key: cord-0784618-c1jzty0u
authors: Roberts, Matthew B.; Izzy, Saef; Tahir, Zabreen; Al Jarrah, Ali; Fishman, Jay A.; El Khoury, Joseph
title: COVID‐19 in solid organ transplant recipients: Dynamics of disease progression and inflammatory markers in ICU and non‐ICU admitted patients
date: 2020-07-22
journal: Transpl Infect Dis
DOI: 10.1111/tid.13407
sha: 3ca2b67f083529577c86d3a847e6f66659f917d3
doc_id: 784618
cord_uid: c1jzty0u

BACKGROUND: COVID‐19 infection varies in severity from minimal symptoms to critical illness associated with a hyperinflammatory response. Data on disease progression in immunosuppressed solid organ transplant (SOT) recipients are limited. METHODS: We examined the electronic medical records of all SOT recipients with COVID‐19 from 12 Massachusetts hospitals between February 1, and May 6, 2020. We analyzed the demographics, clinical parameters, course, and outcomes of illness in these patients. RESULTS: Of 52 COVID‐19‐positive SOT patients, 77% were hospitalized and 35% required ICU admission. Sixty‐nine percent of hospitalized patients had immunosuppression reduced, 6% developed suspected rejection. Co‐infections occurred in 45% in ICU vs 5% in non‐ICU patients (P = .037). A biphasic pattern of evolution of laboratory tests was observed. In the first 5 days of illness, inflammatory markers were moderately increased. Subsequently, WBC, CRP, ferritin, and D Dimer increased with increasing stay in the ICU, and lymphocyte counts were similar. Five patients (16%) died. CONCLUSIONS: Our data indicate that SOT is associated with high rate of hospitalization, ICU admission, and death from COVID‐19 compared to data in the general population of patients with COVID‐19. Despite reduction in immunosuppression, suspected rejection was rare. The clinical course and trend of laboratory biomarkers is biphasic with a later, pronounced peak in inflammatory markers seen in those admitted to an ICU. CRP is a useful marker to monitor disease progression in SOT.

We extracted baseline demographic data (age, gender, race, ethnicity, zip code), smoking status, comorbidities, medications at time of COVID-19 diagnosis, SOT type and date, history of rejection within 3 months prior to COVID-19 diagnosis. For patients admitted within the Mass General Brigham system, details of admission including presenting symptoms and vital signs, therapeutic drugs and strategies, clinical outcomes, serial clinical and laboratory parameters (complete blood count, CBC, creatinine, liver function tests, LFT, C-reactive protein, procalcitonin, ferritin, D Dimer, IL-6 level, hypersensitive troponin T, creatinine kinase, lactate dehydrogenase, LDH, and tacrolimus levels) through COVID-19 illness.

Comparison is made between patients admitted and those managed as outpatients. In addition, among those admitted to the hospital, comparison is made between those admitted to ICU at any point in their admission (ICU patients) and those managed exclusively in a non-ICU, general medical/surgical setting (Non-ICU patients). 

A total of 52 solid organ transplant recipients were identified as COVID-19 positive with demographic data ( Most recipients were immunosuppressed with tacrolimus, mycophenolate, and low-dose corticosteroids. Only 1 recipient had experienced an episode of rejection within 3 months prior to COVID-19 diagnosis. Hypertension (43 subjects, 83%), diabetes (35%), and chronic renal insufficiency were common comorbid conditions.

Comparison between those admitted to any hospital (n = 40) vs those managed at home (n = 12) is shown in Table 1 . Those admitted had a higher median age (61 years vs 50 years, P = .002) and were more likely to have a diagnosis of ischemic heart disease (12 vs 0, P = .047). Pre-admission medications included a statin in 29 (53%) TA B L E 1 Demographic characteristics of SOT recipients diagnosed with COVID-19, with comparison between those admitted and not admitted 

Inpatient management is shown in Table 3 . All of those admitted to ICU were intubated and required vasopressors (11, 100%); 8 (73%) required prone positioning and 5 (45%) required dialysis. Median time to ICU admission was 7 days from symptom onset. Only 12 (57%) of the non-ICU patients required supplemental oxygen at some point in their hospitalization with 8 (38%) of these requiring supplemental oxygen on admission.

Antibiotics were more frequently given to ICU patients than non-ICU patients (11 vs 9, P = .0021). Hydroxychloroquine was given to 11 patients (35%) including 6 (55%) admitted to ICU. Statins were given or continued in 21 (68%), off-label tocilizumab was used in one patient, and nine patients (28%) were enrolled in therapeutic drug trials. Immunosuppression was changed in 22 (69%) of those admitted including 8 (73%) of the ICU patients and 14 (67%) of the non-ICU patients. Of those on an antimetabolite (MMF or azathioprine), 19 (71%) had these drugs held (50%) or reduced by half (29%). Only one patient admitted to ICU on mycophenolate had no adjustment.

Calcineurin inhibitors were held in one patient (4%), and mTOR inhibitors were held in 3 (100%) patients. Belatacept TM was deferred in two of three patients on this agent. Steroids were not withdrawn in any patients; 4 (44%) patients in the ICU group had stress dose steroids, usually in conjunction with reduction in other agents. Median tacrolimus levels pre-COVID diagnosis and during inpatient admission were not different between ICU and non-ICU patients ( Figure   S1 ).

Co-infections were more frequent in those admitted to ICU compared to non-ICU patients (5 vs 1, P = .037) ( Table 4 In addition to the strengths discussed above and the large de- Our data show that a significant proportion of admitted SOT patients require ICU care with high mortality. Close follow-up and a 

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Additional supporting information may be found online in the Supporting Information section

COVID-19 in solid organ transplant recipients: Dynamics of disease progression and inflammatory markers in ICU and non-ICU admitted patients