Cases of COVID-19 are on the rise again, and the pandemic is likely to continue until many can receive an effective vaccine, the first of which was recently authorized for use in both the United Kingdom and the United States, with a second following in the United States soon afterward. With winter – and thus, flu season – rapidly approaching, concerns are growing about the risks of a double pandemic that could further overwhelm hospitals and other health care resources. Already, health departments have reported the first cases of joint COVID-19 and influenza infection, and the medical community is strongly advising everyone to get this year’s flu shot, to reduce their risk of severe illness.
COVID-19 and influenza both cause a spectrum of respiratory symptoms varying from asymptomatic to severe and potentially fatal illness. However, there are significant differences. Influenza has a shorter incubation period and the time for the infection to spread from one person to another is shorter (average of 3 days between successive cases for influenza versus 5-6 for the coronavirus). Symptoms also appear more quickly in flu, within 1-4 days, versus 2-14 days for COVID-19. However, the number of secondary infections generated by SARS-CoV-2 infected person is 2-2.5 higher than for influenza – hence, the recommendation for SARS-CoV-2 infected patients to self-isolate, even within their own household.
While the symptoms of COVID-19 and flu can be very similar, at least initially, the number of patients who suffer severe disease is different, as well as the populations at greatest risk. About 80% of those infected with the coronavirus experience only mild or asymptomatic disease, with age and underlying health issues the greatest risk for severe illness, which can manifest more than a week after initial symptoms appear. In contrast, flu presents the highest risk for children, pregnant women, the elderly and those with underlying chronic conditions or immunosuppression. However, the mortality rate for COVID-19 is higher than that for influenza, especially for hospitalized patients who the Centers for Disease Control (CDC) says are five times likelier to die than hospitalized flu patients. COVID-19 patients are also at higher risk for 17 additional, serious health complications compared with flu patients, including pneumonia, respiratory failure, and blood clots in the heart, lungs, brain and legs.
In addition, while there are approved antiviral drugs that can help limit the duration of a bad case of flu, the only FDA approved treatment for COVID-19 is the antiviral Veklury (remdesivir), for use in hospitalized patients. A few others, notably the monoclonal antibody-based treatments from Eli Lilly and Regeneron — have received emergency use authorization (EUA) for hospitalized patients with severe disease.
For these reasons, it is important for physicians to be able to quickly know which disease they are dealing with, in order to correctly treat and monitor the course of illness in an infected patient. Thus, a number of diagnostics development efforts have been focused on combination tests that can distinguish between COVID-19 and influenza viruses A and B, as well as other respiratory virus infections. While several laboratory PCR-based tests, from companies including GenMark Diagnostics, Avellino, CerTest Biotec, and South Korea researchers, able to distinguish the SARS-CoV-2 from multiple influenza viruses have been authorized, there is a particular call for rapid point-of-care tests than can provide answers within minutes.
In early October, the FDA granted EUA to a rapid, 15-minute test from Quidel that distinguishes between COVID-19 and influenza A and B with a single nasal swab. The new point-of-care test is designed to run on the same Quidel Sofia testing platform that was approved for a rapid flu test in 1999 and granted an EUA for a COVID-19 test in May 2020. Manufacturing is the same for each of the diagnostics, enabling rapid scale-up of the three-antigen test.
Quidel’s immunoassay was reported to be nearly as accurate as a PCR test for COVID-19, matching up with positive results 95.2% of the time, while identifying 100% of negative cases. For flu, the test had a false negative rate of 10% and a false positive rate of 5%. However, the Quidel test only detected 32% of the cases identified by PCR testing when asymptomatic people were randomly screened for the SARS-CoV-2 virus.
Researchers at the University of Arizona, who conducted the study, said that some of the asymptomatic people who tested positive by PCR and negative with the rapid test were likely missed because they were carrying too little of the virus to spread it on. PCR positivity was likely caused by harmless genetic fragments of the virus that remained in the body after the patient recovered. When adjusting the analysis to exclude tests with low positivity, the Quidel rapid test detected more than 85% of the COVID-19 infections found by PCR, regardless of whether the person screened showed symptoms.
At the end of October, another test, from Credo Diagnostics Biomedical, received a CE Mark for a 20-minute combination COVID-19, influenza test and is expecting emergency authorization from FDA. Several additional companies have announced rapid COVID-19/ influenza tests in development.