Could COVID-19 be a latent viral infection?

COVID-19, a respiratory illness caused by a novel coronavirus, spread globally and emerged more than 6 million people by the beginning of June 2020.

Recently South Korean officials reported that nearly 100 people thought to be cured of the novel coronavirus have tested positive for COVID-19 again. Per Jeong Eun-kyeong, director of the Korea Centers for Disease Control and Prevention, the COVID-19 virus may have “reactivated” in the patients rather than them becoming re-infected [1].

A latent viral infection is an infection that is inactive or dormant. As opposed to active infections, where a virus is actively replicating and potentially causing symptoms, latent (or persistent; but not chronic) infections are essentially static which last the life of the host and occur when the primary infection is not cleared by the adaptive immune response [2]. Herpes simplex viruses type 1 and 2, varicella-zoster virus, HIV, Epstein-Barr virus (human herpesvirus 4), and cytomegalovirus are examples of viruses that are well known to cause typical latent infections in human [3-5].

Latent viral infections can be reactivated into a lytic form (the replication of a viral genome). The ability to move back and forth from latent to lytic infections helps the virus spread from infected individuals to uninfected individuals [6].

The brain is in many ways an immunologically and pharmacologically privileged site. The blood-brain barrier (BBB) restricts access of immune cells and immune mediators to the central nervous system (CNS) [7].

Anosmia has been reported in conjunction with well-reported symptoms of COVID-19 [8]. By Lechien, et al. (2020), anosmia even appeared before the other symptoms in 11.8% of COVID-19 cases [9].

Rabies is a fatal zoonotic neuroinfectious disorder caused by the RNA virus. It’s well known that the rabies virus may cause a latent infection in both animals (commonly in bats) and human [10,11].

Could the SARS-CoV-2 virus (causative RNA virus for human COVID-19, which is currently thought to be an animal virus from an as-yet-uncertain animal reservoir, perhaps bats) be another latent viral infection by means of cytoplasmic episomal latency mechanism in the neurons of olfactory tract given the well-known fact that the BBB limits the entry of immune cells and immune mediators into the CNS that may prevent from eradication of this infection?

1. (2020) South Korea reports recovered coronavirus patients testing positive again. Link: https://reut.rs/3gGs6wO
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7. Muldoon LL, Alvarez JI, Begley DJ, Boado RJ, del Zoppo GJ, et al. (2013) Immunologic privilege in the central nervous system and the blood–brain barrier. J Cereb Blood Flow Metab 33: 13-21. Link: https://bit.ly/3dry5n1
8. Vaira LA, Salzano G, Deiana G, De Riu G (2020) Anosmia and ageusia: common findings in COVID-19 patients. Laryngoscope. Link: https://bit.ly/3eJcJ4K
9. Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, et al. (2020) Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. Link: https://bit.ly/3gQUsET
10. Sulkin SE (1962) Bat rabies: experimental demonstration of the “reservoiring mechanism”. Am J Public Health Nations Health 52: 489-498. Link: https://bit.ly/2Mkm8nl
11. Smith JS, Fishbein DB, Rupprecht CE, Clark K (1991) Unexplained rabies in three immigrants in the United States. A virologic investigation. N Engl J Med 324: 205-211. Link: https://bit.ly/2XTMl1o