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Likely order of COVID-19's symptoms — Large analysis of China cases

University of Southern California (USC) researchers have found the likely order in which COVID-19 symptoms first appear: fever, cough, muscle pain, and then nausea, and/or vomiting, and diarrhoea. Knowing the order of COVID-19's symptoms may help patients seek care promptly or decide sooner than later to self-isolate, the scientists say. It also may help doctors rule out other illnesses, according to the study led by doctoral candidate Joseph Larsen and his colleagues with faculty advisors Peter Kuhn and James Hicks at the USC Michelson Centre for Convergent Bioscience's Convergent Science Institute in Cancer.

Recognising the order of symptoms also could help doctors plan how to treat patients, and perhaps intervene earlier in the disease. "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 hospitalisation time," said Larsen, the study's lead author.

Fever and cough are frequently associated with a variety of respiratory illnesses, including 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 (nausea/vomiting) seems to be affected before the lower GI tract (diarrhoea) in COVID-19, which is the opposite from MERS and SARS," the scientists wrote.

The authors predicted the order of symptoms this spring from the rates of symptom incidence of more than 55,000 confirmed coronavirus cases in China, all of which were collected from 16 February-24 February, 2020, by the World Health Organisation. They also studied a dataset of nearly 1,100 cases collected from 11 December, 2019 through 29 January, 2020, by the China Medical Treatment Expert Group via the National Health Commission of China.

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, the lead author, 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, in Chiba, Japan.

Abstract
COVID-19 is a pandemic viral disease with catastrophic global impact. This disease is more contagious than influenza such that cluster outbreaks occur frequently. If patients with symptoms quickly underwent testing and contact tracing, these outbreaks could be contained. Unfortunately, COVID-19 patients have symptoms similar to other common illnesses. Here, we hypothesize the order of symptom occurrence could help patients and medical professionals more quickly distinguish COVID-19 from other respiratory diseases, yet such essential information is largely unavailable. To this end, we apply a Markov Process to a graded partially ordered set based on clinical observations of COVID-19 cases to ascertain the most likely order of discernible symptoms (i.e., fever, cough, nausea/vomiting, and diarrhea) in COVID-19 patients. We then compared the progression of these symptoms in COVID-19 to other respiratory diseases, such as influenza, SARS, and MERS, to observe if the diseases present differently. Our model predicts that influenza initiates with cough, whereas COVID-19 like other coronavirus-related diseases initiates with fever. However, COVID-19 differs from SARS and MERS in the order of gastrointestinal symptoms. Our results support the notion that fever should be used to screen for entry into facilities as regions begin to reopen after the outbreak of Spring 2020. Additionally, our findings suggest that good clinical practice should involve recording the order of symptom occurrence in COVID-19 and other diseases. If such a systemic clinical practice had been standard since ancient diseases, perhaps the transition from local outbreak to pandemic could have been avoided.

Authors
Joseph R Larsen, Margaret R Martin, John D Martin, Peter Kuhn, James B Hicks

 

[link url="https://news.usc.edu/174346/covid-19-symptoms-usc-research-fever-cough/"]University of Southern California material[/link]

 

[link url="https://www.frontiersin.org/articles/10.3389/fpubh.2020.00473/full"]Frontiers in Public Health abstract[/link]

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