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While the serious health impacts of COVID appear to be less today than they were during the Delta wave, it is less than clear how much of that attenuation is due to a weakening of the virus, or to the combined effects of previous infection and vaccinations.
That question might be answered if we could get reliable information out of China as Omicron spreads through their immunologically naive population. But that information is unlikely to be shared, assuming they are even able to effectively track it themselves.
Omicron variants do appear to produce less severe pneumonia, but - as we've seen in numerous studies (see below) - the extrapulmonary impacts of COVID infection can cause significant morbidity and mortality during and after the acute phase of the infection.
A few (of many) studies include:
Neurology: Incidence of Epilepsy and Seizures Over the First 6 Months After a COVID-19 Diagnosis: A Retrospective Cohort Study
The Lancet: Neurological and Psychiatric Risk Trajectories After SARS-CoV-2 InfectionThere is also evidence that these risks appear to increase with every infection (see Nature: Acute and Postacute Sequelae Associated with SARS-CoV-2 Reinfection), both during the acute phase of the illness and the months that follow.
MMWR: Post–COVID-19 Symptoms and Conditions Among Children and Adolescents
Nature: Long-term Cardiovascular Outcomes of COVID-19
Nature: Long-term Neurologic Outcomes of COVID-19
While the exact mechanism behind `Long-COVID' sequelae isn't known, the extrapulmonary spread of the virus - particularly to the brain and the heart - is strongly suspected to be a contributing factor.
This is a topic we've explored repeatedly, including earlier this month in Nature: SARS-CoV-2 Infection and Persistence in the Human Body and Brain at Autopsy, and last month in Nature: Enhanced Replication of SARS-CoV-2 Omicron BA.2 in Human Forebrain and Midbrain Organoids.
Concerns over the neurological impact of COVID began almost immediately in the spring of 2020, after an early report from Wuhan, China (see JAMA: Neurologic Manifestations Of Patients With Severe Coronavirus Disease) found 1/3rd of a study group exhibiting troubling neurological signs and symptoms.
Neurological manifestations ranged from relatively mild (headaches, dizziness, anosmia, mild confusion, etc.) to more profound (seizures, stupor, loss of consciousness, etc.) to potentially fatal (ischemic stroke, cerebral hemorrhage, muscle injury (rhabdomyolysis), etc.).
Since then we've seen a steady stream of studies describing neurological manifestations during, and following, COVID infection. A few (of many) include:
Nat. Comms: Neuropathology and Virus in Brain of SARS-CoV-2 Infected Non-human Primates
J. Neurology: COVID-19 As A Potential Risk Factor For Chronic Neurological Disorders
The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings
Frequent Neurologic Manifestations & Encephalopathy‐Associated Morbidity in Covid‐19 patients
But - as with last Novembers study on Omicron BA.2 in Human Forebrain and Midbrain Organoids, today's preprint deals with newer (in this case, BA.5) Omicron variants.
Human brain organoids (aka `mini-brains') are created from lab-grown stem cells that are designed to simulate the architecture and functionality of the human brain (cite), and have been increasingly used for many types of brain research (see Science: Zika Impairs Growth In Human Neurospheres And Brain Organoids).
Today's preprint from researchers at Australia's QIMR Berghofer Medical Research Institute and Queensland University finds that BA.5 was more neuroinvasive than BA.1, and more pathogenic in K18-hACE2 lab mice, suggesting that the trajectory of Omicron isn't always towards a weaker virus.
I've only reproduced the abstract, follow the link to read the full 38-page PDF. I'll have a brief postscript when you return.
Omicron BA.5 infects human brain organoids and is neuroinvasive and lethal in K18-hACE2 mice
Romal Stewart, Sevannah A Ellis, Kexin Yan, Troy Dumenil, Bing Tang, Wilson Nguyen, View ORCID ProfileCameron R Bishop, Thibaut Larcher, Rhys Parry, Robert K P Sullivan, Mary Lor, Alexander A Khromykh, View ORCID ProfileFrederic A Meunier, Daniel J Rawle, Andreas Suhrbier
doi: https://doi.org/10.1101/2022.12.22.521696
Preview PDF
Abstract
A frequently repeated premise is that viruses evolve to become less pathogenic. This appears also to be true for SARS-CoV-2, although the increased level of immunity in human populations makes it difficult to distinguish between reduced intrinsic pathogenicity and increasing protective immunity.The reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described and appears to be due to reduced utilization of TMPRRS2. That this reduced pathogenicity remains true for omicron BA.5 was recently reported.
In sharp contrast, we show that a BA.5 isolate was significantly more pathogenic in K18-hACE2 mice than a BA.1 isolate, with BA.5 infection showing increased neurovirulence, encephalitis and mortality, similar to that seen for an original strain isolate.
BA.5 also infected human cortical brain organoids to a greater extent than a BA.1 and original strain isolate. Neurons were the target of infection, with increasing evidence of neuron infection in COVID-19 patients.
These results argue that while omicron virus may be associated with reduced respiratory symptoms, BA.5 shows increased neurovirulence compared to earlier omicron sub-variants.
Admittedly, we can't assume that BA.5's enhanced pathogenicity in lab-mice was mirrored in humans, nor can we assume that lab-grown brain organoids are the perfect substitute for the human brain.
But this study does show that BA.5 - at least in some hosts - produced different (and more severe) infection than earlier Omicron variants.
The notion that if we wait long enough, COVID will evolve into a `less pathogenic' virus is comforting, but it may not be rooted in reality. And despite the reduced mortality observed with Omicron, it may be years before we can fully appreciate the long-term impact of COVID infection on human health.
Following the 1918 pandemic, the world saw a decade or more of increased neurological disorders (see The Lancet: COVID-19: Can We Learn From Encephalitis Lethargica?) - killing or disabling millions of people - and while its exact cause remains unknown, a viral infection is strongly suspected.
Which is why, until we know more, it probably in your best interests to avoid being infected with COVID if at all possible.
