key: cord-258381-h0ddqs53
authors: Chhabra, Saurabh; Abedin, Sameem; Graham, Mary Beth; Marrero, Tirsa M. Ferrer; Hari, Parameswaran N.; Shaw, Bronwen E.
title: Diagnostic considerations for COVID-19 in recipients of allogeneic hematopoietic cell transplantation
date: 2020-06-23
journal: Biol Blood Marrow Transplant
DOI: 10.1016/j.bbmt.2020.06.010
sha: 
doc_id: 258381
cord_uid: h0ddqs53

SARS-CoV-2 in hematopoietic cell transplant (HCT) recipients is associated with severe coronavirus disease-2019 (COVID-19) and higher mortality. SARS-CoV-2 infection is definitively diagnosed by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) typically using nasopharyngeal (NP) swabs, and less commonly, samples from the lower respiratory tract, including bronchoalveolar lavage (BAL). In highly prevalent regions, stepwise evaluation, and management, as in the pre-COVID era, risks false-negatives and delay in therapy for COVID-19.

and higher mortality. SARS-CoV-2 infection is definitively diagnosed by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) typically using nasopharyngeal (NP) swabs, and less commonly, samples from the lower respiratory tract, including bronchoalveolar lavage (BAL). In highly prevalent regions, stepwise evaluation, and management, as in the pre-COVID era, risks false-negatives and delay in therapy for COVID-19.

In immunocompromised hematopoietic cell transplant (HCT) recipients, diagnosis of infections is extremely time-sensitive due to the need to rapidly institute therapy. This assumes even greater relevance in the current pandemic of coronavirus disease-2019 (COVID-19) 1,2 wherein allogeneic HCT patients on therapeutic immune suppression are at a higher risk for mortality, and the only approved treatment (remdesivir) appears to be more effective in earlier stages of COVID-19 3-6 . Similarly published studies in COVID-19 and other viral illnesses have shown that convalescent plasma therapy is more effective earlier in the disease course with recovery either less likely or taking much longer in COVID-19 patients who have acute respiratory distress syndrome 7-9 .

and special considerations in the vulnerable population of allogeneic HCT recipients 6 . The authors emphasize that a high index of suspicion is required to test by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) of nasopharyngeal (NP) swab patients who present with fever and/or lower respiratory tract infection (LRTI) symptoms and have been in an area of high community SARS-CoV-2 prevalence or have been exposed to a confirmed or suspected COVID-19 case in the previous 14 days. In addition, in patients with a productive cough, sputum may be tested, but aerosol-generating procedures including bronchoscopy are discouraged and not recommended in patients known to be positive for SARS-CoV-2, unless a co-infection is suspected. The American Association of Bronchology and Interventional

Pulmonology also advocate that bronchoscopy should have a limited role in COVID-19 diagnosis and should only be considered in intubated patients if NP swab samples are negative and alternative diagnoses are considered that would require change in management 10 .

In general, the management of LRTI in allogeneic HCT recipients requires that multiple differential diagnoses need to be considered in parallel. Since such patients can progress rapidly without early effective treatment, a delay in diagnosis leads to much worse outcomes. In hospitalized patients, COVID-19 is mostly diagnosed by NP rRT-PCR, and bronchoscopy is rarely required. We argue that allogeneic HCT recipients with LRTI symptoms and a negative Assuming that a negative NP swab rRT-PCR misses 27-50% 12,13 of true COVID-19 with symptoms in the second week, we recommend early bronchoscopy be undertaken when the clinical stakes are high. Time is of the essence in the immunocompromised host and if ARDS has set in by the time the diagnosis of pulmonary COVID-19 is made, an effective treatment window may have been lost. Making the decision to perform bronchoscopy for BAL sampling in allogeneic HCT patients may involve examining the trade-off between the probability of diagnosing COVID-19 and the risk to staff from aerosolization during the procedure. A multidisciplinary discussion involving transplant, infectious diseases, critical care, and/or pulmonary specialists to estimate pre-test probability of COVID-19 and to ascertain the urgency of performing bronchoscopy would be crucial. Bronchoscopy has had an established role in the evaluation of respiratory pathologies in allogeneic HCT patients 14 and should be considered in the event NP rRT-PCR is negative for COVID-19 and also when a possible co-infection e.g., influenza 15 is suspected. Early bronchoscopy in such cases will likely save time by facilitating early diagnosis of pulmonary COVID-19 and may improve survival with use of effective therapies 14 . Furthermore, early diagnosis can potentially decrease the risk of SARS-CoV-2 exposure to other hospital patients and health care workers caring for such patients. In conclusion, COVID-19 should remain an important differential in patients with LRTI symptoms in the setting of community spread and such patients need early bronchoscopic evaluation even when NP rRT-PCR is negativean expectant stepwise approach is not advised in this population.

SC conceived the letter to the editor and wrote the first draft. BES and PNH critically revised the manuscript. All authors participated in the construction and editing of the manuscript and revisions.

All authors declare no competing interests.

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