And that can also have consequences for the speed at which a particular variant spreads.

COVID-19 affects different people in different ways. The symptoms can vary a lot, or be mild at first. The most common symptoms are fever, cough and fatigue. You can also become very short of breath or short of breath. But which symptom often appears first? Researchers figured it out.


Earlier, researchers developed a mathematical model that predicts the sequence of COVID-19 symptoms. This model is based on data from the first corona outbreak in China, early 2020. In the new study however, the research team wanted to know whether the order of symptoms varies among patients from different geographic regions or with different personal characteristics. To determine that, they studied the order of symptoms of more than 370,000 American corona patients diagnosed between January and May 2020.


The researchers made a surprising discovery. Because the most likely symptom sequence turned out to differ considerably between the Chinese and American corona patients. In China, most corona patients often developed a fever at first. After that, a persistent cough was a common complaint, followed by nausea and sometimes even vomiting. American corona patients, on the other hand, were in many cases the first to deal with an annoying cough. Diarrhea was a frequently mentioned third complaint.

Geographical region… or not?

An interesting question, however, is whether these differences are indeed related to geographical location, or whether they have another cause. The team analyzed additional data from Brazil, Hong Kong and Japan. And that leads to a striking discovery. The different symptom sequences do not appear to be related to the geographical region, the weather or personal characteristics, but to different virus variants.

D614G variant

The so-called D614G variant was dominant in the United States in early 2020. As mentioned, coughing was a common first phenomenon there. When the D614G variant supplanted the original coronavirus in Japan, the symptom order here also changed. The researchers hypothesize that this may be associated with the increased spread of D614G.

Virus variants

The findings of the study thus seem to indicate that each virus variant has a different symptom order. Quite a surprising result. “Although there are clinical observations that symptoms can change, we did not expect this at the start of the pandemic,” said Peter Kuhn in an interview with “We have not seen or measured this before in other virus outbreaks.”


According to the researchers, the discovery could have consequences for the speed at which a particular virus variant spreads. “For example, if a high fever is the first symptom, the patient is incapacitated quite quickly,” explains Kuhn. “The patient stays at home and can no longer pass the virus on to others. However, if coughing, loss of smell or fatigue is the first symptom, it may take longer for the patient to realize he has corona. Then it also takes longer before he gets tested.” And that way, this virus variant can spread to many more people.


What exactly causes the variation in symptoms of different virus variants? Kuhn still owes us the answer. “It’s not clear yet,” he says. “Probably it is related to the mutation or to the change in the spike protein. But the exact mechanism has yet to be elucidated.”

Kuhn emphasizes that it is very important to map the symptom sequence of emerging virus variants. “Our study provides the necessary evidence that symptom sequence changes and that we can model this accurately,” he says. “The next step is to keep doing that for new variants.”