Vicky Bowyer

New research by the COVID Symptom Study team has identified at least three ‘types’ of long COVID in people who experience symptoms for at least 12 weeks. The study, pre-printed on medrXiv, also identifies patterns of symptoms among people infected with the wild-type variant, delta and alpha, among vaccinated and unvaccinated individuals.

The researchers analysed data of 1,459 individuals with post-Covid syndrome (where someone reports ongoing symptoms for longer than 84 days) from the ZOE COVID Symptoms Study app. This study included data from our 2021 long COVID questionnaire completed by CSS Biobank volunteers. 

People with symptoms for 12 weeks or more fell into three groups based on the types of symptoms they were experiencing. The largest group was characterised by a cluster of neurological symptoms such as fatigue, brain fog and headache and was the most common subtype among SARS-CoV-2 alpha and delta variants. A second group experienced chest symptoms including chest pain and severe shortness of breath, which could point to lung damage. This was the largest cluster in the wild-type period when the population was unvaccinated. Finally, there were some people who experienced a diverse range of symptoms including palpitations, muscle aches and pains, and changes in their skin and hair.

While these three subtypes were evident in all variants, additional symptom clusters were also identified which were subtly different between variants. These differences may not be due to variants themselves, but other factors which have changed across the pandemic, such as time of year, social behaviours, and treatments.

The data also suggests that the symptom types for people who did experience symptoms for 12 weeks or more were similar in vaccinated and unvaccinated people at least with variants which had these data. We know from existing data that the risk of long-COVID overall is reduced by vaccination.

The study shows that post-COVID syndrome is not just one condition and the findings can inform the development of personalised diagnosis and management. 

Research by the CSS Biobank into the post-illness metabolic profiles of 4,787 volunteers has been published online. We looked at the full spectrum of COVID-19, from people who had asymptomatic COVID-19 to those who had post-COVID Syndrome (symptoms for more than 12 weeks). We also looked at the metabolic profiles of participants who reported ongoing symptoms like COVID-19 – such as a cough, headache, and fatigue – but who were found to have negative antibodies for the virus.

Our results show that participants who had higher levels of harmful fats commonly linked to heart disease were more likely to experience ongoing symptoms from both COVID-19 and non-COVID disease. That is, both people with longer illness, regardless of whether they had COVID-19, both had a set of compounds in their blood commonly seen in patients who are at risk of heart disease and diabetes. We found no association between illness duration and the gut microbiome.

These findings suggest that treatments for other diseases could inform new ways to treat COVID-19.

The study pre-print is available on mexRxiv.

An online discussion forum has been created to support patient and public involvement in Long COVID research. This is part of the CONVALESCENCE project PPIE (patient and public involvement and engagement) initiative. The forum aims to ensure that a broader cross-section of public/patient perspectives is included in discussions about defining Long COVID and in wider research.

Click here to read more, and this link to view the public forum space dedicated to discussing defining Long COVID. Register for an account if you would like to participate in the conversation. 

The CSS Biobank team is also doing some work in this area. Using symptoms and other data from the ZOE COVID Study app, we are trying to understand if there are different types of long COVID and, if so, what clusters of symptoms define the types. We’ll share our results as soon as they are available.

In December, we invited CSS Biobank volunteers to complete a rapid survey to understand how people’s festive plans might influence the spread of Omicron.

The anonymous results, reviewed by the government’s Scientific Advisory Group on Emergencies (SAGE) committee, showed that over 95% of respondents planned to change some of their behaviours over the Christmas period to reduce the risk of transmitting or catching Omicron. The most frequently reported measures to reduce transmission were getting a vaccination and using rapid testing kits.

The paper has been preprinted (meaning it is a preliminary report of work that has not been vetted yet by other scientists) and will be submitted to a medical journal for peer review. The preprint is available to read here. Please note that the CSS Biobank data is grouped with the TwinsUK data. 

Using some of the blood samples donated by our CSS Biobank participants, we are looking to see if any blood markers associated with diseases like heart disease and diabetes are also linked to having long COVID. This may give us clues as to why long COVID happens and who is at risk of getting it.

About metabolites

When the body breaks down food, drugs, or other chemicals, it creates new biomolecules which have various functions, such as supporting growth or maintaining health. For many diseases, like heart disease and diabetes, we are able to measure the levels of some of these biomolecules (or metabolites), to give an idea of someone’s risk of developing the disease or to tell us how well-controlled it is. An example is measuring cholesterol in the blood.

We noticed early in the pandemic that people who already have certain conditions, such as heart disease and diabetes, got quite unwell with COVID. Research by a Finnish company, which has developed a single test that can measure 249 blood metabolites, shows that if you have less healthy values on some of these tests, you are more likely to get hospitalised with COVID-19. The same markers are linked to health conditions like heart disease and diabetes.

What we are finding

So far, it looks like similar changes to those found by the Finnish researchers are found in participants with long COVID, but not for all. In particular, blood fats like cholesterol and fatty acids might be quite important. This is very useful, as it suggests long COVID might also share similar causes with other conditions that we already know how to prevent and treat, so we are now also looking at links with diet, exercise and the microbes that live in our guts.

We will post updates as we learn more.

Some people with COVID-19 report problems with impaired memory, concentration, and attention, lasting many weeks and months after infection. The problems are sometimes referred to as “brain fog”.

Our CSS Biobank participants took part in our online study in July 2021 looking at cognitive function. Participants completed tasks to measure different aspects of cognitive function, using the Cognitron platform, and completed questionnaires about their mood, levels of fatigue, and how their daily function may have been impacted.

We have been busy looking at the initial results, and our early analysis indicates that there are some differences in test scores between those who have had COVID-19 infection and those who have not. A different study, published in July by the group behind the Cognitron, found similar results in people living with long COVID.

Our very important task now is to understand these differences – are they a result of COVID-19 infection, or other factors? Are differences affected by the duration of COVID symptoms? And, importantly, how do these scores change over time? To help us answer these questions, we will repeat the online assessments in January 2022.