key: cord-0880916-ex5lgs7f authors: Jarrin Tejada, Claudia D.; Zachariah, Mareena; Cruz, Angela Beatriz V.; Hussein, Shakir; Wipula, Elizabeth; Meeks, Nicole; Wolff, Jeff; Chandrasekar, Pranatharthi H. title: Favorable outcome of COVID‐19 among African American (AA) renal transplant recipients in Detroit date: 2020-12-11 journal: Clin Transplant DOI: 10.1111/ctr.14169 sha: da8899f3b999b399938af37ded0465758ce70188 doc_id: 880916 cord_uid: ex5lgs7f Transplant recipients are vulnerable to infections, including COVID‐19, given their comorbidities and chronic immunosuppression. In this study, all hospitalized renal transplant recipients (RTR) with a positive nasal swab for Severe Acute Respiratory Syndrome‐Coronavirus‐2 (SARS‐CoV2) seen consecutively between 03/01/2020 and 05/01/2020 at the Detroit Medical Center were included. Data on demographics, clinical presentation, laboratory findings, management, and outcomes were collected. Twenty‐five patients were included, all African American (AA) and deceased‐donor transplant recipients. The most common presenting symptom was dyspnea, followed by fever, cough and diarrhea. Multifocal opacities on initial chest x‐ray were seen in 52% patients and 44% of patients had a presenting oxygen saturation of less than or equal to 94%. Four patients (16%) required transfer to the intensive care unit, one required intubation and one expired. COVID‐19‐infected RTR in this cohort had low mortality of 4% (n = 1). Despite multiple comorbidities and chronic immunosuppression, our cohort of African American RTR had favorable outcomes compared to other reports on COVID‐19 in RTR. Of the 340 renal transplant recipients who are mostly AA (over 85%) followed at our center, twenty-five RTR were diagnosed with COVID-19 during the study period. All 25 met criteria for hospitalization and none were discharged from the Emergency Department (Table 1 ). The 25 RTR had a median age of 56 years (interquartile range; IQR, 47-66). All were African American and deceased-donor transplant recipients. Fourteen (56%) were men and 11 (44%) were women. Three patients were within 6 months of receiving a kidney transplant. The median time since transplant to diagnosis of COVID-19 was 78 months (IQR 35-121). All RTR were on calcineurin inhibitorbased immunosuppression. Twenty (80%) were on triple immunosuppression consisting of tacrolimus, mycophenolic acid derivative, and low-dose prednisone. Of those who were on dual maintenance immunosuppression, two patients had recently returned to dialysis and were on tacrolimus and prednisone (8%), one patient (4%) was on tacrolimus and prednisone and two patients (8%) were on tacrolimus and mycophenolic acid due to steroid intolerance. One patient had an escalation of immunosuppression for recent antibody-mediated rejection and had completed pulse steroids and plasmapheresis within one week of COVID-19 diagnosis. The majority of patients Reported symptom onset ranged from 1 day to 2 weeks before admission. The most common presenting symptom was shortness of breath in 16 (64%) patients, and diarrhea in 14 (56%). Cough and fever also were reported in 14 (56%) patients, and fatigue in 11 patients. About half of the patients had bilateral/multifocal opacities noted on initial chest x-ray (n = 13, 52%), whereas three (12%) had unilateral opacities and 8 (32%) had unremarkable radiographs initially. Eleven patients (44%) had oxygen saturation less than or equal to 94%, ten (40%) required oxygen supplementation at presentation. Median values for laboratory results obtained at the time of presentation included white blood cell count 5300/mm 2 (IQR, 4300-7000) and absolute lymphocyte count 900/mm 2 (IQR, 600-1100). We observed high levels of inflammatory markers, serum ferritin (1275 ng/ mL, IQR 371 -2293), and C-reactive protein (79 mg/L; IQR 48-175). Immunosuppression management during hospitalization consisted of dual therapy with tacrolimus and maintenance prednisone. The median tacrolimus trough at presentation was 7.2 ng/mL (IQR 6.5-8.7) and adjusted as necessary to maintain the target trough per center protocol (up to 6 months, 8-10 ng/mL; 6 months-24 months, 6-8 ng/mL; > 24 months, 5-7 ng/mL). Treatment with mycophenolic acid was withheld at presentation. Hospital guidelines for COVID-19-specific adjuvant therapy varied as the pandemic evolved (Table 2) . Initially, the guidelines recommended hydroxychloroquine to all patients who were admitted and at risk for severe disease, which included all RTR. Those who met the criteria received 400mg twice daily on day 1, followed by once daily for 4 additional days. Later, the guidelines also included oral or IV steroids for patients times more likely than those of other races to test positive. 21 However, increased likelihood of death was associated with shortness of breath on admission, high BMI and age older than 60 years, but was not linked to race or socioeconomic status. Although our cohort included patients with elevated D-dimer, ferritin, and CRP, it did not necessarily portend poor outcomes as seen in other reports of RTR. 7, 11 In this case series, therapy with calcineurin inhibitors was maintained at target troughs without tapering for severity of disease or acute kidney injury. In vitro studies have shown that SARS-CoV may enhance calcineurin-dependent dephosphorylation of NF-AT to trigger cytokine generation. 27 Therefore, blocking NF-AT signaling pathway with calcineurin inhibitors may have an inhibitory effect on immune cell activation and consequent cytokine dysregulation, seen in severe SARS-CoV infection. In addition, in vitro studies have shown calcineurin inhibitors to decrease SARS-CoV replication. 28, 29 Possibly, use of such drugs may lead to reduced severity of "cytokine storm," hence improving disease outcome. In June 2020, the IDSA guidelines were updated to include the use of glucocorticoids among hospitalized patients with severe COVID-19. 18 A recent study showed that an early course of methylprednisolone in patients with moderate to severe COVID-19 reduced escalation of care and improved clinical outcomes. 30 Preliminary results from the RECOVERY trial report that the use of dexamethasone reduced 28-day mortality among patients receiving invasive mechanical ventilation or oxygen supplementation. 31 Use of steroids in our patients likely contributed to a good outcome. Limitations of this study include the relatively small number of patients, its retrospective nature and short follow-up. In addition, asymptomatic patients or those suspected with COVID-19 were not included. Prognosis was excellent in our consecutive cohort of 25 hospitalized AA RTR with COVID-19 admitted during the height of the pandemic. Most patients, despite risk factors for poor outcome, gradually improved and made full recovery. Use of corticosteroids and perhaps maintaining optimal levels of calcineurin inhibitor may have contributed to a muted adverse host inflammatory response and hence, an improved outcome. More data are needed regarding the role of calcineurin inhibitors during COVID-19 infection, particularly in the AA population. The authors of this manuscript have no conflicts of interest to disclose. The data that support the findings of this study are available on request from the corresponding author, Pranatharthi H. Chandrasekar https://orcid. org/0000-0003-0774-1058 Coronavirus 2019 (COVID-19) Centers for Disease Control and Prevention (CDC).Coronavirus -98163_98173 --,00.html. 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