SARS-CoV-2 is the official name for the virus originating in Wuhan, China in late 2019 and rapidly spreading throughout the world in a devastating pandemic. It is also referred to as the ‘coronavirus strain responsible for COVID-19,’ or the ‘Wuhan virus.’ The overwhelming impact of this single-stranded RNA virus is compounded by the massive damage attributable to a host of neurological complications. These latter complications will be the focus of this discussion by neurologists James C. Johnston, MD, JD and Mehila Zebenigus, MD.
The origin of this virus remains unclear, some purporting it came from a Wuhan, China wet market but recent evidence suggesting it may have originated from the Wuhan biosecurity laboratory. Laboratory mishaps are well documented. For example, the 2003 SARS virus – also originating in China – escaped from the Chinese Institute of Virology in Beijing on at least three separate occasions. Science 2004; 304:659-661.
Perhaps more disconcerting is that the Wuhan Institute of Virology was performing ‘gain-of-function’ experiments, for example by recombining the genome of the bat coronavirus with that of a mouse-infecting coronavirus. The Wuhan facility reported that the resulting virus could “replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis.” Further, “both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein.” Nature Medicine 2015; 21:1508-1513.
The researchers in that paper noted “scientific review panels may deem similar studies building chimeric viruses based on circulating strains too risky to pursue, as increased pathogenicity in mammalian models cannot be excluded.” Id.
This type of work, giving pathogens enhanced powers, or ‘gain-of-function,’ is highly controversial, and raises serious questions regarding these Chinese experiments.
Several of the arguments alleging the virus could not have originated from the Wuhan biosecurity lab are rather tenuous, focus on the lab’s protocols without recognizing the potential for human error, and typically cite reports from unnamed experts or the Wuhan lab itself – for example, concluding that if it was engineered, then one of several reverse-genetic systems available for betacoronaviruses “would probably have been used,” referencing a March 2019 article from the Wuhan Institute of Virology. Nat Med 2020; 26:450-452; Nat Rev Microbiol 2019 17:181-192.
This SARS-CoV-2 or Wuhan virus has an array of unusual features that have ensured it is highly effective in spreading throughout the world’s population, and indeed rapidly seeded the entire planet. One distinctive feature is that asymptomatic people can spread the virus, unknowingly infecting large segments of the population. It is typically spread through the respiratory system, and thus using masks and social distancing reduce spread.
Patients most commonly develop fever, a dry cough and malaise, with a significant portion reporting headache, myalgias, chills and anosmia (loss of smell) with dysgeusia (impaired taste). Gastrointestinal symptoms are not uncommon. Recovery is variable, some patients recover in a few weeks, others suffer lingering symptoms such as fatigue, and up to one-third develop severe respiratory problems due to pulmonary inflammation. Respiratory failure is the leading cause of mortality with SARS-CoV-2, but there are also a host of systemic complications including myocarditis, renal failure, and a coagulopathy that may result in arterial or venous occlusions.
Professor Mehila Zebenigus and Dr. James C. Johnston will focus on the extraordinarily diverse neurological complications associated with the virus, which can affect the entire central and peripheral nervous systems, and may occur during an active infection or as part of a post-viral syndrome.
Headache is common, and some patients develop meningitis or encephalitis. Autopsy studies have demonstrated viral levels in the brains of SARS-CoV-2 patients, not unlike the 2003 SARS epidemic. The virus may spread to the nervous system through the cardiovascular system or by transneuronal means such as the olfactory nerve from the nasal passages or the vagus nerve from the lungs. The major cause of death is an atypical Acute Respiratory Distress Syndrome manifest by severe hypoxemia in the face of well preserved lung capacity which may be attributable to invasion of the brainstem respiratory center leading to a form of Ondine’s curse. Cerebrovascular disease is increasingly recognized with this virus and in fact may be the presenting symptom. There may also be vascular occlusions of other organs. Viral and post-viral syndromes include Guillian-Barre syndrome, myelitis, myositis and a host of other disorders including hearing loss.
This pandemic will continue to plague the world for the foreseeable future, and it is crucial for neurologists and all physicians to recognize the varied and devastating neurological presentations that may occur as a presenting symptom, during the course of the infection, or as a post-viral syndrome.