Asymptomatic spread of the SARS-CoV-2 virus that causes COVID-19 is a big problem. And, this problem does not behave the same as with many other viruses, even the close relative SARS-CoV-1, the virus that caused SARS in 2002-2003. When SARS struck, health authorities controlled and eventually stopped the epidemic by using symptoms to detect cases. Typical symptoms of fever, cough, and shortness of breath about 5 days after exposure led to testing, isolation, and quarantine. Similar to COVID-19, transmission of SARS was primarily via respiratory droplets. In less than a year after approximately 8100 people were infected (primarily in Asia), and about 10% of those infected died, the epidemic ended.
So how has SARS-CoV-2 spread all over the world to over 5.8 million people (1.7 million in the U.S.)? This grim week, how has COVID-19 killed over 100,000 U.S. citizens? One big issue is that screening without testing is inadequate with this virus because there are too many asymptomatic and unknowing cases who are just as capable of spreading the virus as are the symptomatic cases. COVID-19 can be spread by people who appear and feel well. Far worse, if one does not know they are infected, they might not be taking precautions to prevent spread. A significant minority of people don’t wear masks in public and ignore, or are too lax with, social distancing. As I have said before in MPDN, it is so important that everyone act as though they might be capable of spreading or contracting the virus, and take appropriate steps to prevent that until we have a vaccine or at least good therapies for prevention or treatment.
Why doesn’t COVID-19 behave like SARS?
One major difference between SARS and COVID-19 is that the SARS-CoV-2 virus infects, replicates, and sheds in the upper respiratory tract of infected people with and without symptoms. (1) This means coughing, sneezing, talking, or simple breathing might shed virus. The SARS-CoV-1 virus on the other hand, replicated primarily in the lower respiratory tract (2), and cases of SARS were infectious during their symptomatic period, not during the incubation period (the time it takes between exposure and illness). (3) What I am again getting at here is that people with and without symptoms are spreading COVID-19, and this is an important point to understand. For the sake of definitions, an infected person who is symptomatic has symptoms; whereas as an infected person who is asymptomatic does not. Both might shed virus and infect others. An asymptomatic person can remain that way until the infection stops, or the person might be presymptomatic, meaning they are on their way to having symptoms, getting sick, in the incubation period (see below). Viral load (the amount of virus measured from some source such as blood or sputum) in SARS-CoV-1 was usually elevated at symptom onset and made symptom-based detection more likely and more effective. If you had symptoms, you could be isolated, tested, and contacts could be traced, etc. The same is not true for SARS-CoV-2, wherein viral load may be high before a person is symptomatic. (4) This makes detecting cases much more difficult.
Consider the COVID-19 outbreak in a skilled nursing facility in Washington State. (5) Authorities first learned of the outbreak when a symptomatic health care worker tested positive for infection on March 1, 2020. Universal testing of residents in the facility took place with the nasopharyngeal swab test: real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) on two dates: March 13 and March 19–20. Note the delay in testing, which if not ideal, would have at least allowed time for many of those exposed to develop into infection, making the test more likely to detect infections. (footnote) Note also that RT-PCR detects the RNA of virus. You have to have the virus in the nasopharynx (that place very far back in the nasal cavity where test swabs collect a sample) at the time of the test to get a positive result.
The residents were all asked about symptoms over the prior two weeks, including fever, cough, and shortness of breath. From the 76 residents tested, 48 (63%) were positive, 27 (56%) asymptomatic at time of testing. Within an average of 4 days after testing 24 of the 27 became symptomatic. This means 24 had been presymptomatic, and 3 remained completely asymptomatic. Therefore, it is important to note that more than half of those who tested positive overall had no symptoms at the time of the test. Note also that 3 patients were infected but never developed symptoms, very dangerous in a congregate living situation.
This is not like SARS. Asymptomatic spread is a worse situation. And, health authorities wanted to know about levels of virus at the time of these tests. The thought was, and is, that a higher viral load in the nasopharynx is more likely to spread disease. They checked this by measuring quantitative SARS-CoV-2 viral loads, which showed high levels of virus whether the residents were symptomatic, presymptomatic, or completely asymptomatic. And, among the presymptomatic patients 17 (71%) had viable virus 1 to 6 days before the start of symptoms. In other words, live coronavirus was shedding in high concentrations from the nasal cavity before symptoms developed for up to 6 days. Asking people about symptoms did not detect over half of infectious cases. This is why universal testing in congregate living facilities is so important, and why mass testing generally would be much more effective than what we are doing now. This is why health authorities keep saying we need more tests, a lot more.
This congregate living facility is not the only example by far. Another study looked at 94 patients with laboratory-confirmed COVID-19 and found the highest viral load in throat swabs at the time of symptom onset, which the authors interpreted as consistent with a peak of infectiousness at or even before symptom onset. (6) They estimated that 44% of cases had been infected by people who were in a presymptomatic stage: they contracted the virus from another person who they thought was well. In this study, the incubation period averaged about 5 days, while infectiousness started about day 2 or 3 after exposure (rapid in the infectious disease world). In other words, people were spreading the virus for 2-3 days and did not yet know they were sick.
There have been several other reports of asymptomatic carriers infecting others. In one report an asymptomatic 20-year-old woman who tested positive by RT-PCR (but had negative chest imaging) infected friends and relatives. (6) She was kept in isolation for a month and never developed symptoms. In another case an asymptomatic 10-year-old boy with COVID-19 and abnormalities on chest CT spread infection to members of his family. (7)
A paper published this week reported a cruise ship which left Argentina in mid March. (8) On board there were 128 passengers and 95 crew. Before boarding everyone (passengers and crew) had been screened for COVID-19 symptoms and body temperatures were taken. No one on board had passed through China, Macau, Hong Kong, Taiwan, Japan, South Korea, or Iran in the 3 weeks prior. Multiple hand hygiene stations were placed in the ship, including the dining area. The two physicians on board screened all passengers and crew with “regular body temperature reviews.” The first fever of the outbreak, a passenger, was recorded on day 8. Immediately isolation protocols began: all passengers confined to cabins, surgical masks issued to all, full personal protective equipment (PPE) used for any contact with febrile patients, N95 masks worn for any contact by crew with passengers in their cabins. But the outbreak was spreading, or at least incubating. Additional fevers were detected in 3 crew members on day 10, 1 crew member on day 11, and 3 passengers on day 12. The ship had been on its way back to Argentina, but the country had closed its borders due to increasing regulations with the COVID-19 outbreak, and was refused permission to disembark at Stanley, Falkland Islands. The ship sailed to Montevideo, Uruguay, arriving day 13. Passengers were kept on board. Among them 8 (6.2%) required medical evacuation due to impending respiratory failure. For the remaining 217, on day 20 universal testing for COVID-19 with RT-PCR took place (supplied by Uruguay), revealing 128 (59%) positive. Remaining passengers and crew did not disembark until day 28, and the stats on that day are as follows: among the positive 104 (81%) asymptomatic, 24 (19%) symptomatic. That is a staggering figure, and very troubling given the amount of time passengers had to become symptomatic, and the steps taken to prevent spread as soon as the first fever was detected.
This is a complex problem.
Not all asymptomatic carriers seem to pose the same risk. Some seem to pose very low risk. (10) The reasons for this are likely multi-faceted. One interesting reason might be immunity. As previously discussed in MPDN, the coronaviruses are a family of viruses that have been known to science since the 1960s (though likely much, much older than that), and until 2002 were known to cause epidemics of mild upper respiratory tract infections (URI), or sometimes diarrhea. There are two subsets that infect humans: alpha coronaviruses (HCoV-229E and HCoV-NL63) and beta coronaviruses (HCoV-HKU1, HCoV-OC43). Infections with these “benign” viruses would usually cause a cold. But, if a person had been infected with one of these strains, they would usually make antibodies and be immune to re-infection for 2-3 years. The viruses that cause SARS and COVID-19 are newer beta coronaviruses.
The two “benign” beta coronaviruses are recognized by the human immune system, which induces antibodies that can protect us against either virus. In other words, infection with one of those viruses results in antibodies against either. That is known as “cross-reactivity.” And, it is known that SARS-CoV-1 infection can also result in neutralizing antibodies against at least the HCoV-OC43 virus, and that HCoV-OC43 infection results in cross-reactive antibodies against SARS-CoV-1. (11) We don’t know yet if this cross-reactivity protects some people from developing COVID-19, but it is a hopeful thought, that could lead to protective treatments. It might also explain why so many cases of COVID-19 are mild. If you have had a cold due to HCoV-OC43 in the last year or two, you might be protected. We still don’t know, and the issue with antibody testing is too complicated to get into here.
Opposite to these issues are the super spreading events (SSE), when case numbers explode after some episode of people congregating, such as at a church (12) or a nightclub. There are several factors that can lead to super spreading. One factor could be changes with the virus itself. There is at least one preliminary report suggesting SARS-CoV-2 could have 2 distinct genetic subtypes, one more aggressive than the other. (13) There are also super spreaders. An infected person might have a long duration of infection (more time to spread disease than normal), a higher amount of virus in the upper respiratory passage, a high degree of coughing, lots of sneezing. Even loud talking or singing can shed more virus. There are also environmental factors such as the density of the population present (for eg, a crowded market, a party, or a funeral), and whether infection prevention and control measures are being used such as social distancing and wearing a mask. Closed environments such as gyms, restaurants, offices, may drastically increase the risk of infection by trapping air (or recirculating it through ventilation). SARS-CoV-2 has been found in stool (14), meaning toilets need to be kept clean, and hands washed after using the bathroom. And, there are so-called high emitters, who shed many times the amount of virus that is seen in average cases. (15) This obviously increases risk of spread.
So what should we take from this knowledge? One big point is that unless they have been tested, we don’t know who the asymptomatic carriers are. We should continue social distancing and wearing a mask where appropriate. This is especially due to the increasing growth of active cases in our state (currently over 700). This is not simply the effect of increased testing, though that is part of it. We are seeing more cases in our hospitals in Maine, currently 58 people hospitalized, 22 in critical care, and 14 on a ventilator per the Maine CDC. So, take it seriously, follow guidance from the Maine CDC, be careful where you get your information, and be COVID-aware.
FOOTNOTE: In early March testing was very limited, even in Washington State, where the first case in the U.S. was identified. View this episode of Frontline to learn more.
Please note that URLs were collected on date of publication and are subject to change, as are statistics regarding infection, as with any ongoing epidemic.
REFERENCES
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- Guang, et al. Infectivity of Severe Acute Respiratory Syndrome during Its Incubation Period Biomed Environ Sci. 2009 Dec; 22(6): 502–510.
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- Arons, et al. Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facility. N Engl J Med 2020;382:2081-2090.
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- Kissler, et al. Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period Science 22 May 2020:Vol. 368, Issue 6493, pp. 860-868 DOI: 10.1126/science.abb5793
- South Korean city on high alert as coronavirus cases soar at ‘cult’ church. New York: The Guardian, February 20, 2020 [cited 2020 Mar 8]. https://www.theguardian.com/world/2020/feb/20/south-korean-city-daegu-lockdown-coronavirus-outbreak-cases-soar-at-church-cult-clusterExternal Link
- Tang, et al. On the origin and continuing evolution of SARS-CoV-2. Natl Sci Rev. 2020;nwaa036; [Epub ahead of print].
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