The Mayo Clinic has an exclusive partnership with nference, Inc., a company with a software platform to analyze and synthesize biomedical data. Together, they released a preprint* today quantifying how long COVID-19 patients shed the virus after they are tested, and quantifying how many patients flip back and forth between positive and negative tests.
Just under 75,000 patients at Mayo Clinic hospitals in Minnesota, Arizona, and Florida were tested for COVID-19, with just over 12,000 tested multiple times and just under 12,000 tested two or three times each. There were 123 people tested four times, 70 tested five times, 48 people tested six times, and smaller numbers tested anywhere between seven and sixteen times.
Just over 2,200 tested positive for COVID-19 at least once, of whom 39% had at least two tests and 17% tested positive at least twice.
They took the distance between the first and last positive test as the lower bound of the infection time, and the distance between the first positive test and the second of two consecutive negative tests (provided the person didn't flip positive after that) to represent the upper bound.
The mean lower bound was 18.6 days and the mean higher bound was 21.2 days. In other words, on average, people remained positive for between 18.6 and 21.2 days after their first positive test.
However, the variation was enormous.
Of 379 patients who had two positive tests, 14% remained positive for at least four weeks after the first test, which they defined as “long-term shedders.” Most had a lower bound below 30 days and an upper bound below 35 days, but there were handfuls of people who had lower and upper bounds above that, with two patients having positive tests 64 days apart and one patient going 61 days before their second negative test.
In other words, on average, people stay infected for about 20 days after their first positive test, but a sizable chunk of people remain infected for a full month, and a small number remain infected for up to two months.
Unfortunately, this study has nothing to say about whether these people remain infectious to other people, but continuing to test positive does imply that they remain infected themselves and implies that they might be infectious to other people.
Shockingly, there was nothing in the Mayo Clinic's database that could distinguish the characteristics of long-term shedders from average shedders. Hospitalized patients made up roughly 20% of each category. Health care workers were no more likely to be in one group or the other.
They extracted 15,000 “clinical features” from the electronic health records, and narrowed this down to 269 features that occurred in at least ten percent of their patient population. These included, but were not limited to, diagnosis, diseases, medications, vaccinations, medical procedures, vital signs, lab tests, and demographics. None of them distinguished between long-term shedders and average shedders.
Then they looked at when patients had their first positive IgG antibody test. IgG antibodies typically peak later than IgM antibodies, and are expected to be present after peak viral load and generally once the virus is no longer detected. Since they most likely developed antibodies at some time before being tested, they designated this as the upper bound of the time to develop IgG antibodies. The mean was 38.1 days after the first positive COVID-19 test, but there were a few patients each who developed IgG antibodies within 10-15 days or 15-20 days, and there were over 20 patients who took more than 40 days, including a few who took between 55 and 75 days. Seven patients developed antibodies while still testing positive for COVID-19.
This shows that the presence of IgG antibodies itself does not rule out continuing presence of virus, but also shows that in most cases people test positive for IgG antibodies only after the virus is gone.
Finally, they looked at the number of switches between positive and negative status. 1608 didn't switch, meaning they were never tested and confirmed to be negative. 523 only switched once, meaning they were positive, then they were negative, and that was it. However, 108 people switched more than once, meaning they went through at least one cycle of testing negative and then testing positive again. 72 of these had three switches, 3 had four switches, 19 had five switches, 1 each had six or seven switches, and 1 patient had nine switches.
This is a significant number of people oscillating between positive and negative status.
Most likely, this represents a single infection, where the amount of viral RNA in sputum fell below the detection limit without the infection being eliminated, and then crept back up temporarily. While it's not clear whether they are still infectious during such oscillations, it underscores the desirability of having two consecutive negative tests before assuming one is completely free of the infection.
The Bottom Line
People appear to remain infected until an average of 20 days after their first positive test, with a substantial number of people remaining infected for a full month and a small number of people remaining infected for two months. There is nothing about someone's health status or the severity of disease that can distinguish between whether one remains infected for an average period of time or longer. It makes sense to take precautions to protect vulnerable people from catching the disease from you for two months after a positive test, unless one has two consecutive negative tests to confirm the virus is gone. At a minimum, I would voluntarily abstain from spending time in close contact with elderly people, people on immunosuppressants (for example, people who have had organ transplants), and people with other known preexisting conditions that put them at high risk of a severe case.
IgG antibodies suggest one is likely to no longer be infected, but they by no means rule this out.
To what degree being infected means one is infectious toward other people needs more research, but for now it is prudent to assume that one could be infectious toward others if one is infected. For someone who has tested positive and does not have two consecutive negative tests, the above data are the best rule of thumb to follow for the time being.
Stay safe and healthy,
Chris
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Disclaimer
I am not a medical doctor and this is not medical advice. I have a PhD in Nutritional Sciences and my expertise is in conducting and interpreting research related to my field. Please consult your physician before doing anything for prevention or treatment of COVID-19, and please seek the help of a physician immediately if you believe you may have COVID-19.
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*Footnotes
* The term “preprint” is often used in these updates. Preprints are studies destined for peer-reviewed journals that have yet to be peer-reviewed. Because COVID-19 is such a rapidly evolving disease and peer-review takes so long, most of the information circulating about the disease comes from preprints.