Immunosuppressive therapy maintenance in a kidney transplant recipient with SARS-CoV-2 pneumonia: A case report

Abstract

The role of systemic inflammation is proving crucial in determining unfavorable outcome in SARS-CoV-2–infected patients. Limited data are available regarding immunosuppression management in kidney transplant recipients (KTRs) with SARS-CoV-2 pneumonia. We report a case of a 32-year-old KTR who developed SARS-CoV-2 infection and fully recovered in 15 days while maintaining standard immunosuppressive therapy.

1. INTRODUCTION

The novel coronavirus outbreak has startled the world due to its widespread diffusion and socioeconomic burden. Kidney transplant recipients (KTRs) are perceived to be at high risk of infection, and immunosuppressive therapy management during this global emergency can be a challenge. Herein, we report the case of a KTR who developed SARS-CoV-2 pneumonia and recovered in 15 days while continuing administration of his usual immunosuppressive treatment.

2. CASE REPORT

The patient is a 32-year-old man who underwent kidney transplantation in September 2017 from a deceased donor; ESRD etiology was unknown. Prior to admission, February 3, 2020, his most recently measured creatinine level was 1.9 mg/dL (eGFR 46 mL/min/1.73 m²). Immunosuppressive therapy consisted in tacrolimus (trough levels 6-8 ng/mL), mycophenolic acid (360 mg BID), and prednisone (5 mg). Induction therapy included ATG and basiliximab.

Previous medical history was irrelevant except for hypertension and pericarditis treated with colchicine in February, 2017.

On March 12, 2020, the patient was admitted to our emergency room after a fever lasting 3 days, dyspnea and non-productive cough, unsuccessfully treated with amoxicillin-clavulanate 1 g TID.

Physical evaluation was normal: body temperature was 38°C and oxygen saturation was 97% in ambient air, blood pressure was 130/70 mm Hg, and respiratory rate was 25 breaths per minute. Laboratory results demonstrated a low percentage of lymphocytes (17.8%), absolute and relative monocytosis (1000/mmc; 16.7%), C-reactive protein (CRP) elevation (47.9 mg/L), and slightly elevated levels of procalcitonin (PCT) (0.33 µg/L). Renal function impairment was observed (creatinine 2.6 mg/dL, eGFR 31 mL/min/1.73 m²). Pneumococcus and Legionella infections were ruled out by negative urinary antigens. Arterial blood gas analysis was suggestive of respiratory alkalosis.

Chest X-ray demonstrated diffuse septal thickening in the absence of areas of consolidation.

On March 13, nasopharyngeal swab testing was performed and SARS-COV-2 was identified by rRT-PCR (Day 0).

The patient was then transferred to the Infectious Disease Unit. In agreement with the nephrologist, his prednisone dose was increased to 15 mg/d, while the remaining immunosuppressive therapy was left unchanged.

On Day 0, according to the local protocol, hydroxychloroquine 200 mg BID and oseltamivir 30 mg OD were started. The patient was febrile (TA 38°C), respiratory rate increased to 30 breaths per minute, oxygen saturation decreased to 94%, and oxygen administration was started at 4 mL/min by nasal cannula. Due to the concomitant increase in CRP (97 mg/L) and PCT (2.33 µg/L), antibiotic therapy with ceftaroline was started. On Day 2, laboratory results showed a decrease in platelets (minimum 108 000/mmc) and a reduction of prothrombin time (PT 78%). Moreover, a high IL-6 concentration was detected (86.3 ng/L) and lower CD4⁺, CD8⁺, CD3⁺ count was found in the peripheral blood, although with a normal CD4/CD8 ratio (respectively, 131/cmm, 80/cmm, 227/cmm, CD4/CD8:1,7). Increased levels of ferritin, transaminases, and lactic dehydrogenase (LDH) were found. The patient remained febrile until Day 5; on Day 8, oxygen saturation in ambient air reached 96%; on Day 11, the patient was released with indication to solitary confinement. At discharge, CRP and IL-6 levels were significantly decreased (respectively, 18 mg/L and 6.9 ng/L). Renal function was comparable to what it was at admission (creatinine 2.8 mg/dL, eGFR 29 mL/min/1.73 m²) and proteinuria had significantly increased (Day 0:1 g/L; Day 11:3 g/L). Symptoms, laboratory results, and treatments are described in Table 1.

TABLE 1.

Symptoms, laboratory results, and treatments according to day of illness

	Day −3	Day −1	Day 0	Day 1	Day 2	Day 4	Day 6	Day 7	Day 11
Body temperature	38.5	38	38	38.5	37	37.8	37	36.5	36.5
FiO2		AA	AA	35	35	AA	24	AA	AA
SpO2		97	94	94	96	97	95	96	99
Respiratory rate		25	30				30
Arterial pCO2		32.2				24.8	32.3
WBC		6210	4930		7170	6290	5960
Lymphocytes		1100			1100	830	900
Monocytes		1000			500	520	800
PLTs		137 000			108 000	156 000	245 000
Hgb		11.4	11.1		11.0	10.3	10.6
Creatinine		2.6	2.6		2.7	3	2.9		2.8
LDH		178			249	337			218
Ferritin					504				664
IL-6					86.3				6.9
CRP		47.9	97		69.8				18
PCT		0.33	2.33		2.33	1.14			0.08
ALT		40	35		42	62			18
AST					45	80			24
PT		70	65		78				75
TL TAC		6.6					12
Cough and dyspnea
		Chest X-ray
Therapy			Hydroxychloroquine
			Oseltamivir
				Ceftaroline

Abbreviations: AA, ambient air; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CRP, C-reactive protein; FiO₂, fraction of inspired oxygen; Hgb, hemoglobin; IL-6, interleukin 6; LDH, lactate dehydrogenase; pCO₂, partial pressure of carbon dioxide; PCT, procalcitonin; PLTs, platelets; PT, prothrombin time; SpO₂, peripheral capillary oxygen saturation; TAC, tacrolimus; TL, trough levels; WBC, white blood cells. [Color table can be viewed at wileyonlinelibrary.com]

3. DISCUSSION

In December 2019, SARS-CoV-2 was identified in Wuhan, China. In February 2020, the first case was diagnosed in Italy, and within a few weeks, the COVID-19 infection has taken on the characteristics of a “pandemic.”

Immunosuppressed patients are, by definition, at high risk of infections. However, COVID-19 does not appear to cause more severe disease in liver transplant recipients.¹

Systemic inflammatory response plays a main role in provoking viral-induced lung injury and could be largely responsible for the poor respiratory outcome in most patients, thus favoring transition to acute respiratory distress syndrome (ARDS).² Moreover, a study performed in Wuhan identified IL-6 and ferritin as predictors of mortality in COVID-19 patients³ thereby paving the way to experimentation with tocilizumab, an IL-6 receptor blocker.

In their work, Shi et al⁴ suggest the presence of two phases in the COVID-19 infection; in the first, which occurs during incubation and in the non-severe disease period, virus replication activates immune response. Thus, boosting the immune system at this exact moment could be the winning strategy to obtain complete virus clearance. At later stages, when severe disease develops, lung damage is induced by the systemic inflammation itself.

Based on this rationale and on laboratory results demonstrating hyperinflammation,⁵ immunosuppressive therapy was left unchanged and therefore lopinavir/ritonavir was not administered due to proven drug interaction with calcineurin inhibitors.

Even though corticosteroid use in COVID-19 pneumonia remains controversial,^{6 , 7} we increased our patient’s prednisone dose to 15 mg for 9 days as an anti-inflammatory agent.

Interestingly, we did not observe complete recovery of graft function, and moreover, proteinuria developed. Further investigation into these findings is needed. Since discharge, the patient’s clinical condition has been closely monitored via telephone.

Immunosuppression in critically ill patients is still a matter of debate. As recently highlighted by Ritchie and Singanayagam in their letter,⁸ the relationship between virus replication and systemic inflammation may be consequential and directly related rather than an excessive response by the immune system. Therefore, the impact of immunosuppressive therapy is crucial in transplant recipients.

In conclusion, although our evidence is anecdotal, it may provide some clinical insight into therapeutic management. Maintaining immunosuppression could be beneficial in stopping, or at least mitigating the “cytokine storm” that usually leads to poor outcome in these patients and, only secondarily, in preventing graft rejection. Further studies are warranted to confirm these findings and to evaluate the clinical and laboratory characteristics of the KTRs who might benefit from this therapeutic strategy.