If it doesn’t make sense to you that a person can have enough virus in his or her body to be able to spread the infection, but not enough to feel ill, you’re not alone. It doesn’t make sense, but there is an explanation.
The explanation begins and ends with our immune system — our internal defense against foreign invaders. Those invaders are typically viruses and bacteria, but occasionally it’s the wood sliver off your patio deck, or the nickel in a piece of cheap jewelry.
Our immune system offers us two lines of defense: innate and adaptive immunity. Innate immunity includes physical barriers like our skin, as well as a number of different kinds of white blood cells that are hostile to invaders. Innate immunity acts like a security team, providing a routine vigilance that can get an early jump on an infection.
Internal SWAT team
Adaptive immunity is more like a SWAT team, composed of two types of white blood cells (with special weapons and tactics) called B-lymphocytes and T-lymphocytes. B-lymphocytes create antibodies, which are like those arrows you had as a kid with the pink rubber suction cup on the end. Except the rubber cup of an antibody is designed to stick to a very specific molecule found only on the invader (rather than the fridge, or your sister’s bare legs).
Otherwise, these antibodies might stick to our own cells, and that would be bad. Because when an antibody sticks to its target (either the outside of a bacteria or virus, or the outside of a cell that’s infected with a virus), it triggers a cascade of biochemical and immunological assaults. These attacks can blow a hole in the bacteria’s cell wall, an ultimately lethal injury. Alarm signals are broadcast that call in reserve unit white blood cells from other sites in the body (some have been sitting around waiting, and others will be newly manufactured for the event). T-lymphocytes begin physically attacking and demolishing anything tagged with an antibody.
It’s war, and as in the wars we humans wage, there is a lot of collateral damage. Instead of smoke, dust, debris and rubble, an infection war zone creates inflammation, swelling, pain, and lots of cellular debris. Our most intimate experience with this battleground is a bad cold. For a day or so, the nose is open but it’s red-hot and it hurts to inhale. Then, as the battle peaks, it gets plugged up until you can hardly breathe. Finally your body is ready to start clearing debris, and the “gunk” that you blow from your nose goes from green/yellow to white and then clear. You might feel recovered in terms of energy etc., and the virus might be gone, but you’ll be blowing your nose for days until the cleanup in aisle four is over.
Our SWAT-team adaptive immunity is also in charge of our “immunologic memory”: It keeps a log of prior offenders, so that we are “immune” to infections we have seen before. Vaccines allow our cells to create an immunological response and memory without actually having had the infection.
Sometimes our immune system gives us “partial immunity”: We recognize the invader, sort of, and have some antibodies at hand that will loosely attach to the virus. It’s enough to keep the infection under check, mild perhaps, until we can manufacture some more specific antibodies and polish the invader off.
Infectious before becoming ill
So how can a person be infected enough to spread the virus, but not enough to feel ill? We tend to think that the sicker one appears, the more infectious one is, but that may not be the case with a novel virus like COVID-19, where no one’s immune system recognizes it. This allows the virus to enter the cells of our respiratory tract without being recognized for a while. It sets up shop, and immediately begins reproducing millions of new viruses that fall out into our respiratory tract. With no immunological fire alarms triggered, the not yet symptomatic host feels fine, but a simple throat-clearing cough (and we do this fairly often) or an unwitting sneeze (‘must have been some dust off the keyboard’) can send millions of highly infectious viral particles into a shared office space.
It’s hard to discover how (or if) an infection is being spread by asymptomatic-yet-infected individuals. First, even in a pandemic, most people aren’t infected, so you have to screen a lot of individuals. Second, when you do find a person who tests positive for COVID-19, the screening test only checks for traces of viral RNA — not fully intact, fully infective viral particles. It’s proof of infection, but it doesn’t indicate how infective one is. Particularly late in the recovery phase, respiratory secretions might still contain viral debris, but not active, intact viruses.
Although the data is limited, here are a few examples that suggest COVID-19 is both highly infective, and people can spread the disease before they feel ill.
When Germany flew 126 of its citizens home from Hubei on Feb. 1, only two of the passengers on the flight tested positive for COVID-19. They were both asymptomatic. In both cases, officials were able to grow (culture) the virus out of their respiratory tract. That suggests that these two were infective, even though they remained asymptomatic as they were monitored in isolation. [One ultimately had a slight redness of the throat and a faint rash].
A study by Chinese researchers looked at the first 425 confirmed COVID-19 cases in China. Early on, a large majority of infected persons reported they had either been to the ground-zero Huanan Seafood Market, or had direct contact with someone with a respiratory infection (often, a family member). Once the virus began making sustained, person-to-person transmission outside the seafood market, the majority of infected persons reported they had no exposure to the seafood market or contact with anyone who was ill. Despite being armed with information about the infection and with a heightened vigilance for avoiding symptomatic individuals, the infection still spread.
A Chinese businesswoman from Shanghai felt well as she traveled to Munich for two days of meetings in late January. While there, she had a few, very mild symptoms that she attributed to jet lag and business pressures. On the evening of her return to China she began to feel ill, and was confirmed to have COVID-19 five days after leaving Munich. At that point she notified the German company, who then referred her primary business contact there (Pt #1) to the health department. He tested positive for COVID, as did three more employees, one of whom had contact with the Chinese woman, but two of whom only had contact with Pt. #1 — who at that time was completely asymptomatic.
Mild vs. severe cases
So why do most people get a mild case of COVID-19 (80% were reported as mild in China), and others more severe? There are a variety of explanations.
Influenza typically has a “U-shaped” mortality curve, where the very young and the very old have the highest mortality rates. We can thank our lucky stars that COVID-19 has a J-curve that leaves the young mostly untouched. There’s speculation that COVID-19 is sparing children and young adults because they might have partial immunity from having dealt with other less virulent corona strains that can cause colds. Or it may be that they don’t have a high number of the receptors in the lung – “ACE-2 receptors” — that COVID-19 uses to get a foothold.
The reason(s) COVID-19 hits older patients and those with chronic medical conditions harder is because our immune system weakens as we age, and chronic medical conditions make it even more difficult for the body to marshal a potent immune response.
For the 80% who work through their COVID-19 infection without too much difficulty, presumably their immune system gears up appropriately, clears the virus, and goes back to standby position. It’s not yet fully well understood, but sometimes it appears that our sickest infected patients suffer less from the primary infection than from an over-zealous immune response — aka “cytokine storm.” Particularly in respiratory infections, an overexuberant immune response can so damage the delicate tissue of the lungs that even a ventilator machine cannot improve breathing.
This brings us to an odd paradox: Our immune system can make us feel sick. Patients who are on medications to suppress their immune system — for example to keep their immune system from rejecting a donated kidney — are at increased risk of infection. When they do get infected, they often show few signs or symptoms until the virus or bacteria is beginning to overwhelm them.
The “flatten the curve” graphs that are going — forgive me — viral are an excellent visual dramatization of why we need to hunker down, spread out, and starve COVID-19 of any fresh fuel. Evidence that infected patients can spread the virus around before they even feel ill just supports that plan of action. If we can’t tell whom to avoid (based on symptoms), we should avoid everyone for a time. If we do, we may be able to turn a tsunami into a long slow swell. For an infection like this, our communal actions are the best — and only — treatment we have.
Dr. Craig Bowron is a Twin Cities internist and writer.
With respect to “flattening the curve”, here’s an interesting article that’s making the rounds:
https://www.washingtonpost.com/graphics/2020/world/corona-simulator/
Thank you. Pictures tell us more than words when scenarios are compared.
My very most hearty “Thank You” to Dr Bowron, as well as to MINNPOST for this excellent article.
An excellent article, I agree. Dr. Bowron provides the best explanation I’ve read about the most worrisome thing about this insidious disease (it is a disease, isn’t it?) and why what some were predicting weeks ago would be universal spread of the infection. While this article is the best explanation I’ve come across about why some, maybe most, people are asymptomatic, even Dr. Bowron cannot really explain why only some people get very ill. Can anyone? At this stage, with so few people being tested and without the capability of even testing people who are asymptomatic, and without any other data or information, it seems to me that the experts can only speculate or form some hypotheses.
Social isolation, not just social distance, would seem to be the correct remedy. That follows as much from speculation about transmission and social psychology and how to act in the face or uncertainty and the unknown. People will socially distance themselves voluntarily to a certain degree but unless the US begins to experience the level of infections and deaths as in Italy, I don’t see social isolation happening voluntarily. So it will probably require essentially a mass quarantine or what in effect is a lengthy 24/7 curfew to impose such social isolation. I hope I’m wrong but what is the alternative if things get much worse?
Earlier this week, the U.K. government “advised” everyone over 70 as well as everyone with a health condition reducing their physical capacity to cope with a severe respiratory disease, to self-isolate. For the time being, this advice is voluntary but it is expected to made compulsory in the near future. Here is the related National Health Service guidance which also applies to individuals who catch the virus and who are advised to go home, rather than continuing to work: https://www.nhs.uk/conditions/coronavirus-covid-19/self-isolation-advice/
It was not until I read this excellent article that I understood the final paragraph regarding the possible use of ibuprofen for treating the fever, headaches and muscle aches symptoms. It works by suppressing the immune system. Some doctors suspect–no one knows for sure–that it might delay recovery from COVID-19 by a few days. This is especially important for medics or hospital workers or any other public service worker. Dr. Bowron has supplied a scientific explanation. .
In other words: Once acquired, the virus must multiply to a sufficient extent to cause illness. However, prior to reaching that level, virus can be present in sufficient levels to be expelled in droplets, you can have enough virus in your respiratory track to expel and infect others, but not enough to make you sick. It’s important to remember that a symptomatic person, by definition is more inundated with virus, and will be more infectious than a non-symptomatic person.
Not necessarily. It’s the immune response that causes symptoms. One sufferer may have an immune system that hits a huge number of the infected cells spot on and not create much ‘collateral damage,’ and another may have very little actual infection but a huge immune response along with terrible symptoms. Later on top of that, say, hydration levels and the resulting difference in the products of their coughs, and you’ve got another layer of variables entirely.
At this point, we really can’t tell who’s contagious and who isn’t. Not until we have readily-available testing and know whether the post-infection antibodies actually create immunity (among other bits of knowledge, like patterns of contagiousness, that will surface within that time frame) will we be able to properly diagnose a contagious state.
The good news is there are vaccines that are fast in the works. If those take, and everyone gets them, then we don’t need to know. Until then, tests are it. You have to test to know.
Great article. However, we don’t know how long it will take to come up with an effective vaccine; my colleagues and I have been working on this, and it’s going to be a long time.
We originally started working on a vaccine for SARS years ago, yet it passed quite quickly, and we couldn’t acquire the necessary funding to continue. Thankfully, there are a lot of investors now, so hopefully a vaccine can be found that is both reliable and not dangerous, as multiple companies are either skipping or haphazardly running through the animal trials. That’s my biggest concern.
The only thing I wish you had mentioned in this article is that there is only one strain of SARS-CoV-2. The rest are isolates. People seem to think that there’s the L strain, the S strain, and mutations, which there are not. While mRNA viruses tend to mutate over time, this one has not. Only time will tell. It would’ve also been helpful to explain the R-naught, but that may be too complex for the average reader. Also perhaps that SARS-CoV-2 is the name of the virus, while COVID-19 is the name of the illness.
Additionally, we do not know how long the antibodies last for each individual, nor how long each person retains immunity. It’s too early for titers to assist presently, as well.
An interesting peer-reviewed study in Korea demonstrated that when former positive, hospitalized patients recover to negative, then come up positive again, it’s often due to remnants of the weakened attenuated virus. Yet a number of people have shown up negative, then get sick enough to be hospitalized again. We’ll have to wait to see what evidence negates the science of immunity, and how long antibodies last. Polio vaccine lasts a lifetime; influenza A and B need re-vaccination annually.
Lastly, ventilated patients only have a 20%-30% survival rate. It’s horrible when someone recovers, then ends up back in the hospital on a ventilator and loses their life.
As we have never had a cure for any coronavirus ever, it remains to be seen if immunity lasts days, weeks, months, or years – and if it’s different for each individual.
Finally, with 29,000 genomes, this virus is too complex to have been bioengineered in a laboratory. Like other coronaviruses, it has the same history of originating from a bat, into a vector animal, to humans, as it’s zoonotic ancestors. There’s clear evidence of spillover.
I’m very pleased to see this article, and especially your mention of cytokine storms. As a Virologist, and former Professor of Epidemiology, I have published over 300 published studies on epidemiology, and it’s very nice to see an article that explains the science clearly enough for a layperson to understand.
Well done.
Nice article, Craig (a colleague). An important point is, we don’t have all the answers.
The degree of infectivity varies and isn’t necessarily related to symptoms. It may peak just before the immune response kicks in and symptoms appear, and wane while people are still quite ill.
Why such variation in how sick people get? We really don’t know. Smoking, lung disease, age play a role but sometimes it’s just luck.
Really a thoughtful and helpful analysis. Thank you Dr Bowron and MinnPost. RCR
Can you explain how an asymptomatic person spreads the virus? Is it by their breath? If they aren’t coughing and sneezing then how would you get it other than sharing a drink or food or by saliva or something? Like if they just walk past you would you get it? Thanks
Hi. I have been searching the internet about Covid-19 asymptomatic virus carriers and it led me to this article that really made some point clear about how the virus acts and our body reacts.
My question is, will the asymptomatic person heal her/himself after four weeks?
My concern is that what if after community quarantine which is what we in the Philippines are doing now, when we go out of our homes, will the asymptomatic person still be able to spread the virus or will the virus already die after four weeks?
Thanks for the reply! <3
THANK YOU thank you for this excellent explanation of what is going on physiologically when someone that tests positive is asymptomatic. I have been searching for this information repeatedly and I am blown away by how difficult it was to find. Our daughter is a nurse at a homeless hospital, tested positive but then didn’t ever have symptoms. I would like to know what kind of research is being done on these asymptomatic carriers – not just that they are spreading it but why specifically their immune systems are allowing them to remain healthy. And how long that might last…