key: cord-0717324-4lnrbudy authors: Ceccarelli, Giancarlo; d’Ettorre, Gabriele; Innocenti, Giuseppe Pietro; Mastroianni, Claudio M.; Ciccozzi, Massimo; d’Ettorre, Gabriella title: Is previous influenza-like illness a potential Trojan horse for COVID-19? date: 2020-08-14 journal: Crit Care DOI: 10.1186/s13054-020-03226-5 sha: 7c5e414a8f5251f2ce8e8b8668648e6db8398e34 doc_id: 717324 cord_uid: 4lnrbudy nan We read with interest the paper by Verroken et al. underlining that no respiratory virus coinfections were identified in a population of COVID-19 critically ill patients [1] . A recent large cohort study by Nowak et al. confirmed that SARS-CoV-2 and respiratory virus coinfections are rare events observed only in less than 3%, despite the temporal overlap of the two epidemic curves. Interestingly, they observed that 13% of COVID-19-free patients had isolation from the respiratory secretions of influenza virus, rhinovirus/enterovirus, and coronavirus NL63, in the same period [2] . Although with wide geographical variability, this data is in line with the epidemiology of respiratory viral pathogens in the northern hemisphere during the winter period [3] , while deviates from the expected in SARS-CoV-2 infected patients, suggesting a possible viral interference [2] . Otherwise, Italy was affected by the SARS-CoV-2 outbreak since mid-February 2020, immediately after the period in which the incidence of influenza-like illness (ILI) gradually increased until reaching the epidemic peak in the fifth week of 2020, with a level equal to about 13 cases per thousand assisted [4] . The complete epidemiological data from 2019/2020 influenza season are not yet available, but we can assume that the aetiology of ILI was similar to that reported for the 2018/ 2019, when about 8 million of cases were registered in Italy and 31.7% caused by influenza viruses [4] . In accordance with epidemiological data, we also observed that 63.6% of 190 COVID-19 patients (admitted to Policlinico Umberto I Hospital of Rome, one of the larger teaching Italian COVID-19 Medical Centers in March 2020) reported in their clinical history a recent ILI (1-3 weeks prior to the appearance of COVID-19-related symptoms). Previous flu vaccination was reported in only 26.3% of patients. The symptomatology reported for the ILI was mainly characterised by sore throat, cough, runny nose, and conjunctivitis. These findings, although not conclusive, seem to suggest that ILI may represent a risk factor for a subsequent SARS-CoV-2 infection. In confirmation of this, interestingly, a number of ILI-related viral pathogens (i.e. respiratory syncytial virus and influenza virus) have been reported to cause a significant downregulation of ACE2 in the upper and lower respiratory tract, since the early stage after the onset of infection [5] . The consequent reduction of ACE2 activity has been found potentially contributing to severe lung injury and may predispose to a later more severe clinical course of COVID-19 [6] . Moreover, considering that intercurrent viral respiratory infections are a trigger of upper airway mucosal damage and local immune impairment, previous ILI could therefore represent a predisposing factor for subsequent COVID-19 infection. On the basis of these data, influenza vaccine not only has a public health utility permitting to exclude influenza in patients with ILI during the overlapping of the two epidemic curves, but probably also reduces the risk and the severity of COVID-19. Nevertheless, more than 65% of ILI have a non-flu aetiology; for these reasons, the implementation of behavioural containment measures is needed to reduce the risk of ILI spreads in areas affected by the SARS-CoV-2 outbreak. Co-infections in COVID-19 critically ill and antibiotic management: a prospective cohort analysis Co-infection in SARS-CoV-2 infected patients: where are influenza virus and rhinovirus/ enterovirus? Prevalence of respiratory viruses among adults, by season, age, respiratory tract region and type of medical unit season): strengths and weaknesses. Results of a cohort study in two large Italian hospitals. Vaccines (Basel) Angiotensin-converting enzyme 2 inhibits lung injury induced by respiratory syncytial virus Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations All authors contributed equally. The authors read and approved the final manuscript. None