New cases of the novel coronavirus continue to increase worldwide, with 73,332 confirmed global cases of COVID-19 as of today, according to the World Health Organization (WHO). That includes 72,528 cases in China and 804 cases in 25 countries outside of China.
Some have questioned the accuracy of the statistics released by the Chinese government regarding the reported number of cases and deaths due to the outbreak. Now there are concerns about the accuracy of the laboratory tests used to confirm diagnoses.
Reports suggest some people test negative up to six times even though they are infected with the virus, according to the BBC and Chinese media. Such was the case with Dr. Li Wenliang, the ophthalmologist who first identified the outbreak and was reprimanded by Chinese authorities when he tried to warn others.
Dr. Wenliang developed a cough and fever after unknowingly treating an infected patient. He was hospitalized, testing negative for coronavirus several times before eventually receiving a positive result. On Jan. 30 the doctor posted: "Today nucleic acid testing came back with a positive result, the dust has settled, finally diagnosed," according to the BBC. Dr. Wenliang passed away on February 7 in Wuhan, the epicenter of the outbreak.
False-negative test results, where patients are told they do not have a condition when they actually do, cause several problems. Patients may be turned away from hospitals and medical facilities when they require care. They may infect others at home, work, school, or in the community. Patients' conditions may also worsen without treatment.
When faced with a highly infectious, potentially deadly pathogen, even a small number of false negatives can have a potentially serious and widespread impact on the larger population.
How Do Doctors Diagnose COVID-19?
Doctors use a laboratory test called RT-PCR to diagnose severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, the virus that causes COVID-19 illness. RT-PCR detects and amplifies genetic material of interest. MedicineNet author Melissa Conrad Stöppler, MD notes that "RT-PCR has been used to measure viral load with HIV and may also be used with other RNA viruses such as measles and mumps."
However, RT-PCR tests for the novel coronavirus are not perfect and not always accurate. A recent study in the journal Radiology examined medical records from 167 patients with COVID-19 from Hunan province in China. Researchers found that five patients out of 167 -- 3% of the study group -- who had chest CT scan features suggestive of COVID-19 initially tested negative for SARS-CoV-2 infection by RT-PCR. The patients were isolated and all eventually were confirmed through repeated swab tests to have the infection.
False negatives comprised just 3% of the patient population in this study. However, failure to detect a small number of cases of the potentially deadly viral infection may have wide-ranging effects for patients and others who may become infected.
Why Are Coronavirus Tests Inaccurate?
The study authors note that RT-PCR tests may produce false negatives due to laboratory error or insufficient amount of viral material collected from the patient. Samples that are stored or handled improperly also result in false negatives.
Tests may result in false negatives if the patient is tested too early in the course of infection and there is insufficient amount of virus to be detected. Improper sampling may result in a false negative.
Another potential problem with test kits: Faulty reagents. The CDC recently admitted test kits they distributed resulted in inconsistent results due to a problematic reagent required for the test. They are now manufacturing the reagents using stricter quality control measures.
In the middle of cold and flu season, it is possible that some people who are being tested for coronavirus do not actually have the infection. Symptoms like cough and fever are nonspecific and may occur with many conditions other than COVID-19.
What's the Solution?
In addition to the possibility of false negatives, authors of the Radiology study note that lab testing for SARS-CoV-2 is time-consuming and that test kits may be in short supply due to the rising number of infections.
So, what's the solution? Doctors in Hubei recently started diagnosing COVID-19 clinically based on patients' symptoms and lung imaging. These cases are reflected in the global tally of infected individuals. Clinically-diagnosed cases account for the approximately 15,000 new cases reported by China last week.
The study authors note typical CT findings can help medical personnel with early screening of suspected cases. Lung imaging may also help predict potential severe complications of the illness.
The authors note that early detection and isolation are essential tools in fighting the novel coronavirus. They recommend isolation and repeat swab tests for those who have symptoms of the illness and characteristic chest CT findings despite negative RT-PCR tests.
How Many People Really ARE Infected?
Many factors are likely to confound the real number of those who have contracted or died from SARS-CoV-2. The inclusion of clinically diagnosed cases of COVID-19 may further muddle the issue. Professor Paul Hunter of the University of East Anglia told Science Media Centre that previously suspected cases of the illness are now considered confirmed cases even though some may be caused by illnesses other than COVID-19. Translation: Clinical diagnosis may lead to overdiagnosis and misdiagnosis in some cases.
Professor Hunter calls for consistency in case definitions. That is what is needed to get an accurate picture of the extent of the outbreak and the true number of those who have been infected or died. Accurate numbers also help determine the potential danger for the rest of the world.
Insufficient test kits, inaccurate test kits, changing definitions of what constitutes a confirmed case of COVID-19, and overdiagnosis and misdiagnosis of the illness make it difficult to determine the real number of those affected. Accurate diagnosis is necessary so that hospitals and resources are allocated to real cases.
Monitor for Symptoms
MedicineNet author Charles Patrick Davis, MD, PhD said COVID-19 causes flu-like symptoms that worsen to fever, coughing, and shortness of breath. "Complications may include high fever, severe cough, difficulty breathing, pneumonia, organ failure, and death," he states.
"People may prevent or lower the risk of this viral infection by good hygiene, avoiding contact with infected people, not going into an outbreak area, and by leaving an outbreak zone," Dr. Davis concludes.
Anyone who has flu-like symptoms should reach out to their health care team for proper evaluation, diagnosis, and treatment.