What is the truth behind the “reinfection” with COVID-19 in 91 cases in South Korea?

What are the possible explanations for these cases?

Batool Almarzouq, PhD
4 min readApr 12, 2020

The first report of “re-infection” with COVID-19 came from China, Wuhan. NPR news claims that “about 5-10% of patients pronounced “recovered” have tested positive again, Some of those who re-tested positive appear to be asymptomatic carriers. NPR has spoken by phone or exchanged text messages with four individuals in Wuhan who are part of this group of individuals testing positive a second time in March. Two of them are front-line doctors who were sickened after treating patients in their Wuhan hospitals. The other two are Wuhan residents. One of the Wuhan residents who spoke to NPR exhibited severe symptoms during his first round of illness and was eventually hospitalized. The second resident displayed only mild symptoms”.

Similar reports by health officials in Japan said a woman who had been declared virus-free had tested positive again.

The same question about reinfection also did rise again when South Korea reported this Friday that 91 patients thought to have recovered from the new coronavirus had tested positive again.

So, what are the possible explanations behind these cases?

1- It is possible that SARS-CoV-2 is behaving similarly to the varicella-zoster virus (VZV), herpes zoster virus (HSV) and HIV which can be “reactivated” as a part of the virus life-cycle. These viruses lie dormant (latent) within a cell but may later switch to a lytic phase of replication. Jeong Eun-kyeong, director-general of the Korea Centers for Disease Control and Prevention, said in a briefing that the virus may have “reactivated” in those patients after going dormant. He said tests were conducted within a “relatively short time” after the patients were cleared, so it’s unlikely they got reinfected”. However, this mechanism is more common in the viruses who have the ability to convert their RNA to DNA using “reverse transcriptase enzyme” such as HIV or DNA viruses like HSV and VZV. Coronaviruses family including MERS, the common SARS or SARS-CoV-2 are RNA viruses and there is yet no evidence of any mechanism of “re-activation” for this family of viruses.

2- The load of the neutralizing antibody is very low or undetectable to prevent “re-infection”. A recent study (not peer-reviewed in small sample size) by Fudan University analyzed blood samples from 175 patients discharged from the Shanghai Public Health Clinical Centre and found out “ among these patients, there were ten patients whose antibodies titers were under the detectable level of the assay ”. However, we need to better understand the limitations of these assays used in this study. Also, a possible explanation is that those who don’t develop antibodies (under 30%) may be fighting it off with other portions of the immune system as they tend to overwhelmingly young. We have extremely limited information about the immunity provided with SARS-CoV-2 and there is a possibility that even immune people for COVID-19 may be able to pass the virus to others.

3- These are only residual of the virus genome. These cases only had fragments of the coronavirus in their bodies after they recovered which was picked up by the PCR test. It is possible that these cases only a reflection of the limitation of the kits and it’s possible that the symptoms are unrelated but similar to COVID-19.

4- It is very likely that the procedure of sample collection went wrong and the patient wasn’t cured completely. The samples are collected by putting a swab of cotton up deep in the nose and rotate it but this is not always guaranteed to pick up the virus. In other words, false negatives and false positives are possible.

5- The last and least possible explanation is that the virus was able to induce mutation within the Spike protein which binds to the neutralizing antibody. Fauci, the director of the National Institute of Allergy and Infectious Diseases, said it’s unlikely that people can get the coronavirus more than once — at least within a short time period. “If a person gets infected with coronavirus A, and then gets reinfected with a coronavirus, it may be coronavirus B,” Fauci said. “But right now, we don’t think that this is mutating to the point of being very different.”

In short, it is very early to conclude that these cases are results of re-infection with COVID-19 without information about the viral load at the time of diagnosis, the antibody load, the specification of diagnosis tools (e.g. primers), the duration between both presumed infections and genome studies of both the virus and the patients.

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Batool Almarzouq, PhD

I play at the crossroads of data science, bioinformatics, and life. I enjoy applying deep learning to biological problems. Ph.D from the University of Liverpool