key: cord-294906-1m4h116m authors: Jarmoliński, Tomasz; Matkowska‐Kocjan, Agnieszka; Rosa, Monika; Olejnik, Igor; Gorczyńska, Ewa; Kałwak, Krzysztof; Ussowicz, Marek title: SARS‐CoV‐2 viral clearance during bone marrow aplasia after allogeneic hematopoietic stem cell transplantation – a case report date: 2020-09-18 journal: Pediatr Transplant DOI: 10.1111/petr.13875 sha: doc_id: 294906 cord_uid: 1m4h116m BACKGROUND: Respiratory viral infections are known causes of mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Here, we report a unique case of a child with viral pneumonia caused by coinfection with human metapneumovirus (MPV), respiratory syncytial virus (RSV), and SARS‐CoV‐2 after HSCT. CASE REPORT: A 9‐year‐old girl with acute lymphoblastic leukemia underwent allogeneic HSCT from a matched, unrelated donor. During the posttransplant period, in profound leukopenia (below 10 leukocytes/µL), she was diagnosed with SARS‐CoV‐2, MPV and RSV pneumonia and was treated with ribavirin and chloroquine. Before leukocyte recovery, the girl became asymptomatic, and SARS‐CoV‐2 and RSV clearance was achieved. The shedding of SARS‐CoV‐2 stopped before immune system recovery, and one may hypothesize that the lack of an inflammatory response might have been a contributing factor to the mild clinical course. CONCLUSIONS: Posttransplant care in HSCT recipients with COVID‐19 infection is feasible in regular transplant units, provided the patient does not present with respiratory failure. Early and repeated testing for SARS‐CoV‐2 in posttransplant patients with concomitant infection mitigation strategies should be considered in children after HSCT who develop fever, respiratory symptoms and perhaps gastrointestinal symptoms to control the spread of COVID‐19 both in patients and healthcare workers in hospital environments. Training of staff and the availability of personal protective equipment are crucial for containing SARS‐CoV‐2 infection. Case report A 9-year-old girl was admitted to the Department of Bone Marrow Transplantation in March 2020 for HSCT. At the age of 7 years, she was diagnosed with pre-B common acute lymphoblastic leukemia. Due to early bone marrow relapse, the child continued chemotherapy with bortezomib and was enrolled in one course of blinatumomab followed by HSCT from a 9/10 HLA matched unrelated donor. On admission, the patient was in good condition with normal vital signs, mild cough, a slightly sore throat and normal auscultatory findings. This article is protected by copyright. All rights reserved. pneumoniae, and Moraxella catarrhalis) revealed MPV RNA. However, testing for SARS-CoV-2 was not available at the time of admission. Despite MPV replication, the decision was made to proceed with transplantation due to her good condition because the timing for HSCT was optimal and any delay would have increased the risk of leukemia relapse. Pretransplant conditioning consisted of fractionated total-body irradiation (TBI) at a total dose of 12 Gy, etoposide (at a dose of 60 mg/kg BW) and antithymocyte globulin (ATG, Grafalon, Neovii, total dose of 45 mg/kg BW). Cyclosporine A (CsA) from pretransplant day -1 and methotrexate on posttransplant days +1, +3 and +6 were administered as graft-versus-host disease prophylaxis. On the first day of TBI, the patient developed a fever of 39.0 °C, and empiric antibiotic therapy with piperacillin/tazobactam and amikacin was started. On pretransplant day -1, the repeated PCR multitest revealed MPV with concomitant RSV infection. Fenoterol with ipratropium in nebulization and oral ribavirin (Copegus, Roche; 200 mg bid) were initiated. The early post-HSCT period was uneventful, with persistent respiratory symptoms and signs and blood oxygen saturation >95% on room air. As of posttransplant day +4, mucositis was observed, which is a standard complication after HSCT. Her respiratory symptoms progressed, and she exhibited diffuse wheezes and rhonchi with crepitant rales limited to basal areas of the lungs. Due to posttransplant patient isolation, no imaging studies were performed. On posttransplant day +6, the patient complained about weakness, chills, dysuria and mucositis-related oropharyngeal pain, with a temperature of 37.7 °C, an increase in C-reactive protein (CRP) to over 100 mg/L (normal range < 5 mg/L) and an increase in procalcitonin to 0.86 ng/mL (normal range < 0.05 ng/mL) (suppl. Figure 1 ). Because of swallowing difficulties, ribavirin was stopped after six days. On the +7 posttransplant day, information about COVID-19 was revealed in the radiotherapy center where the patient underwent the TBI procedure. A pharyngeal swab was positive for SARS-CoV-2 using a Vitassay qPCR test, which is based on qualitative assessment of two viral This article is protected by copyright. All rights reserved. genes: ORF1ab and N. The COVID-19 diagnosis was made on the +7 posttransplant day, and treatment with chloroquine (10 mg/kg BW/24 h; bid for 10 days) and azithromycin (10 mg/kg BW as the first dose followed by two daily doses of 5 mg/kg BW) was initiated on posttransplant day +8 after COVID-19 confirmation (as recommended for Polish pediatric patients in March 2020); ribavirin was restarted on posttransplant day +10. The identification of COVID-19 was followed by a decision to allow the patient to stay in the area of the pediatric transplantation unit. A part of the transplant unit was isolated for the patient, and she was isolated together with her mother in a single room with separate bathrooms and anteroom. The air conditioning in the patient's room was turned off to avoid spreading of infectious material due to positive pressure. Procedures typical for COVID-19 were initiated (continuous remote vital sign monitoring, call contact, dedicated nursing staff, examination without auscultation). A broad and repeated screening for SARS-CoV-2 among the health care personnel was started, and new regulations on personal protective equipment (PPE) were issued. Visitations were limited to physicians and nurses trained to use class N95/FFP3 PPE and to enter the isolation area, and no SARS-CoV-2 infections were diagnosed among the dedicated staff. Of the remaining personnel, 3 cases of COVID-19 were diagnosed within 10 days, which might have been transmitted by a patient. The patient continued CsA, acyclovir, cefepime and micafungin, and filgrastim was started at a dose of 5 µg/kg/day. The girl's condition gradually improved, and her cough diminished. Bone marrow reconstitution was achieved on posttransplant day +15. A repeated SARS-CoV-2 test on posttransplant days +14, +15, and +21 did not reveal virus replication and secretion. At the time of this report, the patient was alive and well, with full donor engraftment. We were not able to identify the source of infection, but the patient's mother and other members of the family from imminent proximity repeatedly tested negative for SARS-CoV-2 by PCR, and the mother was negative This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved. 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