Covid-19: Up to 10% of recovered patients test positive later, say Wuhan doctors

27 March, 2020

HONG KONG — About three to 10 per cent of patients who recovered from Covid-19 tested positive again after being discharged from hospital, doctors in Wuhan have found.

Researchers around the world are trying to determine whether recovered patients can still infect people with the coronavirus that causes the disease and if they have developed antibodies offering them immunity to the disease.

Doctors from Tongji hospital in the city, where the disease was first identified, told state broadcaster CCTV that they have found no evidence that the recovered patients became infectious after recovery, based on close observations of their family members and laboratory tests.

In spite of its relatively small sample size, the Tongji hospital research is especially relevant as China now has far more recovered patients than new confirmed cases.


The Chinese mainland, where the disease first emerged last December, has discharged over 90 per cent of its infected patients and around 4,300 confirmed patients are still receiving treatment in hospitals.

The country has reported more than 81,000 cases in total and over 3,100 deaths, but most of the new cases have been imported.

Dr Wang Wei, president of Tongji hospital told CCTV's prime-time programme that of the 147 recovered patients they studied, only five — or just over 3 per cent — have tested positive in nucleic acid tests again after recovery.

Meanwhile, Life Times, a health news outlet affiliated with People's Daily, reported this week that quarantine facilities in Wuhan have reported that about 5 to 10 per cent of their recovered patients tested positive again.

Previous reports have also highlighted cases where patients tested positive after recovery, including one on Sunday from Life Times about a family of three in Wuhan, who all tested positive again.

These incidents have raised questions about whether nucleic acid tests might not be reliable in detecting traces of the virus in some of the recovered patients.

Some experts have also expressed concerns about the sensitivity and stability of the test kits, and the collection and handling of patients' samples.

Dr Wang told CCTV that the five patients from his hospital who tested positive again did not have any symptoms, and none of their family members or people in close contact with them has been infected.

He said there was no conclusive evidence to prove that the recovered patients who tested positive again would be infectious to others.

"So far there is no evidence to suggest that they are infectious," Dr Wang said, adding that surveillance of similar patients showed about 80 to 90 per cent of them had no trace of the coronavirus in their blood one month after being discharged from hospitals.

Another sample group of 15 patients from the hospital also confirmed a similar trend, with none infecting their family members.

"These are just small samples and not enough to assure us of the validity of our initial findings," Dr Wang said. "We need a large-scale epidemiological study to guide our disease surveillance and prevention works."

However, he said it was imperative for recovered patients to stay in isolation for two weeks after discharge so they could be tested again for confirmation.

In a separate interview with CCTV also broadcast on Tuesday, Dr Tong Chaohui, a respiratory disease expert from a central government task force in Hubei, where Wuhan is located, agreed that continued monitoring of the recovered patients was important.

"So far, none of the close family members of these recovered patients have been tested positive and we could not find the coronavirus in the laboratory cultured samples [from these patients ]," Dr Tong said.

"Although the nucleic acid tests were positive, random checking suggested that the patients have developed antibodies that were effective in protecting them from the nucleic acid of the virus," he added.

Speaking to official newspaper Hubei Daily early this week, Mr Tu Yuanchao, deputy director of Hubei health commission, said discharged patients who tested positive again and have shown symptoms would be re-hospitalised. Those who do not have symptoms would be sent to quarantine facilities for observation for two weeks. 

SOUTH CHINA MORNING POST

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Can you become immune to the coronavirus?

26 March, 2020

NEW YORK — As the number of people infected with the coronavirus surpasses 450,000 worldwide, and more than 1 billion are locked in their homes, scientists are wrestling with one of the most pressing questions of the pandemic: Do people who survive the infection become immune to the virus?

The answer is a qualified yes, with some significant unknowns. That’s important for several reasons.

People who are confirmed to be immune could venture from their homes and help shore up the workforce until a vaccine becomes available, for example. In particular, health care workers who are known to be immune could continue to care for the severely ill.

Growing immunity in the community also is the way the epidemic ends: With fewer and fewer people to infect, the coronavirus will lose its toehold and even the most vulnerable citizens become more insulated from the threat.

Immunity may also bring an early treatment. Antibodies gathered from the bodies of those who have recovered may be used to aid those struggling with the illness caused by the coronavirus, called Covid-19.

On Tuesday (March 24), the Food and Drug Administration approved the use of plasma from recovered patients to treat some severe cases. A day earlier, Governor Andrew Cuomo announced that New York would become the first state to begin testing serum from people who have recovered from Covid-19 to treat those who are seriously ill.

“It’s a trial for people who are in serious condition, but the New York State Department of Health has been working on this with some of New York’s best health care agencies, and we think it shows promise,” Mr Cuomo said.

The body’s first line of defence against an infectious virus is an antibody called immunoglobulin M, whose job is to stay vigilant in the body and alert the rest of the immune system to intruders like viruses and bacteria.

Days into an infection, the immune system refines this antibody into a second type, called immunoglobulin G, exquisitely designed to recognise and neutralize a specific virus.

The refinement may take as long as a week; both the process and the potency of the final antibodies can vary. Some people make powerful neutralising antibodies to an infection, while others mount a milder response.

The antibodies generated in response to infection with some viruses — polio or measles, for example — bestow a lifetime of immunity. But antibodies to the coronaviruses that cause the common cold persist for just one to three years — and that may be true of their new cousin as well.

A study in macaques infected with the new coronavirus suggested that once infected, the monkeys produce neutralising antibodies and resist further infection. But it is unclear how long the monkeys, or people infected with the virus, will remain immune.

Most people who became infected during the Sars (severe acute respiratory syndrome) epidemic — that virus is a close cousin of the new coronavirus, called Sars-CoV-2 — had long-term immunity lasting eight to 10 years, said Dr Vineet D. Menachery, a virologist at the University of Texas Medical Branch at Galveston.

Those who recovered from Middle East respiratory syndrome (Mers), another coronavirus, saw much shorter-term protection, Dr Menachery said. People who have been infected with the new coronavirus may have immunity lasting at least one to two years, he added: “Beyond that, we can’t predict.”

Still, even if antibody protection were short-lasting and people become reinfected, the second bout with the coronavirus would likely be much milder than the first, said Dr Florian Krammer, a microbiologist at the Icahn School of Medicine at Mount Sinai in New York.

Even after the body stops producing neutralising antibodies, a subset of immune memory cells can reactivate a response effectively, he noted.

“You probably would make a good immune response before you even become symptomatic again and might really blunt the course of the disease,” Dr Krammer said.

A crucial question is whether children and adults who have only mild symptoms still generate a strong enough response to remain immune to the virus until a vaccine is available.

Dr Marion Koopmans, a virologist at Erasmus University in Rotterdam, and her team have screened antibody responses in 15 infected patients and health care workers.

The researchers are also using banked blood samples from about 100 people who were known to be infected with one of four coronaviruses known to cause the common cold.

If those samples show some immune response to the new coronavirus, too, Dr Koopmans said, it might explain why some people — children, for example — have only mild symptoms. They may have antibodies to related coronaviruses that are at last somewhat effective against the new one.

The quickest way to assess immunity is a blood test that looks for protective antibodies in the blood of people who have recovered. But first you have to have the test.

Antibody tests are used in Singapore, China and a handful of other countries. But they are just coming to market in much of the West.

Last week, Dr Krammer and his colleagues developed one such antibody test that could be scaled up in “days to weeks”, he said.

The team validated the test in blood plasma taken from three patients with Covid-19. The researchers are seeking speedy approval from the FDA.

Dozens of other labs are also at work on a dizzying list of tests, although they, too, are mostly based on slim data that has not yet been reviewed by other scientists.

“No matter who makes them, as long as they’re reliable, that’s a super nice tool,” Dr Krammer said. Because this is a new coronavirus, the test should deliver “basically, a yes or no answer, like an HIV test — you can figure out who was exposed and who wasn’t”.

On Wednesday, officials of Public Health England said they had purchased millions of newly developed antibody tests and were evaluating them for patients to use at home. Citizens who discovered they had been exposed and now had some immunity to the coronavirus might be able to return to normal lives, the officials said.

That would be particularly useful for health care workers. Those who know they have at least some immunity could be placed on the front lines of emergency care, sparing colleagues who have not been exposed.

“If this really goes on for months at a time, for 18 months as some people have projected, having health care workers who are immune to the virus will be really, really helpful,” said Dr Angela Rasmussen, a virologist at Columbia University in New York.

But tests like these may not be of much use for diagnosis of coronavirus infection as it gets underway, because of the time it takes for the body to begin producing antibodies.

Dr Krammer’s test picks up an antibody response as early as three days after symptoms emerge. Given that people may not show symptoms for as long as 14 days after infection, however, that is too late for the test to be useful as a diagnostic tool.

Finding people with powerful antibody responses might help point the way to new treatments, however. Essentially, antibodies extracted from the blood of recovered patients are injected into those who are ill.

Several teams have already been working on such an effort, following early reports from China of success. A Beijing-based company called AnyGo Technology has provided 50,000 tests to the Chinese Centre for Disease Control and Prevention, and to hospitals in Wuhan, Beijing and Shanghai, according to its founder, Dr Le Sun.

Dr Shangen Zheng, a doctor with the Chinese military, said his team had treated more than 10 patients so far, and data from many more patients treated with plasma in Hubei province is being assessed.

This approach is actually “something very old-fashioned”, Dr Krammer said. It was used to save American soldiers infected with the hemorrhagic Hantaan virus during the Korean War, and to treat people in Argentina infected with the hemorrhagic Junin virus.

Before the method can be put into wide use, however, scientists must work out safety issues, such as ensuring that the plasma taken from recovered patients is free of other viruses and toxins.

Pharmaceutical companies like Takeda and Regeneron are hoping to sidestep some of those questions by developing antibodies against the coronavirus in the laboratory.

Ultimately, it is only with these tests that scientists will be able to say when enough of the population has been infected and has become immune — and when the virus has begun to run out of hosts. 

THE NEW YORK TIMES