We were sometimes amazed by the blood values

Initially, we mainly included colleagues from our own UMCG Groningen in this study who tested positive for COVID-19. Doctors and nurses but also other employees were included who were not in direct contact with patients, such as secretaries and cleaners. We asked these colleagues to let their family members participate too. Later, we also included families via the municipal health service. A total of 256 people from the north of the Netherlands (the provinces of Groningen, Friesland, Drenthe and Overijssel) participated in this study, of whom 190 had or developed a COVID-19 infection. They all completed a symptom list over a period of 21 days.

We also wanted to know for which period of time they tested positive for COVID-19. We measured that once per week in their nose, but also in the faeces and urine and, for a small group, in vaginal fluid and semen. Back then, we still allowed for the possibility that the virus could also spread that way. In addition, we took blood samples for information about 40 different parameters, such as haemoglobin, white blood cells and all markers for liver and kidney functions. Once a week, we visited the families at home to perform all of these measurements. It was a case of real teamwork within our research group.

It was often said that people recovering from a COVID-19 infection at home had “mild symptoms”. The World Health Organization (WHO) groups the patients into a single category. However, our research revealed that there were big differences. A small group had strikingly few symptoms, a large group had predominantly mild symptoms, but there was also a group – about 30 percent – who clearly had many and severe symptoms. We were sometimes amazed by the blood values: we saw so many deviations. Our conclusion from that part of the study is that the WHO should divide people with “mild symptoms” into three groups.

It was later found that 40 percent of the people continue to experience symptoms even when the virus was no longer detectable in the nasal mucosa for a long time. This made us decide to continue with our research. The study is still running now. We follow the participants at 3, 6, 12, 18 and 24 months. They complete an online questionnaire. Tiredness is the most frequently mentioned symptom in the case of Long COVID but people often also mention mental problems, concentration problems, headaches and disruptions in their sense of taste and smell.

It is known that vaccination reduces the chances of Long COVID. However, vaccination does not completely exclude Long COVID. A striking result from this study is that, after the first infection at the start of the pandemic, a small group of people experienced no lingering symptoms and therefore had no Long COVID. When they were vaccinated later in the pandemic, they were reinfected with the coronavirus and then they did develop Long COVID. How this could be the case and how large this group is must still be examined. During the course of the pandemic, the virus mutated and we have seen different variants. That might well be an explanation.

Is there a link between the blood values in the acute phase – so when the virus is detectable in the nasal mucosa – and the development of Long COVID? We hope to discover that once we have completed the study. The data could help us to predict who will suffer from lingering symptoms. It might even be possible to differentiate this group: for the people with these blood values, we expect these symptoms to be prominent post-COVID, for example the mental part, or the physical part. Thus it will become possible to develop individualised therapies.

At the start of the pandemic, people with a COVID-19 infection really felt alone. When we contact them for our study, they sometimes literally say: ‘I’m so glad that you phoned.’ That is because they had so many questions. Now, in 2023, there is a tendency to shout ‘Hurray! Let’s be happy! COVID-19 is behind us now.’ But that is not the case. An awful lot of people suffer from Long COVID, and new patients are still being added to that number. Everybody can develop Long COVID, even now. We should remain vigilant and continue with our research.

• Tami A, van der Gun BTF, Wold KI, Vincenti-González MF, Veloo ACM, Knoester M, Harmsma VPR, de Boer GC, Huckriede ALW, Pantano D, Gard L, Rodenhuis-Zybert IA, Upasani V, Smit J, Dijkstra AE, de Haan JJ, van Elst JM, van den Boogaard J, O' Boyle S, Nacul L, Niesters HGM, Friedrich AW (2022). The COVID HOME study research protocol: Prospective cohort study of non-hospitalised COVID-19 patients. PLoS One., 17(11):e0273599. doi: 10.1371/journal.pone.0273599. 
  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0273599
• Flikweert AW, Kobold ACM, van der Sar-van der Brugge S, Heeringa P, Rodenhuis-Zybert IA, Bijzet J, Tami A, van der Gun BTF, Wold KI, Huckriede A, Franke H, Emmen JMA, Emous M, Grootenboers MJJH, van Meurs M, van der Voort PHJ, Moser J (2022). Circulating adipokine levels and COVID-19 severity in hospitalized patients. Int J Obes (Lond). Dec 12:1–12. doi: 10.1038/s41366-022-01246-5.
  https://www.nature.com/articles/s41366-022-01246-5
• van Eijk LE, Tami A, Hillebrands JL, den Dunnen WFA, de Borst MH, van der Voort PHJ, Bulthuis MLC, Veloo ACM, Wold KI, Vincenti González MF, van der Gun BTF, van Goor H, Bourgonje AR. (2021). Mild Coronavirus Disease 2019 (COVID-19) Is Marked by Systemic Oxidative Stress: A Pilot Study. Antioxidants (Basel). Dec 20;10(12):2022. doi: 10.3390/antiox10122022. PMID: 34943125; PMCID:PMC8698810. 
  https://www.mdpi.com/2076-3921/10/12/2022

• Long Covid
• Blog series "I'm researching long COVID"