Can dengue be sometimes mistaken for COVID-19? Two independent research studies — one from a group in Israel and another from the Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB) in Kolkata — show that tests specific to check for dengue sometimes led to a positive SARS-CoV-2 test and this, the scientists warn, could lead to misdiagnoses and skew public health responses in places where dengue is endemic and known to seasonally spike. This also prompts deeper investigation into whether there are crucial similarities in the structure of these viruses.
The study from Israel, that was published in the peer-reviewed Clinical Infectious Diseases last week, describes testing 55 people, who had been confirmed to have a SARS-CoV-2 infection, for dengue. This was done by using a serology test, or a blood-based test, where antibodies that are produced by the body during a dengue infection are used to probe for the presence of the virus. The principle is that when an antibody binds to a specific place on the virus, called an antigen, like a key that goes into a lock, a test is returned as ‘positive’. Antibodies and antigens are highly specific to each other.
Among the 55, 12 (21%) returned positive. Because the viruses that causes dengue and coronaviruses belong to entirely different families, it is not expected for one to show affinity to the other.
Further, another lot of 95 samples obtained from patients diagnosed with dengue before September 2019, or the advent of COVID-19, targeting the spike (S) protein was positive, the report adds.
The study by CSIR-IICB used dengue antibody- positive serum samples from 2017 (pre-dating the COVID-19 outbreak) and produced false-positive results in SARS-CoV-2 IgG/IgM rapid strip tests, according to Subhajit Biswas, senior scientist at the IICB. This study is yet to be peer-reviewed and has not been published in a journal but appears in Medrxiv, a preprint repository of scientific publications that are open to public evaluation. “In places with recurrent epidemics of dengue, there is a risk that dengue may be identified as COVID-19 and so there ought to be confirmatory testing with other tests to rule this out,” he told The Hindu.
“22% testing positive is a significant number as the inherent error of the test itself is 4%. So we need to study further if the dengue virus is able to stimulate the body’s immune system to produce antibodies that could then bind to the coronavirus,” Dr. Biswas said.
Current confirmatory tests for COVID-19 are the rapid RT-PCR (real-time polymerase chain reaction) tests that returns a result after checking for multiple genes to confirm the presence of the virus. However, several antigen tests that are commercially deployed are strip based-antibody tests that return results for the presence for the virus quickly but are also prone to error, particularly false negatives. This is why the Indian Council of Medical Research guidelines recommend repeat tests. The dengue test widely employed is an antibody test and used to look for antibodies against the dengue virus protein.
Better understanding of the relationship between the two viruses could help understand variations in mortality. “India and Brazil are highly endemic for dengue as are many parts of southeast Asia. Could that explain relatively lower per million mortality compared to Europe and the United States, where there’s little dengue? That may be worth investigating,” he added.