Understanding Long COVID: Symptoms, Causes, and Risk Factors

Berlin – Around 10 to 15 percent of individuals infected with SARS-CoV-2 experience symptoms of Long COVID, according to a review by researchers at the Department of Epidemiology and Health Monitoring at the Robert Koch Institute (RKI). For the majority, these symptoms resolve within a year. The RKI provides an overview of the consequences for population health and the care system in a recent narrative review.

Defining Long COVID: A Temporal Classification

The World Health Organization (WHO) and the US National Academies of Sciences, Engineering, and Medicine (NASEM) have proposed a temporal classification of long-term health consequences following a SARS-CoV-2 infection:WHO definition

• Acute SARS-CoV-2 infection: Up to four weeks
• Long COVID: Complaints and symptoms after four weeks
• Post-COVID-19: Complaints and symptoms after 12 weeks

The WHO notes that this case definition is provisional and subject to adaptation as new research emerges.

What Causes Long COVID?

The underlying causes and mechanisms of Long COVID remain unclear. Several hypotheses are being investigated:

• Virus persistence: The SARS-CoV-2 virus may remain in the body, even after the acute infection subsides, leading to ongoing health problems.
• Viral reactivation: SARS-CoV-2 infection may reactivate latent viruses, such as the Epstein-Barr virus.
• Immune dysregulation: The virus may trigger immunological processes that mistakenly target the body’s own cells and tissues, causing chronic inflammation and endothelial dysfunction.
• Gut microbiome changes: Alterations in the intestinal flora may contribute to the development of Long COVID.

Common Long COVID Symptoms

Long COVID encompasses a variety of potential long-term health consequences affecting different organ systems, either individually or in combination. Symptoms are often non-specific and can vary greatly in their clinical presentation, and progression.

Commonly reported symptoms include:

• Severe exhaustion/tiredness (fatigue)
• Cognitive limitations such as concentration and memory problems (“brain fog”)
• Persistent respiratory symptoms such as shortness of breath and persistent cough
• Changes in smell and taste
• Hair loss
• Palpitations
• Chest pain
• Muscle or joint pain
• Stomach and intestinal problems

Post-exertional malaise (PEM), a pronounced worsening of symptoms after even mild physical or psychological stress that can last for days or weeks, is also frequently reported and considered a core outcome of Long COVID. PubMed

Other Potential Symptom Complexes

Epidemiological and clinical observation studies have linked previous SARS-CoV-2 infection to other potential symptom complexes, including:

• Postural Tachycardia Syndrome (POTS)
• Organ damage (e.g., chronic lung damage)
• Worsening of underlying diseases
• Increased incidence of new diseases, such as neurodegenerative diseases (dementia), metabolic diseases (diabetes), cardiovascular diseases, autoimmune diseases, and gastrointestinal disorders.

Data from German health insurance evaluations indicate that adults diagnosed with COVID-19 are more likely to receive new health diagnoses at least three months post-infection compared to uninfected individuals.

Risk Factors for Long COVID

Both the severity of an acute COVID-19 illness and the risk of developing Long COVID are influenced by pre-existing health conditions. An increased risk has been reported for conditions such as asthma, chronic obstructive pulmonary disease (COPD), and cardiovascular diseases. Lifestyle factors, including smoking and physical inactivity, may also increase risk.

Sociodemographic factors also play a role. Women appear to have a higher risk of Long COVID symptoms than men, with reported differences in symptom type, severity, and duration. Gender-specific differences in the immune system and autoimmune reactions are being investigated. Individuals living in areas with greater socioeconomic deprivation may also be at increased risk, although data on this is limited.

Existing social inequalities in pre-existing illnesses, lifestyle factors, and vaccination status likely contribute to disparities in Long COVID outcomes.