Healthy 33-year-old man was the first to confirm reinfection with SARS-CoV-2

A healthy 33-year-old man in Hong Kong is now the first person in the world confirmed to have been re-infected with the pandemic coronavirus, SARS-CoV-2 – which has currently infected more than 23 million people worldwide.

The man’s first infection took place at the end of March. He reported coughing with sputum, fever, sore throat and headache for three days before testing positive for the virus on March 26. Although his symptoms eased a few days later, he was hospitalized on March 29 and remained in the hospital until April 14. , when he tested negative for SARS-CoV-2 in two tests taken 24 hours apart.

About 4.5 months later, the man tested positive for the virus again. This time, his infection was detected during entry screening at an airport in Hong Kong, while returning from a trip to Spain, via the UK, on ​​August 15. Although he had no symptoms, he was hospitalized again. Clinical data showed he was showing signs of acute infection, but he remained asymptomatic throughout his hospital stay.

The researchers decoded all the genetic sequences of the SARS-CoV-2 viruses isolated from humans in the two infections and found that his two infections were caused by clearly different strains of the coronavirus. The first strain looked a lot like strains of SARS-CoV-2 collected in April and March in the United States and England. The second was closely related to strains collected in England and Switzerland in July and August. Overall, there were 24 genetic differences between the two infecting viral strains, including significant differences in the code for the famous spike protein.

Hong Kong researchers report the case on August 24 in a scientific study that has been accepted, but not yet published, by the journal Clinical Infectious Disease. A preliminary version of the accepted study has been published in Ars by the University of Hong Kong and a PDF is available HERE. The PDF does not include all three digits of the study, but the University has published a phylogenetic tree (Figure 2), which you can see HERE. Ars requested the other numbers and will update this text as they become available.

Do not panic

With tens of millions of cases worldwide piling up in eight months, cases of reinfection are not surprising – or even necessarily worrying. Studies so far have suggested that immune responses to SARS-CoV-2 may be variable, meaning some people may develop stronger and more protective immune responses than others. There is a growing body of evidence suggesting that certain immune responses may be completely protective against reinfection – at least for some time. From this new study, it’s also rather encouraging that the second human infection was even milder than the first – it was completely asymptomatic, in fact – hinting at helpful immune responses specifically against SARS – CoV-2.

While there have been other, more anecdotal reports of reinfection, these have not been confirmed like this one, with full genome sequencing and other data. And, while documenting this case is certainly important, it still leaves all of the most important questions about immunity against SARS-CoV-2 unanswered.

Simply put, we still don’t know what levels of immune responses are needed to prevent reinfection and / or disease. We still don’t know what proportion of people develop such protective immune responses after infection. And we don’t know how long protective immune responses last. more people.

Several studies have suggested that antibody responses to SARS-CoV-2 may decrease after a period of two to three months. Antibodies are the Y-shaped proteins that circulate in the body after infection and are specifically designed to detect different fragments of SARS-CoV-2. When they do, they can greet immune responses or even completely neutralize the virus, potentially thwarting another infection. Antibody levels naturally decline after an acute infection, but some researchers have expressed concern that anti-SARS-CoV-2 antibodies appear to decline faster than expected. As such, some have speculated that the protective immune responses against SARS-CoV-2 might resemble those seen during infections with other human coronaviruses, the ones that cause the common cold. Infections with these garden variety coronaviruses typically only produce immunity that lasts for months rather than years or decades, and re-infections are common.

But again, this is all still speculative. We don’t know what levels of antibodies are needed to protect against a second infection with SARS-CoV-2, but how long those levels last. So, we don’t know if any of the measured declines are significant. Moreover, antibodies are not the only protective immune response to consider; there are also responses of immune cells, called B cells and T cells, which can also be protective.

Wrinkles and limitations

It is also important to note that the case report of confirmed reinfection has some interesting wrinkles and significant limitations. On the one hand, the researchers point out that the two strains of SARS-CoV-2 that infected humans had significant differences in their peak proteins.

In general, each SARS-CoV-2 virus has many copies of the spike protein that comes out of its spherical virus particle, much like the spikes of a marine mine. These protruding barbs can grab human proteins called ACE2 receptors, which protrude from the surface of some human cells. When this interaction occurs, it essentially opens the door for viral SARS-CoV-2 infection in human cells coating ACE2.

Because the SARS-CoV-2 spike protein is so prominent on viral particles, and so critical for infection, some of the more potent and neutralizing antibodies against SARS-CoV-2 target the spike protein. Some antibodies glomerate on the specific bit of the spike protein used to interact with ACE2, preventing it from infecting cells.

But researchers studying human reinfection have found that the two strains of SARS-CoV-2 that infected him have different spike proteins – there are four significant differences in the spike proteins of viruses, to be exact. These changes may have made it more difficult for the anti-spike antibodies produced after the first infection to recognize and neutralize SARS-CoV-2 in the second infection. So, researchers believe it may help explain the asymptomatic reinfection.

AWOL Antibodies

But the point is perhaps undermined by a quirk in the data. The researchers looked at the antibody levels of the re-infected man in the blood collected 10 days after the onset of his first infection – and they found no antibodies. In this case, they were looking for antibodies targeting the SARS-CoV-2 nucleoprotein, which is a protein associated with the genetic material of the virus. Antibodies to the nucleoprotein usually appear faster in people than antibodies to the spike protein. However, the man did not appear to be 10 days after developing symptoms during his first infection.

Researchers believe he may not have developed antibodies to the infection. Alternatively, he may have developed antibodies very quickly and the levels fell just as quickly, or he could have developed antibodies. after every 10 days. After the second infection, they tested for antibodies one, three and five days after he tested positive. They only detected antibodies on the fifth day.

Previous studies have suggested that most people infected with SARS-CoV-2 do indeed develop antibodies against the coronavirus. Thus, the lack of detection of antibodies after the man’s first infection raises questions about the frequency of his experience of reinfection. That said, given that researchers only had a blood sample from the only time – 10 days – after her first infection, it is impossible to draw firm conclusions.

Overall, the case indicates that reinfection with SARS-CoV-2 is possible. But the most important questions, such as how likely reinfection is and how long the protective immune responses are usually last – go unanswered.

For now, researchers say people who have recovered from SARS-CoV-2 infection should continue to undergo masking and distancing measures to be safe. They should also be considered for vaccination. And of course, “further studies on re-infection, which will be vital for research and development of more effective vaccines, are warranted,” they conclude.