key: cord-0843388-bu2vw4gv
authors: Lamoth, Frederic; Glampedakis, Emmanouil; Boillat-Blanco, Noémie; Oddo, Mauro; Pagani, Jean-Luc
title: Incidence of invasive pulmonary aspergillosis among critically ill COVID-19 patients
date: 2020-07-10
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2020.07.010
sha: 284c4bd52921ffad674233bd55118c3bea725366
doc_id: 843388
cord_uid: bu2vw4gv

nan

The devastating pandemia of the novel Coronavirus Disease 2019 (COVID-19) resulting from 34 the emergence of SARS-CoV-2 is of particular concern because of the development of acute 35 respiratory distress syndrome (ARDS), which is associated with high mortality rates. Besides 36 the impact of viral pneumonia itself, the prognosis can be affected by other infectious 37 complications, such as ventilator-associated bacterial pneumonia or fungal infections. Influenza-associated IPA [2] . Because bronchoscopy and BAL sampling were minimized in 53 the setting of COVID-19 unless clearly indicated (due to the risk of aerosolization), results of 54 bronchial aspirates cultures were also considered for defining a putative IPA category 55 (Aspergillus spp. recovered from culture of ≥2 consecutive bronchial aspirates in the absence 56 of bronchoscopy and BAL sample). Cases with a single positive Aspergillus culture of 57 bronchial aspirate were classified as colonization or "undetermined". 58

A total of 118 patients were admitted to ICUs with confirmed COVID-19 between March 6 th 59 and May 11 th 2020, and 80 of them underwent mechanical ventilation. Among them, 3 (3.8%) Group (MSG) [3] . However, they received tocilizumab for treatment of the COVID-19 65 inflammatory conditions within 4 days from IPA diagnosis. All three patients experienced 66

worsening respiratory conditions despite broad-spectrum antibacterial therapy and no other 67 pathogens were isolated in concomitant cultures except for one case (Haemophilus 68 influenzae). All three patients were treated with voriconazole with a favorable outcome for 69 two of them and a fatal issue for one of them. None of the other patients received empirical 70 antifungal therapy for suspected IPA or anti-mold active prophylaxis. 71

The association of IPA with severe COVID-19 remains an important question to elucidate. A 72

Dutch-Belgian study previously showed an incidence of IPA of 14% among non-73 immunocompromised ICU patients with severe Influenza compared to only 5% in those with 74 non-Influenza community-acquired pneumonia [1] . Similarly, the lung injury and cytokine 75 storm observed in COVID-19 could predispose to IPA. The occurrence of probable/putative 76 IPA among ICU COVID-19 has been previously reported among smaller cohorts of patients 77 under mechanical ventilation (N=13 to 31) with a prevalence of 19% to 35% [4] [5] [6] [7] . 78

Our larger cohort of consecutive COVID-19 patients requiring mechanical ventilation (n=80) 79 suggests a much lower incidence (3.8%), which did not differ from that observed in the 80

Influenza in the Dutch-Belgian study [1] . However, the actual incidence is difficult to assess 82 because IPA diagnosis can be missed in this setting. The screening strategy in our cohort 83 included weekly monitoring of galactomannan in serum, which provided positive results in 84 only one case. A limitation was that bronchoscopy and BAL were performed in a relatively 85 small proportion of patients (28%). Therefore, the diagnosis of putative IPA was also 86 considered in two patients with repeated positive fungal cultures of bronchial aspirates in the 87 absence of BAL sampling. The fact that these patients experienced worsening clinical and radiological respiratory conditions despite broad-spectrum antibacterial therapy argues 89 against simple colonization. Some IPA cases could have been missed in the absence of BAL 90 sampling and galactomannan testing in BAL. 91

The role of tocilizumab (monoclonal antibody targeting the interleukine-6 receptor) in favoring 92 IPA can be questioned. The three IPA cases reported here received tocilizumab, as it was 93 the case for most patients of the present cohort. While tocilizumab is frequently use for the 94 treatment of auto-immune diseases, no association with IPA has been previously reported in 95 the literature. 96

Further prospective studies are warranted to assess the actual incidence, risk factors and 97 impact of IPA in severe We are grateful to all the medical staff and nurses of the Service of Intensive Care Medicine 103 of Lausanne for their strong commitment and outstanding management of patients during the 104 COVID-19 outbreak. 105

All authors: none to declare with respect to the present work. 108 F. Lamoth reports personal fees from Gilead, outside the submitted work. 109 110

There was no external source of funding for this study. 

Invasive aspergillosis in patients admitted to the intensive care unit with severe 131 influenza: a retrospective cohort study

Review of influenza-137 associated pulmonary aspergillosis in ICU patients and proposal for a case definition: 138 an expert opinion

Prevalence of putative 153 invasive pulmonary aspergillosis in critically ill patients with COVID-19

COVID-19 associated pulmonary aspergillosis

COVID-19-associated invasive pulmonary aspergillosis

COVID-19 Associated Pulmonary Aspergillosis