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Los Angeles, Apr 28: People who experience loss of smell as one of the COVID-19 symptoms are likely to have a mild to moderate clinical course of the disease, according to a study which may help health care providers determine which patients require hospitalisation.

The findings, published in the journal International Forum of Allergy & Rhinology, follows an earlier study that validated the loss of smell and taste as indicators of infection with the novel coronavirus, SARS-CoV-2.

According to the scientists from the University of California (UC) San Diego Health in the US, patients who reported loss of smell were 10 times less likely to be hospitalised for COVID-19 compared to those without the symptom.

"One of the immediate challenges for health care providers is to determine how to best treat persons infected by the novel coronavirus," said Carol Yan, first author of the current study and rhinologist from the UC San Diego Health.

"If they display no or mild symptoms, can they return home to self-quarantine or will they likely require hospitalisation? These are crucial questions for hospitals trying to efficiently and effectively allocate finite medical resources," Yan said.

The findings, according to the researchers, suggest that loss of smell may be predictive of a milder clinical course of COVID-19.

"What's notable in the new findings is that it appears that loss of smell may be a predictor that a SARS-CoV-2 infection will not be as severe, and less likely to require hospitalisation," Yan said.

"If an infected person loses that sense, it seems more likely they will experience milder symptoms, barring other underlying risk factors," she added.

Risk factors for COVID-19 previously reported by other studies include age, and underlying medical conditions, such as chronic lung disease, serious heart conditions, diabetes, and obesity.

In the current study, the scientists made a retrospective analysis between March 3 and April 8 including 169 patients who tested positive for COVID-19 at UC San Diego Health.

They assessed olfactory and gustatory data for 128 of the 169 patients, 26 of whom required hospitalisation.

According to the researchers, patients who were hospitalised for COVID-19 treatment were significantly less likely to report anosmia or loss of smell -- 26.9 per cent compared to 66.7 per cent for COVID-19-infected persons treated as outpatients.

Similar percentages were found for loss of taste, known as dysgeusia, they said.

"Patients who reported loss of smell were 10 times less likely to be admitted for COVID-19 compared to those without loss of smell," said study co-author Adam S. DeConde.

"Moreover, anosmia was not associated with any other measures typically related to the decision to admit, suggesting that it's truly an independent factor and may serve as a marker for milder manifestations of Covid-19," DeConde said.

The researchers suspect that the findings hint at some of the physiological characteristics of the infection.

"The site and dosage of the initial viral burden, along with the effectiveness of the host immune response, are all potentially important variables in determining the spread of the virus within a person and, ultimately, the clinical course of the infection," DeConde said.

If the SARS-CoV-2 virus initially concentrates in the nose and upper airway, where it impacts olfactory function, that may result in an infection that is less severe and sudden in onset, decreasing the risk of overwhelming the host immune response, respiratory failure, and hospitalisation, the scientists added.

"This is a hypothesis, but it's also similar to the concept underlying live vaccinations," DeConde explained.

"At low dosage and at a distant site of inoculation, the host can generate an immune response without severe infection," he added.

Loss of smell, according to the study, might also indicate a robust immune response which has been localised to the nasal passages, limiting effects elsewhere in the body.

Citing the limitations of the study, the scientists said they relied upon self-reporting of anosmia from participants, which posed a greater chance of recall bias among patients once they had been diagnosed with COVID-19.

They added that patients with more severe respiratory disease requiring hospitalisation may not be as likely to recognise or recall the loss of smell.

So the researchers said more expansive studies are needed for validating the results.

Paris, Apr 17: Even as virologists zero in on the virus that causes COVID-19, a very basic question remains unanswered: do those who recover from the disease have immunity?

There is no clear answer to this question, experts say, even if many have assumed that contracting the potentially deadly disease confers immunity, at least for a while.

"Being immunised means that you have developed an immune response against a virus such that you can repulse it," explained Eric Vivier, a professor of immunology in the public hospital system in Marseilles.

"Our immune systems remember, which normally prevents you from being infected by the same virus later on."

For some viral diseases such a measles, overcoming the sickness confers immunity for life.

But for RNA-based viruses such as Sars-Cov-2 -- the scientific name for the bug that causes the COVID-19 disease -- it takes about three weeks to build up a sufficient quantity of antibodies, and even then they may provide protection for only a few months, Vivier told AFP.

At least that is the theory. In reality, the new coronavirus has thrown up one surprise after another, to the point where virologists and epidemiologists are sure of very little.

"We do not have the answers to that -- it's an unknown," Michael Ryan, executive director of the World Health Organization's Emergencies Programme said in a press conference this week when asked how long a recovered COVID-19 patient would have immunity.

"We would expect that to be a reasonable period of protection, but it is very difficult to say with a new virus -- we can only extrapolate from other coronaviruses, and even that data is quite limited."

For SARS, which killed about 800 people across the world in 2002 and 2003, recovered patients remained protected "for about three years, on average," Francois Balloux director of the Genetics Institute at University College London, said.

"One can certainly get reinfected, but after how much time? We'll only know retroactively."

A recent study from China that has not gone through peer review reported on rhesus monkeys that recovered from Sars-Cov-2 and did not get reinfected when exposed once again to the virus.

"But that doesn't really reveal anything," said Pasteur Institute researcher Frederic Tangy, noting that the experiment unfolded over only a month.

Indeed,several cases from South Korea -- one of the first countries hit by the new coronavirus -- found that patients who recovered from COVID-19 later tested positive for the virus.

But there are several ways to explain that outcome, scientists cautioned.

While it is not impossible that these individuals became infected a second time, there is little evidence this is what happened.

More likely, said Balloux, is that the virus never completely disappeared in the first place and remains -- dormant and asymptomatic -- as a "chronic infection", like herpes.

As tests for live virus and antibodies have not yet been perfected, it is also possible that these patients at some point tested "false negative" when in fact they had not rid themselves of the pathogen.

"That suggests that people remain infected for a long time -- several weeks," Balloux added. "That is not ideal."

Another pre-publication study that looked at 175 recovered patients in Shanghai showed different concentrations of protective antibodies 10 to 15 days after the onset of symptoms.

"But whether that antibody response actually means immunity is a separate question," commented Maria Van Kerhove, Technical Lead of the WHO Emergencies Programme.

"That's something we really need to better understand -- what does that antibody response look like in terms of immunity."

Indeed, a host of questions remain.

"We are at the stage of asking whether someone who has overcome COVID-19 is really that protected," said Jean-Francois Delfraissy, president of France's official science advisory board.

For Tangy, an even grimmer reality cannot be excluded.

"It is possible that the antibodies that someone develops against the virus could actually increase the risk of the disease becoming worse," he said, noting that the most serious symptoms come later, after the patient had formed antibodies.

For the moment, it is also unclear whose antibodies are more potent in beating back the disease: someone who nearly died, or someone with only light symptoms or even no symptoms at all. And does age make a difference?

Faced with all these uncertainties, some experts have doubts about the wisdom of persuing a "herd immunity" strategy such that the virus -- unable to find new victims -- peters out by itself when a majority of the population is immune.

"The only real solution for now is a vaccine," Archie Clements, a professor at Curtin University in Perth Australia, told AFP.

At the same time, laboratories are developing a slew of antibody tests to see what proportion of the population in different countries and regions have been contaminated.

Such an approach has been favoured in Britain and Finland, while in Germany some experts have floated the idea of an "immunity passport" that would allow people to go back to work.

"It's too premature at this point," said Saad Omer, a professor of infectious diseases at the Yale School of Medicine.

"We should be able to get clearer data very quickly -- in a couple of months -- when there will be reliable antibody tests with sensitivity and specificity."

One concern is "false positives" caused by the tests detecting antibodies unrelated to COVID-19.

The idea of immunity passports or certificates also raises ethical questions, researchers say.

"People who absolutely need to work -- to feed their families, for example -- could try to get infected," Balloux.

The Covid-19 pandemic has made an unprecedented impact on the Indian businesses, particularly small and medium enterprises (SMEs) and startups. According to a joint survey by FICCI and Indian Angel Network (IAN), the pandemic has hit the businesses of around 70% startups.

With uncertainty in the business environment and an unexpected shift in priorities of the government as well as corporates, many startups are struggling to survive, it says.

In a nationwide survey on the 'Impact of Covid-19 on Indian Startups' involving 250 startups, 70% participants said their businesses had been impacted by Covid-19 and around 12% had shut operations.

The survey shows only 22% startups have cash reserves to meet the fixed cost expenses over the next 3-6 months, and 68% are reducing operational and administrative expenses.

Around 30% of the companies said they would retrench employees if the lockdown was extended too long. The 43% startups have already started 20-40% salary cuts over April-June.

Over 33% startups said investors had put the investment decision on hold and 10% said the deals had been scrapped. Only 8% startups had received funds as per the deals signed before Covid-19 outbreak, the survey revealed.

The reduced funding has forced startups to put a hold on business development and manufacturing activities, which has resulted in loss of projected orders.

The survey highlights the need of an urgent relief package for startups, including possible purchase orders from the government, tax relief and swifter tax refunds, and immediate fiscal support measures, including grants, soft loans and payroll grants.

Besides 250 startups, 61 incubators and investors also participated in the survey.

While 96% of investors accepted that their investments in startups had been impacted by Covid-19, 92% said their investments in startups would continue to be low over the next six months.

Around 59% investors said they would prefer to work with the existing portfolio firms in the coming months. Only 41% said they would consider new deals.

"A comparison of priority investment sectors before and during Covid-19 shows 35% investors are now looking at investments in healthcare startups, followed by EdTech, AI/Deep Tech, FinTech and Agri," said the survey.

Around 44% incubators surveyed said their day-to-day operations had been considerably hit by Covid-19. Most incubators are now supporting their portfolio firms by providing them virtual platforms to interact with mentors, investors and industries.

Dilip Chenoy, FICCI Secretary General, said, "The startup sector is stressed for survival at the moment. The investment sentiment is also subdued and is expected to remain so in the coming months. Lack of working capital and cash flows may lead to major layoffs over the next 3-6 months."

Indian startups needed an enabling ecosystem and flow of funds to continue operations, the survey said.

Padmaja Ruparel, President, Indian Angel Network & Co-Chair of FICCI Startup Committee, said, "In these uncertain times, as investors, we must play an important role to provide the Indian startups funding, mentoring and hand-holding support to stay afloat and come out at the other end of this crisis."

To that end, IAN recently announced a debt fund to help IAN portfolio companies raise working capital and ensure business continuity by partnering with debt providers.

This must be replicated on a wider scale, so a larger number of startups are provided the capital support to make it during these tough times, Ruparel said.