Sunday, September 25, 2022

Nature: Long-term Neurologic Outcomes of COVID-19


 Credit CDC

#17,027

More than two years ago (April 2020), in JAMA: Neurologic Manifestations Of Patients With Severe Coronavirus Disease, we saw the first major report on the neurological impact of COVID-19 infection, one which found that more than 1/3rd of a study group (n=214) hospitalized in Wuhan, China showed signs of neurological involvement.

Findings that led some researchers over that first summer of COVID to wonder; Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms by Emily A. Troyer, Jordan N. Kohn, and Suzi Hong.

Despite narratives attempting to dismiss COVID as `no worse than influenza', we continue to see evidence of long-term damage in some patients from SARS-CoV-2 infection.  Dubbed `Long-COVID', or Post-COVID Syndrome, studies have suggested that 1 in 5 adults may be affected. 

Post-COVID sequelae may include cardiovascular, renal, pulmonary, neurological, and endocrine disorders. A few (of many) studies over the past few months include:



There is also some evidence (see Outcomes of SARS-CoV-2 Reinfection) suggesting that the more times a person is reinfected with COVID - even when the illness is mild - the greater the chances of developing serious (even fatal) post-COVID sequelae.  

Seven months ago we looked at a report (see Nature: Long-term Cardiovascular Outcomes of COVID-19 by Yan Xie, Evan Xu, Benjamin Bowe & Ziyad Al-Aly) that described long-term cardiac damage among COVID survivors.  Today, we've a new report in Nature by 3 of those 4 authors, on long-term Neurologic impacts among Post-COVID patients. 

This is a lengthy, and highly detailed report, and I've only post the Abstract and some highlights from the Discussion.  Follow the link to read it in its entirety.  I'll have a postscript when you return. 
 
Open Access
Evan Xu, Yan Xie & Ziyad Al-Aly

Abstract

The neurologic manifestations of acute COVID-19 are well characterized, but a comprehensive evaluation of postacute neurologic sequelae at 1 year has not been undertaken. Here we use the national healthcare databases of the US Department of Veterans Affairs to build a cohort of 154,068 individuals with COVID-19, 5,638,795 contemporary controls and 5,859,621 historical controls; we use inverse probability weighting to balance the cohorts, and estimate risks and burdens of incident neurologic disorders at 12 months following acute SARS-CoV-2 infection.
 
Our results show that in the postacute phase of COVID-19, there was increased risk of an array of incident neurologic sequelae including ischemic and hemorrhagic stroke, cognition and memory disorders, peripheral nervous system disorders, episodic disorders (for example, migraine and seizures), extrapyramidal and movement disorders, mental health disorders, musculoskeletal disorders, sensory disorders, Guillain–Barré syndrome, and encephalitis or encephalopathy. 

We estimated that the hazard ratio of any neurologic sequela was 1.42 (95% confidence intervals 1.38, 1.47) and burden 70.69 (95% confidence intervals 63.54, 78.01) per 1,000 persons at 12 months. The risks and burdens were elevated even in people who did not require hospitalization during acute COVID-19. Limitations include a cohort comprising mostly White males. Taken together, our results provide evidence of increased risk of long-term neurologic disorders in people who had COVID-19.

(SNIP)

Discussion

In this study involving 154,068 people who had COVID-19, 5,638,795 contemporary controls and 5,859,621 historical controls, which altogether correspond to 14,064,985 person-years of follow up, we show that beyond the first 30 days of infection, people with COVID-19 are at increased risk of an array of neurologic disorders spanning several disease categories including stroke (both ischemic and hemorrhagic), cognition and memory disorders, peripheral nervous system disorders, episodic disorders, extrapyramidal and movement disorders, mental health disorders, musculoskeletal disorders, sensory disorders and other disorders including Guillain–Barré syndrome, and encephalitis or encephalopathy. The risks and burdens were evident in subgroups based on age, race, sex, obesity, smoking, ADI, diabetes, chronic kidney disease, hyperlipidemia, hypertension or immune dysfunction. The risks were evident even in people who did not need hospitalization during the acute phase of the infection and increased according to the care setting of the acute phase of the disease from nonhospitalized to hospitalized to admitted to intensive care. The findings were consistent in comparisons involving the contemporary control group and the historical control group. The results were robust to challenge in sensitivity analyses; the application of negative-exposure and negative-outcome controls yielded results consistent with prior expectations. Altogether, our results show that the risks and burdens of neurologic disorders in the COVID-19 group at 12 months are substantial. The long-term consequences of SARS-CoV-2 infection should be taken into account in devising policies for managing the ongoing pandemic, and developing exit strategies for a postpandemic era. Health systems should consider these findings in capacity planning and in designing clinical care pathways to address the care needs of people who survive the acute phase of COVID-19.

More than 2 years into the COVID-19 global pandemic, it is abundantly clear that infection with SARS-CoV-2 may result in a broad array of long-term disorders9,10,11,12,13,14. Our report adds to this growing body of evidence by providing a comprehensive account of the neurologic consequences of COVID-19 at 12 months. 

Given the colossal scale of the pandemic, and even though the absolute numbers reported in this work are small, these may translate into a large number of affected individuals around the world—and this will likely contribute to a rise in the burden of neurologic diseases. This places more emphasis on the continued need for multipronged primary prevention strategies through nonpharmaceutical interventions (for example, masking) and vaccines to reduce—to the extent possible—the risk of contracting SARS-CoV-2. There is also an urgent need to develop long-term sustainable strategies to prevent mass infection with SARS-CoV-2 and to determine whether and how these long-term neurologic (and other) complications could be prevented or otherwise mitigated in people who are already infected with SARS-CoV-2.

          (SNIP)

In conclusion, our report provides a comprehensive analysis of neurologic outcomes at 12 months. We show increased risk of an array of neurologic disorders spanning several neurologic disease categories including stroke (both ischemic and hemorrhagic), cognition and memory disorders, peripheral nervous system disorders, episodic disorders, extrapyramidal and movement disorders, mental health disorders, musculoskeletal disorders, sensory disorders, and other disorders including Guillain–Barré syndrome, and encephalitis or encephalopathy. The risks were evident in all examined subgroups and were evident even in people who were not hospitalized during the acute phase of the disease. Altogether, the findings call for attention to the long-term neurologic consequences of SARS-CoV-2 infection. Both healthcare system planning, and more broadly, public policy making, should take into account the long-term neurologic (and other) consequences of infection with SARS-CoV-2. 

          (Continue . . . )

Two years ago, in The Lancet: COVID-19: Can We Learn From Encephalitis Lethargica?, we looked at the still unexplained increase in neurological disorders in the decade following the 1918 pandemic. A cruel epidemic that affected millions worldwide. 

While a direct link to the H1N1 influenza virus has never been established, many researchers believe it was caused by a viral infection (see Evidence for an enterovirus as the cause of encephalitis lethargica).

It may take another 5 or 10 years before we can accurately assess the impact of COVID infection on society's health and well being. But current evidence suggests that COVID - even when it only produces mild acute illness - is an infection best avoided whenever possible. 

Which is why I'm still wearing a face mask in public, and am keeping current with my booster shots. 

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