“If you’re not confused, you’re not paying attention!”
Tom Peters
“Infections can actually be transmitted during the incubation period.”
Dr. Camilla Rothe
On June 25, 2020, the Center for Disease Control and Prevention (CDC) reported that nearly 25 million Americans may have contracted the coronavirus that causes COVID-19. This figure is 10 times higher than the number of previously confirmed cases. In a briefing with reporters, CDC Director Robert Redfield said surveys of blood samples taken from around the country suggest millions of Americans may have contracted the virus either without knowing it or with only minimal symptoms. And, for every confirmed case, Redfield said, the CDC estimates that 10 times more people have been infected than previously suggested.
This pronouncement had to be both confusing and alarming to many Americans. My goal in this Germ Gem post is to clear-up the confusion and to tamp down the attendant distress. To do so, it’s first necessary not only to reiterate some basic definitions but also to understand some new ones. Especially important is the definition of asymptomatic infection as this kind of an infection applies to the new number of infections reported by the CDC and also plays a key role in the spread of the pandemic.
Infection versus infectious disease: back to the basics. As discussed in a previous post, infectious diseases specialists differ on how to define an infection versus an infectious disease. To me, an infection refers to any established relationship between a microbe and a host (here we are referring to the human host). By this definition we are all infected from head to toe and from the tip of our tongue to the other end of our gastrointestinal tract (some prefer the term colonized to infected). But, this definition doesn’t tell you anything about the relationship between the microbe and host. Such relationships are, however, generally benign and sometimes essential.
In contrast to such infections, an infectious disease denotes a disturbed relationship between the microbe and host that is dis-ease. The dis-ease can be manifest clinically by development of symptoms (feeling sick or ill) or by laboratory tests (for example, antibodies to the offending microbe detected in the blood).
What are the symptoms of COVID-19? At the beginning of the pandemic, COVID-19 was largely considered a respiratory tract infection, and symptoms, such as cough, shortness of breath, and fever were highlighted. As SARS-CoV-2 has marched (or more commonly flown) around the world, the multisystem nature of this disease has become more fully recognized (involving not only the lungs, but the heart, nervous system, gastrointestinal tract, kidneys, skin, clotting and immune systems). An appreciation has grown for the incredible variety of symptoms it provokes. In addition to COVID-19-related symptoms, that is, feelings of illness, we’ve also learned more about its many signs (abnormalities detected only by physical examination or laboratory testing). And, we’ve learned more about of the dangers of asymptomatic infections.
What is asymptomatic COVID-19? In the case of asymptomatic COVID-19, people have no symptoms of disease; they are not ill—no coughing, shortness of breath, sneezing, fever, fatigue, etc. But antibodies can be found in their blood or the virus can be detected by a swab of the nasopharynx. For an infection to be considered an asymptomatic infectionrequires a detailed negative history about any of the myriad of symptoms that are associated with COVID-19 as well as a normal physical examination.
How common is asymptomatic infection? As antibody testing for SARS-CoV-2 has increased nationwide, so too has the number of cases of asymptomatic infections. It is these infections that Dr. Redfield was referring to in his pronouncement about a 10-fold rise in cases.
Serological surveys assess the prevalence of antibodies to SARS-CoV-2 in a community. As the number of these surveys has increased around the world, it now appears that between 35% to 45% of all cases of COVID-19 are asymptomatic infections. And, as you would expect, as the number of asymptomatic infections are picked up by testing the blood for antibodies or swabbing the nasopharynx for the virus, the infection fatality rate (IFR) goes down (the current estimate of the IFR is between 0.5% to 1.0%). This number varies, however, by country (in the U.S., the current CDC estimate is 0.26%, meaning that only 0.26% ofall cases—symptomatic and asymptomatic—are fatal), as well as by risk group (the highest IFR is in residents of long-term care facilities and the lowest is in young healthy children).
Symptomless transmission— the Achilles heel of stopping SARS-CoV-2 spread. You might think that because people with asymptomatic infection aren’t coughing or sneezing, they aren’t a hazard to anybody. But you’d be wrong. Surprisingly, asymptomatic individuals carrying SARS-CoV-2 in their nasopharynx shed the virus longer than those with COVID-19 symptoms. In one study, median duration of viral shedding among 37 asymptomatic people was 19 days versus 14 days among 37 matched symptomatic patients. And, some asymptomatic individuals are pre-symptomatic, that is they go on to develop symptoms.
These symptomless individuals are “silent spreaders.” They play a pivotal role in the transmission of this virus. Recognizing this aspect of COVID-19 in controlling the pandemic was appreciated early on by some researchers, like Dr. Camilla Rothe and her colleagues at University Hospital LMU Munich. But, until recently, the enormous importance of the role of silent spreaders in this pandemic was pooh-poohed by many top epidemiologists.
How does the asymptomatic spread of the virus factor into strategies to open up the economy? It is now clear that transmission of the virus is primarily by an airborne route. It is estimated that asymptomatic carriers are responsible for close to 80% of viral infections during the course of routine breathing and speaking. Recent evidence suggests that a large proportion of viral spread occurs by inhalation of aerosols that are <5 uM (about the size of particles in tobacco smoke) as opposed to airborne droplets that are 5 uM or larger. This is because the smaller aerosols not only carry farther in the air than the larger droplets but also may make their way down into the lungs.
Thus it is highly recommended that measures should be implemented to reduce aerosol transmission. One such measure is universal masking (including for people with no symptoms). This shouldn’t be controversial. According to a recent article in Science News, “Why scientists say wearing masks shouldn’t be controversial,” even cloth masks work, if they’re worn properly.
And, some infected individuals are superspreaders. They are responsible for passing the virus on to six to eight or more individuals. It is estimated that 20% of all people infected with SARS-CoV-2 are responsible for 80% of all transmissions. The mechanism behind why some individuals are superspreaders is unknown. But, people with asymptomatic infections are among them.
Given the greater recognition of the importance of asymptomatic people in transmitting SARS-CoV-2, public health organizations are increasingly recommending testing of everyone for the virus. This, of course, will lead to a further increase in the total number of cases, but will also help in understanding more about how the virus is spread and how to better contain it.
As you’ve likely seen in the news, virus surges among young people are on the rise. It is clear to most people that for the sake of the economy, as well as for everyone’s sanity, strict social distancing can’t be sustained indefinitely. It is equally clear, however, that this is not the time to throw all caution to the wind. Rather it’s the time for everyone to wear a mask, whether they have symptoms of COVID-19 or not. Also, it’s important to continue hand washing and to social distance. Stay at least 6 feet apart and by all means avoid crowds and indoor events where shouting and loud singing are featured.
As for those who are distressed or confused regarding the changing of advice about masks (you may recall that back on March 3, I suggested in a Germ Gem post that routine wearing of masks was not recommended), we need only to recognize that as our knowledge about this disease grows and we have better scientific evidence, it may be necessary to change our minds and follow different protocols. For now, however, wearing masks makes sense based on the evidence, and many states have made masks mandatory for those out in the public.
Finally, while we all await what is considered the key to prevention of COVID-19, that is, a vaccine, you can now better understand the current debate about whether vaccines need to protect only against symptomatic infection, that is, infectious disease, or whether they must also prevent asymptomatic infection to stop the COVID-19 pandemic. Personally, I vote for a vaccine that does both.
