Long-Term Effects of COVID-19: What We Know

The past few years have been a very interesting time in the world. The appearance of the SARS-CoV-2 (COVID-19) virus in Wuhan, China, in December 2019 marked the beginning of a huge transition in the world. We use many terms to describe frequent and geographically widespread diseases, but pandemic is one term that has been used to describe a continuously spreading disease since the mid-1600s.

A modern pandemic

Throughout history, we’ve seen many pandemics—cholera, yellow fever, tuberculosis, polio, smallpox, measles, plague, and influenza. COVID-19 has killed almost 7 million people as of July 2023. An estimated 700,000 people in the United States have COVID-19 symptoms that have persisted beyond three weeks. Because of the newness of COVID-19, most of the information and guidelines for treatment of long-term COVID-19 is by expert consensus, which means that healthcare professionals have looked at the evidence and come to an agreement on how to approach the condition because studies aren’t available at this time. So what do we know about the long-term effects of COVID-19?

How do we define long COVID-19?

The National Institute for Health and Care Excellence (NICE) working document proposes definitions based on the effects of COVID-19 at different time points. Acute COVID-19 includes symptoms for the first 4 weeks. Ongoing symptomatic COVID-19 (subacute) infection included people with signs and symptoms from 4 to 12 weeks not explained by another diagnosis. Post-COVID-19 syndrome (long-COVID-19) is for signs and symptoms that are present or develop and continue for >12 weeks and are not explained by an alternative diagnosis. Some of the studies reviewed define post-acute COVID-19 as symptoms extending beyond 3 weeks and chronic COVID-19 as extending beyond 12 weeks. Current estimates are that about 10% of patients have post-acute COVID-19, and a smaller percentage of patients will have long-term effects from COVID-19.

Who gets long COVID-19?

People who had more severe diseases or who required hospitalization or intensive care are at high risk of developing long COVID-19. Women and older people are also more likely to develop long COVID-19. Patients who develop long COVID-19 are more likely to have chronic conditions such as kidney disease, heart disease, lung disease, fibromyalgia, or asthma. Other common comorbidities include depression, anxiety, and asthma. COPD, benign prostatic hyperplasia, fibromyalgia, erectile dysfunction, migraines, multiple sclerosis, and celiac disease also increase your risk for developing long COVID-19.

Patients who were incompletely vaccinated or unvaccinated for COVID-19 are more likely to develop long COVID-19. Lifestyle factors also play a role. Obesity and smoking also increase the risk of developing long COVID-19. Some studies have shown that socioeconomic status also can play a role and socioeconomically deprived people are more likely to develop long COVID-19 symptoms.

A 2021 meta-analysis of 41 studies worldwide showed that up to 43% of people who contract COVID-19 may go on to develop long COVID-19 symptoms. Other studies have placed that number at 10-20%. Whether we look at the higher or lower percentages suggested by the studies, the number of people affected by this disabling disease is potentially in the tens of millions.

What causes long COVID-19

Scientists aren’t completely sure what causes long COVID-19, but there are many proposed causes. Some of the proposed theories for the process include the SARS-CoV-2 virus hiding in the tissues, dysfunction of the immune system, reactivation of other diseases including Epstein-Barr virus (mono) or the human herpesvirus 6, activation of autoimmune diseases, molecular mimicry, small amounts of blood clotting, and dysfunctional signaling of the nervous system.

Researchers are evaluating changes in the immune system related to COVID-19. Some studies have suggested that there are high levels of autoantibodies in people with long COVID-19 symptoms, but other studies have not shown this relationship. Damage to the organs can be related to long COVID-19 symptoms. COVID is mostly a respiratory illness, but it has been shown to have large inflammatory responses, which can contribute to problems in many systems in the body.

Symptoms of long COVID-19

The symptoms of long COVID-19 are as varied as the symptoms associated with the acute form of the illness. The most common symptoms are fatigue which can be severe enough to interfere with daily life, neurologic symptoms such as difficulty concentrating, cognitive impairments, and memory deficits, psychiatric symptoms such as anxiety or depression, cough, dyspnea, decreased exercise tolerance, and problems with taste and smell.

Many people will develop diarrhea or stomach pain. Joint pain, rashes, and changes in the menstrual cycle are also possible. Autonomic dysfunction such as postural orthostatic tachycardia syndrome (POTS) is also common with long COVID-19. One study showed that in patients who would recover within the first 90 days, the symptoms usually peaked during the second week. In patients who went on to have long COVID-19, the symptoms peaked at two months.

Evaluating COVID-19 symptoms

If you are concerned that you may have long COVID-19, you may wonder how your doctor can tell. The first thing your doctor will do is take a complete history and physical. The diagnosis of long COVID-19 can be made based on a prior diagnosis of COVID-19 but doesn’t require a positive COVID-19 PCR or antigen test. This is because some people may have decreased access to testing or may not have had symptoms. The symptoms associated with long COVID-19 are varied and non-specific which means that there are lots of diseases that can cause these symptoms.

These other diseases and diagnoses should be considered when evaluating for long COVID-19. COVID-19 can exacerbate other conditions or unmask preexisting health conditions. The history and physical should also include an evaluation for other conditions that could increase the likelihood of long-term complications from COVID-19. Some of these conditions include asthma, chronic fatigue syndrome, chronic kidney disease, diabetes, cardiac or pulmonary conditions, mood disorders and trauma.

The symptoms associated with long COVID-19 can vary. They fluctuate and can come and go. The severity of the symptoms may not be consistent with your physical exam and lab findings. More than 85% of patients who have symptoms of long COVID-19 will experience relapses, which can be triggered by activity, stress, or exercise.

Basic laboratory testing to evaluate for other conditions is a possible next step. Complete blood counts, comprehensive metabolic panel, inflammatory markers such as c-reactive protein and erythrocyte sedimentation rate, iron studies, thyroid studies, vitamin D, and vitamin B12 may be a reasonable initial panel. Further laboratory studies should be guided by history and physical exam. A chest x-ray may be necessary if you have respiratory symptoms. You may also benefit from lung function testing or other respiratory evaluation. If you have heart symptoms may need to be evaluated by cardiology with electrocardiogram (EKG), ultrasound of your heart, stress testing, or additional labs. Evaluation for POTS involves orthostatic vital signs or a tilt table test. If you have signs of cognitive impairment, you may benefit from neuropsychiatric testing or other formal cognitive evaluation.

Treatment of long COVID-19

Treatment of long COVID-19 is mostly symptomatic. It is a balancing act between treating the symptoms and avoiding giving multiple medications that can cause side effects. If you have autonomic dysfunction such as POTs, you may receive fluids, electrolytes, compression socks as well as reconditioning and trigger avoidance. If you have cognitive challenges, you may benefit from sleep hygiene, medication discontinuation, or returning to activities in a slow-paced manner. If you have respiratory symptoms, you may benefit from a special type of physical therapy called pulmonary rehab, breathing exercises, or medications. Chronic fatigue symptoms may benefit from energy conservation, paced return to activity, and healthy diet and improved hydration. Sometimes stimulant medications are used for fatigue, but the use of these medications is not fully supported by studies.

The CDC recommends setting achievable goals for COVID-19 through shared decision-making. It’s important to know that long COVID-19 is not well understood, and there is no consensus regarding how to support and treat this condition. Regular follow-up and reassessment are important.

Long COVID-19 is a complex and poorly understood process. The symptoms of the disease can be debilitating. Your symptoms may be far more severe than the testing indicates, which can be very frustrating. It is easy to feel like your symptoms are being dismissed because of the lack of consensus on treatment. Long COVID-19 syndrome is now considered a disability by the Americans with Disabilities Act. Research into this complex process is ongoing and hopefully will yield more information as time progresses.

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Dr. Foglesong Stabile is a board-certified Family Physician who enjoys full scope Family Medicine, including obstetrics, women’s health, and endoscopy, as well as caring for children and adults of all ages. She also teaches the family medicine clerkship for Pacific Northwest University of Health Sciences.

References:

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https://www.nature.com/articles/s41579-022-00846-2