Week 8: Long COVID and post-COVID conditions
Follow-up
In our Wednesday class, we wondered of they were still looking at waste water for COVID instructions. Student Martha Garcia confirmed that they were and provided us with the link.
Long Covid or Post-Covid Conditions & the Brain
Some of us may be wondering when, if ever, we will truly have moved past COVID. It may be impossible to find a person who has either not had COVID or known someone who had COVID. Indeed, COVID-19 has impacted each of us, and all of us.
Video: From CDC, a great introduction to our lesson (13 minutes)
What is COVID-19?
COVID-19 (coronavirus disease 2019) is a disease caused by a virus named SARS- CoV-2. It can be very contagious and spread quickly. Over one million people in the United States have died from COVID-19. (Centers for Disease Prevention and Control, 2023, National Institutes of Health, 2024)
COVID-19 most often causes respiratory symptoms that can feel much like a cold, the flu, or pneumonia. COVID-19 may attack more than your lungs and respiratory system. Other parts of your body may also be affected by the disease. Most people with COVID- 19 have mild symptoms, but some people become severely ill.
Some people, including those with minor or no symptoms, will develop Post-COVID Conditions – also called “Long COVID.” (Centers for Disease Prevention and Control, 2023, Mayo Clinic, 2023, National Institutes of Health, 2024)
How does it spread?
COVID-19 spreads when an infected person breathes out droplets and very small particles that contain the virus. Other people can breathe in these droplets and particles, or these droplets and particles can land on their eyes, nose, or mouth. In some circumstances, these droplets may contaminate surfaces they touch. (Centers for Disease Prevention and Control, 2023, National Institutes of Health, 2024)
Anyone infected with COVID-19 can spread it, even if they do NOT have symptoms. (Centers for Disease Prevention and Control, 2023, Mayo Clinic, 2023, National Institutes of Health, 2024)
The risk of animals spreading the virus that causes COVID-19 to people is low. The virus can spread from people to animals during close contact. People with suspected or confirmed COVID-19 should avoid contact with animals (Centers for Disease Prevention and Control, 2023, National Institutes of Health, 2024)
What is Long COVID?
Many people recover fully within a few days or weeks of being infected with SARS-CoV- 2, the virus that causes COVID-19. But others have symptoms that linger for weeks, months, or even years after their initial diagnosis. Some people seem to recover from COVID-19 but then see their symptoms return, or they develop new symptoms within a few months. Even people who had no symptoms when they were infected can develop symptoms later. Either mild or severe COVID-19 can lead to long-lasting symptoms. (Centers for Disease Prevention and Control, 2023, Mayo Clinic, 2023. National Institutes of Health, 2024)
Some people who have been infected with the virus that causes COVID-19 can experience long-term effects from their infection, known as Long COVID or Post-COVID Conditions (PCC). Long COVID is broadly defined as signs, symptoms, and conditions that continue or develop after acute COVID-19 infection. This definition of Long COVID was developed by the Department of Health and Human Services (HHS) in collaboration with CDC and other partners. (National Institutes of Health, 2024)
Long COVID, long-haul COVID, post-COVID-19 conditions, chronic COVID, and post- acute sequelae of SARS-CoV-2 (PASC) are all names for the health problems that some people experience within a few months of a COVID-19 diagnosis. (Centers for Disease Prevention and Control, 2023, National Institutes of Health, 2024).
The term post-acute sequelae of SARS CoV-2 infection (PASC) is also used to refer to a subset of Long COVID. (Centers for Disease Prevention and Control, 2023).
How many people experience Long COVID?
Research suggests that between one month and one year after having COVID-19, 1 in 5 people ages 18 to 64 has at least one medical condition that might be due to COVID-19. Among people aged 65 and older, 1 in 4 has at least one medical condition that might be due to COVID-19. (Mayo Clinic, 2023).
Video: From PBS, more on Long COVID and the most common symptoms
What are the symptoms of Long COVID?
Most people with Long COVID experienced symptoms days after first learning they had COVID-19, but some people who later experienced Long COVID did not know when they got infected. (Centers for Disease Prevention and Control, 2023, National Institutes of Health, 2024)
There is no test that determines if your symptoms or condition is due to COVID-19. Long COVID is not one illness. Your healthcare provider considers a diagnosis of Long COVID based on your health history, including if you had a diagnosis of COVID-19 either by a positive test or by symptoms or exposure, as well as based on a health examination. (Centers for Disease Prevention and Control, 2023, Mayo Clinic, 2023, National Institutes of Health, 2024)
Symptoms of Long COVID may be the same or different than symptoms of COVID-19, and some symptoms are similiar to those of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Long COVID can also trigger other health conditions, such as diabetes or kidney disease (Centers for Disease Prevention and Control, 2023, National Institutes of Health, 2024, Mayo Clinic, 2023, National Institutes of Health, 2024).
People with Long COVID can have a wide range of symptoms that can last weeks, months, or even years after infection. Sometimes the symptoms can even go away and come back again. For some people, Long COVID can last weeks, months, or years after COVID-19 illness and can sometimes result in disability.
Long COVID may not affect everyone the same way. People with Long COVID may experience health problems from different types and combinations of symptoms that may emerge, persist, resolve, and reemerge over different lengths of time. Though most patients’ symptoms slowly improve with time, speaking with your healthcare provider about the symptoms you are experiencing after having COVID-19 could help determine if you might have Long COVID. (Centers for Disease Prevention and Control, 2023, Mayo Clinic, 2023, National Institutes of Health, 2024)
People who experience Long COVID most commonly report: (Centers for Disease Prevention and Control, 2023, Mayo Clinic, 2023, National Institutes of Health, 2024)
• Fatigue
• Symptoms that get worse after physical or mental effort
• Fever
• Lung (respiratory) symptoms, including difficulty breathing or shortness of breath and cough
Respiratory, circulatory, and heart symptoms
• Difficulty breathing or shortness of breath
• Cough
• Chest pain
• Heart symptoms or conditions, including chest pain and fast or pounding heartbeat
• Blood clots and blood vessel (vascular) issues, including a blood clot that travels to the lungs from deep veins in the legs and blocks blood flow to the lungs (pulmonary embolism)
Neurological symptoms
• Difficulty thinking or concentrating (sometimes referred to as “brain fog”)
• Headache
• Sleep problems
• Dizziness when you stand up (lightheadedness)
• Pins-and-needles feelings
• Change in smell or taste
• Depression or anxiety
Digestive symptoms
• Diarrhea
• Stomach pain
Other symptoms
• Joint or muscle pain
• Rash
• Changes in menstrual cycles
Are some symptoms hard to explain and manage?
Yes. People with Long COVID may develop or continue to have symptoms that are hard to explain and manage. Clinical evaluations and results of routine blood tests, chest X- rays, and electrocardiograms may be normal.
The symptoms are similar to those reported by people with myalgic encephalomyelitis/chronic fatigue syndrome, and other poorly understood chronic illnesses that may occur after other infections. People with these unexplained symptoms may be misunderstood by their healthcare providers, which can result in a delay in diagnosis and receiving the appropriate care or treatment. (Centers for Disease Prevention and Control, 2023, Mayo Clinic, 2023, National Institutes of Health, 2024)
Interactive Graphic: https://covid19.nih.gov/covid-19-topics/long-covid
Are some people more likely to develop Long COVID?
Yes. It seems that some people may be more at risk of developing Long COVID.
Studies are ongoing to understand which people or groups of people are more likely to have Long COVID, and why. Studies have shown that some groups of people may be affected more by Long COVID. (Centers for Disease Prevention and Control, 2023, Mayo Clinic, 2023, National Institutes of Health, 2024)
These are examples and not a comprehensive list of people or groups who might be more at risk than other groups for developing Long COVID:
• People who have experienced more severe COVID-19 illness, especially those who were hospitalized or needed intensive care.
• People who had underlying health conditions prior to COVID-19. These may include diabetes, asthma, autoimmune diseases, and obesity.
• People who experience multisystem inflammatory syndrome (MIS) during or after COVID-19 illness.
Other factors that may be important include:
• Female gender
• Older age
• Immune response to initial infection
• The SARS-CoV-2 variant that caused the initial infection
In March 2023, a study of 800,000 people published in Health Affairs added another possible predictor: People with Long COVID were, on average, more likely to be older and female. (Katell, 2023)
Post-COVID-19 syndrome also appears to be more common in adults than in children and teens. However, anyone who gets COVID-19 can have long-term effects, including people with no symptoms or mild illness with COVID-19. (Mayo Clinic, 2023)
Health inequities may contribute to risk of Long COVID. Some people are at increased risk of getting sick from COVID-19 because of where they live or work, or because they can’t get health care. Some people from racial or ethnic minority groups and some people with disabilities seem to be at greater risk of developing Long COVID. (Mayo Clinic, 2023)
Below is research which may help predict who is most likely to get Long COVID
What causes Long COVID?
Scientists don’t know for sure what causes Long COVID, but research is providing some clues. (Centers for Disease Prevention and Control, 2023, Mayo Clinic, 2023)
• SARS-CoV-2 particles may become active again, causing symptoms to reappear.
• Overactive immune cells may release high levels of inflammatory substances that can injure organs and tissues.
• The infection may cause the immune system to start making autoantibodies that attack a person’s own organs and tissues.
Potential causes of Long COVID
https://www.the-scientist.com/long-covid-likely-doesn-t-have-just-one-cause-70559
Why does COVID-19 cause ongoing health problems?
Organ damage could play a role. People who had severe illness with COVID-19 might experience organ damage affecting the heart, kidneys, skin and brain. Inflammation and problems with the immune system can also happen. It isn't clear how long these effects might last. The effects also could lead to the development of new conditions, such as diabetes or a heart or nervous system condition. (Mayo Clinic, 2023)
The experience of having severe COVID-19 might be another factor. People with severe symptoms of COVID-19 often need to be treated in a hospital intensive care unit. This can result in extreme weakness and post-traumatic stress disorder, a mental health condition triggered by a terrifying event. (Centers for Disease Prevention and Control, 2023)
What are the results of current studies of Long Covid?
A Swedish led study involving 113 COVID patients and 39 health controls, found that after 6 months, 40 patients had developed Long COVID. Blood samples from those 40 patients revealed a group of proteins showing that a part of the immune system continued to be on high alert after the COVID virus. Without COVID in the body, this part of the immune system began to damage healthy cells. Tissue damage and microclots found in the blood could reduce levels of oxygen and nutrients available to a variety of organs, and lead to symptoms of Long COVID. These symptoms may include issues with memory, brain fog, and fatigue. (Cervia-Hasler, et. al., 2024)
COVID (SARS-CoV-2 )damage to the immune system (A) and adaptive immune system (B). Infection might increase accumulation of cytokine storms and hyperactivation of inflammasome. Apart from lymphopenia, the critical factor for poor prognosis in patients with severe COVID-19. Part of the acquired immune system damage, patients with severe COVID-19 are also accompanied by acute function exhaustion of T cells.
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1130398/full
Akiko Iwasaki, Ph.D. a Yale School of Medicine immunobiologist, is director of the Yale Center of Infection & Immunity and leads multiple studies investigating the pathobiology of Long COVID. Iwasaki says research has shown that Long COVID is not a single disease. (Katella, 2023)
She also proposes 4 hypotheses that could explain Long COVID's initiation and progression:
• After a person has COVID, a persistent virus or remnants of it cause chronic inflammation and ongoing symptoms.
• The body’s disease-fighting B and T cells trigger an immune response—and subsequent inflammation—in a process called autoimmunity. The stimulus that triggers this occurs continuously in the body, making it difficult to pinpoint and shut down.
• Latent (or dormant) viruses inside an individual reactivate. (Every person carries multiple viruses that are dormant. Under certain circumstances, they can be reactivated.)
• Chronic changes occur in the body after the acute inflammatory response (COVID infection). Inflammation in one tissue can damage other tissues.
“Our research thus far has shown hints of all of these,” Iwasaki says. “It’s also possible that these things can happen in sequence. You may start with a persistent virus that then leads to the reactivation of latent viruses, leading to inflammation. It's also possible that some people have only one of these things going on while others have all of them.” (Katella, 2023)
In a collaboration between the University of Pennsylvania’s departments of Microbiology, Pathology and Laboratory Medicine, and Physical Medicine and Rehabilitations’ Post COVID Assessment and Recovery Clinic, researchers evaluated the effects of Long COVID in blood and stool samples from various human clinical studies and small animal models. (Penn Medicine, 2023)
Researchers determined that a subset of patients with Long Covid had traces of the SARS-CoV-2 virus in their stool samples even months after acute COVID-19 infection. This seemed to suggest that parts of the virus remain in the gut of some patients long after infection. The lingering virus triggers the immune system to release proteins that fight the virus. This causes inflammation that reduces the absorption of an amino acid, tryptophan, in the gastrointestinal (GI) tract. Tryptophan is a building block for many neurotransmitters, including serotonin. You may recall that serotonin, important for regulating memory, sleep, digestion, healing, and other functions, is primarily produced in the GI tract. Serotonin is also an important regulator of the vagus nerve, which mediates communication between the body and the brain.
Persistent inflammation in the GI tract can deplete serotonin, leading to disrupted vagus nerve signals to and from the brain, and thus leading to many Long COVID symptoms, such as memory loss. (Penn Medicine, 2023).
Indeed, several studies have found that depleted levels of serotonin are associated with Long COVID symptoms. (Wong, et. al., 2023)
A study published in Brain, Behavior, and Immunity concluded that COVID-19 and especially Long COVID are associated with severe central nervous system (CNS) symptoms and may place persons at risk to develop long-term cognitive impairments. Results provide evidence that the SARS-CoV-2 can cross the blood-brain barrier (BBB) and induce neuroinflammation, a major mechanism underpinning CNS and cognitive impairments, even in the absence of productive infection. (Erickson, 2023)
What should you do if you have Long COVID symptoms?
If you're having symptoms of post-COVID-19 syndrome, talk to your health care provider. To prepare for your appointment, write down:
• When your symptoms started
• What makes your symptoms worse
• How often you experience symptoms
• How your symptoms affect your activities
Your health care provider might do lab tests, such as a complete blood count or liver function test. You might have other tests or procedures, such as chest X-rays, based on your symptoms. The information you provide and any test results will help your health care provider come up with a treatment plan. (Mayo Clinic, 2023)
Resources for those with Long COVID or their loved ones
Visiting your physician for assistance
before-appointment.pdfImage: Prepare for your visit to discuss Long COVID
https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/post-covid-appointment/index.html
Post-COVID-Symptoms-Log.pdfKeep a log of your symptoms
https://www.cdph.ca.gov/Programs/OPA/Pages/Communications-Toolkits/long-covid.aspx
Do you or someone you know have Long COVID?
Helping someone with Long COVID.pdfPost-covid-resources.pdfBrain Fog with Long COVID
Video: Effects of COVID on the brain. Includes research by Dr. Akiko Iwasaki mentioned earlier in the lesson.
Resources on Long COVID and the Brain:
From Everyday medicine: More information on brain fog and Long COVID
From EurekAlert: COVID-19 infections increase risk of long-term brain problems
From University of Minnesota: Possible mechanism behind brain fog in Long COVID
From Washington University: What we know so far about Long COVID (February 2024)
Research mentioned in Frontier: Can Exercise benefit brain fog and Long COVID?
Biomarkers to help identify Long COVID? Here is the latest in research, but more is needed.
Long COVID is considered a disability. Here is more on the HHS site.
Summary
COVID-19, and particularly Long COVID, require additional studies to bring greater clarity to causes and effective treatments. Research suggests that between one month and one year after having COVID-19, 1 in 5 people ages 18 to 64 has at least one medical condition that might be due to COVID-19. Among people age 65 and older, 1 in 4 has at least one medical condition that might be due to COVID-19. There are many symptoms of Long COVID, including brain fog, memory loss, respiratory and heart impacts, neurological and digestive challenges, and more. If you feel that you may be experiencing Long COVID, keep track of your symptoms and reach out to a trusted health care professional.
References
Centers for Disease Prevention and Control (2023). About COVID 19. Downloaded February 19, 2024 from https://www.cdc.gov/coronavirus/2019-ncov/your- health/about-covid-19.html
Cervia-Hasler, C., Bruninggk, S. C., Hoch, T., Fan, B., Muzio, G., Thompson, R. C., Ceglarek, L., Meledin, R., Westerman, P., Boyman, O. et al. (2024). Persistent complement dysregulation with signs thromboinflammation in active Long Covid. Science, 383(6680).
Erickson, M. A., Logsdon, A. F., Rhea, E. M., Hansen, K. M., Holden, S. J., Banks, W.
A., Smith, J. L., German, C., Farr, S. A., Morley, J. E., Weaver, R. R., Hirsch, A. J., Kovac, A., Kontsekova, E., Baumann, K. K., Omer, M. A., Raber, J. (2023). Blood brain barrier penetration of non-replicating SARS-CoV-2 and S1 variants of concern induce neuroinflammation which is accentuated in a mouse model of Alzheimer’s disease. Brain, Behavior, and Immunity, 109, 251-268.
Katella, K. (2023). What happens when you still have Long COVID symptoms? Yale Medicine, Family Medicine. Downloaded February 19, 2024 from https://www.yalemedicine.org/news/long-covid-symptoms
Mayo Clinic (2023). COVID-19: Long term effects. Downloaded February 19, 2024 from https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus- long-term-effects/art-20490351
National Institutes of Health (2024). Long COVID. National Institutes of Health, COVID- 19 Research. Downloaded February 19, 2024 from https://covid19.nih.gov/covid-19- topics/long-covid
Penn Medicine (2023). Viral persistence and serotonin reduction can cause Long COVID symptoms, Penn Medicine Research finds. Downloaded February 19, 2024 from https://www.pennmedicine.org/news/news-releases/2023/october/penn-study- finds-serotonin-reduction-causes-long-covid-symptoms
Wong, A. C., Devason, A. S., Umana, I. C., Cherry, S., Thaiss, C. A., Levy, M., et. al. (2023). Serotonin reduction in post-acute sequelae of viral infection. Cell, 186(22). Downloaded February 20, 2024 from https://www.cell.com/cell/fulltext/S0092-