Coronavirus is most contagious before & during the 1st week of symptoms

As sweeping efforts to contain the COVID-19 pandemic go into effect around the globe, researchers are starting to get hints of just when patients are most contagious.

People infected with the SARS-CoV-2 virus, which causes the disease, may test positive for the virus both before and after they have symptoms. But a new study of nine people who contracted the virus in Germany suggests that people are mainly contagious before they have symptoms and in the first week of the disease.

Infectious viruses were isolated from about 17 per cent of nose and throat swabs and more than 83 per cent of phlegm samples during that first week, researchers report March 8 in a study posted at medRxiv.org.

Patients produced thousands to millions of viruses in their noses and throats, about 1,000 times as much virus as produced in SARS patients, Clemens Wendtner, director of infectious disease and tropical medicine at Munich Clinic Schwabing, a teaching hospital, and his colleagues found. That heavy load of viruses may help explain why the new Coronavirus is so infectious.

Scientists identified these nine people sometime after they had been exposed to the Coronavirus, so researchers don't know for sure when exactly people begin giving off the virus.

After the eighth day of symptoms, the researchers could still detect the virus' genetic material, RNA, in patients' swabs or samples, but could no longer find infectious viruses. That's an indication that antibodies that the body's immune system makes against SARS-CoV-2 are killing viruses that get out of cells, Wendtner says.

The study brings an important point to light; finding RNA or pieces of a virus in a swab or sample is no guarantee that the virus is "live," or infectious, says Ali Khan, Dean of the College of Public Health at the University of Nebraska Medical Center in Omaha. "Some of it is discouraging news because when you are mildly [ill] or just [getting] sick, you're putting out a whole lot of virus, which explains why we're seeing so much transmission within our communities," says Kahn, who was not involved in the study.

But there's encouraging news, too. Plummeting numbers of the infectious virus after antibody production turns on "means that after about 10 days or so, you're not likely to be infecting other people," Khan says. Other studies also suggest that people with very mild or asymptomatic infections don't shed as much virus and aren't as likely to infect other people as people with more severe cases, he says.

Wendtner and colleagues put the nine patients through tests every morning during their hospital stay, collecting blood, urine, stool, nasal and throat swabs and asking the people to cough up sputum, or phlegm.

"We were learning with the patients because we did not know when would be the best and safest time to discharge them," Wendtner says.

The high levels of virus shedding from the nose and throat happened very early in infection — by the time of testing, most patients' upper airway virus production had already peaked. As the infection progresses, the virus moves deeper into the lungs, the findings suggest.

The team never found evidence of the virus in blood or urine and has stopped collecting those samples from a "second wave" of 23 COVID-19 patients now being treated at the hospital. Researchers did detect viral RNA in feces, but no infectious virus there. That suggests that the virus isn't spread through stool, an unknown until now.

All nine patients are employees of Webasto, an auto supplier in Stockdorf. They caught the virus from a male coworker, who became known as Patient 1. He originally got the virus from a business colleague from Shanghai who came to Germany in January for a series of meetings (SN: 1/31/20). Both Patient 1 and his Shanghai colleague transmitted the virus before developing symptoms, the first documented cases of asymptomatic spread.

As health officials tested other employees of the company, they found the study participants and placed them in isolation at the Munich clinic. In one case, Patient 1 sneezed during a meeting with one person, Wendtner says. "That was enough for infection." In other cases, "they had simple business meetings, sitting together for 60 minutes, 90 minutes [at a table or] in front of a computer, with no physical contact — just one handshake, that's all," Wendtner says. "The infectivity is quite high."

Most had coughs, but only two developed a fever, the most common symptom reported in other studies.

Most symptoms were mild and one person never developed any at all. One patient developed severe pneumonia.

Two of the nine had runny noses, previously reported as a rare symptom of COVID-19. Another four had stuffy noses and reported that they couldn't smell or taste anything. "In all of our patients, it cleared up, but it was a little bit annoying for two weeks or so," Wendtner says. "They could order anything they wanted [to eat], but [if] you can't taste it, it doesn't matter."

A temporary lack of smell or taste also affected some SARS patients in 2003, he says. That symptom may indicate that in addition to causing swelling in the nose, the virus may infect nerve cells responsible for identifying odors, he says.

Patients in the study started making antibodies against the virus about six to 12 days after symptoms started. Once antibody production kicked in, researchers still found high levels of viral RNA in phlegm and in nose and throat swabs, but patients were no longer giving off the infectious virus.

The early and extreme contagiousness of the virus "tell us that gatherings of people should be avoided," Wendtner says. But the results also may suggest that isolation periods could be shorter for people who have RNA but no virus. Researchers thought that because tests could still detect RNA for up to weeks after symptoms had cleared patients were infectious for that long. Most patients are not released from the hospital until two separate tests within 24 hours come back negative, Wendtner says.

But Wendtner isn't suggesting letting people out of quarantine before their two weeks are up. "Fourteen days is safe, and you have to keep it simple," Wendtner says. "Maybe it's safe 10 days after symptoms start, but you have to prove they have those neutralizing antibodies." Tests for the antibodies, however, are not widely available. Singapore has developed a test for Covid-19 antibodies and China is also testing a similar kit.

WHICH DRUGS COULD 'CURE' CORONAVIRUS?

Researchers at University of Queensland Centre for Clinical Research in Australia believe two drugs in combination may eradicate the virus entirely. While two top doctors in the USA believe another experimental drug has helped save the lives of American coronavirus patients.

The first is a medication used to suppress HIV, while the other is an anti-malaria treatment known as chloroquine, which has been largely forgotten due to an increased genetic resistance to the mosquito borne disease. The drugs have shown success in treating patients with COVID-19 in China and Thailand.

Professor David Paterson said one of the medications was given to some patients who were first identified as carriers in Australia, and appeared to lead to the 'disappearance of the virus'. .

He said it wouldn't be wrong to consider the drugs a possible 'treatment or cure' for the deadly respiratory infection.

He said it's a 'potentially effective treatment' that should be considered for a large scale medical trial immediately.

"What we want to do at the moment is a large clinical trial across Australia, looking at 50 hospitals, and what we're going to compare is one drug, versus another drug, versus the combination of the two drugs," Professor Paterson said.

The decision to test the drug was first made after Chinese people in Australia who returned a positive reading suggested the treatment after hearing positive anecdotes from sufferers in mainland China.

"That first wave of Chinese patients we had (in Australia), they all did very, very well when they were treated with the HIV drug," Prof. Patterson said.

LOPINAVIR/RITONAVIR

The combined fixed dose drug has been used in the fight against HIV and AIDS since 2006.

It has been successful in treating an Italian couple who came as tourists to the state of Rajasthan in India. The wife, who, along with her husband had been admitted to SMS Hospital in Jaipur with severe respiratory symptoms, and tested positive for COVID-19, showed such dramatic improvement in a few days that she was discharged from hospital and is now looking after her husband.

The Drug Controller General of India (DCGI) had approved the 'restricted' use of the combination of medications-lopinavir and ritonavir, before they were administered to the elderly couple. The DCGI had given the approval after the Indian Council of Medical Research (ICMR) had sought an emergency approval for using the drugs for treating COVID- 19.

Dr S Meena, the Medical Superintendent of SMS Hospital, said that the Italian man, who himself is a doctor, is on oxygen support. "Even before he acquired the infection, he had some respiratory issues. His condition had deteriorated and he developed severe respiratory problems after getting the Coronavirus infection and thus was given these drugs. His condition is stable now,'' Dr. Meena said. The couple was among the 16 Italian tourists who with their Indian guide tested positive for Coronavirus.

Some of the negative side affects to the drug include diarrhea, vomiting, feeling tired, headaches, and muscle aches.

Chinese medical researchers suggested the drug had successfully cured Coronavirus patients after the December 2019 outbreak.

Requests have been submitted in China to start a clinical trial to accurately determine its effectiveness in fighting COVID-19.

Australia and Thailand are also testing the drugs on local patients.

CHLOROQUINE

Chloroquine is a drug which was once commonly used to prevent and treat malaria.

As humans have developed an increased natural resistance to the mosquito-borne disease, the drug has been used less frequently.

Researchers now believe it may hold the key to treating COVID-19, the latest strain of Coronavirus.

Common side affects include muscle problems, loss of appetite and diarrhea.

In February 2020, Chinese medics determined the drug may be safe and effective in treating Coronavirus induced pneumonia.

REMDESIVIR

George Thompson, an infectious disease specialist at the University of California Davis Medical Center, was part of the team that administered the drug, Remdesivir, to a sickly American woman who tested positive for the virus on February 26. Remdesivir was first used for testing on Ebola patients but was considered a failed drug, though it has shown much better results on patients in China, which is conducting a large-scale clinical trial, the results of which haven't yet been published.

"We thought they were going to pass away," Thompson said of the American patient - who was the first known 'community spread' case in the United States.

However, 36 hours after the woman was admitted to hospital, doctors decided to treat her with remdesivir, which is administered by intravenous drip and 'cripples an enzyme named RNA polymerase - used by many viruses to copy themselves'.

Because the patient was in critical condition, the doctors were able to get 'compassionate use permission' from the FDA to test remsdesivir outside a clinical trial setting.

Within a day, the woman saw a drop in her 'viral load' and her condition began to improve.

Thomson did not reveal whether the patient has been discharged from the hospital due to privacy concerns, but stated that she is 'doing well'.

Similarly, Remsdesivir helped 14 Americans in Japan, who tested positive for Coronavirus after they traveled on board the Diamond Princess cruise ship. The patients who were treated with the experimental drug in a Japanese hospital were critically ill people and their average age is 75.

"Many of them were probably going to die in a short amount of time, and two weeks later nobody has died and more than half of them have recovered. It's just absolutely amazing," he remarked.

The blood of recovered patients in certain countries is also being monitored and analysed. Scientists have developed a "unique" protein that can detect antibodies - the hope is that it will help create a vaccine in the future.

Meanwhile, the first participant in a clinical trial in the USA, for a vaccine to protect against the new Coronavirus, received an experimental dose on Monday, March 16, according to a an American government official.

The National Institutes of Health is funding the trial, which is taking place at the Kaiser Permanente Washington Health Research Institute in Seattle. Testing will begin with 45 young, healthy volunteers with different doses of shots co-developed by NIH and Moderna Inc. Volunteers cannot get infected from the vaccine. Public health officials say it will take a year to 18 months to fully validate any potential vaccine.

Article credit: sciencenews.org