COVID-19 and Long-Term Effects

Anadolu Medical Center Pulmonology Specialist Assoc. Dr. Tayfun Çalışkan provided important information about how COVID-19 infection affects our bodies, particularly the lungs. In our article, you can also find information about the long-term effects of COVID-19, which refers to symptoms that can persist for a long time after the disease has passed.

Eighty-one percent of COVID-19 infections are mild (mild pneumonia or non-pneumonic cases), 14% experience low oxygen levels, shortness of breath, and more than 50% lung involvement on imaging, while 5% exhibit critical illness symptoms such as respiratory failure and multiple organ failure.

In a meta-analysis of 4,598 patients diagnosed with COVID-19, it was found that lung involvement was detected in 94.5% of cases upon evaluation of lung tomography. In a study involving 30 million COVID-19 patients, it was noted that 40% of patients showed no symptoms. Patients with radiological evidence of lung involvement may also be asymptomatic. For example, in a study involving 24 patients diagnosed with COVID-19 who showed no symptoms, lung tomography revealed 50% ground-glass opacities and 20% atypical findings for COVID-19. However, a few days later, five of these patients developed fever and typical COVID-19 symptoms. Even if patients show lung involvement at the time of diagnosis, symptoms can emerge within an average of four days (ranging from 3 to 7 days).

As previously mentioned, approximately 80% of COVID-19 patients experience mild disease. In a study conducted by the U.S. Centers for Disease Control and Prevention evaluating 1.3 million COVID-19 patients, it was found that 14% of patients were hospitalized, and 2% required intensive care. It was reported that 5% of patients lost their lives. Critical illness appears in about 5% of cases, while no deaths have been observed in mild or advanced disease cases.

Who is at Risk?

Risk factors for critical illness due to COVID-19 vary based on age, underlying health conditions, and vaccination status. COVID-19 vaccines significantly prevent the development of critical illness. Age is an important risk factor for developing critical illness. Looking at hospital admissions, the rate is 1% for those aged 20-29, 4% for those aged 50-59, and rises to 18% for those over 80.

Mortality rates also increase with age. While the overall COVID-19 case fatality rate is 2.3%, it is 8% for those aged 70-79 and 15% for those over 80. Underlying health conditions that could be risk factors for critical illness include asthma, cancer, cerebrovascular diseases, kidney failure, chronic lung diseases, liver diseases, diabetes, congenital diseases (those unable to perform daily tasks or with developmental delays), heart disease, AIDS, psychogenic disorders (such as depression and schizophrenia), Alzheimer’s, obesity, physical inactivity (sedentary lifestyle), pregnancy, immune system disorders, smoking, organ transplant recipients, tuberculosis, and patients using cortisone or other immunosuppressive medications.

What to Do if Lung Involvement Occurs?

In cases of lung involvement, patients may experience fever, cough, shortness of breath, and bilateral involvement on lung imaging. There is no symptom that can distinctly differentiate COVID-19 from other infections. However, shortness of breath that occurs about a week after the onset of symptoms may suggest COVID-19.

For patients with mild to moderate COVID-19 with a risk of disease progression (due to advanced age, underlying health conditions, or vaccination status), specific treatments are recommended. However, in patients without risk factors, no special treatment is recommended even if symptoms are present. Additionally, no special treatment is suggested for patients who have no symptoms or complaints. There are medications available in our country for this purpose.

For outpatients, inhaled corticosteroids and oral corticosteroids are not recommended. Antibiotic use is not recommended unless COVID-19 diagnosis is unclear, or if there is a new fever and evidence of a newly formed infection on lung imaging.

Patients who were on anticoagulant therapy for their underlying health conditions prior to COVID-19 infection should continue this therapy during the infection. However, for COVID-19 diagnosed and treated outpatients, routine anticoagulant therapy is not recommended. Only patients receiving inpatient care are recommended to have preventive anticoagulant therapy. Furthermore, for patients with detected obstructions in lung or leg veins, therapeutic doses of anticoagulant treatment are administered.

Outpatients are advised to drink plenty of water and primarily use paracetamol (PAROL) for fever and muscle/headaches. If inadequate, the use of non-steroidal anti-inflammatory drugs (NSAIDs) is recommended. It is known that patients with the Omicron variant experience COVID-19 infection more mildly compared to previous variants.

How Effective is the COVID-19 Vaccine?

It is recommended to wait at least 3 months after recovering from a COVID-19 infection before vaccination. Vaccines are effective against the Omicron variant as well. Although their effectiveness has slightly decreased over time compared to other variants, vaccinated individuals experience fewer hospitalizations and deaths compared to those who are unvaccinated. In a study, individuals who received three doses of the mRNA vaccine had a 94% reduction in emergency department visits and hospitalizations for the Delta variant, and an 82% reduction in emergency visits and a 90% reduction in hospitalizations for the Omicron variant. Although the vaccine's effectiveness appears to have slightly decreased compared to previous variants, it remains quite effective compared to unvaccinated patients.

What are the Long-Term Effects in Individuals Who Have Had COVID-19?

Acute COVID-19 diagnosis encompasses the period up to 4 weeks after the onset of the patient's symptoms. Therefore, in the normal course of COVID-19, a patient’s complaints can persist for up to 4 weeks. The definition of “Post-Acute Sequelae of SARS-CoV-2 infection” (PASC), commonly referred to as "Long COVID," describes the situation where symptoms continue for 3 months or longer after the onset of the disease.

Preventing Long COVID is dependent on COVID-19 preventive measures (vaccination, mask-wearing, social distancing, hand hygiene). Vaccination, in particular, significantly reduces the development of Long COVID. In a study involving 2,560 patients with mild COVID-19, Long COVID was found in 42% of the unvaccinated, 30% of those with one dose of vaccine, 17% of those with two doses, and 16% of those with three doses. It appears that the incidence of Long COVID is also related to the number of vaccination doses.

The symptoms that can persist for a long time, according to their frequency, include:

• Fatigue (13-87%)
• Shortness of breath (10-71%)
• Chest pain (12-44%)
• Cough (17-34%)

These are the four most common symptoms. Other less frequently observed symptoms include loss of smell, joint pain, headache, dryness of the eyes and mouth, loss of taste, rhinitis, loss of appetite, dizziness, muscle pain, insomnia, hoarseness, hair loss, sweating, decreased libido, and diarrhea. Additionally, symptoms such as memory loss, concentration difficulties, decreased quality of life, anxiety, depression, and post-traumatic stress disorder may also be observed.

Does the Vaccine Reduce the Long-Term Effects of COVID-19?

In a study involving 97,000 vaccinated patients, persistent symptoms after COVID-19 infection were found to be less common with the Omicron variant (4.5%) compared to the Delta variant (10.8%).

Symptoms tend to disappear within approximately 2 weeks for those who have mild acute illness, while those with more severe illness may experience symptoms lasting 2-3 months or longer. Furthermore, symptoms persist longer in patients who were hospitalized, older patients, those with underlying health conditions, patients who developed secondary bacterial infections after COVID-19, patients diagnosed with vascular occlusion, and those who were in the hospital or intensive care for extended periods.

How Long Do Long-Term Effects Last?

Some symptoms tend to resolve more quickly (2-4 weeks, such as fever, chills, and symptoms of smell/taste), while others may persist for months (2-12 months, such as fatigue, shortness of breath, muscle pain, and cognitive impairments). Routine follow-up is not recommended for patients who have mild to moderate COVID-19, are being treated as outpatients, and do not have persistent or new symptoms. However, for patients requiring hospitalization, follow-up should be scheduled within one week after discharge, but no later than 2-3 weeks later. Remote video examination methods can also be utilized for this purpose.

Patients with symptoms lasting longer than 3 months are advised to consult a center experienced in COVID-19.

What should be done in treatment?

Routine laboratory test monitoring is not recommended for patients with mild COVID-19 infection. For patients who experience more severe illness and have abnormalities in laboratory tests at the time of diagnosis, who require hospitalization for treatment, or who have unexplained persistent symptoms, tests such as complete blood count, electrolytes, urea, creatinine, liver function tests, and albumin may be requested. Additionally, in cases of heart failure or myocarditis, BNP and troponin tests may be necessary. For patients with unexplained persistent or newly emerging shortness of breath, D-dimer may be requested. Thyroid tests may be indicated for those with unexplained fatigue. Creatine kinase tests can be used for fatigue and muscle pain.

Routine monitoring of coagulation parameters (fibrinogen, INR, D-dimer) and inflammatory markers (sedimentation, CRP, ferritin, IL-6) is not recommended. It is also not advised to repeat PCR testing after a COVID-19 infection.

In patients without lung imaging during the illness and who have no cardiopulmonary complaints afterward, lung imaging is not recommended. For patients with abnormal lung imaging during the illness, lung imaging is necessary, considering their current symptoms. Additionally, patients with newly emerging or worsening symptoms will require lung imaging. Generally, a chest X-ray is sufficient for imaging. However, for patients suspected of having other diseases during their illness (such as cancer, widespread lung involvement - ARDS -, interstitial lung disease, etc.), a lung CT may be necessary.

When do the lungs heal?

In cases of mild lung involvement, it may take 2-4 weeks for the lungs to return to normal, although this period can sometimes extend to 12 weeks. In cases of severe involvement, recovery may take up to one year. Therefore, it is advisable to perform imaging 12 weeks later to determine whether the lungs have returned to normal. If lesions in the chest X-ray are still present at the 12th week, further evaluation with a lung CT is recommended. If symptoms worsen or new symptoms emerge, imaging may be needed earlier.

In patients with COVID-19 that presents with widespread lung involvement known as ARDS, it is still uncertain how frequently lung CT should be performed (e.g., at 3, 6, 12, 24 months). Even with a normal chest X-ray, patients with unexplained cardiopulmonary symptoms and low fingertip oxygen saturation should be considered for pulmonary angiographic CT to evaluate for pulmonary vascular occlusion.

For patients whose symptoms have resolved or decreased, routine respiratory function tests are not recommended. However, respiratory function tests (spirometry, diffusion capacity, lung volumes) may be necessary for patients with persistent or worsening symptoms or those with new symptoms.

In patients with widespread involvement like ARDS, if respiratory function test abnormalities are found, monitoring can be done primarily with a 6-month respiratory function test, followed by annual tests for 5 years.

For patients with mild shortness of breath who do not require oxygen, breathing exercises are recommended. Two different methods can be applied.

The first method involves sitting upright or slightly reclining, with neck and shoulder muscles relaxed. While keeping the mouth closed, the patient should inhale through the nose for 2 seconds as if smelling flowers, then exhale through pursed lips for 4 seconds as if blowing out a candle. This cycle should be repeated for 2 minutes and can be done multiple times throughout the day.

The second method involves lying down with pillows under the head and knees. One hand should be placed on the chest and the other on the abdomen. The patient should slowly inhale through the nose, allowing the hand on the abdomen to rise higher than the hand on the chest, then slowly exhale through the nose, allowing the hand on the abdomen to lower below the one on the chest. This cycle can be repeated for 2-5 minutes and done multiple times during the day.

In patients with moderate to severe shortness of breath and persistent low oxygen levels (SpO2 ≤ 92%), oxygen support should be evaluated, and corticosteroids should be considered for selected patients (such as those with organized pneumonia).

What should be done for persistent cough complaints?

For cough in prolonged COVID, the approach should be similar to that for coughs associated with other viral infections. First, the patient should be evaluated for other conditions such as asthma, reflux, and allergic rhinitis. If no underlying condition is found, supportive treatment is recommended. Cough suppressants can be used if necessary. While inhaler treatments (bronchodilators or corticosteroids) may be beneficial for some patients, they are not commonly used. Opioids are used very sparingly due to their potential side effects. They may be considered, especially in patients with cough that significantly affects quality of life or leads to sleep disturbances.

What to Do About Chest Pain?

The disappearance of chest pain and the feeling of pressure in the chest can take a long time. If it does not affect the patient's quality of life, treatment is generally not recommended. If it does affect quality of life, NSAID painkillers may be used in patients without renal failure. If the feeling of pressure in the chest is due to bronchospasm, inhaler bronchodilators may be used.

How is Blood Clotting Treated?

In COVID-19 patients, an increase in coagulation factors is often detected during acute illness. Especially in severe cases, clotting may be found in the legs or lungs. Patients with detected clotting are treated similarly to those with clotting unrelated to COVID-19. However, if the patient is treated as an inpatient and has no detected clotting, it is recommended to discontinue anticoagulant therapy upon discharge, even if they have been receiving anticoagulant treatment

What to Do in Case of Persistent Shortness of Breath?

In prolonged COVID, 12 weeks after onset, in patients with shortness of breath and low oxygen saturation, the presence of fibrosis in the lungs should be considered in those where radiological tests and pulmonary function tests show low results. Antifibrotic drugs are used in idiopathic pulmonary fibrosis. These drugs have been considered in COVID-19-related fibrosis. Studies indicate that antifibrotic medications may lead to greater improvement in lung function and radiological fibrosis compared to other treatment interventions (such as corticosteroids and pulmonary rehabilitation). The World Health Organization currently has no specific recommendations regarding antifibrotic medications. While it is thought that the use of antifibrotic drugs may be appropriate in suitable patients, it is suggested that the results of ongoing advanced studies should be monitored for conclusive outcomes.