Decoding virus reactivation: Some insights for Covid-19

06Jun 2020
The Guardian
Decoding virus reactivation: Some insights for Covid-19

Cases of Covid-19 reactivations are rising. South Korea has reported more than 200 cases of recovered patients who were later tested positive for SARS-CoV-2 again. But the reactivated virus seems to have “little or no infectivity”, says the Korea Centres for Disease Control and Prevention (KCDC).

By Shin Jie Yong

In an April letter to the American Journal of Infection Control, Chinese physicians reported: “Seven discharged patients turning positive again for SARS-CoV-2 on quantitative RT-PCR.” Common reactivated symptoms were cough and fever, and diseases were milder than the first-time infection.

Similarly, in a small China study in the Journal of Infection with 55 discharged patients, 9 per cent returned to the hospital with fever, fatigue, cough, sore throat and abnormal white blood cell count, while also testing positive again for SARS-CoV-2.

“There is currently evidence to suggest that a proportion of recovered Covid-19 patients could reactivate,” the study authors wrote.

“Few researchers think that this is actually a case of reinfection or an issue of accuracy in test kits,” said the epidemiologist, Hwang Seung-sik, MD, Ph.D. at the Seoul National University, adding: “Many are looking at this more as a virus reactivation.” This is not to mention that South Korea has more stringent criteria for defining Covid-19 recovery than other countries.

Kevin Roe, a semi-retired researcher at San Jose State University, detailed in a letter to Transboundary and Emerging Diseases the “Explanation for Covid-19 infection neurological damage and reactivations”.

In this published paper, he provided new insights into Covid-19 reactivation by drawing connections to another bat-derived virus called the Nipah virus – known for its outbreaks in Asia – that causes respiratory and neurological symptoms.

Roe mentioned that SARS-CoV-2 and Nipah virus are both RNA enveloped viruses of bat origin. These two viruses cause similar neurological symptoms such as headache, convulsions, seizures, muscle twitches, disorientation and brain inflammation (encephalitis).

The CDC reported that for the Nipah virus, these signs are known to re-appear in about 8 per cent of survivors “months and even years after exposure” as a result of virus reactivation in neurons. That’s why scientists have started cautioning on the neurological repercussions of Covid-19 over the coming years, as evidence suggests that Covid-19 might have neuropsychiatric after-effects

“There is a very good reason for viruses, such as Covid-19 and Nipah virus, to selectively infect neurons,” Roe wrote. He said this is because neurons lack MHC proteins required for presenting a foreign molecule – like virus proteins – to alert T-cells to destroy infected cells.

So virus replication in neurons often goes undetected by the host immune system – hence, a perfect hiding place. That’s why other neuroinvasive viruses like herpes simplex virus type 1 (HSV-1) also establish latency in neurons to evade the host immune system.

“And by this means, they can create life-long infections that can be reactivated whenever some stress weakens the host immune system,” Roe remarked.

Data from animal and human brain autopsy studies also suggest that “human coronaviruses (HCoV) can be added to the growing list of viruses that persist in the central nervous system, a viral flora of the brain that could have pathological consequences in some individuals but remain subclinical”.

This is according to researchers at the laboratory of neuroimmunovirology at the University of Quebec. In other words, HCoV persists in neurons with potential subclinical effects “whenever some stress weakens the immune system”.

What causes virus reactivations?

This is best understood from HSV-1 that reactivates in response to external immunosuppressive stimuli. The best-known one is psychological stress that releases cortisol that, when prolonged, undermines the immune system. Prolonged or excessive cortisol also serves as a cue for HSV-1 to enter the lytic (infectious; opposite of latent) phase of its life cycle.

This explains why psychologically stressed people have a reappearance of cold sores – a sign of reactivated HSV-1. Other stressors for HSV-1 reactivation include fever, fatigue, hormonal changes, prolonged exposure to UV radiation, surgical resection, organ transplants, immunosuppressive drugs, and aging of the immune system.

This is to paraphrase Bjørn Grinde, said a Norwegian doctorate specialising in genetics and evolution – who wrote: “In most cases, reactivation does not lead to serious disease.”

Fortunately, the same seems to apply to Covid-19 reactivations that have been milder than the first-time infection, as observed in Korean and Chinese cases detailed above.

In essence, the moment Covid-19 shows neurological symptoms, it provides a clear indication that SARS-CoV-2 can infect neurons and possibly becomes latent therein, which may reactivate in later life with milder symptoms.

Inferences from other related viruses – like the Nipah virus, HSV-1, and HCoV – support this contention. Reported cases of Covid-19 reactivation could very well be the smoking gun. But whether Covid-19 infection is life-long still remains to be confirmed over the coming years, Roe stated.

Fortunately, there’re ways to suppress or prevent a latent virus reaction. Physical fitness has also been shown to prevent herpes virus reactivation in astronauts experiencing long periods of social isolation. Minimising or coping with psychological stress, immunological aging, or the other immunosuppressive stimuli cited would certainly help too.

A Medium feature. Shin Jie Yong, a postgraduate student in dementia research student in Malaysia, is a published academic author.