Detection of respiratory viruses in patients with suspected SARS-CoV-2 infection

The SARS-CoV-2 virus is considered to be the cause of the current acute respiratory disease (COVID-19) pandemic which started in the city of Wuhan on 31 December 2019. The clinical signs of COVID-19 (fever, cough and dyspnoea) are seen in many other acute respiratory infections caused by other conventional viruses, although its morbidity and mortality rates are much higher. The presence of this new virus in the winter months amidst circulation of seasonal strains of many other respiratory viruses, primarily influenza and respiratory syncytial virus (RSV), complicates differential clinical diagnosis despite initial epidemiological links.¹ Consequently, initial testing for other respiratory viruses, in addition to SARS-CoV-2, has been recommended to learn about their aetiological role in this group of patients.¹

We present a prospective study, conducted from the second week of March 2020, on the detection of respiratory viruses in patients with clinically suspected SARS-CoV-2 infection (COVID-19). The minimum required symptoms were fever >38 °C and cough with some sort of epidemiological history, whether geographical or personal (contact).¹

Nasopharyngeal exudate was taken from each patient and sent to the laboratory in a virus transport medium (Vircell Transport Medium [VTM], Vircell, Granada). SARS-CoV-2 was detected by means of a commercial real-time reverse transcriptase–polymerase chain reaction (RT–PCR) assay which uses the sequences that correspond to the E, RpRd and N genes (Allplex™ 2019-nCoV Assay; Seegene, South Korea).^2,3 Respiratory viruses were detected from the same sample using a multiplex real-time PCR assay (Allplex™ Respiratory Assay; Seegene, South Korea) for simultaneous and differential detection of 21 different viruses.

In this study, 183 consecutive samples were analysed; of them, 48 (26.2%) tested positive for SARS-CoV-2 and 4 (2.1%) showed concomitant infection with this virus and rhinovirus in 2 cases, influenza B virus in one case and coronavirus OC43 in one case (28.3% positive for SARS-CoV-2). In 35 (19.1%) samples, only other respiratory viruses were detected: 13 cases of rhinovirus, 7 cases of influenza A virus, 5 cases of metapneumovirus, 3 cases of influenza B virus, 3 cases of coronavirus OC43, 2 cases of enterovirus and 2 cases of respiratory syncytial virus A (RSV-A). The remaining 96 (52.4%) samples were considered negative (with no other viruses present). Overall, 47.6% of all the respiratory samples tested positive for some type of respiratory virus.

There are few studies on the detection of other respiratory viruses in patients with suspected COVID-19. In a study by Bordi et al.⁴ in 126 patients in Italy, only 3 cases of SARS-CoV-2 were detected (2.4%) versus the 48 (26.2%) in our study. This was because the Italian study was conducted at the start of the pandemic, with a low incidence of infection caused by the novel coronavirus.

This data is corroborated by the fact that said study detected influenza viruses in 28.5% of its patients, while our study only detected 11 cases of influenza (6%), probably because our study was conducted at the end of the current seasonal influenza epidemic. The percentage of negative samples in our study was 52.4% versus 44.4% in the Italian group, but it should be noted samples were tested not only for viruses but also for other bacteria (5.6%). A Chinese study by Lin et al.⁵ reported a 40.8% rate of negativity versus other respiratory viruses, considering that an undetermined percentage could be caused by other respiratory pathogens.

Our study detected 4 patients (2.1%) with concomitant infections with SARS-CoV-2 and other respiratory viruses, whereas the same rate in the Italian study was 4.8%.⁴ The viruses detected in our study were the same as those reported by Bordi et al.,⁴ apart from coronavirus OC43, of which those researchers did not detect any cases. This virus is also a beta-coronavirus, but belongs to subgroup 2a, and therefore genetically distant from SARS-CoV-2 (Sarbecovirus 2b). As a result, we do not believe that represents cross-amplification. Furthermore, among the cases that tested positive for other viruses and negative for SARS-CoV-2, we also detected 3 patients infected with coronavirus OC43, which was prevalent in the conventional respiratory infections during the study week. A Chinese study by Lin et al.⁵ on concomitant infections between SARS-CoV-2 and other respiratory viruses detected 18 patients (9.7%) with this type of infection; this percentage was higher than that detected in this study and the Italian study, although the Chinese study was conducted in the second week in January 2020.

These preliminary studies suggest that SARS-CoV-2 would behave like all other conventional respiratory viruses in that it would present as a concomitant infection in a variable percentage (4%–9%). Therefore, initial detection of influenza or RSV as a process for ruling out COVID-19 should not be continued. If this new infection is suspected, inevitably, it is necessary to initially rule out this virus and then, if possible, simultaneously test for other respiratory viruses.