Post-viral syndromes beyond Long COVID – Part 2

Post-viral syndromes beyond Long COVID – Part 2

Post-viral syndromes have been widely ignored in medical research in the past decades. The second blog of this series concentrates on what is known about the occurrence and pathology of the condition.

In this blog series we want to shed some light on post-viral syndromes, which have recently gotten a small boost in attention due to the emergence of Long COVID. Post-viral syndromes have been known for years, but since they are difficult to characterize and can include a wide range of symptoms, there is only limited knowledge on how to treat affected individuals.

Because of this symptom variety and since the condition can be caused by different viral infections, people with post-viral syndrome often do not get an appropriate treatment. Again and again, they are not taken seriously, and their physiological symptoms are being considered psychologically induced and misdiagnosed accordingly (e.g., as depression).

In the first blog, the most common symptoms of post-viral syndrome were discussed. This second blog will concentrate on the occurrence and some theories on the pathology of the condition. Finally, in an upcoming blog, we will focus on the diagnosis and management of post-viral syndromes.


How many suffer from lingering symptoms after a viral infection?

There is limited information on how common post-viral syndrome is and what happens to patients over time. This is mainly due to a lack of well-designed, long-term studies and issues like small sample sizes.

For years, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other post-viral syndromes have been largely ignored in medical research and remain not well-understood by many physicians. However, the focus on COVID-19 and its long-term effects could finally bring more attention and research funding to help understand post-viral syndromes.

While there have been challenges in studying post-viral symptoms, some clear patterns emerge for those who experience lingering symptoms. For example, studies looking at young people show that while up to 40% might have lasting symptoms a few weeks after getting infectious mononucleosis caused by the Epstein-Barr virus. This number drops to approximately 9% after a year and 4% after two years.

Similarly, while most people recover from COVID-19 within the first few months, 23% reported lingering symptoms after six months according to a Swiss study. In around 17% of people in this study, COVID-19-realted symptoms did not resolve after two years.

The SARS outbreak between 2002 and 2004 has also offered some clues about what long-term symptoms might be expected from COVID-19, as the viruses are similar. After recovering from SARS, people commonly reported long-term issues like fatigue, sleep problems as well as mental health concerns and cognitive problems such as memory impairment, depression, and anxiety. About 10–20% of people experienced these lingering symptoms, based on studies with a follow-up of up to 12 years.

Even common illnesses can lead to long-term problems

Long-lasting symptoms following COVID-19 have brought attention to the issue of lingering health problems after viral infections. Interestingly, the long-term symptoms after a mild or moderate course of COVID-19 are quite similar to chronic illnesses caused by other infections.

Common symptoms include extreme tiredness, trouble thinking, difficulty with senses like taste and smell, flu-like symptoms, restless sleep, muscle and joint pain and various other nonspecific symptoms. The similarities between different post-viral syndromes indicate shared underlying causes and researchers need to identify them to better treat and understand these lasting health challenges.

Two common herpesviruses, cytomegalovirus (CMV) and human herpesvirus-6 (HHV-6), are also suspected to be linked to lasting fatigue syndrome. These viruses stay in the body for life, and they can stay inactive throughout the whole lifetime of an infected individual without causing any symptoms.

However, they can also be reactivated, e.g., due to a weakened immune system, stress, illness, certain medications, or aging. Some researchers believe that when these viruses reactivate, they could harm the immune system and contribute to ME/CFS.

Another idea is that people with ME/CFS are more sensitive to these viral infections due to their weakened immune system. It is hard to say for sure if these viruses can cause ME/CFS since they are so common. It is estimated that 60-70% of people get infected with CMV throughout their lifespan and the estimate is even higher for HHV-6 with over 90%.


Theories behind lingering viral symptoms

The reasons behind post-viral syndrome are not fully understood yet but we have a few theories. One theory is that even when tests show no signs of infection, some parts of the virus can remain in the body and hide in various tissues like the colon, liver, and lymph nodes. These leftover parts can continuously activate the body's immune system, leading to ongoing inflammation and symptoms.

A second theory is that long-term health issues after infections can be related to the way our immune system reacts to viral infections. When our immune system fights a virus, it might accidentally target parts of the body that look similar to that virus. Even when the virus is gone, the immune system still reacts to these virus-like parts leading to a permanent inflammation. 

This hypothesis has been suggested to be an explanation for certain autoimmune diseases like multiple sclerosis and type 1 diabetes. It has been shown that people infected with Epstein-Barr virus have a much higher risk of developing multiple sclerosis, supporting this theory.

The factors that predict who will experience long-term symptoms after a viral infection are still widely unclear, although some patterns have been noted. For example, women, people with underlying medical conditions, and people who experienced severe initial infections are more likely to report long-term symptoms.