Since the outbreak of the COVID-19 pandemic in late 2019, it has had a huge impact on health, society and economy around the world. As the virus continues to spread, we realize that the impact of COVID-19 infection goes far beyond the acute phase. Some patients still suffer from persistent symptoms weeks or even months after infection, a condition known as "Long COVID" or "Post-acute sequelae of COVID-19" (PASC).
At present, there are still many uncertainties about the definition, diagnosis and treatment of long COVID. The World Health Organization (WHO), the Centers for Disease Control and Prevention (CDC), etc. are trying to develop relevant clinical definitions and guidelines. In addition, the continuous mutation of SARS-CoV-2 virus has an impact on the occurrence and severity of long COVID. These variant viruses have changed the transmission pattern of the epidemic and may also affect the clinical manifestations of long COVID.
Recently, a research team from the Faculty of Medicine of Macau University of Science and Technology, China, published a review paper entitled "Long COVID Across SARS-CoV-2 Variants: Clinical Features, Pathogenesis and Future Directions" in the journal MedComm - Future Medicine. The article explores in depth the impact of different variants of SARS-CoV-2 on Long COVID or PASC. It also discusses the impact of vaccination and reinfection on long COVID, and how these factors increase the complexity of studying and managing long COVID.
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Different SARS-CoV-2 variants can lead to different incidences of long COVID
The SARS-CoV-2 virus has the ability to mutate rapidly, allowing it to continuously evolve new variants. As the virus spreads, multiple variants gradually formed, such as Alpha, Beta, Delta, Omicron, etc. These variant viruses differ in transmissibility, pathogenicity, and immune evasion capabilities. Different SARS-CoV-2 variants may lead to different incidence rates of long COVID. For example, Omicron variants may be associated with milder long COVID symptoms, especially in vaccinated people. This may be because the Omicron variant, although more transmissible, causes relatively less severe disease. Research shows that vaccination can significantly reduce the risk of developing long COVID after infection. In addition, vaccination may also reduce the severity of long COVID. However, the constant mutation of the virus also poses challenges to the effectiveness of vaccines.
Different SARS-CoV-2 variants can cause different symptoms of long COVID
The symptoms of long COVID vary from person to person. Studies have found that these symptoms may be related to the SARS-CoV-2 variants that are infected, and this difference is related to the characteristics of the virus itself and the body's immune response to different variants. For example, some studies have shown that patients infected with the Delta variant are more likely to experience severe symptoms, including persistent dyspnea and fatigue. Although the Omicron variant is highly transmissible, the risk of developing long COVID after infection may be lower, and the symptoms are relatively mild. This is related to the ability of the Omicron variant to escape immunity in some aspects, which makes the symptoms after infection different. It is worth noting that the symptoms of long COVID are not limited to the respiratory system, but may also involve multiple organ systems such as the nervous system and cardiovascular system. Some patients may experience cognitive dysfunction, such as "brain fog", while others may experience heart problems or persistent loss of taste and smell.
Figure 1. Incidence and overall symptomatology affected by long COVID. (Lok L S C, et al., 2024)
Pathogenesis of long COVID
The pathogenesis of long COVID-19 is complex and involves multiple biological pathways. Scientists have proposed several possible mechanisms to explain why some COVID-19 patients continue to experience symptoms after acute infection.
1) Dysregulation of the immune system
The immune system's response plays an important role in the pathogenesis of long COVID-19. Some patients may experience a persistent immune activation state after SARS-CoV-2 virus infection, leading to chronic inflammation. This inflammation may involve a variety of immune cells and molecules, such as cytokines and chemokines, which play a key role in regulating the body's response to infection.
2) Persistence of the virus
In some cases, the SARS-CoV-2 virus persists in the patient's body, even after the symptoms of acute infection have subsided. This continued presence of the virus can trigger or maintain the activation of the immune system, leading to the persistence of long COVID symptoms.
3) Reactivation of latent viruses
Long COVID is also associated with the reactivation of latent viruses. For example, other viruses such as Epstein-Barr virus (EBV) may be reactivated after SARS-CoV-2 infection, which can exacerbate immune system disorders and lead to long COVID symptoms.
4) Autoimmune response
An autoimmune response is when the body's immune system mistakenly attacks its own tissues. In long COVID, this response can lead to a variety of symptoms, including fatigue, muscle pain, and neurological problems. The production of autoantibodies is a characteristic of long COVID, and these antibodies may target the body's own cells and tissues.
5) Vascular and microvascular damage
The SARS-CoV-2 virus can cause damage to vascular endothelial cells, leading to obstructed blood flow and thrombosis. This vascular damage can persist in patients with long COVID, causing difficulty breathing, fatigue, and other symptoms.
Figure 2. Mechanisms of long COVID pathogenesis. (Lok L S C, et al., 2024)
Diagnosis, treatment and prevention of long COVID
The diagnosis and treatment of long COVID are major challenges facing the current medical community. Currently, the diagnosis of long COVID mainly relies on the evaluation of clinical symptoms, but there is a lack of specific biomarkers. Researchers are exploring a variety of possible biomarkers, such as inflammatory markers in the blood, autoantibodies or molecules related to viral infection, in the hope of finding indicators that can accurately diagnose long COVID. In addition, imaging tests, such as MRI and CT scans, are also used to evaluate patients for ongoing organ damage. The treatment of long COVID is currently mainly symptomatic treatment, including the use of drugs to relieve specific symptoms, such as the use of anti-inflammatory drugs to treat persistent inflammatory reactions, or the use of antiviral drugs to inhibit the persistence of the virus. In addition, physical therapy and rehabilitation exercises are used to help patients regain strength and function.
The most effective way to prevent long COVID is to prevent COVID-19 infection. This includes getting vaccinated, wearing a mask, social distancing and good personal hygiene. Vaccination has been shown to significantly reduce the risk of developing long COVID after infection, so all eligible people are encouraged to get vaccinated. In conclusion, although the current understanding of long COVID is still limited, existing studies have provided important information on its clinical manifestations, underlying mechanisms, and influencing factors. The development of effective diagnostic tools and treatments, as well as the assessment of the long-term impact of vaccination on the risk of long COVID, are important research directions in the future.
Reference
Lok L S C, et al. Long COVID across SARS‐CoV‐2 variants: Clinical features, pathogenesis, and future directions. MedComm–Future Medicine, 2024, 3(4): e70004.