Long COVID May Have Long-Term Impact on Surgery

More than 77% of people in the US had been infected with SARS-CoV-2 as of 2022.¹ Of these, approximately 30% of survivors report having persistent symptoms classified as long COVID² and 11% describe persistent symptoms at 6 months.³

Patients frequently complain of brain fog, cognitive difficulties, and other neurologic sequelae as the primary drivers of decreased quality of life. These patients also perform worse in cognitive measures of working memory, attention, and processing speed compared to controls.⁴

A recent study that gave cognitive assessments to more than 100,000 people with and without long COVID confirmed that complaints of brain fog in long COVID patients were correlated with lower cognitive performance in memory, reasoning, and executive function tasks.⁵ Although mRNA vaccines against SARS-CoV-2 have been extremely effective in preventing severe acute disease, the incidence of long COVID has not significantly decreased in the US despite widespread vaccine uptake.⁶ This indicates that long COVID, also referred to as postacute sequelae of SARS-CoV-2 infection, will remain a medical concern for the foreseeable future.

As a result, it is important that surgeons become familiar with this syndrome in order to continue providing the best care for their patients.

How Does Surgery Affect Cognition?

The lay press is filled with stories of patients who were “never the same” after surgery.⁷ Patients describe cognitive deficits in focus, memory, and attention, all affecting their ability to function.⁸ Data suggest that approximately 10% to 12% of patients suffer cognitive dysfunction that persists up to 3 months postoperatively.⁹

In 2015, the American Society of Anesthesiologists launched the Brain Health Summit, with participation from the ACS, to discuss the state of the science of perioperative cognition.¹⁰ Subsequently, a working group proposed new nomenclature to better align perioperative terminology to diagnoses already used in medical fields.¹¹

For example, the term “postoperative cognitive dysfunction” had no consensus definition and was primarily used in research, disconnected from patients’ real-world experiences. The currently recommended term for cognitive impairment identified during the overarching perioperative period is “perioperative neurocognitive disorder,” with specific subclassifications defined by timing (see Table).

Postoperative delirium deserves special attention, as it may occur as a common complication distinct from other perioperative neurocognitive disorders. It is characterized by an acute onset of waxing and waning confusion, with changes in the levels of consciousness, attention, orientation, and disorganized thinking. The clinical presentation differs according to psychomotor subtype, ranging from hypoactive (e.g., slowed movements, quiet affect—symptoms that are easy to miss) to hyperactive delirium (e.g., restlessness and agitation), as well as mixed subtypes.

The rate of postoperative delirium across the literature is highly variable from 5% to 52%¹² and dependent on the detection method (from prospective screening using validated tools to retrospective chart reviews using keywords). However, there is some evidence that rates vary by specialty and operative stress load.^13,14

Across multiple studies, common risk factors include age, preexisting cognitive impairment, previous episodes of postoperative delirium, and low education levels. Despite recommendations from the ACS and American Geriatrics Society to perform routine screening for baseline cognition,¹⁵ this is rarely performed.

The lack of baseline data can lead to a true “blind spot” in the ability of clinicians to best identify, educate, and enact preventive measures for patients at highest risk for postoperative delirium. Unfortunately, patients who suffer delirium, particularly when combined with surgical complications, experience prolonged length of stay, higher hospitalization costs, need for institutional discharge, and even face long-term consequences.^16,17

Growing evidence suggests that postoperative delirium is associated with long-term cognitive decline, both for those with normal cognition at baseline and those with preexisting dementia.¹⁸ The Successful Aging after Elective Surgery study cohort has demonstrated a dose-response relationship wherein higher severity delirium is associated with worse cognitive outcomes.¹⁹ Furthermore, these effects persist up to 6 years, with delirium accelerating cognitive decline by 40% over normal aging-related changes.²⁰

Whether preceded by delirium or not, postoperative neurocognitive disorders can significantly decrease long-term health and quality of life. Patients with postoperative neurocognitive disorders are twice as likely to experience impaired instrumental activities of daily living.²¹ Furthermore, cognitive and functional decline are associated with higher rates of long-term mortality and healthcare utilization.²²

Long COVID’s Potential Impact on Surgery

Given the risks associated with delirium and postoperative neurocognitive disorder, the preoperative cognitive impairment in long COVID patients may be a problem that obscures a clinician’s ability to recognize subtle symptoms and properly care for patients undergoing elective surgery.

Recent studies have suggested that long COVID may be caused by a prolonged, subclinical infection leading to the establishment of a viral reservoir, potentially in the gut,²³ that can modulate host immune responses and contribute to persistent cognitive symptoms.^24-26

Surgery in such patients could result in unintentional spread of the SARS-CoV-2 viral reservoir to distal tissues such as the lung, where infection can cause severe damage.²⁷ Autoantibody responses directed against central nervous system antigens, including myelin and G-protein-coupled receptors, also are detectable in plasma and cerebrospinal fluid and strongly correlate with abnormal cognitive status in long COVID patients.²⁸ Surgery in patients with already elevated autoantibody levels may induce further autoimmunity due to tissue damage leading to epitope spreading.²⁹

Finally, defects in mitochondrial oxidative phosphorylation and lipid catabolism have been linked with cognitive and noncognitive symptoms of long COVID,^30,31 and surgery in long COVID patients with mitochondrial dysfunction may prolong the recovery phase. Further studies are needed to determine if the prevalence of these various biomarkers is reflective of underlying disease processes or of preexisting long COVID both before and after surgery.

Mitigating the Impact of Long COVID on Surgery

Though cognitive symptoms caused by long COVID may be difficult to diagnose, there are strategies to help surgeons identify biomarkers of import. For example, clinical diagnostic testing can be used to identify long COVID patients who may have a persistent infection. In addition to testing for the presence of SARS-CoV-2 in the nasopharynx, it may be important to test for viral RNA or protein present in stool samples from long COVID patients before elective surgery, as the gut may be a cryptic viral reservoir.

One possible intervention for patients suspected of having a persistent infection may be to administer nirmatrelvir/ritonavir (Paxlovid) as preoperative prophylaxis to help clear infection. There is some evidence that nirmatrelvir/ritonavir may help alleviate long COVID symptoms as well,²⁶ and it is currently being tested as a treatment for long COVID in clinical trials.³²

Another option for surgeons when confronted with patients at risk for postoperative delirium who also may have long COVID is to refer them to a long COVID clinic for evaluation. Not only can their baseline cognitive status be determined, but further testing—if needed—can be suggested during this evaluation. There are multiple long COVID clinics that are associated with large academic medical centers as well as community hospitals located throughout the US.³³ Many offer televisits for patients who are not local. Long COVID clinics offer consultation across multiple specialties of internal medicine, and therefore, could be used to assess the status of long COVID patients with both cognitive and noncognitive symptoms. These are just two examples of how surgeons might consider modifying their care plans for patients with long COVID who also are at risk for postoperative delirium. Much work remains to be done before the root causes of long COVID-related cognitive dysfunction can be determined and effective treatments developed.

Given that the number of adults with long COVID who are experiencing prolonged though often subtle and nuanced cognitive changes, is growing and that surgical intervention can adversely affect long-term cognition, it remains unknown how this syndrome will affect the health outcomes of surgical patients.

Dr. Lavanya Visvabharathy is a research assistant professor of neurology (neuro-infectious disease and global neurology) at Northwestern Medicine Feinberg School of Medicine in Chicago, Illinois.

Dr. Julia Berian is an assistant professor of colorectal surgery in the Department of Surgery at the University of Wisconsin School of Medicine and Public Health in Madison.

Dr. John Alverdy is the Sara and Harold Lincoln Thompson Professor of Surgery and executive vice-chair of the Department of Surgery at The University of Chicago Medicine.

References

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