USC scientists find the likely order of COVID-19 symptoms

The scientists at USC Michelson Center see gastrointestinal issues may set the coronavirus apart from other illnesses like influenza, helping doctors to diagnose it.

Contact: Emily Gersema, [gersema@usc.edu] or (213) 712-3168

USC researchers have found the likely order in which COVID-19 symptoms first appear: fever, then cough and muscle pain, followed by nausea, and/or vomiting, and diarrhea.

Knowing the order of COVID-19’s symptoms may help patients seek care promptly or decide sooner than later to self-isolate, says scientists at the USC Michelson Center for Convergent Bioscience. The information also may help doctors rule out other illnesses, or help doctors plan how to treat patients, and perhaps intervene earlier in the disease.

The study, which appears today in the journal Frontiers in Public Health, was led by doctoral candidate Joseph Larsen and scientists Peter Kuhn and James Hicks at the USC Michelson Center’s Convergent Science Institute in Cancer.

Kuhn is also a Dean’s Professor at USC Dornsife College of Letters, Arts and Sciences and Hicks is a research professor there.

“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 Kuhn, 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.”

“Given that there are now better approaches to treatments for COVID-19, identifying patients earlier could reduce hospitalization time,” said Larsen.

Fever and cough are frequently associated with a variety of respiratory illnesses, including influenza, Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). But the 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,” the scientists wrote.

To determine COVID symptom chronology, the authors analyzed more than 55,000 confirmed coronavirus cases in China collected from Feb. 16-Feb. 24, 2020 by the World Health Organization. They also studied 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 addition, to compare the order of COVID-19 symptoms to influenza, the researchers examined data from 2,470 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,” Larsen said.

In addition to Larsen, Kuhn and Hicks, other study co-authors were Margaret R. Martin of Nexus Development PA LLC and John D. Martin at NanoCarrier Co., Ltd., in Chiba, Japan.

The Michelson Center brings together a diverse network of scientists and engineers from USC Dornsife, USC Viterbi School of Engineering and Keck School of Medicine of USC to solve some of the greatest intractable problems of the 21st century — from cancer, to neurological disease, to cardiovascular disease.

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Funding for the study came from the National Cancer Institute (Award Number U54CA143906 and P30CA014089) and the Carol Vassiliadis fellowship. Larsen also had support from the USC Dornsife College and the Schlegel Family Endowment Fellowship.