What common viral laboratory tests should be ordered if influenza and COVID-19 (Coronavirus Disease 2019) tests are negative?

From the Guidelines

If influenza and Covid-19 tests are negative, common viral labs to order include Respiratory Syncytial Virus (RSV) PCR, Adenovirus PCR, Human Metapneumovirus (HMPV) PCR, and Rhinovirus/Enterovirus PCR 1. Additionally, consider ordering labs for other viral respiratory pathogens such as Parainfluenza virus (PIV) and Coronavirus (other than SARS-CoV-2). It's also important to consider ordering a Mononucleosis spot test or EBV PCR if clinical suspicion for infectious mononucleosis is high.

Key Considerations

• The choice of labs to order may depend on the patient's symptoms, medical history, and epidemiological factors, such as the prevalence of specific viruses in the community 1.
• The IDSA panel suggests performing a single NAAT and not repeating testing routinely in symptomatic or asymptomatic individuals suspected of having COVID-19 whose initial NAAT result is negative 1.
• In cases where the initial test results are negative, but clinical suspicion remains high, repeat testing as well as considerations regarding SARS-COV-2 variants or other community-acquired-respiratory-viral-infections may need to be considered 1.

Laboratory Testing

• Nasopharyngeal or naso-oropharyngeal swab are recommended to diagnose SARS-CoV-2 upper respiratory tract infections 1.
• Lower respiratory tract fluid sampling may be recommended in certain cases, such as in patients with symptoms/signs of LRTI and negative nasopharyngeal or naso-oropharyngeal swab molecular test for SARS-CoV-2 1.

From the Research

Common Viral Laboratory Tests

If influenza and COVID-19 tests are negative, the following common viral laboratory tests should be ordered:

• Respiratory syncytial virus (RSV) test 2, 3, 4, 5
• Rhinovirus test 2
• Parainfluenza test 2
• Human metapneumovirus test 2
• Adenovirus test 2
• Seasonal coronavirus test 2

Multiplex Real-time Reverse Transcription PCR Assays

Multiplex real-time reverse transcription PCR assays can simultaneously detect multiple respiratory viruses, including:

• SARS-CoV-2
• Influenza A and B
• RSV
• These assays have been shown to be accurate and reliable in detecting these viruses 3, 4, 5

Epidemiology and Molecular Diagnostics

In the post-COVID-19 era, the concurrent circulation of SARS-CoV-2 with other respiratory viruses is a new diagnostic reality 6

• Multiplex molecular testing on automated platforms can detect multiple respiratory viruses in a single tube, including Influenza A, Influenza B, HRSV, and SARS-CoV-2 6
• Co-detections of these viruses can occur, highlighting the importance of simultaneous testing 6