Post-COVID-19 syndromes can affect several systems

SARS-CoV-2 infection can trigger multiple syndromes, even in asymptomatic patients.

“There are several striking realities of COVID-19, including the highly variable severity of acute illness, the number of organs that can be affected, and the increased risk for developing new, non-COVID diseases,” said Anthony L. Komaroff, MD, Simcox-Clifford-Higby Professor of Medicine, Harvard Medical School, and Senior Physician, Brigham and Women’s Hospital.

Dr. Komaroff opened a symposium on Post-COVID Syndrome at ACR Convergence 2021. The session, which was originally presented on Monday, Nov. 8, can be viewed by registered meeting participants through March 11, 2022.

Among the 5% of patients who are hospitalized for COVID-19, half show post-COVID symptoms 30 days or more after discharge, Dr. Komaroff said. Of the 55% of patients who are asymptomatic, 19% have post-COVID symptoms.

“The post-acute sequelae of SARS-CoV-2 infection include chronic injury to the brain, lungs, heart, kidneys, gut, and endocrine organs, as well as the less-well-defined post-acute COVID syndrome, or long COVID,” he explained. “All of these illnesses can provide symptoms that are very similar.”

The most important neurological sequelae of COVID-19 include encephalopathy, acute ischemia, intracranial hemorrhage, neuropsychiatric disorders, neurogenic respiratory failure, and dysautonomia, Dr. Komaroff continued. Viral infection, severe inflammation, metabolic abnormalities, and severe hypoxia may all play pathologic roles.

COVID survivors have a 60% increased risk for all-cause mortality post-infection, as well as increased risk for new diseases, including myopathies (5.1X), respiratory failure (3.9X), pneumothorax (2.8X), and cardiac arrest (1.7X).

An observational study in the United Kingdom found 1.6% of COVID-19 patients reporting persistent post-COVID neurological symptoms, with 38% remaining symptomatic at least one year later. The most frequent symptoms included fatigue (55%), dyspnea (41%), myalgias (31%), and difficulty concentrating (29%).

Long COVID symptoms are similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia, and other post-infection and post-injury syndromes. Nearly half (47%) of patients hospitalized with COVID-19 have persistent fatigue six months later and 13% meet criteria for ME/CFS.

Multiple psychiatric issues are associated with the peri-acute and post-acute phases of COVID-19.

“Delirium is the most common symptom,” said Matthew Ehrlich, MD, Assistant Professor of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham Heersink School of Medicine. “Presentation may be subtle, with alterations in alertness and orientation, or frank. And delirium can have a long tail, especially in older adults.”

Individuals with preexisting mental illness are at elevated risk for COVID-related mortality. A premorbid diagnosis of schizophrenia ranks second behind age in strength of association with mortality.

Many COVID treatments, approved or not, have related psychiatric effects, including corticosteroids, monoclonal antibodies, fluvoxamine, interferons, hydroxychloroquine, azithromycin, and ivermectin. There are no commonly observed psychiatric side effects from COVID-19 vaccines, Dr. Ehrlich said.

“Neuropsychiatric symptoms can be present in people who did not have symptomatic COVID,” he cautioned. “Anxiety and depression are among the most common symptoms in any phase. Rates of [post-traumatic stress disorder] are high, with those receiving ICU care most at risk — and so are healthcare workers.”

Neuropsychiatric sequelae are not a surprise, Dr. Ehrlich added. There are strong associations between other respiratory infections and psychiatric symptoms and disorders.

“There may be a spike yet to come,” he warned.

Pulmonary sequelae are also common regardless of whether patients had asymptomatic, mild, severe, or critical disease. Patients who had pneumonia or acute respiratory distress syndrome are more likely to have more severe post-acute symptoms, including dyspnea, decreased exercise capacity, cough, and other pulmonary symptoms.

“One of the challenges can be unraveling overlapping acute and post-acute symptoms,” said George A. Alba, MD, pulmonary and critical care physician and Associate Director, Coronavirus Recovery Clinic, Massachusetts General Hospital. “The World Health Organization clinical case definition of post-COVID conditions focuses on new or persistent symptoms at least 12 weeks from the onset of initial symptoms and lasting longer than eight weeks that cannot be explained by another diagnosis.”

The pathobiology of post-COVID lung conditions remains unclear, he continued. Acute systemic inflammation has resolved and tissue-resident activated T cells are associated with impaired lung function. More severe COVID results in more interstitial parenchymal changes, but about a quarter of all convalescent patients have air trapping due to small airway involvement, Dr. Alba said.

Patients who were intubated also may have tracheal stenosis obstructing air flow, he noted. ICU patients could have post-intensive care syndrome, or new or worsened impairment in physical function, cognition, and/or mental health.

“Disease severity, complications, and interventions can all affect post-acute sequelae,” he said. “But be aware of your own cognitive bias. Consider your differential diagnosis as usual and don’t assume symptoms are necessarily due to COVID-19.”