While past studies have found that women are more frequently affected by long COVID than men, the new study published today in the Annals of Clinical and Translational Neurology showed for the first time that women report more neurologic symptoms of long COVID and experience worse impacts on quality of life and cognitive function than men. 

“We were surprised to see such a significant difference between female and male patients,” said Igor Koralnik, MD, chief of neuroinfectious disease and global neurology at Northwestern Medicine. “Both in the frequency of neurologic long COVID symptoms and in levels of self-reported fatigue, as well as in a cognitive task of attention.”

Study highlights

• The study looked at the first consecutive 2,329 patients who have been seen at the Northwestern Medicine Neuro COVID-19 Clinic.
• Approximately 2/3 of patients were women.
• Women more frequently reported neurologic symptoms such as brain fog, dizziness, headache, numbness and tingling and pain.
• No neurologic symptoms were more common in men.
• Women also reported more non-neurologic symptoms, such as fatigue, shortness of breath, chest pain, dysautonomia and gastrointestinal issues.
• Women also reported worse alteration of their quality of life caused by fatigue than men on standardized questionnaires.
• Women scored lower than men in a task of attention on objective cognitive tests.

“We think that the reason women are more frequently and severely affected by long COVID than men is because long COVID is an autoimmune disease, and women are more prone to autoimmune diseases than men, including multiple sclerosis and rheumatoid arthritis,” Dr. Koralnik said. “We and others have found evidence of immune dysregulation and autoimmunity in patients with long COVID. We next want to understand the underlying causes for the neurologic symptoms of long COVID and identify and validate biological markers that show how active the disease is. We hope our study will alert providers about the importance of timely diagnosis and targeted interventions in female patients, who are often negatively affected by gender bias in medicine.

“A Household Pulse Survey conducted by the National Center for Health Statistics estimated that nearly 18 percent of U.S. adults had experienced long COVID and that five percent were experiencing it as of September 2024. It is safe to estimate that long COVID still affects millions of adults in the United States currently,” said Dr. Koralnik. 

To date, the Neuro COVID-19 Clinic has treated more than 3,300 patients with long COVID from 44 states. While severe cases of COVID-19 requiring hospitalization have become rare, Dr. Koralnik says COVID-19 continues to occur and the risk of developing long COVID increases with repeat occurrences of COVID-19.

Northwestern Memorial Hospital is ranked No. 6 in the nation for neurology and neurosurgery by U.S. News & World Report, 2025-2026. For more information, visit nm.org and to schedule an appointment with the Neuro COVID-19 Clinic, call 312.695.7950.

CHICAGO – February 18, 2025 – How much can the eyes reveal about a person? A first-of-its-kind study from Northwestern Medicine and published in the Journal of Imaging is giving experts an idea how long COVID affects the body by looking through the eyes. The research could help doctors diagnose and track how the condition impacts people over time and provide insight into the cause of long COVID.

In the study, researchers used advanced imaging techniques to examine the retinas of non-hospitalized long COVID patients from the Northwestern Medicine Neuro COVID-19 Clinic and found that patients with long COVID experienced a significant reduction in the density of blood vessels in the back of the eye, compared to healthy individuals.

“This finding bridges gaps between ophthalmology, neurology, and COVID-19, helping us better understand how inflammation affects different organs in the body,” said Manjot K. Gill, MD, senior author of the study and ophthalmology lead of the Northwestern Medicine Comprehensive COVID-19 Center. “The change in blood vessels in the deep part of the retina supports the hypothesis that long COVID affects similar blood vessels in other parts of the body, like the brain, which can potentially contribute to the symptoms of long COVID such as memory loss, brain fog and fatigue.”

In patients with long COVID, researchers found that the most significant change was a decrease in blood flow in the smallest blood vessels in the deeper layers of the retina. Researchers believe this decrease in circulation may be reflective of decreased blood circulation in the brain, which may lead to neurologic symptoms.

“In oculomics – the field of study that examines the relationship between eye health and systemic diseases – we are understanding the power of the retina as a biomarker for disease, identifying early signs of diabetes, cardiovascular disease, and neurodegenerative disorders. It’s exciting to see how long COVID could fit into this framework,” said Dr. Gill. “Retinal imaging allows us to see the blood vessels that we cannot readily image elsewhere, so in this context, the eyes really are the ‘window to the soul.’”

Building on these findings, researchers are launching a longitudinal study that will examine how the changes in the deep retinal blood vessels relate to patient symptoms and other established markers of long COVID. They hope to determine if retinal imaging could be used as a tool to diagnose, manage and predict the progression of long COVID over time, as well as identify its cause.  

“Even though the immediate threat of the COVID-19 pandemic has decreased, approximately one-third of COVID-19 survivors experience lingering effects. This issue affects an estimated 17 million adults in the U.S. and comes with significant healthcare and economic burdens, costing about $600 million in lost wages,” said Igor Koralnik, MD, chief of neuroinfectious diseases and global neurology at Northwestern Medicine, who oversees the Neuro COVID-19 Clinic and is the co-director of the Northwestern Medicine Comprehensive COVID-19 Center. “There are currently no specific treatments for long COVID, and this research helps to advance our understanding of the condition. By studying the effects of COVID-19 on the body, we can improve diagnosis, management, and support for those affected.”

To date, the Neuro COVID-19 Clinic has cared for nearly 3,000 long-haulers from 44 states. For more information, visit nm.org and to schedule an appointment, please call 312.695.7950.

CHICAGO – Jan. 7, 2025 – COVID-19 vaccinations have protected people from severe complications, hospitalizations and death, but their impact on long COVID has been unknown.

According to new research published in Brain Communications, Northwestern Medicine researchers found that vaccination prior to COVID-19 infection did not significantly affect neurological symptoms in long COVID patients, both in patients who had a severe infection that required hospitalization and those with a mild infection who did not require hospitalization. Common neurological symptoms of long COVID include brain fog, numbness and tingling, headache, dizziness, problems with smell and taste and intense fatigue.

“Since COVID-19 vaccines reduce the severity of the infections, we hypothesized that vaccines may also affect the neurological manifestations of subsequent long COVID,” said Igor Koralnik, MD, chief of neuroinfectious diseases and global neurology at Northwestern Medicine, who oversees the Neuro COVID-19 Clinic and is the co-director of the Northwestern Medicine Comprehensive COVID-19 Center. “We aimed to identify what effects – if any – vaccination prior to infection has on neurological symptoms of long COVID, as well as the quality of life and cognitive function of our patients. These findings are sobering since it shows that vaccination prior to infection does not reduce the neurological manifestations of long COVID.”

STUDY HIGHLIGHTS

·       The study included the first 1,300 patients at the Northwestern Medicine Neuro COVID-19 Clinic with neurologic long COVID symptoms between May 2020 and March 2023.

·       Among those patients, 200 had been previously hospitalized for severe COVID-19, while the rest had mild initial COVID symptoms and never required hospitalization.

·       The study is a first-of-its-kind at Northwestern Medicine looking at whether vaccination prior to infection affects neurological symptoms of long COVID.

·       The study used quantitative metrics to assess quality of life and found patients had impaired quality of life in cognitive, fatigue, sleep, anxiety and depression with no differences between the breakthrough infection and pre-vaccination groups.

·       The study assessed cognitive function and found that patients performed worse on a range of cognitive tests compared to the general population with no difference between the patients who had a breakthrough infection after vaccination and those who were infected before being vaccinated.

“Long COVID is a debilitating condition that can affect multiple organ systems and can have considerable impact on an individual’s daily function and quality of life,” Dr. Koralnik said. “Because vaccination prior to infection does not decrease the neurological manifestations of long COVID, it is critical to keep our communities safe from both acute COVID-19 infection and potential long-term neurological manifestations.”

To date, the Neuro COVID-19 Clinic has treated more than 2,800 long-haulers from 44 states. For more information, visit nm.org and to schedule an appointment, please call 312.695.7950.

To read the full study, click here.

CHICAGO – Nov. 22, 2024 – Since older adults have been more severely affected by acute COVID-19, researchers have hypothesized that older adults may have worse long COVID symptoms as well. But according to new research published in the Annals of Neurology, an official journal of the American Neurological Association, Northwestern Medicine researchers found on an average of 10 months after COVID-19 onset, younger (ages 18-44) and middle-aged (ages 45-64) adults had worse neurologic symptoms of long COVID than adults 65 and older. Symptoms included headache, numbness and tingling, problems with smell and taste, blurred vision, depression, anxiety, insomnia, fatigue and a decrease in cognitive function. These symptoms occurred regardless of if the patient had mild or severe COVID-19 infections.

“While deaths from COVID-19 continue to decrease, people still get repetitive infections with the virus and may develop long COVID along the way,” said Igor Koralnik, MD, chief of neuroinfectious diseases and global neurology at Northwestern Medicine, who oversees the Neuro COVID-19 Clinic and is the co-director of the Northwestern Medicine Comprehensive COVID-19 Center. “Long COVID is causing an alteration in patients’ quality of life. Despite vaccinations and boosters, about 30 percent of COVID patients develop some long COVID symptoms. These findings have an immense public health impact, given that long COVID significantly contributes to the leading global burden of disability and disease caused by the neurological disorders.”

STUDY HIGHLIGHTS

·       The study included the first 1,300 patients at the Northwestern Medicine Neuro COVID-19 Clinic with neurologic long COVID symptoms between May 2020 and March 2023.

·       Among those patients, 200 had been previously hospitalized for severe COVID-19 pneumonia while the rest had mild initial COVID-19 symptoms and never required hospitalization.

·       The study is a first-of-its-kind to look at the neurologic symptoms of long COVID over an adult lifespan.

·       The goal was to determine if the neurologic symptoms of long COVID affect adults differently based on their age group.

 “The impact of long COVID is causing disproportionate morbidity and disability in younger adults in their prime who provide much of the workforce, productivity and innovation in our society,” Dr. Koralnik said. “This may have a negative impact on the economy and cause additional burden on the health care system. This study highlights the importance that people of all ages suffering from Long COVID should be provided with the necessary treatment and rehabilitation services to alleviate their symptoms and improve their quality of life.”

To date, the Neuro COVID-19 Clinic has treated more than 2800 long-haulers from 44 states. For more information, visit nm.org and to schedule an appointment, please call 312.695.7950.

CHICAGO – November 15, 2024 – Can lessons from the COVID-19 pandemic help treat cancer? A new study led by researchers at the Northwestern Medicine Canning Thoracic Institute and published in the Journal of Clinical Investigation has revealed a connection between COVID-19 infection and cancer regression. The team’s discovery could pave the way for novel cancer treatments.

In an unexpected twist, researchers observed that the RNA from the SARS-CoV-2 virus – responsible for COVID-19 – triggered the development of a unique type of immune cell with anti-cancer properties. These cells, dubbed “inducible nonclassical monocytes (I-NCMs),” were found to attack cancer cells and could potentially be harnessed to treat cancers that are resistant to current therapies. These findings possibly explain the mechanism behind the reported regression of certain cancers following COVID-19 infection.

“This discovery opens up a new avenue for cancer treatment,” said Ankit Bharat, MD, chief of thoracic surgery and director of the Canning Thoracic Institute. “We found that the same cells activated by severe COVID-19 could be induced with a drug to fight cancer, and we specifically saw a response with melanoma, lung, breast and colon cancer in the study. While this is still in the early stages and the effectiveness was only studied in preclinical animal models, it offers hope that we might be able to use this approach to benefit patients with advanced cancers that have not responded to other treatments.”

The study, conducted using both human tissues and animal models, found that these unique immune cells could be pharmacologically stimulated using small molecules, potentially creating a new therapeutic option for cancer patients. This discovery could have significant implications, particularly for patients with aggressive or advanced cancers who have exhausted traditional treatment options such as immunotherapies.

How the Body’s Response to COVID-19 Could Help Fight Cancer
The researchers discovered that during COVID-19, a special subset of immune cells can be stimulated in the body. This process begins when the RNA from the virus activates certain signals in the immune system. These signals cause the transformation of common monocytes – an ordinary type of white blood cell – into I-NCMs. These newly formed cells have the ability to move into both the blood vessels and the surrounding tissue where tumors grow, something most other immune cells can’t do.

“What makes these cells so special is their dual capability,” said Dr. Bharat, who is also professor of surgery at Northwestern University Feinberg School of Medicine. “Typically, immune cells called non-classical monocytes patrol blood vessels, looking for threats. But they can't enter the tumor site itself due to the lack of specific receptors. In contrast, the I-NCMs created during severe COVID-19 retain a unique receptor called CCR2, allowing them to travel beyond blood vessels and infiltrate the tumor environment. Once there, they release certain chemicals to recruit body’s natural killer cells. These killer cells then swarm the tumor and start attacking the cancer cells directly, helping to shrink the tumor.”

What’s Next?
While this research is promising, Dr. Bharat cautions that more work is needed before this approach can be used in clinical settings.

“We are in the early stages, but the potential to transform cancer treatment is there. Our next steps will involve clinical trials to see if we can safely and effectively use these findings to help cancer patients,” added Dr. Bharat.

The team hopes that, with further research, they can develop therapies that specifically target these cells to treat cancers that are currently difficult to manage. This could lead to new treatment options for patients who have exhausted all other possibilities.

The research could potentially play an important role with the Canning Thoracic Institute’s Double Lung Replacement and Multidisciplinary Care (DREAM) Program, a first-of-its-kind clinical initiative at Northwestern Medicine that provides double-lung transplants to select patients with advanced lung cancers who are not responding to conventional treatments. To date, more than 40 patients have received double-lung transplants through the DREAM Program.

“While the program has been highly successful, we do anticipate that some patients might have recurrence. Since we’re using monocytes with our research, we could potentially treat DREAM patients without risking rejection of their new lungs,” said Dr. Bharat.

The research was funded by the National Institutes of Health (NIH), Canning Thoracic Institute, and conducted by a team of scientists from Feinberg School of Medicine and clinicians at Northwestern Memorial Hospital. For more information about Northwestern Medicine, visit nm.org. 

CHICAGO – October 4, 2024 – Long COVID occurs in approximately a third of COVID-19 survivors, with the CDC estimating 1 in 13 adults in the United States have long COVID symptoms such as brain fog, shortness of breath and chest pain. In a new study published in Nature Immunology, pulmonologists at the Northwestern Medicine Comprehensive COVID-19 Center (CCC) noticed that many patients referred to the CCC for long COVID symptoms had persistently abnormal CT scans of their lungs. Some patients would recover, while others would remain with scar tissue. They called this respiratory post-acute sequelae of COVID-19 (PASC) with radiographic abnormalities (RPRA). In collaboration with Brigham and Women’s Hospital, The Ohio State University and Duke University, Northwestern Medicine researchers combined state-of-the-art gene expression technology and CT scan analysis to determine which cells and molecules were responsible for radiographic abnormalities in long COVID patients, which could help inform future treatment options.

“Our understanding of long COVID is still in its early stages and there are no FDA-approved or even widely agreed-upon treatments for long COVID,” said Marc Sala, MD, co-director of the Northwestern Medicine Comprehensive COVID-19 Center and a pulmonary and critical care specialist with the Northwestern Medicine Canning Thoracic Institute. “The underlying cells and molecules that contribute to radiographic abnormalities in long COVID patients are now better established, and equally important, it appears to be the same biological processes responsible for other types of lung injury that result in pulmonary fibrosis. This common denominator explanation may help not only in developing treatments for long COVID as it continues to evolve in the future, but also contributes to our understanding of pulmonary fibrosis due to other conditions.”

The team evaluated 35 patients who had long COVID at the CCC between November 2020 and May 2022. These patients had respiratory symptoms such as cough and shortness of breath, but also had abnormal lung tissue on their CT scans. Researchers focused on this group to better understand what was causing some cases of radiographic abnormalities to worsen or improve. 

AMONG THE PATIENTS TESTED

-        Median age was 62 (range from 32 to 83)

-        43% were female

-        66% were white, 17% were Black and 20% were Hispanic

-        All patients had respiratory symptoms on presentation with shortness of breath being the most common symptom (97%) followed by cough (69%)

-        Nine patients had never been hospitalized; and of the 26 who had been hospitalized, 17 were admitted to the intensive care unit

-        Two patients ultimately required lung transplantation after their COVID diagnosis

-        43% of patients required oxygen therapy, including the two patients who required lung transplantation

Researchers compared patients within this cohort whose lungs improved on subsequent imaging to patients who did not improve. In additional analyses, data were compared between RPRA and previous studies involving patients who required lung transplantation after COVID, healthy control specimens, and samples from patients who had idiopathic pulmonary fibrosis.

KEY FINDINGS

1.     CT scans done an average of 145 days after COVID infection were analyzed and showed 39% pulmonary fibrosis and 22% inflammatory changes in the 35 patients tested.

2.     Samples from lung fluid on a subset of these patients an average of 5.3 months (but up to 1.5 years after COVID infection), showed high levels of pro-inflammatory molecules leading to ongoing immune cell migration into their lungs.

3.     There was a persistent migration of white blood cells (including neutrophils and monocytes) into the lungs of people with radiographic abnormalities that was correlated with the severity of CT scan changes. In particular, monocyte-derived alveolar macrophages (MoAM) have been found in both mice and humans to be involved in the progression to pulmonary fibrosis.

4.     The MoAMs did not appear to switch to a “repair mode.” Patients with radiographic abnormalities that improved, worsened or remained the same all had similar-appearing MoAMs. This was supported by comparing their molecular characteristics to samples from patients who had end-stage pulmonary fibrosis from COVID and idiopathic pulmonary fibrosis.

“What surprised us the most was the ongoing influx of pro-inflammatory and pro-fibrotic immune cells from blood into lungs even one year after the COVID infection. Historically, we assume infection-related lung inflammation resolves by this point. The highly overlapping biological processes involving radiographic abnormalities and other non-COVID conditions that lead to fibrosis is an important finding,” said Dr. Sala.

NEXT STEPS

According to researchers, understanding the underlying drivers for protracted lung inflammation in radiographic abnormalities is an important step in addressing long COVID, which can involve nearly any organ system. Steroids were given to many patients in this cohort, but it remains to be determined whether this strategy is helpful in some patients more than others. The study serves as a step forward in understanding pulmonary fibrosis in general to aid investigations in the discovery of better medical treatments.

“The more invisible manifestations of long COVID, such as brain fog, shortness of breath, rapid heart rate and fatigue, may well involve similar prolonged inflammation and this study is an important step forward in supporting this idea,” said Dr. Sala. “The study also supports a broader point that understanding COVID and its ongoing impacts can serve to inform our understanding of other chronic respiratory illnesses that lead to pulmonary fibrosis.”

To date, the CCC has treated more than 4,000 patients since May 2020 with neurology, pulmonology and cardiology being the most commonly sought specialties. For more information on the CCC, visit nm.org and to schedule an appointment, please call 312.926.9900.

Chicago, IL – August 23, 2023 – Early in the COVID-19 pandemic, testing was limited, and many individuals couldn’t get a positive diagnosis during the window of viral shedding. This was especially important for COVID long-haulers, who were struggling with lingering symptoms such as brain fog, fatigue and cognitive impairment. Without a positive COVID-19 test, many were denied appointments at post-COVID clinics in the United States, but the Northwestern Medicine Neuro COVID-19 Clinic was an exception, evaluating new patients without a confirmed COVID-19 diagnosis.  

According to new research published in Neurology® Neuroimmunology & Neuroinflammation, an official journal of the American Academy of Neurology, Northwestern Medicine researchers show 41% of long-haulers who initially tested negative for COVID-19 had antibody or T cell responses indicating they were exposed to the virus. This new research performed with very sensitive immunologic assays suggests post-COVID clinics shouldn’t require a positive COVID-19 test in order to provide care to long-haulers.

“It’s estimated that nearly 10 million Americans experienced neurologic manifestations of long COVID without an official COVID-19 diagnosis due to limited access to COVID testing in the first year of the pandemic or testing outside the window of detection,” said Igor Koralnik, MD, chief of neuroinfectious diseases and global neurology at Northwestern Medicine, who oversees the Neuro COVID-19 Clinic and is co-director of the Northwestern Medicine Comprehensive COVID-19 Center. “Millions of people in the United States have been rejected by the medical establishment and stigmatized because they didn’t carry a definite diagnosis of COVID-19 when they presented with their long COVID symptoms. We hope those people feel vindicated by our study.”

STUDY HIGHLIGHTS

-        Researchers looked at 29 long-haulers who presented to the Neuro COVID-19 Clinic between June 2020 and April 2022 with a negative COVID-19 test.

-        The median age was 43 and 93% of patients identified as female.

-        Of the 29 tested, 41% had detectable antibody or T cell responses indicating they were exposed to the virus.

-        The patients had striking similarities to long-haulers with positive COVID-19 tests in clinical presentation, quality of life measures and objective cognitive testing.

“We tested two types of immunity, both antibody and T cell responses, against two different proteins from the virus that causes COVID-19. Patients’ responses were mixed rather than all or nothing, suggesting that a comprehensive evaluation is necessary and that immunologic tests are not a one-size-fits-all for confirming prior exposure to the virus,” said Dr. Koralnik. “Post-COVID clinics shouldn’t require a positive test to provide care for long-haulers after suspected COVID-19. More research is needed to determine what causes long COVID and how to effectively treat its many symptoms.”

To date, the Neuro COVID-19 Clinic has treated more than 2,100 long-haulers from 44 states. For more information, visit nm.org and to schedule an appointment, please call 312.695.7950.

CHICAGO – July 13, 2023 – Long COVID occurs in approximately a third of COVID survivors and is now the third leading neurologic disorder in the United States. In May 2020, during the height of the pandemic, Northwestern Medicine physicians noticed this growing trend and established one of the first Comprehensive COVID-19 Centers in the United States to treat patients suffering from lingering impacts of the virus such as brain fog, shortness of breath and chest pain. Three years later, a new study published in the American Journal of Medicine reports key findings from more than 1,800 patients who were evaluated during the first 21 months at the Northwestern Medicine Comprehensive COVID-19 Center (CCC) with neurology, pulmonology and cardiology being the most commonly accessed specialties and still in high-demand today.  

“The COVID-19 public health emergency may be over, but the need for long COVID care still remains. To date, we’ve treated nearly 4,000 patients from 44 states at the CCC, and our team of 42 clinicians continue to see approximately 100 patients each month,” said Igor Koralnik, MD, chief of neuroinfectious diseases and global neurology at Northwestern Medicine, who is co-director of the Comprehensive COVID-19 Center. “The disease burden of long COVID continues to grow in this country with significant implications for the economy and population health.”

“Due to widespread vaccination, rates of acute COVID infection have decreased significantly, however, millions of patients are still suffering from persistent symptoms that may have occurred years ago,” said Marc Sala, MD, pulmonary and critical care specialist at Northwestern Medicine, who is co-director of the Comprehensive COVID-19 Center. “To date, little is known about the characteristics and outcomes of patients seeking care at multidisciplinary post-COVID centers and the approach to caring for these patients widely varies among institutions and providers. This study will help us understand what the biological causes of those symptoms are and how to structure clinics to care for them.”

KEY FINDINGS

The team evaluated 1,802 patients (350 post-hospitalization and 1,452 non-hospitalized) via telehealth or in-person at the CCC between May 2020 and February 2022. Patients were seen in 2,361 initial visits in 12 specialty clinics including neurology, pulmonology, cardiology, otolaryngology, gastroenterology, infectious diseases, endocrinology, nephrology, hematology, dermatology, psychiatry and rheumatology. Patients most commonly sought treatment from neurology (49%), pulmonology (25%) and cardiology (12%) specialists.

Among patients tested:

-        85% of patients reported decreased quality of life

-        51% had cognitive impairment

-        45% had altered lung function

-        83% had abnormal CT chest scans

-        12% had elevated heart rate on rhythm monitoring

-        Frequency of cognitive impairment and pulmonary dysfunction was associated with severity of acute COVID-19

-        Non-hospitalized patients with positive COVID-19 testing had similar findings than those with negative or no test results

DEMOGRAPHICS

-        65% of patients identified as female

-        Average age at first clinic visit was 47 years old

-        72% were White, 10% were Black, 4% were Asian and 13% were Hispanic

“The population predominantly consisted of females in their forties, and our data shows that critically ill, hospitalized, and non-hospitalized patients have distinct neurologic, pulmonary and cardiac manifestations of long COVID, which should be studied and treated differently,” said Joseph Bailey, MD, pulmonary and critical care specialist at Northwestern Medicine, who treats patients in the CCC.

“One of the key findings of this study is that there is a very wide range of long COVID manifestations that depend largely on the severity of acute COVID-19 illness, and that they can’t be treated with a ‘one size fits all’ approach,” said Dr. Koralnik. “Some patients who had severe COVID-19 may have sustained permanent organ damage, while persistent symptoms in those with mild initial disease may be caused by different mechanisms. This requires an individualized, precision medicine approach to long COVID care.”

“There is a great need for multidisciplinary clinics to form the backbone of the response to long COVID. With multiple clinicians caring for and evaluating patients under the same roof, multidisciplinary long COVID clinics can recognize and respond to different presentations and manifestations of long COVID more quickly than other care models,” added Dr. Sala. “This study is the first to show the impact of a multidisciplinary effort and could be an example for use in future viral outbreaks.”

For more information on the CCC, visit nm.org and to schedule an appointment, please call 312.926.9900.

CHICAGO - April 19, 2023 - A new Northwestern Medicine study published in Annals of Neurology shows neurological symptoms, findings and patterns of cognitive dysfunction differ between long COVID patients who were hospitalized during their acute infection and those who didn’t require hospitalization. Researchers studied the first 600 long-haulers who were evaluated at the Northwestern Medicine Neuro COVID-19 Clinic and discovered those initially hospitalized for acute COVID-19 pneumonia showed a broad pattern of cognitive impairment and lack of insight into their cognitive dysfunction, while non-hospitalized long-haulers mainly had difficulties with attention tasks.

“We were surprised to find that even though both post-hospitalization and non-hospitalized long-haulers report brain fog, there were marked differences in their pattern of cognitive dysfunction, which suggests distinct causes and mechanisms of long COVID in these populations,” said Igor Koralnik, MD, chief of neuroinfectious diseases and global neurology at Northwestern Medicine, who oversees the Neuro COVID-19 Clinic and is co-director of the Northwestern Medicine Comprehensive COVID-19 Center.

Researchers focused this study on the first 600 patients (100 post-hospitalization, 500 non-hospitalized) who had a documented COVID-19 infection and came to the Neuro COVID-19 Clinic either in person or via telemedicine between May 2020 to August 2021. Patients reported an average of seven neurologic symptoms due to COVID-19, with 91% experiencing more than four neurological symptoms.

NEUROLOGIC SYMPTOMS

-        81% experienced brain fog

-        70% experienced headaches

-        56% lost their sense of smell

-        55% had an altered sense of taste

-        50% experienced dizziness

Hospitalized patients had more abnormal neurologic exams (62% vs 37%) and performed worse on processing speed, attention and working memory tasks. Non-hospitalized patients had lower results in attention tasks only.

NON-NEUROLOGIC SYMPTOMS

-        86% experienced fatigue

-        69% experienced depression/anxiety

-        57% had insomnia

-        48% experienced shortness of breath

-        34% self-reported variation of heart rate and blood pressure

-        30% experienced chest pain

-        27% had gastrointestinal symptoms such as nausea, vomiting or diarrhea

Of these symptoms, only shortness of breath and chest pain were significantly more frequent in the post-hospitalization group than non-hospitalized.

DEMOGRAPHICS AND COMORBIDITIES

Both groups demonstrated significant altered quality of life in domains of cognition, fatigue, sleep, anxiety and depression compared to the U.S. normative population, but have significant differences in demographics and comorbidities.

Of the 100 post-hospitalization patients

-        Average age was 54, 58% were female, 62% were White, 18% Black, 3% Asian, and 19% Hispanic

-        Post-hospitalization patients more frequently than non-hospitalized had hypertension (39% vs 15%), high cholesterol (22% vs 13%), type II diabetes (21% vs 4%), lung diseases (16% vs 4%) and cardiovascular diseases (10% vs 2%)

Of the 500 non-hospitalized patients

-        Average age was 45, 66% were female, 77% were White, 8% were Black, 4% were Asian and 12% were Hispanic   

-        Non-hospitalized patients were more likely than post-hospitalization patients to suffer from depression/anxiety prior to COVID-19 (40% vs 9%)

The demographic, comorbidities, clinical and cognitive differences highlighted in the study suggest distinct etiologies of long COVID in hospitalized and non-hospitalized patients, warranting targeted interventions.

“For patients previously hospitalized with COVID-19, it’s possible they suffered diffuse brain damage, which could have been caused by a combination of hypoxemia, cytokine storm, multi-organ failure, or encephalopathy which may not be visible on brain CT or MRI. This is consistent with the broad cognitive dysfunction harbored by these patients,” said Dr Koralnik. “Conversely, the female predominance of non-hospitalized patients suggests an autoimmune etiology of long COVID in this population, perhaps triggered by viral persistence. Indeed, women are more likely than men to develop autoimmune diseases.”

Of the 600 patients involved in the study, 43% were vaccinated and all but one patient became infected before vaccination. At the time of their clinic visit, patients felt approximately 60% recovered back to their pre-COVID baseline.

Northwestern Medicine researchers plan to continue studying long COVID over the adult lifespan, comparing patients 18-44 years old, 45-64 years old, and over 65 years old to determine if there are differences between those groups and if either group was more affected at a specific time of the pandemic by different circulating strains.

“Long COVID occurs in approximately a third of COVID-19 survivors and is now the third leading neurologic disorder in the United States. Long COVID has a significant detrimental effect in patients’ quality of life and has pushed an estimated one million people out of work in the U.S.,” said Dr. Koralnik. “Considering the large number of people impacted by long COVID and the continuing potential for infection leading to persistent and potentially disabling neurological symptoms, there should be a greater emphasis on funding research on the root causes of long COVID leading to clinical trials in the U.S.”

To date, the Neuro COVID-19 Clinic has treated nearly 2,000 long-haulers. For more information, visit nm.org and to schedule an appointment, please call 312.695.7950.

CHICAGO – A new study published in Annals of Clinical and Translational Neurology* looked at the evolution of neurologic symptoms in non-hospitalized COVID-19 long-haulers at the Northwestern Medicine Neuro COVID-19 Clinic and discovered most long-haulers continue to experience symptoms such as brain fog, numbness/tingling, headache, dizziness, blurred vision, tinnitus and fatigue on average of 15 months after disease onset. Researchers analyzed patients 6-9 months after their initial visit to the Neuro COVID-19 Clinic and discovered heart rate, blood pressure variation and gastrointestinal symptoms increased in long-haulers, while loss of taste and smell decreased overall. The findings are a follow-up to the Northwestern Medicine research team’s March 2021 study that discovered 85% of long-haulers experience four or more neurologic symptoms which impact their quality of life, and in some patients, their cognitive abilities.

“This new study is novel and reports the longest follow-up period of neurologic symptoms impacting non-hospitalized patients suffering from long-COVID anywhere in the world,” said Igor Koralnik, MD, chief of Neuro-infectious Diseases and Global Neurology at Northwestern Medicine, who oversees the Neuro COVID-19 Clinic. “We were surprised by the persistence of most of the debilitating neurologic symptoms of our patients, and by the late appearance of symptoms that suggest dysfunction of the autonomic nervous system.”

Researchers focused this study on patients evaluated initially between May and November 2020 who had mild initial COVID-19 symptoms (ex: transient cough, sore throat) and never required to be hospitalized for pneumonia or low oxygen levels. Of the 52 patients who completed the follow-up study:

- Average age was 43

- 73% were female

- 77% received the COVID-19 vaccine

- Most continued to experience neurologic symptoms, fatigue, and compromised quality of life 11-18 months after disease onset, an average of 15 months

Overall, there was no significant change in the frequency of most neurologic symptoms between first and follow-up appointments including brain fog (81 vs 71%), numbness/tingling (69 vs 65%), headache (67 vs 54%), dizziness (50 vs 54%), blurred vision (34 vs 44%), tinnitus (33 vs 42%) and fatigue (87 vs 81%).

While loss of taste (63 vs 27%) and smell (58 vs 21%) decreased overall, heart rate and blood pressure variation (35 vs 56%) and gastrointestinal symptoms (27 vs 48%) increased at follow-up.

Patients reported improvements in their recovery, cognitive function, and fatigue, but quality of life measures remained lower than the average population of the United States. Seventy-seven percent of the patients had been vaccinated for COVID-19, but the vaccine didn’t have a positive or detrimental impact on cognitive function or fatigue.

“Vaccination didn’t cure long COVID symptoms, but didn’t worsen them either, which is a reason given by some long-haulers for not getting vaccinated,” said Dr. Koralnik. “As new variants emerge and the number of patients impacted by long COVID rises, we’re now focusing our research on understanding the root cause of long COVID. We’re also devising interventions to improve the management of those patients and find the best treatment options for them.”

To date, the Northwestern Medicine Neuro COVID-19 Clinic has treated nearly 1,400 long-haulers from across the U.S. For more information, visit nm.org and to schedule an appointment, please call 312.695.7950.