Is it coronavirus or something else? Harvard Medical School study offers insight for clinicians evaluating symptoms

A doctor measured temperature to test for the coronavirus.Ronald Zak/Associated Press

A recent Harvard Medical School study offers insights on determining whether patients with coronavirus symptoms are infected with the contagion or with a different ailment.

The study, published April 20 in Mayo Clinic Proceedings, was conducted by researchers at the medical school and Harvard-affiliated Cambridge Health Alliance, the school said in a statement. Researchers crunched data from 1,000 patients who visited an outpatient COVID-19 clinic in Greater Boston.

The findings, the statement said, offer clues to help clinicians distinguish between patients with COVID-19 and those who have other ailments with symptoms that mimic those of COVID-19.

According to the researchers, one common symptom of COVID-19, shortness of breath, can also be anxiety-induced, rather than indicative of infection.

Anxiety-induced shortness of breath comes on rapidly, or “seemingly out of the blue,” the statement said. By contrast, COVID-19 shortness of breath normally develops gradually over a few days, the study says.

And, the statement said, patients with anxiety-induced shortness of breath often report the sensation coming on during rest or while trying to sleep, but it doesn’t get worse with daily activities.

COVID-19-induced shortness of breath, on the other hand, worsens with physical exertion and even simple activities like walking, climbing stairs, or cleaning, the statement said. And unlike COVID-19, anxiety-induced shortness of breath doesn’t cause drops in blood oxygen levels, according to the statement.

The release said almost no one with COVID-19 develops shortness of breath in the first day or two of infection, but the symptom can appear four or more days after onset. The findings indicate a small number of people infected with COVID-19 may never have shortness of breath but show other symptoms suggestive of low oxygen levels, such as dizziness or falling, the statement said.

The study also found fever “is not a reliable indicator,” the statement said, adding that the virus, if present, can “manifest only with mild elevations in temperature.” And COVID-19 onset can start with coughing, without other symptoms including fever, sore throat, diarrhea, abdominal pain, headache, body aches, back pain and fatigue, the study found.

The statement said one “reliable early hint” of COVID-19 is the loss of sense of smell during the first days of onset. The virus can also “present with severe body aches and exhaustion,” the statement said.

In addition, the statement said, several types of pneumonia can show “striking similarity” to COVID-19. The study found that symptoms of the virus appear to closely mimic a condition known as pneumocystis pneumonia, an infection that mainly affects tiny air sacs lining the surface of the lungs.

Both COVID-19 patients and those with pneumocystis pneumonia have “precipitous drops in oxygen levels with exertion and shortness of breath,” the statement said, but in cases of pneumocystis pneumonia, breath shortness usually develops over weeks, not days as with COVID-19.

“Here, a careful patient history detailing evolution of symptoms would be critical,” the statement said.

During initial days of infection, the study found, both flu and COVID-19 can have “identical presentations,” but then the course of the infections will diverge, the statement said.

“People with uncomplicated flu rarely develop significant shortness of breath,” the statement said. “When they do experience trouble breathing, the shortness of breath is mild and remains stable. On the rare occasion of when flu causes a viral pneumonia, patients deteriorate rapidly, within the first two to three days.”

That contrasts with COVID-19 patients, who don’t start developing shortness of breath until “several days” after first becoming sick, the statement said.

Dr. Pieter Cohen, an associate professor at Harvard Medical School and the study’s lead author, said in the statement that recognizing signs of the virus is critical for clinicians, especially since not all COVID-19 tests are accurate.

“Early recognition and proper triage are especially important given that in the first days of infection, people infected with SARS-CoV-2 may experience symptoms indistinguishable from a variety of other acute viral and bacterial infections,” said Cohen, who’s also a physician at Cambridge Health Alliance.

“Even when point-of-care diagnostic tests are available, given the potential for false-negative results, understanding the early natural history of COVID-19 and good old-fashioned clinical skills will remain indispensable for proper care," he said.