Living with respiratory viruses: The next saga in human/viral coexistence?

Testing for respiratory viruses and SARS-CoV-2 in clinical and epidemiological settings has contrasting purposes and utility. Symptomatic patients are best tested with respiratory virus panels to establish the pathogen and guide personalized treatment. Asymptomatic patients are tested for a single infectious pathogen to establish carrier status and guide containment.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus causing COVID‐19, is an infectious respiratory disease spread from person‐to‐person through respiratory droplets expelled during coughs, sneezes, and vocalization by an infected person (Centers for Disease Control and Prevention, 2020; accessed November 11, 2020). The outbreak of COVID‐19 first occurred in Wuhan, China,[ ] and has since spread rapidly around the world, leading the World Health Organization (WHO) to declare a global pandemic on March 11, 2020.[ ] COVID‐19 is the new entity in an ecosystem of several airborne respiratory viruses. It joins four other coronaviruses and several varieties of influenza, adenovirus, rhinovirus, bocavirus, metapneumovirus, and respiratory syncytial virus. This viral menagerie is the reality of daily life. How many of us carry these viruses is not known, because prior to COVID‐19, testing was available only for selected respiratory agents, and only when clinical symptoms required testing for the causative virus in order to guide therapy.

But now simultaneous testing for SARS‐CoV‐2 and other respiratory viruses will become routine. Nine multivirus testing panels have so far received Emergency Use Authorization from the FDA including one from the Center for Disease Control and Prevention (US Food and Drug Administration, 2020; accessed November 12, 2020). This number is likely to expand, given that six of these have been approved just since September 2020. All panels include tests for SARS‐CoV‐2 and influenza (A and B) viruses. Some tests now include the four other coronaviruses circulating in the population (229E—discovered in 1965, HKU1, NL63, and OC43),[ ] influenza A strains (H1, H3, and H1N1/pdm09), parainfluenza viruses (1, 2, 3, and 4), adenovirus, metapneumovirus, rhinoviruses, or respiratory syncytial viruses (A and B).[ ]

Prior to COVID‐19, we would only have tested symptomatic patients as a way of determining appropriate therapy and clinical care. But now, we are also testing asymptomatic individuals as carriers of infection in order to inform contact tracing, quarantines, isolation, and surveillance. These are very different scenarios in which to employ testing. The clinical scenario is safeguarded by the medical imperatives to diagnose and treat when the same symptoms could be caused by more than one virus, ideally disambiguating, and pinpointing the agent of respiratory illness. The outbreak of COVID‐19 has placed the population scenario at the scale of screening in uncharted territory.

With the advent of multivirus testing panels in the population scenario, we will discover coinfection rates, and will likely identify carriers of the other viruses. How many individuals are coinfected? What do we advise them to do? There's no doubt that once we start testing for viruses, we will find them. Because of this plethora of potential positive test results, the medical profession usually applies great care in deciding what to test for: there must be a good clinical reason. But in the population screening mode, we will likely find numerous cases of individuals carrying various individual viruses and combinations. Viruses have been a companion of modern humans and Neanderthals since the dawn of the species, and we even carry some viruses integrated into our chromosomes.

Are we to insist on quarantine for individuals who test positive for all respiratory viruses? No. That would depend on the infectiousness of the virus, the severity of the illness it causes, and the availability of treatments. Beginning with the four previous coronaviruses, we can conclude that these are highly infectious but mild in severity. We have never routinely tested for them. In fact, these viruses were intermingled with adenovirus, rhinovirus, and respiratory syncytial virus as part of the common cold, and treated symptomatically. Influenza viruses are the most serious threats, as agents of the flu, but these have been managed with the annual preventative vaccine and treatments. With SARS‐CoV‐2, we are challenged with a virus that is very infectious and clinically menacing for vulnerable sectors of the population. But an asymptomatic positive individual is a far less serious situation than a positive symptomatic patient. We will discover that a substantial portion of the population is asymptomatic and positive for some of these respiratory viruses, but that ultimately it is the clinical symptoms and vulnerability that drive care.

There is now a documented mutation conferring higher infectiousness in SARS‐CoV‐2, to the point where the variant constitutes more than 95% of infectious cases in the United States, Europe, and Asia. There is also a concurrent decline in virulence, which could be a result of native immunity in the large population of asymptomatic patients. In fact, the common coronaviruses are also transmitted via zoonoses, which could have been virulent, but “morphed” into the common cold over time. SARS‐CoV‐2 may end joining its relatives 229E, HKU1, NL63, and OC43 as the fifth common coronavirus (Orent, 2020; assessed November 15, 2020). An estimated R0 of 2.5 (ranging from 1.8 to 3.6) has been proposed for SARS‐CoV‐2 recently, which is comparable to 2.0–3.0 for SARS‐CoV.[ ] However, SARS‐CoV‐2 is far less virulent. While SARS‐CoV self‐limited its spread by killing a sufficiently large number of its hosts, SARS‐CoV‐2 seems to be on its way to becoming endemic in the population.

Thus, the status of individuals is foremost in selecting strategies for containment. Immunity will be variable from individual to individual, meaning that the same viral insult will result in many different responses. One window on the immune response is the amount of antibody produced by the individual from a viral infection. Tests for antibodies are available to assess the dynamics of immunity. Such monitoring will be fundamental for the launch of vaccines designed to elicit an immune response. We know that protection afforded by influenza vaccine is estimated to persist for 6 months. Antibody levels decline with time, but the rate of decline again varies from individual to individual.

Antibody tests are available for immune responses to both influenza and COVID‐19. These will be fundamental for public health and individual health monitoring. It will be important for asymptomatic individuals to know whether they have been exposed, and for recovered individuals to assess their immune status. Contact tracing is therefore a very important strategy for identifying infection sources. However, contact tracing is challenging for the COVID‐19 because the virus is highly contagious, can prove fatal, and asymptomatic patients can spread COVID‐19, making it extremely difficult to trace chains of transmission (The Hub, Johns Hopkins University, 2020; accessed December 4, 2020). Another important aspect is that contact tracing is dependent on availability of testing.

We do not yet know whether human antibodies to SARS‐CoV‐2 are neutralizing. But from results of trials for convalescent sera and monoclonal antibodies derived from patients who have recovered from COVID‐19, it would appear that the antibodies do confer some protection. Whether antibodies developed by asymptomatic individuals persist or confer protection is unknown, but that variable should be a priority for epidemiological monitoring. While we wait in anticipation for an effective vaccine to prevent the disease, we should be reminded that the vaccine might not be as effective at preventing asymptomatic infection. We should evaluate how we fared with the other respiratory viruses before COVID‐19. Incidence of infection was high, and immunity and illness developed in parallel, but only a fraction of the pathology rose to the level of clinical attention. COVID‐19 has turned the tables in this respect, focusing attention on the large base of infection typical of a contagious virus, but at a price: the difficulty of determining the fraction of infections that will become clinically significant. Living with a collection of respiratory viruses that will continue to grow with additions such as SARS‐CoV‐2 is the next chapter in the saga of human and viral coexistence. We are moving into an era that will require new epidemiological frameworks based—more than ever before—on distinctions between mere infection and infection with high risk of severe clinical outcome.

CONFLICT OF INTEREST

The author has no conflict of interest.