key: cord-0817681-auidg9sr authors: Nair, Vinay; Jandovitz, Nicholas; Hirsch, Jamie S.; Nair, Gayatri; Abate, Mersema; Bhaskaran, Madhu; Grodstein, Elliot; Berlinrut, Ilan; Hirschwerk, David; Cohen, Stuart L.; Davidson, Karina W.; Dominello, Andrew J.; Osorio, Gabrielle A.; Richardson, Safiya; Teperman, Lewis W.; Molmenti, Ernesto P. title: COVID‐19 in kidney transplant recipients date: 2020-05-27 journal: Am J Transplant DOI: 10.1111/ajt.15967 sha: b3007b8049c8c2479b4a5b6a47738ab0628567c7 doc_id: 817681 cord_uid: auidg9sr There is minimal information on coronavirus disease 2019 (COVID‐19) in immunocompromised individuals. We have studied 10 patients treated at 12 adult care hospitals. Ten kidney transplant recipients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) by polymerase chain reaction, and 9 were admitted. The median age was 57 (interquartile range [IQR] 47‐67), 60% were male, 40% Caucasian, and 30% Black/African American. Median time from transplant to COVID‐19 testing was 2822 days (IQR 1272‐4592). The most common symptom was fever, followed by cough, myalgia, chills, and fatigue. The most common chest X‐ray and computed tomography abnormality was multifocal patchy opacities. Three patients had no abnormal findings. Leukopenia was seen in 20% of patients, and allograft function was stable in 50% of patients. Nine patients were on tacrolimus and a mycophenolic antimetabolite, and 70% were on prednisone. Hospitalized patients had their antimetabolite agent stopped. All hospitalized patients received hydroxychloroquine and azithromycin. Three patients died (30%), and 5 (50%) developed acute kidney injury. Kidney transplant recipients infected with COVID‐19 should be monitored closely in the setting of lowered immunosuppression. Most individuals required hospitalization and presenting symptoms were similar to those of nontransplant individuals. There is minimal information on coronavirus disease 2019 (COVID-19) in immunocompromised individuals. We have studied 10 patients treated at 12 adult care hospitals. Ten kidney transplant recipients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by polymerase chain reaction, and 9 were admitted. The median age was 57 (interquartile range [IQR] 47-67), 60% were male, 40% Caucasian, and 30% Black/African American. Median time from transplant to COVID-19 testing was 2822 days (IQR 1272-4592). The most common symptom was fever, followed by cough, myalgia, chills, and fatigue. The most common chest X-ray and computed tomography abnormality was multifocal patchy opacities. Three patients had no abnormal findings. Leukopenia was seen in 20% of patients, and allograft function was stable in 50% of patients. Nine patients were on tacrolimus and a mycophenolic antimetabolite, and 70% were on prednisone. Hospitalized patients had their antimetabolite agent stopped. All hospitalized patients received hydroxychloroquine and azithromycin. Three patients died (30%), and 5 (50%) developed acute kidney injury. Kidney transplant recipients infected with COVID-19 should be monitored closely in the setting of lowered immunosuppression. Most individuals required hospitalization and presenting symptoms were similar to those of nontransplant individuals. clinical research/practice, infection and infectious agents -viral, kidney (allograft) function/ We performed an ongoing study at 12 acute care hospitals in Northwell Health. All COVID-19-positive patients with a functioning kidney allograft who presented to the emergency department and were either discharged or hospitalized between March 1, 2020 Ten kidney transplant recipients were found to be COVID-19 positive by PCR. Nine of the 10 patients included were hospitalized. Of the 9, 5 were admitted to the intensive care unit (ICU). Three patients who required intubation died. The 10 patients with COVID-19 had variable presentations and courses (see Table 2 ). The most common documented symptom was fever followed by cough, myalgia, chills, and fatigue. Two patients Leukopenia was seen in 20% of patients during hospitalization. Eight of the 9 hospitalized patient had at least 1 ferritin level and C-reactive protein (CRP) checked (see Table 2 ). Median ferritin was 788 ng/mL (IQR 563-1162) and CRP 13.35 mg/dL (IQR 4.82-23.72). Allograft function was stable in 50% of patients. Five patients had acute kidney injury (AKI): three stage 3, one stage 2, and one stage 1. No kidney biopsies were performed during the hospitalization. Immunosuppression at baseline and changes undertaken can be seen in All hospitalized patients had their antimetabolite agent stopped. Tacrolimus doses were titrated to a target trough of 3-5 ng/mL. Tacrolimus was stopped for Patients 5 and 6 who were intubated in the ICU and sirolimus was stopped for Patient 9. All hospitalized patients received hydroxychloroquine (HCQ) and azithromycin (the latter no longer routinely administered as part of Table 4 ). Patient 1 was discharged home without any antiviral or antimicrobial agents. Patients 5, 6, and 10 in the ICU were also placed on thiamine. Patients 6 and 7 were given methylprednisolone and Patient 10 was given high-dose prednisone for ARDS. Risk factors for poor outcome among patients in our series were similar to those of the general population, including age, male gender, and preexisting comorbidities. [7] [8] [9] Comorbid conditions including hypertension and diabetes were highly prevalent in our population. The overall mortality in our patient cohort was high. In our experience immunosuppression did not seem to reduce the incidence of ARDS or death. associated with a higher risk of infection. Our cohort was split evenly between those known with ATG induction and IL2rAb induction. There is yet no proven treatment for COVID-19. Chloroquine and HCQ have been reported to have antiviral activity, to inhibit cytokine production, and to be associated with improved CT pulmonary images, a rapid decline in fever, and a quicker recovery period. [10] [11] [12] [13] The effect seems to be reinforced by azithromycin. 11 Corticosteroids are not routinely recommended but have also been utilized. 14,15 Current treatments include supportive care as well as chloroquine, HCQ, and various agents currently under investigation such as interleukin-6 (IL-6) inhibitors and remdesivir. 8, 12, 16 All of our hospitalized patients were treated with HCQ and azithromycin. Since the writing of this manuscript, azithromycin has been discontinued as a routine therapy at our institution. Notably both CNI and HCQ can prolong the QT interval, resulting in fatal torsades. For this reason, it is imperative to assess the QT interval before initiation of therapy and possibly monitor posttherapy as well. It is intuitive that T cell immunity should be important in controlling viral replication and disease. Based on this assumption, antimetabolite therapy was stopped in all patients. 17 15 It is likely that the development of ARDS is mediated by the uncontrolled release of cytokines. 10, 16 There seems to be evidence pointing to the fact that a subgroup of patients with severe COVID-19 may have a cytokine storm syndrome. 15 Some form of immunosuppression may be of benefit in this setting of hyperinflammation. 15 Interleukin-6 (IL-6) and interleukin-1 (IL-1) blockade is currently being tried with COVID-19. Administration of agents such as immunoglobulin, other cytokine blocking agents, and statins may also be of use. 15 The current report is based on the experience of a large health system and its transplant center at the epicenter of a pandemic. We believe that kidney transplant recipients infected with COVID-19 should be monitored closely in the setting of a lowered immunosuppression. Most individuals sick enough to present to the emergency room required hospitalization, and rates of ICU admission are high. Presenting symptoms are similar to those of nontransplant individuals. Although all recipients in our series had at least 1 comorbidity, this is an almost universal finding in the transplant population. There were no viral coinfections. In our cohort of hospitalized patients, mortality was high. Home-bound patients (both with and without COVID-19) are being followed via telehealth. Morbidity and mortality rates continue to evolve. We would like to acknowledge (1) Fran Wallach, MD, for her collaboration; (2) all the COVID-19 victims who did or did not survive; and The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. The data that support the findings of this study are available on request from COVID19@northwell.edu. The data are not publicly available due to restrictions as it could compromise the privacy of research participants. China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China Case report of COVID-19 in a kidney transplant recipient: Does immunosuppression alter the clinical presentation Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China Identification of kidney transplant recipients with coronavirus disease 2019 Management of patients on dialysis and with kidney transplant during SARS-COV-2 (COVID-19) pandemic in Coronaviruses and immunosuppressed patients. 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In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury COVID-19: consider cytokine storm syndromes and immunosuppression Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies Inhibitions of human parainfluenza virus type 2 replication by ribavirin and mycophenolate mofetil are restored by guanosine and S-(4-nitrobenzyl)-6-thioinosine COVID-19 in kidney transplant recipients