Long COVID, rest, and helping our immune systems recover

As of July 29, 2022, the World Health Organization (WHO) has put the confirmed cases of COVID-19 at more than half a billion and the number of COVID-related deaths at over 6.3 million. In addition to the identified COVID infections or reported cases, there is also a large fraction of covert infections due to a multitude of reasons including asymptomatic infections, barriers to testing and underreporting.

But it is not just the acute illness that has an impact on society, nor simply the deaths that have ripple effects within communities. A recent study reports approximately 200 million individuals currently experience or have previously experienced long-term, health-related consequences of COVID-19, which in itself is a significant burden on individuals, families, communities and healthcare systems.

The same study, which was a meta-analysis of many other research papers, showed that a higher percentage of women reported long COVID symptoms than men (49 percent vs 37 percent, respectively) and that pre-existing asthma was a predisposing factor for lingering symptoms. Risk factors identified in the studies that were not meta-analysed included severe initial illness, older age, and underlying conditions such as obesity and hypothyroidism.

The WHO defines long COVID or “post COVID-19 condition” as that which occurs in people with a history of SARS-CoV-2 infection, usually three months from the onset of COVID, with symptoms and that last for at least two months and cannot be explained by an alternative diagnosis. It lists common symptoms as fatigue, shortness of breath, cognitive dysfunction and others that may have an impact on everyday functioning. Symptoms may persist from the time of COVID illness, or they can occur after a period of recovery from the initial disease; these symptoms may also fluctuate or relapse over time.

What makes long COVID particularly difficult to diagnose and manage is that there are more than 200 reported symptoms linked to it, yet many will need to be investigated for other causes first before attributing them to long COVID.

What could be causing long COVID?

Identifying those at risk of long COVID is important, but to be able to manage it scientists and healthcare professionals need to be able to understand the underlying causes of the illness.

One theory being looked at by scientists is that of finding a blood biomarker in those people suffering with long COVID that is not present in those who do not have symptoms beyond the acute phase of the infection.

A team at Harvard Medical School analysed blood plasma samples collected from patients with long COVID and typical COVID-19 infection over a period of 12 months. They looked to see if there were specific parts of the virus still present in the blood of those with long COVID that might account for their persistent symptoms.

They sought to determine the levels of three parts or “antigens” found on the SARS-CoV-2 virus:

1. The spike protein: the part of the virus that protrudes out and allows it to bind to human cells
2. S1 subunit of spike protein: one of the units that make up the spike protein
3. Nucleocapsid: the viral protein coat that surrounds its genetic material.

The researchers found (PDF) that one or more of these three SARS-CoV-2 antigens were present in the blood of 65 percent of the long COVID-19 patients they tested, up to 12 months after their initial COVID infection. The most common biomarker was the spike protein, which was present in 60 percent of those tested who had persistent symptoms. In contrast, the spike protein was not detected in any of the patients with typical COVID-19 infections that did not persist. Although they did detect the S1 subunit and nucleocapsid in the blood of those who did not report long COVID symptoms, that was immediately after the infections and these levels quickly dropped below the detectable levels.

This study adds to the growing pool of evidence supporting the hypothesis that persistent bits of virus, known as “viral reservoirs” which linger in the body may cause long COVID.

Another team of scientists at Stanford University reported that almost 13 percent of individuals were still shedding viral RNA in their stools four months after catching COVID, and nearly four percent continued to do so at seven months.

It was established early on in the pandemic that COVID was not simply a respiratory infection, and that the virus can infect and cause symptoms in many of the body’s organs, including the gastrointestinal system where many people shed viral matter through faeces during the acute phase of the infection and shortly afterwards. But the findings of the study show that a small number of people continue to shed viral matter months after their infection. These people also often reported continuing gastrointestinal symptoms such as nausea, vomiting and abdominal pain.

The question for researchers going forward is whether these viral reservoirs could be causing long COVID, either through direct causation itself or through stimulating the immune system to react in such a way that it over-responds in a way where it starts to attack healthy cells. More work is needed, but if viral reservoirs are contributing to long COVID then treatment with antiviral agents to clear the body of the virus may be used to treat those suffering from long-term persistent symptoms.

The importance of rest

As many countries move to a “living with COVID” strategy, it is important to remember that COVID-19 can be a debilitating illness for many people during the acute phase and trying to “work through it” may not be the best approach.

The fact that COVID affects people in different ways has always been one of the challenges facing those who are responsible for public health messaging about the disease. Some people will have mild or even no symptoms, others will have a wide array of significant symptoms. It is important to remember that “living with COVID” does not mean ignoring it, and that even if you have mild symptoms, resting during the acute phase will help in your recovery.

Rest and sleep are vital to an immune system that will help fight off your infection; our bodies require seven to nine hours of quality sleep a day to recharge and to keep our immune system strong. Research has shown that sleep is essential in the production of white blood cells that fight off infection.

Scientists have found that quality sleep can bolster the T cells, a type of immune cell, in our bodies that fight off infection. Good sleep does this by enhancing the ability of T cells to adhere to and destroy cells infected by viruses and other pathogens. During sleep, the immune system releases proteins called cytokines. Certain cytokines are important for fighting infections and inflammation and help us respond to stress. But when we do not get enough sleep, or our sleep is disrupted, our bodies produce fewer of these important cytokines. In contrast, sleep deprivation has been associated with alterations of innate and adaptive immune parameters, leading to a chronic inflammatory state and an increased risk for infectious/inflammatory pathologies.

A UK study looking at almost 1,200 people found poor sleep in the month preceding SARS-CoV-2 infection resulted in a 2.4- to 3.5-fold increase in the risk of developing long COVID. Although this study is relatively small and yet to be peer reviewed, it does highlight the importance of sleep in the health of our immune system.

Although sleep will not cure your COVID infection, getting regular, good-quality sleep will mean your immune system will be in a better place to deal with the infection.

Sleep does not come easily to everyone, but a few small changes in your sleep routine may help:

1. Stick to a sleep schedule: Go to bed and get up at the same time each night; aim for 7-8 hours in bed
2. Create a restful bedroom environment, free from clutter; keep it cool and dark
3. Limit daytime naps to no more than 20 minutes, they can affect nighttime sleep
4. Exercise during the daytime can help sleep at night; just remember to steer clear of anything too vigorous right before bedtime
5. Avoid screens such as laptops, tablets, televisions and phones in the bedroom; they emit blue light which can trick your brain into thinking it is daytime.

Remember, you do not have to work through your illness. If you are sick with COVID-19 or feeling tired, take time out to rest. It will be key to your recovery.