key: cord-0988788-nh9q1wp0
authors: Obenaus, Matthias; Schildgen, Oliver; Schürmann, Dirk; von Brünneck, Ann-Christin; Janz, Martin; Keller, Ulrich; Gebauer, Bernhard; Schilling, Johannes; Schwartz, Stefan; Weissbrich, Benedikt; Schneider, Thomas; Hofmann, Jörg; Mathas, Stephan
title: High-dose glucocorticoid treatment of near-fatal bocavirus lung infection results in rapid recovery
date: 2021-04-12
journal: ERJ Open Res
DOI: 10.1183/23120541.00060-2021
sha: 370a27401d6f2db675188110b91e68beb1318bee
doc_id: 988788
cord_uid: nh9q1wp0

Human bocavirus (HBoV) has to be considered a life-threatening pathogen in adults with atypical pneumonia. Pulsed high-dose glucocorticoid treatment may be beneficial in patients suffering from severe pulmonary disease caused by HBoV or other viruses. https://bit.ly/3epiMyO

copies (3.2×10 8 cp·mL −1 in BAL), HBoV detection by fluorescence in situ hybridisation (figure 1b) and pronounced T-lymphocytic infiltrates (figure 1c and d) in the lung tissue confirmed this scenario. Given the lack of HBoV-specific treatments, we aimed to mitigate the immune reaction and subsequent pulmonary damage by pulsed high-dose glucocorticoid therapy (5 March (day 1), 500 mg prednisolone; days 2 and 3, 1000 mg methylprednisolone) followed by rapid reduction to 20 mg·day −1 prednisolone and tapering. Respiratory parameters and radiological findings improved rapidly (figure 1e and f ), allowing termination of mechanical ventilation on day 4 (8 March) of intensive care unit treatment and discharge on 17 March. In parallel to the clinical improvement, CRP values rapidly decreased and remained normal. A CT scan 2 months after treatment confirmed complete resolution of all infiltrates (figure 1g).

Given the virtually unknown frequency of HBoV in adult patients with respiratory symptoms [1] , we retrospectively analysed a total of 5328 consecutive adult respiratory samples, mainly consisting of tracheobronchial secretions and BALs, and which were all examined by PCR-based respiratory panel analyses, for HBoV. We identified 17 HBoV-positive patients, most of them heavily immunocompromised. Given the reconstitution of white blood cells (4.45 nL −1 , normal range 3.90-10.50 nL −1 ) with normal neutrophils (3.03 nL −1 , normal range 1.50-7.70 nL −1 ) and slightly reduced lymphocytes (0.95 nL −1 , normal range 1.10-4.50 nL −1 ), even though platelets (30 nL −1 , normal range 150-370 nL −1 ) and haemoglobin (8.9 mg·dL −1 , normal range 13.5-17.0 mg·dL −1 ) were reduced on admission, as well as almost normal immunoglobulin levels (IgG 6.61 g·L −1 , normal range 7.00-16.00 g·L −1 ; IgA 1.72 g·L −1 , normal range 0.7-4.00 g·L −1 ; and IgM 0.30 g·L −1 , normal range 0.40-2.30 g·L −1 ) at the time of HBoV-induced respiratory failure, we judged our patient to be largely immunocompetent. Thus, even though rare, HBoV must be considered a life-threatening pathogen in adults with atypical pneumonia and should be included in the respective diagnostic work-up, with HBoV-DNA quantification if positive. Only recently, it has been demonstrated that dexamethasone is beneficial in COVID-19 patients with respiratory failure requiring respiratory support [3]; however, the benefit of glucocorticoid treatment in other severe viral respiratory diseases is unclear [4] . In contrast to the dexamethasone scheme used in the RECOVERY trial in COVID-19 patients (6 mg once daily for up to 10 days), we applied a pulsed high-dose glucocorticoid therapy scheme deduced from treatment of autoimmune diseases. Notably, the application of such pulsed "very high-dose" glucocorticoid therapy is supposed to extend the glucocorticoid mode of action compared to lower doses [5, 6] . We assume that this short-term high-dose glucocorticoid therapy effectively dampened the detrimental virus-induced immune response, most likely by glucocorticoid-induced cell death of immune effector cells including infiltrating T-lymphocytes, and anti-inflammatory effects by modulation of monocyte and macrophage function [7, 8] . Furthermore, glucocorticoid therapy can inhibit fibroblast proliferation and support the clearance of inflammation-induced tissue damage [7] . We are aware of glucocorticoid therapy-induced side-effects; that corticosteroid treatment of ARDS or SARS patients, or patients suffering from viral pneumonia, has generated conflicting results [4, 5, [9] [10] [11] ; and that prolonged intake of corticosteroids predisposes to invasive aspergillosis in the context of severe influenza infection [12] . However, short pulsed high-dose glucocorticoid therapy has been used for decades for the treatment of various severe autoimmune diseases, with limited and well-known side-effects [13] . Therefore, we decided to use such a "very high-dose" short-term scheme and not a lower-dose, longer-lasting scheme for our patient. We believe that in selected patients, in which the virus-induced immune response is profound and likely to be more harmful to lung tissue than damage by the virus itself, and in which fatal lung damage has not yet passed the point of no return, glucocorticoid therapy may preserve lung tissue and function. Notably, most recently, it has been shown that severe COVID-19 patients benefit from pulsed methylprednisolone administration if given during the early phase of pulmonary infection [14] . Thus, high-dose glucocorticoid therapy may be beneficial in patients suffering from severe pulmonary disease caused by HBoV, as demonstrated in our case, or other viruses.

Institute of Pathology, Kliniken der Stadt Köln gGmbH, Kliniken der Privaten Universität Witten/Herdecke mit Sitz in Köln

E-mail: stephan.mathas@charite.de Received: 12

Schildgen has nothing to disclose. D. Schürmann has nothing to disclose. A-C. von Brünneck has nothing to disclose. M. Janz has nothing to disclose. U. Keller reports personal fees from Takeda, Hexal, Abbvie, Pentizapharm and AstraZeneca, and personal fees and other support from Roche, Janssen-Cilag, Pfizer and BMS, outside the submitted work. B. Gebauer reports personal fees from Parexek/CALYX, ICON

MSD and Novartis, personal fees and nonfinancial support from Gilead Sciences, AMGEN and Jazz Pharmaceuticals, and nonfinancial support from Basilea, outside the submitted work. B. Weissbrich has nothing to disclose. T. Schneider has nothing to disclose

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Standardized nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: Current questions and tentative answers in rheumatology

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