Mutations, unusual symptoms, and other COVID-19 mysteries that remain unsolved

NEW DELHI: Possibility of the novel coronavirus mutating into different strains, unknown reasons behind unusual symptoms like loss of smell, and patient samples yielding false positives in dengue diagnosis tests are some of the COVID-19 mysteries that remain unsolved, scientists say.

Ever since the novel coronavirus outbreak in the Chinese city of Wuhan in December 2019, studies have pieced together important clues about COVID-19, however, scientists believe solving some important mysteries may yield a potential therapeutic against the disease which has so far infected over 5.6 million people and claimed more than 3,55,000 lives.

One of the key mysteries, related to the development of therapeutics against the novel coronavirus is the rate and significance of the mutations observed in the spike protein on its surface, virologist Upasana Ray told .


Ray, a senior scientist at CSIR-Indian Institute of Chemical Biology (IICB) in Kolkata, said the spike protein helps the virus attach to host cells and gain entry into them.

In a study, which is yet to be peer-reviewed, Ray and her team observed mutations in SARS-CoV-2 samples isolated from Indian patients.

The researchers found changes in the folded structure of specific regions of the spike protein which they said might impact the interactions of the virus with host cells.

While most of the mutations they reported were located in the S1 subunit of the spike protein, they said one of the variations in one of the isolates was more towards the end of the S2 subunit.

Ray explained that the S1 subunit is responsible for binding to the host cell receptor while the S2 portion of the spike protein is involved in the fusion of the viral and cellular membranes.

She said mutations happening in the spike protein of the novel coronavirus should be carefully considered for vaccine engineering.

"Although mutations are emerging with new sequences been announced, there are patches that remain unchanged, and these should be the Achille's Heel for future SARS-CoV-2 vaccine," Ray noted in an email interview with .

Another puzzling discovery related to SARS-CoV-2 is that patients infected with the virus may test positive for other antibody diagnosis tests.

In one case study, published in March in The Lancet Infectious Diseases journal, serum samples from a man and a woman in Singapore, who were later diagnosed with COVID-19, showed reaction to a dengue antibody test, though they did not have any history of suffering from the mosquito-borne disease.

According to this study, the dengue diagnosis test, which works by undergoing a detectable chemical reaction if the patient's body has antibodies against the dengue virus, yielded a false-positive result in COVID-19 patients.

This indicates that their body's immune system may have been acting to SARS-CoV-2 infection in a way similar to how it would to dengue, explained virologist Subhajit Biswas from CSIR-IICB.

Based on this one-off case report, and the observation that dengue endemic countries have had less severe COVID-19 outbreak with fewer deaths due to the pandemic, Biswas hypothesises that the dengue vaccine may offer some protection to countries which are not endemic to the mosquito-borne disease.

He believes that in parts of the western world which has not had any exposure to dengue, the immune response triggered by a dengue vaccine may help protect, or reduce the severity of COVID-19.

According to Biswas, the need of the hour is to test the ability of the dengue vaccine to offer protection against SARS-CoV-2 infection in appropriate animal models.

There are also unanswered questions about the biology of some unusual COVID-19 symptoms, one of them being the loss of smell reported by several patients.

Scientists believe the symptom could be due to the presence of the viral 'entry gate' receptor ACE2 in the lining of the olfactory system of the nose.

"There is evidence that SARS-CoV-2 gains cell entry through two proteins: ACE2 and TMPRSS2. Both are expressed within the respiratory system, which could lead to its impacts on respiration," neuroscientist Shannon Olsson from the National Centre for Biological Sciences (NCBS) in Bengaluru told .

Citing a study, published earlier this month in the journal Nature Medicine, Olsson said ACE2 is expressed in the supporting cells of the olfactory epithelium.

She said SARS-CoV-2 may be causing impairment of the sense of smell through disruption of supporting cell function in the nose. Studies have also reported COVID-19 symptoms like clots, and inflammation in blood vessels called Kawasaki-disease.

One study, published in April in the journal Thrombosis Research, found that nearly 31 per cent of the 184 critically ill COVID-19 patients had blood-clot related symptoms.

In children, who form a small fraction of those suffering from severe COVID-19, lesions on hands and feet have been recognised as symptoms of SARS-CoV-2 infection.

A study, published earlier this month in the journal Pediatric Dermatology, noted a series of 22 children and adolescents with these lesions like chilblains, which are painful swelling on a hand or foot caused by poor blood circulation.

However, the researchers said the biological process by which this symptom - called "COVID toes" - manifests is unknown.

"In conclusion, acute chilblains are a newly recognised manifestation of COVID-19 in children and teenagers," the scientists from the Hospital Infantil Universitario Nino Jesus in Spain, said.