Growing evidence of COVID-19 reinfection

Growing evidence of COVID-19 reinfection

By Henry Hakamaki

31 august 2020

The author is an American who works as graduate Immunobiology researcher in Germany.

Recently published research indicated that surviving COVID-19 may not confer lasting immunity, although there is conflicting data. Perhaps most notable are studies that have shown a decrease in circulating neutralizing antibodies after just a couple of months after COVID infection (which is in line with most seasonal coronaviruses, where immunity does not last long. ).

However, some more recent studies have shown that despite an early decline, the decline stabilizes after the initial dip and we still maintain relatively high levels of neutralizing antibodies, indicating that perhaps immunity would last longer than we feared at the time. beginning. it can be (perhaps on the order of a couple of years, as long-term antibody studies in SARS-1 have indicated).

It is important to determine whether or not reinfections are occurring and in what period of time. So far, we have seen some cases (mainly in healthcare workers) where people tested positive for COVID using RT-PCR, then cleared the infection, and after a while, tested positive again.

In these isolated cases, however, reinfections have not been confirmed, because the RT-PCR test is looking for viral RNA and not live virus in the system. While the live virus would lead to the presence of viral RNA (which is why this test works very well for active infections), it sometimes detects some viral “junk” after the infection has passed.

Let’s think of it this way: our immune system, in the course of its response, totally destroyed all the viral particles in our body, leaving viral debris in its wake. Some of this waste is the RNA from the virus itself, and this RNA may remain in our systems for some time after the virus is destroyed. Since the people who tested positive the second time were asymptomatic, it was simply assumed that it was actually just rubbish that the test picked up a second time.

Now, however, the story changes. We have several cases that have appeared in the last week in which people who tested positive for the second time have had their viral RNA sequenced from their first and second positive tests, and there was enough genetic variation between the two RNA samples to convince the researchers. that it was in fact a new infection the second time around.

When viruses travel through a population, they detect small mutations along the way. By sequencing viral genetic information, we can trace these mutations and therefore find out where a specific sample came from, based on how many of the mutations it had.

You can think of it this way (although this is incredibly simplified for illustration purposes): For every 10 people you infect a virus, you detect one mutation on average. Then after 10,000 people have been infected, we will have roughly 1,000 mutations. So if we take a sample of the viral RNA in someone’s system and find that they had 600 mutations from the original virus, that means that the person had been infected by the time the 6,000th person had been infected. Of course, it is much more complex than this, but the point is simply that we can look for these mutations to determine if it is the same virus or if it comes from a different stage in the development of the virus.

Now we have cases in Hong Kong (to be published in Clinical Infectious Diseases, as of now only excerpts from the study are available: Belgium and the Netherlands, and La Crosse, Wisconsin, of people who were sequenced in their first and second positive tests and Enough differences were found where it is more than likely that there were cases of reinfections.The cases have been mild, but these reinfections have occurred three to six months after the initial infection.

While these are isolated cases, and much more sequencing will be necessary in other people who test positive more than once, this is certainly not a good sign. While it is certainly possible for most people to maintain antibodies at a sufficient level to protect themselves from further infection after a first infection (or possible vaccination), it now appears that at least some people will become susceptible to infection soon after. your initial infection. This further questions the possibility of generating “herd immunity”, producing high levels of immunity in the population against SARS-CoV-2, even with a vaccine.

Meanwhile, another new preprint has just been released today that is frankly even more concerning than the previous cases discussed. This new document, published as a preprint of The lancet , looks at a case study of a probable reinfection in Nevada. The 25-year-old individual had originally been infected in April, tested positive for COVID, and developed a sore throat, cough, headache, nausea and diarrhea. After nine days, the symptoms had resolved, and two tests, performed 12 and 29 days after the resolution of the symptoms, were negative, indicating that the infection had been cured.

However, 31 days after the symptoms had initially subsided, the individual began experiencing symptoms again and was hospitalized two days later. Within a week, symptoms had escalated to hypoxia (low oxygen levels) and atypical pneumonia, requiring supplemental emergency oxygen. When the test was retested, the individual tested positive for COVID.

Importantly, a sample from the initial test in April and a sample from this post-test in June were genetically sequenced. Once the sequencing was complete, the mutations between the two samples were mapped and the two samples were determined to have enough mutations between them, so it is almost certain that two separate infections occurred.

The two main things to note here is that the second infection was significantly MORE severe than the initial infection, which is something we had not seen in previous cases of probable reinfection, and that the time between initial infection and reinfection was just 48 days. .

We have not yet seen direct evidence of SARS-CoV-2 antibody-dependent enhancement (ADE) (which is where a low level of antibodies actually helps the virus enter cells and makes infection worse), but we do have some evidence. of ADE that occurs in SARS-CoV-1, the virus closest related to the causative agent of COVID-19, leading to more severe disease and acute lung damage when there are low levels of antibodies due to vaccination of animal models.

This evidence not only complicates the picture when it comes to “herd immunity,” but potentially even complicates the vaccine development process. This shows once again that proper public health measures would have been much more rational if they had sought to understand the science of the virus rather than looking for biomolecular “magic bullets”.

The author also recommends:

The origins and evolution of the SARS-CoV-2 virus

[24 August 2020]