Researchers from the University of Southern California (USC) have found what appears to be the likely order in which COVID-19 symptoms first appear.

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Scientists may have identified a specific order for COVID-19 symptoms.

All data and statistics are based on publicly available data at the time of publication. Some information may be out of date.

The study findings reveal individuals infected with COVID-19 will likely experience symptoms in the following order:

  1. fever
  2. coughing and muscle pain
  3. nausea, vomiting, or both
  4. diarrhea

The research appears in the journal Frontiers in Public Health. Doctoral candidate Joseph Larsen and his colleagues conducted the study in collaboration with faculty advisers Peter Kuhn and James Hicks, at the USC Michelson Center for Convergent Bioscience’s Convergent Science Institute in Cancer.

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a catastrophic global impact.

According to current data from Johns Hopkins University, there are now more than 23.9 million confirmed cases of COVID-19 globally and more than 820,000 recorded deaths.

Individuals infected with COVID-19 are highly infectious, demonstrating a rate two to three times more contagious than influenza. Also, as outbreaks of COVID-19 occur in clusters, early identification of the disease may reduce their number and size. However, experts are unable to define the initial symptoms accurately.

The researchers note that an improved understanding of how COVID-19 symptoms appear helps patients promptly seek care or decide to self-isolate.

This information may also help medical professionals identify patients with the disease, rule out other illnesses, and design appropriate treatments more quickly.

“Given that there are now better approaches to treatments for COVID-19, identifying patients earlier could reduce hospitalization time,” says Prof. Larsen, the study’s lead author, and a USC Dornsife professor.

Fever and coughing are frequently associated with an assortment of respiratory illnesses, including influenza, Severe Acute Respiratory Syndrome (SARS), and Middle East Respiratory Syndrome (MERS).

To determine the order that COVID-19 symptoms appear, the researchers evaluated the rates of symptom incidence of 55,924 confirmed coronavirus cases in China. The World Health Organization (WHO) collected these cases between February 16 and February 24, 2020.

The researchers expanded their analysis with data from 1,099 cases collected by the China Medical Treatment Expert Group via the National Health Commission of China from December 11 to January 29, 2020.

Furthermore, to compare the order of COVID-19 symptoms to influenza, the team looked at the influenza dataset from 2,470 confirmed cases of mostly unvaccinated patients in Europe, North America, and the Southern Hemisphere that was reported to health authorities from 1994 to 1998.

The results revealed that in the three diseases studied caused by coronaviruses COVID-19, SARS, and MERS the most probable initial symptom is fever. By contrast, influenza initiates with coughing.

Additionally, although these diseases’ symptoms overlap with COVID-19, what distinguishes the novel coronavirus from them is the timing and symptoms in the upper and lower gastrointestinal tract.

“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 researchers wrote. In all diseases, the scientists observed that fever and coughing occur before nausea, vomiting, or both, and 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,” emphasizes senior author, Peter Kuhn, Professor of Biological Sciences and Professor of Medicine, Biomedical Engineering, and Aerospace & Mechanical Engineering at USC Dornsife.

“Doctors can determine what steps to take to care for the patient, and they may prevent the patient’s condition from worsening.”

The scientists recommend that personnel should test people for fever before they are allowed entry to facilities.

Furthermore, as public spaces start to reopen after the outbreak of the virus, they suggest physicians and other healthcare professionals should record the order of symptom occurrence in COVID-19 and other diseases as part of good clinical practice.

The researchers call for future studies to investigate different strains of COVID-19 and determine whether the onset of symptoms differs in specific strains.

The team also suggests that future research should determine whether risk factors, such as obesity and environmental factors, such as temperature, can affect symptom order. Prof. Larsen and colleagues conclude:

“To slow the spread of COVID-19, our results support the practice that fever should be tested before allowing entry to facilities and that those with fever should immediately seek medical attention for diagnosis and contact tracing. Such measures as these may help to reduce transmission despite the high contagion of SARS-CoV-2.”

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