What Symptoms Come First in COVID-19? Study Provides Some Answers

Pharmacists often are asked to help patients differentiate symptoms between COVID-19 or another illness, such as influenza. Now, a new model offers the order of symptoms that occur with novel coronavirus, as well as specific signs that can differentiate the infection from other respiratory illness. Here is more information.

LOS ANGELES – Pharmacists field a lot of questions about what symptoms indicate likely COVID-19 infections and which do not.

Now, University of Southern California researchers have come up with some advice that could help patients know when to seek care promptly or when to self-isolate.

In an article in Frontiers of Public Health, the USC study team identify the likely order in which COVID-19 symptoms usually appear:

  1. fever,
  2. cough,
  3. muscle pain,
  4. nausea, and/or vomiting, and
  5. diarrhea

"This order is especially important to know when we have overlapping cycles of illnesses like the flu that coincide with infections of COVID-19," said Peter Kuhn, PhD, a USC professor of medicine, biomedical engineering, and aerospace and mechanical engineering. "Doctors can determine what steps to take to care for the patient, and they may prevent the patient's condition from worsening."

While fever and cough are frequently associated with a variety of respiratory illnesses, including Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS), the study points out that timing and symptoms in the upper and lower gastrointestinal tract set COVID-19 apart.

"The upper GI tract (i.e., nausea/vomiting) seems to be affected before the lower GI tract (i.e., diarrhea) in COVID-19, which is the opposite from MERS and SARS," according to the report.

To determine the order of symptoms, the authors looked at several databases, including the rates of symptom incidence of more than 55,000 confirmed coronavirus cases in China, all of which were collected from Feb. 16-Feb. 24, 2020, by the World Health Organization. The study team also analyzed a dataset of nearly 1,100 cases collected from Dec. 11, 2019 through Jan. 29, 2020, by the China Medical Treatment Expert Group via the National Health Commission of China.

In order to compare the order of COVID-19 symptoms to influenza, the researchers examined data from 2,470 flu cases in North America, Europe and the Southern Hemisphere, which were reported to health authorities from 1994 to 1998.

"The order of the symptoms matter. Knowing that each illness progresses differently means that doctors can identify sooner whether someone likely has COVID-19, or another illness, which can help them make better treatment decisions," explained lead author Joseph Larsen, a doctoral candidate. “Given that there are now better approaches to treatments for COVID-19, identifying patients earlier could reduce hospitalization time.”

Researchers assumed that symptoms and their orders are independent variables and created a model that approximates the probability of symptoms occurring in specific orders using available, non-ordered patient data. Specifically, they applied a Markov Process to determine the order of occurrence of common symptoms of respiratory diseases.

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