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Postacute Sequelae of SARS-CoV-2 Infection and Implications for Recovery

Steven Deeks, professor of medicine in residence at the University of California, San Francisco, introduced the second session of the workshop. In this session, experts described the pathology and clinical presentation of symptoms caused by SARS-CoV-2, and they explored what is known about the mechanisms and long-term potential consequences of this disease in different body systems. Speakers discussed effects on the neurological, neuromuscular, neuropsychiatric, cardiovascular, pulmonary, and musculoskeletal systems, and explored the burden of pain and fatigue associated with Long COVID.

NEUROLOGICAL AND NEUROMUSCULAR SEQUELAE

There are acute, subacute, and chronic neurological complications of COVID-19, said Avi Nath, clinical director of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health. In the acute phase, patients can suffer from anosmia, metabolic and hypoxic encephalopathy, strokes, and more rarely, viral encephalitis or sudden death caused by hypoventilation. Subacute sequelae are inflammatory syndromes and can include acute disseminated encephalomyelitis, acute necrotizing hemorrhagic encephalopathy, and limbic encephalitis; children can experience multisystem inflammatory syndrome (MIS-C). Chronic neurological complications fall under the umbrella of Long COVID.

When considering the pathology of neurological complications, said Nath, the first question is whether the virus actually invades the brain. While there is a potential route for SARS-CoV-2 to enter the brain through the

olfactory pathway, Nath said that researchers have only very rarely detected virus in the brain; when it has been detected, it is in small amounts and is not accompanied by inflammation (Lee et al., 2021). However, the acute effect of COVID-19 on the brain can be severe. Patients may suffer from ischemic strokes, hemorrhage, and clots in venous sinuses. Autopsies of brain tissue have found fibrinogen leaking into the brain, as well as blood vessels that are almost completely occluded. These findings, said Nath, are uniquely associated with COVID-19. Tinnitus, dizziness, and vertigo are also common occurrences in patients with COVID-19 (Viola et al., 2021); the prevailing hypothesis is that these are caused by a vascular phenomenon affecting the small blood vessels in the ear.

Subacute conditions associated with COVID-19 include different types of neuroinflammation; Nath noted that many of these conditions are seen in other viral infections and thus are well characterized. These conditions may include acute disseminated encephalomyelitis, which is T cell mediated (Novi et al., 2020), and acute necrotizing hemorrhagic encephalopathy, which is cytokine mediated (Poyiadji et al., 2020). MIS-C in children is associated with acute symptoms including fever, dyspnea, rash, vomiting, and circulatory failure; longer-term symptoms include encephalopathy, dysarthria, dysphagia, and generalized flaccid weakness (Abdel-Mannan et al., 2020). Fortunately, said Nath, the neurological manifestations of MIS-C tend to respond to treatment with corticosteroids and intravenous immunoglobulin. In addition to inflammation in the brain, inflammation may also affect the peripheral nerves, including cranial nerves. Researchers have reported Miller Fisher syndrome, polyneuritis cranialis, ophthalmoparesis, and acute polyradiculitis in COVID-19 patients (Dias et al., 2021). These conditions also tend to respond well to corticosteroids, he said.

Most COVID-19 patients, said Nath, recover within 3 months (Whitaker et al., 2021). However, if they do not recover by this time, symptoms may not abate. Nath shared research from the National Health Service in the United Kingdom (Whitaker et al., 2021) that found that among those symptomatic at onset, 52 percent were symptomatic at 4 weeks, and 38 percent at 12 weeks. Those with more symptoms at the beginning tend to continue to have more symptoms, and women experience both more initial and lingering symptoms than men. Early manifestations of COVID-19, said Nath, may be useful for predicting what happens in the long term.

Some patients, however, fully recover from mild initial symptoms but then develop new symptoms days or weeks later. These symptoms tend to persist for extended periods of time. Nath mentioned that unpublished research data on a small cohort of these patients showed that nearly all reported cognitive dysfunction and fatigue, and smaller percentages reported palpitations, paresthesias, psychiatric issues, and dizziness. Long COVID symptoms, said

Nath, can be divided into four categories: exercise intolerance; cognition, mood, and sleep disorders; pain syndromes; and dysautonomia (Figure 3-1). Brain scans of patients experiencing Long COVID show morphological and metabolic changes in the brain, said Nath, including differences in amyloid proteins, decreased ratio of brain to total intracranial volume, and atrophy of olfactory tracks.

Nath ended with three main points:

• Direct invasion of the brain by SARS-CoV-2 is rare and does not explain the neurological complications.
• Neuroimmune dysfunction is driven by activation of innate immunity, immune exhaustion, and antibody-mediated phenomenon.
• Endothelial cell damage by immune complexes is the primary pathophysiological process in neuro-COVID.

NEUROPSYCHIATRIC SEQUELAE

Emily Troyer, director of the child and adolescent psychiatry track for the community psychiatry program at the University of California, San Diego, began by sharing a historical perspective from the influenza pandemic that began in 1918. Effects on physical and mental health were still reported many years later, said Troyer, which emphasizes that the full scope of neuropsychiatric sequelae following COVID-19 might not be known for years or even decades. Research on past coronavirus outbreaks—SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome)—found that cognitive, mood, and trauma-related symptoms were common among survivors (Rogers et al., 2020). Further, she said, nearly a quarter of survivors had not returned to work 3 years postillness.

Psychiatric symptoms are commonly seen during the acute infection phase of COVID-19, as well as in the first 3 months following illness, said Troyer. Having a preexisting psychiatric disorder, particularly schizophrenia, has been associated with increased risk of COVID-19 infection, hospitalizations, and death. Longer-term psychiatric symptoms—those that occur more than 3 months after the acute phase of the illness—include sleep disturbance, depression, anxiety, and trauma-related symptoms. Psychosis is rare, said Troyer, but has been reported. Interestingly, she said, research does not show an association between the severity of the acute COVID-19 infection and the risk for depression or anxiety. In fact, some studies suggest that milder infection is actually associated with a greater risk for depression and anxiety. Troyer noted, however, that any of these studies have important limitations and further research is needed. One large retrospective study (Taquet et al., 2021) that used electronic health records to look at postinfection outcomes found that almost 24 percent of patients experienced a mood, anxiety, or psychotic disorder within the first 6 months, and that almost 9 percent of survivors experienced a disorder that was not present prior to COVID-19 infection. The study compared COVID-19 patients to survivors of influenza and other respiratory tract infections, and found that the risk of several psychiatric disorders was significantly greater following COVID-19 infection. These findings, said Troyer, point out the “scale of the issue facing us as we try to recover from the pandemic.”

Troyer described the potential pathogenic mechanisms that create the association between COVID-19 and neuropsychiatric symptoms. In short, she said, it is “likely complex and multifactorial.” One potential mechanism is inflammatory cytokines in the peripheral and central nervous systems shunting the brain’s energy away from the production of neurotransmitters such as serotonin, dopamine, and norepinephrine, and toward the production of toxic metabolites such as quinolinic acid (Boldrini et al., 2021). Troyer noted that

the lack of clinical or objective biomarkers for these processes makes it challenging to screen or diagnose patients at risk. Another potential mechanism for neuropsychiatric symptoms is the maternal immune activation hypothesis. This hypothesis suggests that individuals who are exposed to inflammation in utero—whether caused by infection, stress, or other causes—are at increased risk for neurodevelopmental disorders later in life. Going forward, said Troyer, it will be important to continue to try to understand how COVID-19 infection could affect individuals throughout their lives.

Neuropsychiatric sequelae in children following COVID-19 infection is much less well understood compared to adults, said Troyer. The good news, she said, is that the prevalence of Long COVID in children seems to be lower, with about one to five percent of youth who have had acute COVID experiencing Long COVID (Stephenson et al., 2021). The pandemic in general has negatively affected mental health among the youth, she added. Another interesting finding, she said, is that Danish teenagers who had a history of COVID-19 infection were more likely to miss school than teenagers who had not been infected, even though there were no reported differences in psychiatric or general health outcomes (Kikkenborg Berg et al., 2022). This finding, said Troyer, suggests a possible mismatch between reported mental health impairment and actual functional impairment in children.

Troyer summarized her main points:

• COVID-19 infection is associated with a risk for exacerbation of and new-onset psychiatric disorders, including mood, anxiety, and trauma-related disorders, as well as sleep disturbances.
• Nearly all studies to date have been conducted in adult samples, and findings may not be generalizable to other stages of human development.
• Longer-term outcomes, pathogenic mechanisms, biomarkers, and effective treatments for post-COVID-19 psychiatric disorders remain to be elucidated.
• Disentangling effects of COVID-19 infection versus pandemic-related stress will be difficult, as both may contribute to long-term sequelae via neuroimmune mechanisms.
• The scale of the pandemic will require that brain and mental health be integral components of research and clinical and social service planning in the coming years.

CARDIOVASCULAR SEQUELAE AND AUTONOMIC SYNDROME

Survey data show that a significant proportion of patients with PASC report symptoms of autonomic dysfunction,¹ said Peter Novak, director of the Autonomic Laboratory at Brigham and Women’s Hospital. To characterize and understand the autonomic symptoms associated with PASC, Novak and his colleagues designed a retrospective study that enrolled patients with PASC who were experiencing fatigue and brain fog (Novak et al., 2022). The protocol for evaluating patients consisted of cerebrovascular, respiratory, autonomic, and small fiber assessment, as well as testing for markers of low-grade inflammation. The first cohort of patients were nine white women, all of whom had mild COVID-19 and none of whom were vaccinated. These patients were age and sex matched with 10 women who had postural orthostatic tachycardia syndrome (POTS) and 15 healthy controls.² Novak noted that the POTS controls were used because there is a great deal of overlap in terms of presentation and clinical findings between patients with POTS and those with PASC.

Novak described the study findings. Small fiber neuropathy (damage of the nerves) was found in 89 percent of patients with PASC, 60 percent of patients with POTS, and none of the healthy controls. Cerebrovascular dysregulation was found in all PASC patients; the pattern of decrease in cerebral blood flow velocity while in a tilted position was similar between POTS and PASC patients. In addition, said Novak, dysautonomia in at least one domain was found in all of the PASC and POTS patients and in none of the healthy controls.³ Respiratory dysregulation occurred in 100 percent of PASC patients, in 75 percent of POTS patents, and in none of the healthy controls. Elevated inflammatory markers were found in 67 percent of PASC patients and 70 percent of POTS patients, but the markers were heterogeneous and there was no typical pattern.

In concluding, Novak described the implications of this research:

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¹ The autonomic nervous system is a control system that acts largely unconsciously and regulates bodily functions, such as the heart rate, digestion, respiratory rate, pupillary response, urination, and sexual arousal.

² POTS is an autonomic nervous system disorder that creates an abnormal increase in heart rate that occurs after sitting up or standing. The various symptoms of POTS, including dizziness and fainting, can range from mild to disabling.

³ Dysautonomia refers to medical conditions caused by problems with the autonomic nervous system. These disorders can be mild to debilitating, and usually involve abnormal symptoms in many organ systems, including cardiac, gastrointestinal, neurological, and pulmonary, and others.

• PASC is associated with multisystem dysfunction affecting the cerebrovascular, autonomic, peripheral, respiratory, and inflammatory systems; this is most likely caused by low-grade inflammation that is either systemic or targets the vascular system.
• A number of clinical manifestations are correlated with system dysfunction, including pain and sensory disturbances (neuropathy); orthostatic intolerance, fatigue, and brain fog (cerebrovascular dysregulation); dyspnea and increased fatigue (respiratory dysregulation); and fatigue, exercise intolerance, dry mouth, and urinary and GI symptoms (dysautonomia). Several studies have confirmed these findings.
• The severity of the symptoms experienced by PASC patients is similar to the severity of symptoms experienced by patients with other disabling conditions, including POTS, chronic fatigue syndrome, and small fiber neuropathy.

PULMONARY SEQUELAE

Breathlessness is a common symptom of COVID-19, but it is a complex and multifactorial symptom, said Ann Marie Parker, intensivist and assistant professor of pulmonary and critical care medicine at the Johns Hopkins School of Medicine. Recent data (Montani et al., 2022) show that breathlessness is the most common respiratory symptom reported at 12 months with between 5 to 81 percent of previously hospitalized patients experiencing breathlessness, and around 14 percent of nonhospitalized patients. Breathlessness is not closely associated with the initial severity of COVID-19, said Parker; patients with mild or severe initial illness can have long-lasting breathlessness. Cough is also commonly reported, with between 2 and 42 percent of PASC patients experiencing cough (Montani et al., 2022). Both breathlessness and cough are associated with worse quality of life, said Parker.

Parker gave an overview of the incidence and prevalence of post-COVID-19 respiratory sequelae, noting that most evidence comes from China and Europe because they are ahead of the United States in the timeline of the pandemic. One study (Huang et al., 2021a) found that among patients who were hospitalized but largely not in the ICU, about 75 percent had one symptom at 6 months, and about 25 percent had breathlessness. The most common abnormality in pulmonary function testing was a decrease in oxygen diffusing capacity, and some patients had abnormal physical function, as demonstrated by a low score on the 6-minute walk test. Patients who had required respiratory support during hospitalization were more likely to report breathlessness and decreased mobility at 6 months, she said. A follow-up study (Huang et al., 2021b) observed a subset of these patients at 12 months. About half reported

one symptom, and about 30 percent reported breathlessness at 1 year. Pulmonary function and physical function tests did not show improvement between 6 months and 12 months. However, she said, the proportion of patients with restrictive lung disease decreased, from about 40 percent at 6 months to about 30 percent at 12 months.

Another study (Wu et al., 2021) prospectively followed 83 patients who were hospitalized with severe COVID-19 but who did not receive steroids or other medications that are now used. Patients who had preexisting comorbidities were excluded to isolate the pulmonary complications of COVID-19 itself. The most common symptom at 3, 6, and 12 months was mild to moderate decrease in oxygen diffusing capacity,⁴ which generally improved over time. Physical function as measured by the 6-minute walk test and abnormalities on chest imaging similarly improved over time. However, said Parker, a quarter of patients still had abnormal chest imaging at 12 months, and in these patients the need for respiratory support or having a long hospital stay were associated with this outcome. A third of patients continued to have a decrease in oxygen diffusing capacity at 12 months; females were more likely than males to experience this complication (Wu et al., 2021).

These studies, Parker observed, demonstrate that pulmonary complications after COVID-19 infection tend to be mild to moderate and tend to improve over time without intervention. Parker described the reasons patients might report a perception of breathlessness following an acute COVID-19 infection; one reason, for example, is asthma. Parker indicated there is no robust evidence confirming the hypothesis that people with asthma might be susceptible to more severe COVID-19. A few studies have looked at the long-term outcomes of patients with asthma after a COVID-19 infection, said Parker. One study (Philip et al., 2022) of 471 patients with asthma and self-reported COVID-19 infection found that about half reported experiencing Long COVID. A greater percentage of those with Long COVID reported worsened breathing, an increase in rescue inhaler use, and worsened asthma management. In addition to asthma, other factors that could contribute to a perception of breathlessness, said Parker, include hyperventilation, peripheral deconditioning, respiratory or diaphragmatic weakness, interstitial lung disease, pulmonary embolism, cardiovascular complications, POTS, and chronic fatigue syndrome. Evaluation of patients with respiratory complications from COVID-19 can include chest imaging, pulmonary function tests, CT scans, walk tests, and echocardiogram (George et al., 2020). Parker noted that

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⁴ Diffusing capacity is a measure of how well oxygen and carbon dioxide are transferred (diffused) between the lungs and the blood and can be a useful test in the diagnosis and treatment monitoring of lung diseases.

because there are no COVID-19-specific interventions in the post-COVID care setting, referring patients to subspecialists is appropriate.

Parker summarized three main points:

• Breathlessness and cough are common following acute COVID-19 infections; they are complex and multifactorial symptoms.
• Few COVID-19-specific therapeutic options exist, so treatments are based on what is known about related conditions (e.g., asthma).
• Research priorities include investigations of the natural history of the disease; risk factors (patient specific, acute phase, and recovery); therapeutic interventions; and long-term patient-centered outcomes.

MUSCULOSKELETAL, FATIGUE, AND PAIN SEQUELAE

Anthony Komaroff, professor of medicine at Harvard Medical School and senior physician at Brigham and Women’s Hospital, gave participants an overview of what is known about musculoskeletal symptoms, fatigue, postexertional malaise, and pain in people with Long COVID. The incidence of Long COVID, and the associated sequelae, is difficult to determine because studies have used a variety of designs and definitions, he said. For example, some studies require COVID-19 to be diagnosed by a lab test, while others accept self-report; some use electronic health records to track symptoms, while others survey patients about their symptoms. However, some evidence can be gleaned from the existing studies, said Komaroff.

One systematic review of 57 studies (Groff et al., 2021) found frequent persistent symptoms in patients 6 months after a COVID-19 infection, including fatigue, pain, postexertion malaise, and loss of mobility and function. Komaroff explained that postexertional malaise is a cardinal symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); it is defined as prolonged exacerbation of patient’s baseline symptoms after physical, cognitive, or orthostatic exertion or stress (IOM, 2015). The exacerbation of symptoms may be delayed relative to the trigger, he said; for example, in people with ME/CFS, physical exertion does not produce the symptoms until 12 to 48 hours after exertion. A study that conducted cardiopulmonary exercise testing (Singh et al., 2022) found that while peak cardiac index did not differ between patients with Long COVID and healthy controls, the Long COVID patients had significantly lower levels of peak VO2 and systematic oxygen extraction. This suggests, said Komaroff, an underlying physiologic abnormality that is correlated with and could explain some of the postexertional malaise found in Long COVID patients.

Another study (Beauchamp et al., 2022) found that people with probable or confirmed acute COVID-19 infections were more likely to experi-

ence functional impairment than those without a history of COVID-19 infections. Over the 9-month study period, COVID-19 patients were about twice as likely to have a reduced ability to engage in normal household activities, reduced physical activity, and difficulty standing from a sitting position. Fatigue following an infection is not unique to COVID-19, said Komaroff. Similar symptoms have been found in patients infected with viral, bacterial, and protozoal infections ranging from Ebola to Lyme disease to enteroviruses.

A number of similarities exist between Long COVID and ME/CFS, said Komaroff, with similarities both in symptoms and in pathophysiology. Studies that examined whether and to what extent Long COVID patients resembled patients with ME/CFS found that 6 to 9 months after acute COVID-19, between 13 and 25 percent of patients met the diagnostic criteria for ME/CFS (González-Hermosillo et al., 2021; Mirfazeli et al., 2022; Townsend et al., 2020). Similarities between Long COVID and ME/CFS include:

• Dysautonomia/brainstem dysfunction
• Autoantibodies, many to neural targets
• Decreased generation of ATP⁵
• General hypometabolic state, including in brain
• Gut microbiome dysbiosis
• Endothelial dysfunction and coagulopathy
• Small fiber neuropathy
• Cognitive deficits
• Neuroinflammation

Researchers are exploring a number of potential biological triggers for this wide range of pathophysiology, said Komaroff, including inflammation caused by injury and repair in multiple organs; persistent reservoirs of the virus in the body that generate a chronic immune response; integration of the viral genome into the host genome; reactivation of neurotropic pathogens; mitochondrial dysfunction; and chronic inflammation and autoimmunity caused by gut dysbiosis.

To summarize, Komaroff stated the following points:

• Musculoskeletal disease and symptoms, fatigue, postexertional malaise, and pain can often persist for at least 6 months following acute COVID-19.
• Functional impairment, often attributed to these symptoms, is common.

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⁵ ATP stands for adenosine triphosphate, a molecule that provides energy to drive many processes in living cells.

• Long COVID patients have similar symptoms to people with ME/CFS and other postinfectious syndromes.
• Long COVID and ME/CFS appear to have similar underlying pathophysiology.

DISCUSSION

Deeks moderated a question-and-answer session between workshop participants and the panelists.

Given that the pandemic had a huge impact on everyone’s mental health, how do we distinguish between mental health issues that are potentially related to Long COVID and general mental health issues?

“We will never have a nonpandemic exposed control group,” said Troyer, which makes it very difficult to measure and disentangle mental health issues that are related to COVID-19 infection. There is an increased prevalence of a lot of different mental health conditions, she said, but specific conditions are being observed in Long COVID patients, including cognitive dysfunction and fatigue. While idiopathic psychiatric conditions can also cause dysfunction and fatigue, the mechanisms are likely different for Long COVID patients. Interestingly, she continued, there is evidence that standard treatments for mental health conditions, such as selective serotonin reuptake inhibitors (SSRIs), may affect COVID-19 infection and severity. This creates a possibility for a better understanding of how standard psychiatric treatments affect other body systems, and how COVID-19 treatments (e.g., anti-inflammatory agents) may affect psychiatric outcomes. This relationship, said Troyer, may start to “break down some of the barriers between psychiatric and medical illness.”

What are the differences and similarities between Long COVID and POTS? Are POTS treatments working in Long COVID patients?

The traditional presentation of POTS, said Novak, is a young female who develops orthostatic intolerance and tachycardia palpitation after an infection, usually a viral infection. There are a lot of similarities between Long COVID and POTS; for example, the decrease in orthostatic blood flow velocity is similar in patients, although the mechanisms may be different. Reduced orthostatic cerebral blood flow velocity can result in cerebral hypoperfusion that can be linked to brain fog and fatigue. Immunomodulatory treatments used for some patients with POTS may be effective for Long COVID, such as intravenous immunoglobulin and steroids. Novak said that diagnosing these syndromes can be challenging, and that it typically requires finding a correlation between objective evidence and the symptoms that the patient reports.

What is the potential relationship, if any, between post-ICU syndrome and Long COVID?

Prior to COVID-19, patients who were in the ICU with acute respiratory distress syndrome experienced functional impairment after their ICU stay that seemed to be driven by neuromuscular and psychiatric impairments, rather than pulmonary complications, said Parker. Patients who have been in the ICU have high rates of anxiety, depression, posttraumatic stress disorder (PTSD), and cognitive impairment, she said, and decline in physical function is extremely common. Parker said that half of ICU patients have not returned to work 1 year after their stay in the ICU. Even if the specific effects of the SARS-CoV-2 virus could be isolated, Parker said we could anticipate that COVID-19 would further exacerbate recovery from critical illness. For example, patients in the ICU during the pandemic may not have access to early rehabilitation or may not be able to have visitors because of infection and prevention control measures. These differences could further impair physical and cognitive recovery, as well as exacerbate anxiety, depression, and PTSD symptoms. “The truth is, we don’t know” how post-ICU syndrome and Long COVID may be related, said Parker, and it will take rigorous prospective cohort studies to tease out the relationship.

What diagnostic tests are used in the clinic to help diagnose Long COVID, and to what extent are these tests able to assess patient functioning or predict their functioning in the future?

What is important to keep in mind, said Parker, is that many patients with Long COVID are not able to do the things they need and want to do on a regular basis. Identifying the functional impairment and considering potential contributors are first and foremost. For some patients, she said the issue could be neuromuscular weakness, for others it could be pulmonary issues, and others may have symptoms that are related to ME/CFS. While CT scans, echocardiograms, or other such tools are important for investigating dysfunction, more weight placed on the findings of tests that measure function (e.g., pulmonary function tests) is needed. She noted that radiological improvement and functional improvement may not always go hand in hand. The starting point for assessment, she said, should be the patient’s functional impairment, rather than the results of clinical tests.

Komaroff identified some of the functional tests used in the assessment of Long COVID patients, including the 10-minute NASA Lean Test (Lee et al., 2020), which demonstrates similarly abnormal orthostatic function in patients with ME/CFS and Long COVID. The most important kind of tests, he said, are those that assess the stamina of people both physically and cognitively on repetitive challenges, because this deficit is commonly seen in people with ME/CFS and Long COVID.

In terms of using tests to predict longer-term outcomes, said Novak, we can possibly extrapolate from other conditions. For example, if someone has postviral small fiber neuropathy, it will likely take longer than 6 months to recover.

Why do females seem to be disproportionately affected by Long COVID?

Females are disproportionately affected by many autoimmune disorders, said Komaroff, and, with animal models for autoimmune diseases, if you give the males female hormones, they become more affected by these disorders. He said that there is “no doubt” in his mind that this difference is caused by hormones, but the mechanism by which sex hormones affect the expression of autoimmunity is unclear. Komaroff shared his hypothesis that female hormones increase the production and levels of autoantibodies, which explains some of the pathology. Troyer said there are also sex disparities in psychiatric disorders, with depression and anxiety more common in women, and autism and schizophrenia more common in men. One hypothesis is that it is related to inflammation, because there are hormone receptors for most of the inflammatory cytokines. Nath observed that there are multiple mechanisms by which symptoms and conditions can be affected, and the important thing is to figure out the underlying phenomenon and target that.

How do race and ethnicity factor into the risk for, and treatment of, Long COVID?

There is no doubt, said Nath, that African Americans and Hispanics have an increased risk of acquiring COVID-19 because of socioeconomic factors related to neighborhood or occupation, for example. In health care, the search for a genetic basis for patient differences is important, but so is an understanding of socioeconomic factors. Troyer said that issues of access are critical as well. For example, if a Long COVID patient needs to document her condition for the purposes of an SSA disability application, she may need to visit specialists for repeated testing over time. Accessing this care may be more difficult for low-income people or people of certain racial and ethnic groups. When determining whether and how to incorporate Long COVID into SSA disability programs, it is critical that disparities are not exacerbated, said Troyer.

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