbidities included hypertension and obesity (body mass index, 31 kg/m²). Maintenance immunosuppression consisted of mycophenolic acid (1500 mg) and cyclosporine (120 mg). On April 2, 2020, he was admitted to our unit with dyspnea and hypoxia (blood oxygen saturation of 94% with an oxygen flow rate of 2 L/min). The reverse transcription polymerase chain reaction test to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was positive. There was also evidence of acute kidney injury—Kidney Disease: Improving Global Outcomes stage 1. Immunosuppression reduction consisted of mycophenolic acid withdrawal and reduced-dose cyclosporine. The patient was hydrated, and antibiotic prophylaxis was started (Table 1 ). Unfortunately, the patient’s respiratory function further deteriorated, and laboratory findings were suggestive of cytokine release syndrome with remarkably elevated (431 pg/ml) serum interleukin-6 levels. A single i.v. infusion of tocilizumab (8 mg/kg per d) was attempted. Two days after, oxygen was no longer required (Figure 1 ). The patient was discharged home and completely recovered from acute kidney injury.

Table 1.

Treatment approach and temporal course of clinical and laboratory parameters observed in the patient during hospitalization

Characteristics	April 2	April 4	April 5	April 6	April 7	April 9	April 10	April 11	April 13
Days from symptom onset	12	14	15	16	17	19	20	21	23
Highest recorded body temperature, °C	36.5	36.7	37.1	36.7	38.5	36.2	36.1	36.3	36.6
O2 requirement, l/min	2	2	2	2.5	3	6	2	1	0
Lung infiltration on chest CT, %	25	NA	NA	NA	50	NA	NA	NA	NA
Tocilizumab, 680 mg	NA	NA	NA	NA	NA	—	NA	NA	NA
Dexamethasone, 10 mg	NA	NA	NA	NA	—	—	—	—	—
Ceftriaxone	—	—	—	—	—	NA	NA	NA	NA
Azithromycin	—	—	—	—	—	—	—	—	—
Piperacillin-tazobactam	n/a	n/a	n/a	n/a	n/a	—	—	—	—
Serum creatinine, μmol/l	446	380	313	260	249	280	n/a	n/a	213
Serum albumin, g/l	37	34	32	34	36	n/a	n/a	n/a	31
C-reactive protein, mg/l	229	112	67	56	133	n/a	n/a	n/a	8.9
Procalcitonin, μg/l	n/a	5.05	n/a	1.02	0.65	n/a	n/a	n/a	0.14
Lactate dehydrogenase, U/l	n/a	243	n/a	n/a	348	n/a	n/a	n/a	n/a
High-sensitivity troponin, ng/l	n/a	n/a	43	42	44	n/a	n/a	n/a	n/a
Interleukin-6, pg/ml	n/a	36.6	n/a	244.9	430.8	n/a	3.4	n/a	n/a
Fibrinogen, g/l	n/a	6.82	n/a	6.44	7.52	n/a	n/a	n/a	3.75
Ferritin, μg/l	n/a	857	n/a	745	861	n/a	n/a	n/a	n/a
D-dimer, μg/l	n/a	660	n/a	1060	1580	n/a	n/a	n/a	n/a
Lymphocytes, ×109/l	0.31	0.12	0.15	0.2	0.19	0.33	n/a	n/a	0.48
Hemoglobin, g/dl	10.2	8	7.1	9.8	10.3	9.8	n/a	n/a	10.3
Platelet count, ×109/l	229	198	171	182	196	164	n/a	n/a	121

CT, computed tomography; n/a, not available; NA, not applicable.

Figure 1.

Temporal course of serum inflammatory biomarkers—C-reactive protein (CRP) and interleukin (IL)-6—in relation to the patient’s need for oxygen therapy. The timing of tocilizumab infusion and administration of dexamethasone is shown by the arrows.

Early detection of cytokine release syndrome biomarkers is recommended and should prompt anti-inflammatory interventions. Larger studies are needed to confirm the utility and safety of interleukin-6 inhibition combined with dexamethasone in kidney transplant recipients with COVID-19.