key: cord-347499-7q47jh14
authors: Burrel, Sonia; Hausfater, Pierre; Dres, Martin; Pourcher, Valérie; Luyt, Charles-Edouard; Teyssou, Elisa; Soulié, Cathia; Calvez, Vincent; Marcelin, Anne-Geneviève; Boutolleau, David
title: Co-infection of SARS-CoV-2 with other respiratory viruses and performance of lower respiratory tract samples for the diagnosis of COVID-19
date: 2020-10-25
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.10.040
sha: 
doc_id: 347499
cord_uid: 7q47jh14

OBJECTIVES: We performed a study during the early outbreak period of coronavirus disease 2019 (COVID-19) and the seasonal epidemics of other respiratory viral infections in order to describe the extent of co-infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with other respiratory viruses. A second objective consisted in the comparison of the diagnostic performances of URT and LRT samples for SARS-CoV-2 infection and to compare diagnostic performances of upper and lower respiratory tract (URT and LRT) samples for SARS-CoV-2 infection. METHODS: From January 25(th) through March 29(th), 2020, all URT and LRT samples collected from patients with suspected COVID-19 received in the virology laboratory of Pitié-Salpêtrière University Hospital (Paris, France) were tested simultaneously for SARS-CoV-2 and other respiratory viruses. RESULTS: A total of 1423 consecutive patients were tested: 677 (47.6%) males, 746 (52.4%) females, median age of 50 [1-103] years. Twenty-one (1.5%) patients were positive for both SARS-CoV-2 and other respiratory viruses. The detection rate of SARS-CoV-2 was significantly higher in LRT than in URT (53.6% versus 13.4%; P < 0.0001). The analysis of paired samples from 117 (8.2%) patients showed that SARS-CoV-2 load was lower in URT than in LRT samples in 65% of cases. CONCLUSION: The detection of other respiratory viruses in patients during epidemic period cannot rule out SARS-CoV-2 co-infection. Furthermore, LRT samples increases the accuracy of diagnosis of COVID-19.

Sonia Burrel a,b , Pierre Hausfater c,d , Martin Dres e,f , Valérie Pourcher b,g , Charles-Edouard Luyt h,i , Elisa Teyssou a,b , Cathia Soulié a,b , Vincent Calvez a,b , Anne-Geneviève Marcelin a,b , David Boutolleau a,b* a AP-HP.Sorbonne Université, Hôpital Pitié-Salpêtrière, Service de Virologie, Paris, France The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for coronavirus disease 2019 (COVID-19) emerged in Wuhan, China, in December 2019 , (Zhu et al., 2020 . Only few studies reported proportions of SARS-CoV-2 co-infections with other respiratory viruses, ranging from 0% to 20% (Chen et al., 2020; Kim et al., 2020; Leuzinger et al., 2020; Lin et al., 2020a; Wee et al., 2020) .

Furthermore, lower respiratory tract (LRT) samples improve significantly the efficiency of diagnosis compared to upper respiratory tract (URT) samples for non-SARS-CoV-2 respiratory infections (Branche et al., 2014; Falsey et al., 2012) . This study, performed during the early outbreak period of (Table 1) . Among patients negative for SARS-CoV-2 (n=1122), those positive for other respiratory viruses were statistically younger than those negative (median, 39 versus 52 years, P<0.0001). Conversely, among patients positive for SARS-CoV-2 (n=301), no significant age difference was observed between patients positive for other respiratory viruses and those negative (median, 56 versus 54 years, not significant).

Among the 21 patients co-infected with SARS-CoV-2, other respiratory viruses detected were non-SARS-CoV-2 coronavirus (n=6), influenzavirus (n=5), adenovirus (n=3), rhinovirus/enterovirus (n=3), parainfluenzavirus (n=3), and adenovirus+rhinovirus/enterovirus (n=1). Only 4/21 (19.0%) co-infected patients were hospitalized in ICU, which was significantly lower than the 113/280 (46.4%) patients infected with SARS-CoV-2 alone (P=0.020) ( Table 1) A total of 1160 URT and 379 LRT samples were collected. The detection rate of SARS-CoV-2 was significantly higher in LRT (203, 53.6%) than in URT (1160, 13.4%; P<0.0001). Paired samples from URT and LRT were obtained from 117 (8.2%) patients. Among the 85 patients positive for SARS-CoV-2, 52 (68.2%) showed concordant positive results in URT and LRT samples ( Figure 1A ), but SARS-CoV-2 load was at least 1 log-higher in LRT than in URT samples for 38 (65%) ( Figure 1B In the present study, 7% (21/301) of SARS-CoV-2-positive patients were co-infected with other respiratory viruses. This co-infection rate is similar to some rates (0% to 6.5%) previously reported (Chen et al., 2020; Leuzinger et al., 2020; Lin et al., 2020a) , but lower than others, up to 20% (Kim et al., 2020) . This might be due to different study populations or potential spatiotemporal variations in viral epidemiology. In particular, it is very likely that the lockdown in France, that started on March 17 th and lasted until May 11 th , 2020, had no (or very few) influence on the circulation of respiratory viruses during the present study performed from January 25 th through March 29 th , 2020. In line with previous studies, different types of other respiratory viruses were detected together with SARS-CoV-2 among co-infected patients, including non-SARS-CoV-2 coronavirus, influenzavirus, adenovirus, rhinovirus/enterovirus, and parainfluenzavirus (Kim et al., 2020; Leuzinger et al., 2020; Lin et al., 2020a; Wee et al., 2020) . Patients co-infected with SARS-CoV-2 and other respiratory viruses did not differ significantly in age and gender from those infected with SARS-CoV-2 alone, as previously described (Kim et al., 2020) . Among ICU patients, the proportion of co-infected patients was significantly lower than the one infected with SARS-CoV-2 alone, possibly indicating that co-infection with other respiratory viruses might not worsen the severity of SARS-CoV-2-associated respiratory disease, in accordance with previous study (Wee et al., 2020) . We evidenced the higher efficiency of LRT than URT samples for COVID-19 diagnosis, with a significantly higher rate of detection of SARS-CoV-2 and a 1 log-higher SARS-CoV-2 load for the majority of infected patients. This discrepancy could be explained, in part, by the variability of the delay between the onset of symptoms and the sampling among patients. However, this higher diagnostic performance of LRT samples for respiratory J o u r n a l P r e -p r o o f 6 infections, including COVID-19, has been previously reported (Branche et al., 2014; Falsey et al., 2012; Lin et al., 2020b , Wang et al., 2020 . In our study, the proportion of patients positive for SARS-CoV-2 with discordant results was significantly lower than the one of patients positive for other respiratory viruses with discordant results. Those different profiles of compartmentalization of PCR positivity within the respiratory tract may suggest some differences of pathophysiology of SARS-CoV-2 infection compared to infections by other respiratory viruses.

In conclusion, the detection of other respiratory viruses in patients during epidemic period cannot rule out SARS-CoV-2 co-infection, and LRT samples increases the accuracy of diagnosis of viral respiratory infections, including COVID-19.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. 

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ICU: intensive care unit; y: years a p<0.0001 (Mann-Withney U test) b Rates of hospitalization in ICU only for the patients from Pitié-Salpêtrière University Hospital (n=1167)

We thank all healthcare workers involved in the diagnosis and treatment of COVID-19 patients in Pitié-Salpêtrière University Hospital (Paris, France).