Virus World

The city kept the pandemic at bay for two years. Why didn’t it take measures that would help in an inevitable outbreak—like an all-out campaign to vaccinate the elderly? Around 8 p.m. one evening in late February, an elderly man in a Hong Kong nursing home began struggling to breathe. He wasn’t the only one who was ill. An unprecedented outbreak of Covid-19 was gathering pace, and roughly half of the facility’s 100 residents had already tested positive for the virus. Less than a third were fully vaccinated; even fewer had received a booster dose. Isolating the infected was impossible. Like most dwellings in the city of 7.4 million, the nursing home was cramped. Instead of a private room, each resident’s dedicated space was only big enough for a 2½-foot-wide bed, separated from neighbors by thin wooden dividers. As the man’s condition worsened, staff called an emergency hotline for help. According to Cheng Ching-fat, the secretary-general of a union representing nursing-home workers, they waited more than 10 hours before an ambulance arrived to bring the man to a hospital. He died on the way, one of more than 4,000 Hong Kongers age 80 and older who’ve succumbed to the virus in the past few months. More than two years after Covid began spreading around the globe, Hong Kong is experiencing one of the deadliest outbreaks of the entire pandemic. It began early this year, when the omicron variant breached the Chinese territory’s ferocious quarantine system for inbound travelers, which had previously kept cases almost at zero. Soon it became clear that the authorities had done little to prepare for the possibility that the travel restrictions wouldn’t be enough. Within weeks, parts of the health-care system had effectively collapsed, and since January there have been about 5,600 fatalities. Although there are tentative signs that the worst may be over, right now more people are dying from Covid in Hong Kong, relative to population, than anywhere else in the world. For some, the situation has engendered a sort of dazed shock. How could a wealthy, sophisticated city, with a top-notch health-care system and ample time to learn from experiences elsewhere, get its response so wrong? “During the past two years the government has done nothing,” Cheng says. “It seems like it’s never come across to them that Hong Kong may face a serious outbreak.”

Hong Kong’s situation is the product of several specific policy failures, which stem partly from Beijing’s decision to take greater control of the financial hub after 2019’s pro-democracy protests. Above all, the city’s government utterly failed at vaccinating older adults, botching public-education campaigns and allowing misinformation about the shots to run rampant among those residents. As of March 18 just 37% of people 80 and older had received at least two doses, mostly of the Chinese-made Sinovac vaccine—perhaps the lowest rate in the developed world. Other missteps resulted from the doctrinaire application of China’s Covid-zero strategy, a suite of policies designed to stamp out every outbreak the moment it’s detected. Aggressive contact tracing and mandatory hospitalization of infected people, regardless of symptoms, worked well enough with daily case counts in the single digits, but they became useless as omicron raced through densely packed high-rises. Under pressure from China’s central government, Hong Kong officials stuck to them anyway, forcing people into daylong waits for compulsory testing and dedicating precious hospital beds to patients who could have easily stayed at home. The authorities maintained, and in some cases deepened, Hong Kong’s international isolation, completely banning flights from “high-risk” countries such as the U.S. and the U.K., as though the virus was still something that could be kept out.  Hong Kong’s situation is the product of several specific policy failures, which stem partly from Beijing’s decision to take greater control of the financial hub after 2019’s pro-democracy protests. Above all, the city’s government utterly failed at vaccinating older adults, botching public-education campaigns and allowing misinformation about the shots to run rampant among those residents. As of March 18 just 37% of people 80 and older had received at least two doses, mostly of the Chinese-made Sinovac vaccine—perhaps the lowest rate in the developed world. Other missteps resulted from the doctrinaire application of China’s Covid-zero strategy, a suite of policies designed to stamp out every outbreak the moment it’s detected. Aggressive contact tracing and mandatory hospitalization of infected people, regardless of symptoms, worked well enough with daily case counts in the single digits, but they became useless as omicron raced through densely packed high-rises. Under pressure from China’s central government, Hong Kong officials stuck to them anyway, forcing people into daylong waits for compulsory testing and dedicating precious hospital beds to patients who could have easily stayed at home. The authorities maintained, and in some cases deepened, Hong Kong’s international isolation, completely banning flights from “high-risk” countries such as the U.S. and the U.K., as though the virus was still something that could be kept out.

The most significant implications, however, could be felt in the rest of China, where authorities are rushing to contain the largest surge of infections since the 2020 outbreak in Wuhan. “What is happening in Hong Kong seems to vindicate their worst fears of what would happen if China were to open,” says Yanzhong Huang, a senior fellow at the Council on Foreign Relations and an expert on the Chinese health system. Outside of large cities, mainland facilities are rudimentary, and in a large outbreak, “you’re going to see hospitals quickly inundated with people seeking care. And it’s very possible the health-care system could be overwhelmed, which could lead to panic that would threaten political stability.” Until early this year, the total number of Covid deaths in Hong Kong stood near 200—about one-fifth of the current daily total in the U.S. This remarkable record was essentially the result of a single policy, implemented consistently and remorselessly: putting everyone who wanted to enter from abroad in quarantine in a hotel room for up to 21 days. It hardly mattered that, with mandatory PCR tests before departure and again on arrival at Hong Kong International Airport, almost no one who made it as far as checking into their isolation room actually tested positive. The point was to eliminate even the tiniest risk that the virus could enter, regardless of the consequences to the economy. On the rare occasions that an infected person slipped through, contact tracers swung into action, ordering everyone they’d been in contact with to Penny’s Bay, a spartan dormitory complex on an outlying island. Sometimes all it took to be sent there was having dined at the same restaurant as a positive case. But as long as a Hong Konger didn’t travel and avoided being swept up in a contact tracing dragnet, daily life retained a reassuring normalcy, with eateries, offices, and beaches still open and busy, even as cities in the U.S. and Europe swung in and out of sweeping social distancing campaigns......

A man in Hong Kong was found to be reinfected with COVID-19, but what that means for vaccines and immunity is unclear. Scientists have found the first solid evidence that people can be reinfected with the virus that causes COVID-19. A new study shows a 33-year-old man who was treated at the hospital for a mild case in March harbored the virus again when he was tested at the Hong Kong airport after returning from Europe on 15 August, less than 5 months later. He had no symptoms this time. Researchers had sequenced the virus, SARS-CoV-2, from the first infection; they did so again after the patient’s second diagnosis and found numerous differences between the two, bolstering the case that the patient had been infected a second time. “This case proves that at least some patients do not have life-long immunity,” Kelvin To, a clinical microbiologist at the University of Hong Kong (HKU) and one of the authors of a paper on the case, told Science today. Exactly what that finding means is unclear, however. To and his colleagues make some sweeping statements in their paper, parts of which Science has seen. “It is unlikely that herd immunity can eliminate SARS-CoV-2,” the authors write, referring to the idea that the epidemic will peter out once enough people have been infected and become immune. “Second, vaccines may not be able to provide life-long protection against COVID-19.”

But it’s too early to draw those conclusions, says Columbia University virologist Angela Rasmussen. “I disagree that this has huge implications across the board for vaccines and immunity,” she wrote in an email, because the patient described in the study may be a rare example of people not mounting a good immune response to the first infection. Mark Slifka, a viral immunologist at Oregon Health & Science University, says his takeaway from the paper is the opposite of what the authors write: “Even though [the patient] got infected with a very different strain that’s distinct from the first time around, they were protected from disease,” he says. “That is good news.” Fueling the debate over the importance of the case is that the paper on it isn’t public yet, which means scientists can’t scrutinize its data in full. HKU put out a press release about the study today and said the paper had been accepted for publication by the journal Clinical Infectious Diseases. To confirmed that a few pages of the manuscript circulating online were from the paper but said he could not make the full text available. “This is why I loathe data disclosure by press release,” Rasmussen wrote. “It seems designed to stoke sensationalism by leaving all these provocative questions unanswered, some of which could probably be answered by just reading the paper and examining the figures.” There have been several reports of COVID-19 patients testing positive for SARS-CoV-2 again after apparently clearing their infection, but in those cases there was less time between the tests and researchers did not have sequences of the viruses to confirm there were two different infections. Many of these cases were likely testing errors, says Jeffrey Barrett, a genomic epidemiologist at the Wellcome Sanger Institute: “I wasn’t convinced by any of them.” 

In the current case, the press release and paper excerpts say, the HKU scientists found 24 differences between the first and second viral genome, including one in the first virus that truncates a gene known as ORF8. “There’s sort of no chance that it’s the same infection twice,” Barrett says. “It is much more convincing than any other anecdotal reports that have come out so far,” agrees virologist Charlotte Houldcroft of the University of Cambridge. Even if the finding settles the question of whether people can be reinfected with the pandemic virus, it raises many additional questions: How often does this happen? Do people have milder infections, or no symptoms at all, the second time around? Can they still infect others? If natural infection does not always confer solid protection, will that be true for vaccines as well? To says he believes reinfections are not rare—just difficult to find. “This case is very special because he was screened at the airport,” he says. “Under normal circumstances, he may not even have been aware that he was infected again.” If reinfections are more likely to lead to asymptomatic cases, To notes, they may be tougher to spot. In a press conference on Monday morning, epidemiologist Maria Van Kerkhove of the World Health Organization warned against jumping to conclusions. “We need to look at this at a population level,” she said. Given that there have been more than 24 million reported SARS-CoV-2 infections worldwide, a single reinfection report may signal a very rare event, Barrett says. “Biology is complicated. You always find some strange exceptions.” He hopes efforts like the COVID-19 Genomics UK Consortium, which is sequencing viral samples from tens of thousands of patients, will provide data on how often reinfection occurs. Houldcroft says studies in health care workers may be key, because they are most likely to be exposed repeatedly....

There are now several cases of people becoming reinfected with Covid-19. But experts stress that’s not cause for panic. Here’s how to assess the news. Following the news this week of what appears to have been the first confirmed case of a Covid-19 reinfection, other researchers have been coming forward with their own reports. One in Belgium, another in the Netherlands. And now, one in Nevada. What caught experts’ attention about the case of the 25-year-old Reno man was not that he appears to have contracted SARS-CoV-2 (the name of the virus that causes Covid-19) a second time. Rather, it’s that his second bout was more serious than his first.  Immunologists had expected that if the immune response generated after an initial infection could not prevent a second case, then it should at least stave off more severe illness. That’s what occurred with the first known reinfection case, in a 33-year-old Hong Kong man.  Still, despite what happened to the man in Nevada, researchers are stressing this is not a sky-is-falling situation or one that should result in firm conclusions. They always presumed people would become vulnerable to Covid-19 again some time after recovering from an initial case, based on how our immune systems respond to other respiratory viruses, including other coronaviruses. It’s possible that these early cases of reinfection are outliers and have features that won’t apply to the tens of millions of other people who have already shaken off Covid-19.  “There are millions and millions of cases,” said Michael Mina, an epidemiologist at Harvard’s T.H. Chan School of Public Health. The real question that should get the most focus, Mina said, is, “What happens to most people?” But with more reinfection reports likely to make it into the scientific literature soon, and from there into the mainstream press, here are some things to look for in assessing them.

What’s the deal with the Nevada case?

The Reno resident in question first tested positive for SARS-CoV-2 in April after coming down with a sore throat, cough, and headache, as well as nausea and diarrhea. He got better over time and later tested negative twice.  But then, some 48 days later, the man started experiencing headaches, cough, and other symptoms again. Eventually, he became so sick that he had to be hospitalized and was found to have pneumonia. Researchers sequenced virus samples from both of his infections and found they were different, providing evidence that this was a new infection distinct from the first.

What happens when we get Covid-19 in the first case?

Researchers are finding that, generally, people who get Covid-19 develop a healthy immune response replete with both antibodies (molecules that can block pathogens from infecting cells) and T cells (which help wipe out the virus). This is what happens after other viral infections. In addition to fending off the virus the first time, that immune response also creates memories of the virus, should it try to invade a second time. It’s thought, then, that people who recover from Covid-19 will typically be protected from another case for some amount of time. With other coronaviruses, protection is thought to last for perhaps a little less than a year to about three years. But researchers can’t tell how long immunity will last with a new pathogen (like SARS-CoV-2) until people start getting reinfected. They also don’t know exactly what mechanisms provide protection against Covid-19, nor do they know what levels of antibodies or T cells are required to signal that someone is protected through a blood test. (These are called the “correlates of protection."

Why do experts expect second cases to be milder?

With other viruses, protective immunity doesn’t just vanish one day. Instead, it wanes over time. Researchers have then hypothesized that with SARS-CoV-2, perhaps our immune systems might not always be able to prevent it from getting a toehold in our cells — to halt infection entirely — but that it could still put up enough of a fight to guard us from getting really sick. Again, this is what happens with other respiratory pathogens. And it’s why some researchers actually looked at the Hong Kong case with relief. The man had mild to moderate Covid-19 symptoms during the first case, but was asymptomatic the second time. It was a demonstration, experts said, of what you would want your immune system to do. (The case was only detected because the man’s sample was taken at the airport when he arrived back in Hong Kong after traveling in Europe. “The fact that somebody may get reinfected is not surprising,” Malik Peiris, a virologist at the University of Hong Kong, told STAT earlier this week about the first reinfection. “But the reinfection didn’t cause disease, so that’s the first point.” The Nevada case, then, provides a counterexample to that....

The case raises questions about the durability of immune protection from the coronavirus, though it remains unclear whether it's an outlier. Researchers in Hong Kong on Monday reported what appears to be the first confirmed case of Covid-19 reinfection, a 33-year-old man who was first infected by SARS-CoV-2 in late March and then, four and a half months later, seemingly contracted the virus again while traveling in Europe. The case raises questions about the durability of immune protection from the coronavirus. But it was also met with caution by other scientists, who questioned the extent to which the case pointed to broader concerns about reinfection. There have been scattered reports of cases of Covid-19 reinfection. Those reports, though, have been based on anecdotal evidence and largely attributed to flaws in testing. But in this case, researchers at the University of Hong Kong sequenced the virus from the patient’s two infections and found that they did not match, indicating the second infection was not tied to the first. There was a difference of 24 nucleotides — the “letters” that make up the virus’ RNA — between the two infections. “This is the world’s first documentation of a patient who recovered from Covid-19 but got another episode of Covid-19 afterwards,” the researchers said in a statement.

Experts cautioned that this patient’s case could be an outlier among the tens of millions of cases around the world and that immune protection may generally last longer than just a few months. They said that ongoing studies tracking patients who had recovered from Covid-19 would help reach more definitive conclusions. “There’s been more than 24 million cases reported to date,” Maria Van Kerkhove, a coronavirus expert at the World Health Organization, said at a briefing Monday, when asked about the Hong Kong report. “And we need to look at something like this at a population level.” The question of how long someone is protected from Covid-19 after being infected and recovering looms large. Studies are increasingly finding that most people who recover from the illness mount a robust immune response involving both antibodies (molecules that can block the virus from infecting cells again) and T cells (which can help clear the virus). This has suggested that people would be protected from another case for some amount of time. But based on what happens with other coronaviruses, experts knew that immunity to SARS-CoV-2 would not last forever. People generally become susceptible again to the coronaviruses that cause the common cold after a year or even less, while protection against SARS-1 and MERS appears to last for a few years. “What we are learning about infection is that people do develop an immune response, and what is not completely clear yet is how strong that immune response is and for how long that immune response lasts,” Van Kerkhove said. She added she was still reviewing the Hong Kong case.

The strength and durability of the immune response is also a crucial factor in how long vaccines will be effective for, and for how often people might need a booster dose. In the Hong Kong case, the man had traveled to Spain and returned to Hong Kong via the United Kingdom. A saliva sample was taken upon arrival in Hong Kong as part of a screening protocol and tested positive for SARS-CoV-2 on Aug. 15. During his second infection, the man did not have any symptoms. Some patients go through their course of Covid-19 without showing symptoms, but researchers have also hypothesized that secondary cases of the coronavirus will generally be milder than the first. Even if immune systems can’t stop the virus from infecting cells, they might still rally some level of response that keeps us from getting sicker. During his first case, the patient had classic Covid-19 symptoms of cough, fever, sore throat, and headache...

Original study published in Clinical Infect. Diseases (August 25, 2020):

https://doi.org/10.1093/cid/ciaa1275