A sore throat, a light headache, a slight case of the sniffles — could these be COVID-19 symptoms?

A year ago, we might not have paid attention to such minor complaints, if we even noticed them at all.

But now, in the fall of 2020, things look very different. One sneeze is enough to set our thoughts churning: "Where have I been these last few days? How close did I get to people? What did I touch? Can I still smell and taste? I am a little short of breath, come to think of it ..."

Stop! If it's any comfort: You are not alone. Researchers and physicians are also constantly busy with the same sorts of churning thoughts as they try to trace the wide range of symptoms that COVID-19 can cause. 

But researchers at the Medical University of Vienna have now been able to put a little more structure into the long list of coronavirus symptoms by identifying seven forms  of COVID-19 when the disease takes a mild course. 

In their study, published in the scientific journal Allergy, the scientists, led by immunologist Winfried Pickl and allergologist Rudolf Valenta, aimed to find out what form effective immunity takes when people have recovered from a coronavirus infection, and how this immunity can be measured. 

For their research, they interviewed 109 convalescents and 98 healthy people in a control group and examined their blood.

Seven forms of COVID-19 

Using this data, the researchers were able to show that different symptoms of COVID-19 are related and occur in so-called symptom groups. They identified the following seven groups:

1. Flu-like symptoms (with fever, chills, fatigue and cough)
2. Common cold-like symptoms (with rhinitis, sneezing, dry throat and nasal congestion)
3. Joint and muscle pain
4. Eye and mucosal inflammation
5. Lung problems (with pneumonia and shortness of breath)
6. Gastrointestinal problems (including diarrhoea, nausea and headache) 
7. Loss of sense of smell and taste and other symptoms

"In the last group, we found that loss of smell and taste predominantly affects individuals with a young immune system," study leader and immunologist Winfried Pickl said in an interview with DW.  It should be noted here that a "young immune system" is not measured by the age of the patient but by the number of immune cells (T lymphocytes) that have recently emigrated from the thymus gland.

"This means that we were able to clearly distinguish systemic forms of primary COVID-19 disease (e.g., groups 1 and 3) from organ-specific forms (e.g., groups 6 and 7)," Pickl said.

This does not mean that there can be no overlapping between the symptom groups, he said. However, the different groups were demonstrated to have connections with specific immune parameters.

For example, a COVID-19 disease course with high fever correlates with the body's immunological memory and could indicate a comparatively long period of immunity. The loss of taste/smell, on the other hand, was associated with a higher level of T lymphocytes.

COVID-19 fingerprint in the blood

Using blood tests, the researchers were able to identify several important COVID-19 markers. They found out that the illness leaves behind significant changes in the immune system after 10 weeks — like a kind of fingerprint in the blood of the patients.

The number of granulocytes, which are otherwise responsible in the immune system for fighting bacterial pathogens, was significantly lower than usual in the COVID-19 group. "This was amazing and completely new," Pickl told DW. 

"However, both the CD4 and CD8 T cell compartment developed memory cells and CD8 T cells remained strongly activated. This indicates that the immune system is still intensively engaged with the disease several weeks after initial infection," he said.

This could be one of the reasons why many patients may feel weak for a long time after a COVID-19 infection. At the same time, the regulatory T cells were severely reduced — a dangerous combination that could also lead to an autoimmune disease, according to Pickl.

In addition, an increased number of antibody-producing immune cells could also be detected in the blood of convalescents. The stronger the fever of the affected person was during a mild course of the disease, the higher the immunity was that developed against the virus.

"Our findings contribute to a better understanding of the disease and help us in the development of potential vaccines, since we now have access to promising biomarkers and can perform even better monitoring," the researchers wrote in their article. "We now know that B or T lymphocytes are important parameters when evaluating vaccines," Pickl said. 

Above all, the researchers said, the study showed that when defending the body against COVID-19, the human immune system "doubles up" with the combined action of immune cells and antibodies — like the defense in a modern soccer team. In this way, the cells are also able to "memorize" certain "moves" on the part of the virus and respond to them. 

Now, they said, it was "a matter of implementing these findings and using them for the development of highly effective COVID-19 vaccines."