Enlarge /. During the coronavirus pandemic on August 13, 2020, a nurse performs COVID-19 tests in the parking lot of Brockton High School in Brockton, MA under a tent.
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A 25-year-old resident of Reno, Nevada was infected twice with the pandemic coronavirus SARS-CoV-2, about 48 days apart, with the second infection causing a more severe case of COVID-19 than the first and requiring hospitalization and oxygen support.
This comes from a draft study led by researchers from the University of Nevada and published online. The study was not published by a scientific journal and was not peer-reviewed. Nonetheless, the attention of researchers who examined data from the first confirmed case of SARS-CoV-2 reinfection, reported earlier this week, has caught the attention.
Reinfections with SARS-CoV-2 are not surprising – or even absolutely worrying. Person-to-person immune responses to infection develop along a spectrum, with some people showing robust, protective responses and others leaving weaker responses. Amid the more than 24.5 million cases worldwide, it is expected that some recovered patients will be found who are not fully protected by their immune responses and are therefore prone to re-infection.
The big question is: how common is this scenario? Researchers still don't know. This case may well be a very rare occurrence, but there are many massive questions about SARS-CoV-2 immune responses that researchers are trying to understand. Why do some people develop a more serious illness than others? What immune responses protect those who recover from further infection? How many of the recovered will develop these protective responses? And how long do these protective reactions last?
While the new reinfection report is an important data point, like the previous reinfection report, it doesn't answer any of these big questions.
Genetic detective work
All we can say from these reports is that re-infection is possible – at least for some people. Again, this is not surprising, but it is difficult to prove. Like the report earlier this week, the Nevada researchers turned to whole genome sequencing to prove that their patient actually had two different infections.
In particular, the researchers deciphered all of the SARS-CoV-2 genetic material obtained from nasal swabs removed during the first and second illnesses. The researchers found that viruses that were present in the patient's nose during the two diseases had many small differences in their codes. The first virus was missing four code variants in the second – and the second virus was missing seven variations in the first. While small genetic changes naturally accumulate in viruses over time, the researchers calculated that if the two diseases were actually caused by the same virus, the virus should have developed more than 3.6 times faster in this one patient than before would have been documented. In addition, four of the changes between the two viruses could only be explained by genetic "reversals," and the likelihood of these occurring is "vanishingly small," the authors say.
Apart from the genetic evidence of two different infections, the question always arises as to whether there was a mix-up with the samples. That is, maybe the patient hadn't ripped the various strains of the virus out of his nose; Perhaps the swabs were simply mislabeled or misused in the lab. To address this concern, the researchers performed genetic forensic tests on the liquid in which the swabs were stored and on sample preparation. The researchers found that all of the human-derived material scraped off and associated with the nasal swab samples came from the same person.
Holes in immunity
While the researchers convincingly claim that their patient was indeed infected twice, there is a lack of critical data on the patient's immune responses. Specifically, the researchers did not test for antibodies after the person was first infected in April, who was characterized by a sore throat, cough, headache, nausea, and diarrhea. Although data so far suggests that most people develop antibodies that may help protect against SARS-CoV-2 after infection, researchers don't know whether this patient did or not. However, they note that the patient was not immunocompromised and did not appear to have a condition that would make re-infection appear more likely.
In the first report of reinfection in a Hong Kong man, the researchers tested for antibodies at a time after the patient was first infected, but found none. Although this suggests that the person may not have developed antibodies (which could explain the reinfection), the researchers say they would need more testing at different times to definitely show a deficiency in antibodies after the initial infection. Importantly, the patient's second COVID-19 attack in Hong Kong was asymptomatic, suggesting that he had some protective immune responses.
The Nevada patient wasn't so lucky. At the second infection, which started in late May, the patient developed shortness of breath and a cough. Lung scans later showed signs of atypical pneumonia. The person was admitted to the hospital and needed ongoing oxygen support. In early June, the patient tested positive for SARS-CoV-2 antibodies, but the researchers did not closely examine the antibody types.
Overall, like the first, this case leaves all the big questions unanswered. Akiko Iwasaki, Yale Immunology Specialist, summarized: “This case underscores the need to further investigate the range of results of re-infection from COVID19. As more reinfection cases are reported, we should get a better sense of how well the immune system protects against disease after a natural infection. "