As the pandemic escalates, epidemiologists and public health authorities are scrambling to understand who is most vulnerable and how to protect them. The data from countries such as Italy and South Korea show that the disease can take wildly different paths.
Exactly what makes a group vulnerable — and how to protect them — has experts “mystified,” said Carlos del Rio, chair of the department of global health at Emory University. “This difference in mortality is creating a lot of anxiety,” he added.
ITALY: An aging country with overwhelmingly male deaths
The outbreak of covid-19 in Italy is the deadliest in the world. As of March 17, more than 40,000 people there have been sickened with the virus, and 3,405 have died. That means that, based on these current and unavoidably incomplete figures, 8.2 percent of people infected in the country have died. That is more than double the global figure presented recently by the World Health Organization.
Italy’s aging population is probably particularly susceptible to the disease, researchers say. With a median age of 46.5, according to the CIA World Factbook, it is the fifth-oldest country in the world. These elderly citizens are those who have become the sickest: People over age 70 represent more than 87 percent of deaths there.
Older people are typically hit harder with respiratory diseases, del Rio said. They are more likely to get pneumonia — an infection that inflames the lungs and fills them with fluid or pus — and to have underlying health conditions that could make older people vulnerable to the virus.
“With older people,” del Rio said, “sometimes it doesn’t take very much to push you over the edge.”
The gender disparity in illness and death is harder to explain. Even before the covid-19 pandemic reached Italy, early reports out of China suggested men were especially at risk. A study of 99 patients at a hospital in Wuhan, where the virus originated, found that men made up two-thirds of patients, and half of all the people who were hospitalized had chronic conditions such as heart disease or diabetes. More recent figures from China’s Center for Disease Control, based on tens of thousands of cases, showed a strong gender breakdown of deaths, which were 64 percent male.
But the figures in Italy have been even more staggering. Nearly 60 percent of diagnoses have been in men, according to Italy’s top health research agency, Istituto Superiore di Sanità. Across the first 1,697 coronavirus deaths, 71 percent — 1,197 — were in men. Just 29 percent, or 493, were in women.
In a recent study published in the Lancet, meanwhile, the figures were even higher. It found that 80 percent of the deaths were in men and just 20 percent were in women.
It is certainly possible that as death tolls rise in other countries, the pattern of greater male deaths seen so far in Italy, China, and South Korea could shift. But so far, this is what the evidence shows in the two countries with the largest death tolls, Italy and China, and in a third country (South Korea) acclaimed for keeping very good tabs on the disease.
“The honest truth is that today we don’t know why covid-19 is more severe for men than women or why the magnitude of the difference is greater in Italy than China,” said Sabra Klein, a professor at Johns Hopkins’s Bloomberg School of Public Health. “What we do know is that in addition to older age, being male is a risk factor for severe outcome and the public should be made aware.”
The gendered death gap was also seen in the smaller SARS and MERS outbreaks, added Angela Rasmussen, a virologist at Columbia University.
“It’s clearly something that has happened consistently with coronaviruses, it could inform clinical practices and improve patient outcomes, and it’s definitely a question worth investigating,” she added.
These statistics could be a product of behavior, biology or both, scientists say.
For one thing, demographic figures suggest many men have more health risks to begin with. In China, Italy and South Korea, women tend to live longer than men, according to the WHO.
Men also drink and smoke more in all of these countries, particularly in China, where 48 percent of men above 15 smoke, compared with just 2 percent of women, according to the WHO. Probably not coincidentally, men in these countries also tend to die more frequently from heart disease, cancer, diabetes and respiratory diseases between ages 30 and 70.
But there are also underlying biological differences between men and women that may make covid-19 worse in men, several researchers pointed out. Years of research have found that women generally have stronger immune systems than men and are better able to fend off infections. The X chromosome contains a large number of immune-related genes, and because women have two of them, they gain an advantage in fighting disease, according to a recent study in the journal Human Genomics. Studies have also found that estrogen was protective in female mice infected with the virus that caused the 2003 SARs outbreak. During that epidemic, men had a much higher case fatality rate than women.
“When [a] severe outcome is caused by an inability to rapidly control the infection, then it is often adult males who suffer worse outcomes than females,” Klein wrote in an email.
SOUTH KOREA: Few fatalities when patients are young and female
South Korea presents a stark contrast to Italy. Rapid action by public health authorities, who have administered coronavirus tests at a higher rate than any other country in the world, has slowed the spread of the outbreak there. As of March 19, the country had 8,565 confirmed cases and 91 deaths. As a result, its current case fatality rate of 1.06 percent is far below the global average.
That low death rate is testament to the country’s aggressive coronavirus response; Korean hospitals were not overloaded, as they are in Italy, and “life treatment centers” were set up for patients with milder symptoms.
But it is also a function of who is getting sick, del Rio said. Whereas the typical coronavirus patient in Italy and elsewhere is male and in his 60s, women represent more than 60 percent of infections in South Korea, and nearly a third of the cases there have been people between ages 20 and 29.
“What we’re beginning to see is that the disease presents in multiple ways, and it’s pretty mild in people who are young,” del Rio said.
Young women are overrepresented in South Korea’s coronavirus patient figures because of the demographics in the fringe religious sect Shincheonji Church of Jesus, where the country’s biggest coronavirus cluster took place.
South Korea saw a sudden spike in virus cases after an infection cluster emerged at a local branch of the church mid-February. Later that month, South Korean health authorities launched a testing blitz on more than 200,000 members of the church across the country.
In a briefing earlier this month, the country’s center for disease control director, Jung Eun-Kyeong, said the number of young female patients is high “because women in their 20s and 30s make up a big portion of Shincheonji church membership.”
Experts say the mass testing of the church members possibly gave rise to detection bias in epidemiological statistics surrounding South Korea’s coronavirus outbreak.
“If you test all members of a church, the likelihood of disease detection in that group naturally goes up,” said Choi Jae-wook, professor of Preventive Medicine at Korea University in Seoul. The skewed representation of young patients from the church cluster helped make South Korea’s case fatality rate so low, Choi said.
It may be that more young people are getting sick in Italy as well, but because their symptoms are mild and the country has not been testing aggressively, those cases are not being counted, del Rio said.
The age and gender discrepancies could offer important insights into how the coronavirus interacts with hosts’ immune systems, said Andrew Pekosz, a virologist at Johns Hopkins. Symptoms such as high fever and a bad cough suggest the virus triggers an extreme inflammatory response, in which the body counters attacks with an army of defensive cells.
“Sometimes it can be those cells that are driving the disease,” Peskov said, “causing more damage than they are controlling infection.”
Understanding this response, particularly as it unfolds differently in different demographics, may help researchers develop treatments, he added.
But Harlan Krumholz, a professor of cardiology and outcomes research at Yale Medical School, cautioned that comparing countries is a tricky endeavor. “We don’t know numerators or denominators. The information is not comparable,” he said.
He said the best information was probably from South Korea, because it tested so many people. “Everywhere else is biased,” he said, depending on who is doing the testing, who is considered severe enough to be hospitalized, and how you determine whether a death is related to the virus or not.
He worries that insufficient data is hampering doctors, scientists and public officials, making it more difficult to have a real-time understanding of the extent of the disease and the most effective ways to respond.
“We should be able to do this,” he said. “This is revealing our great ignorance in the midst of an information age.”
Kaplan and Mooney reported from Washington and Andy Kim from Seoul. Steven Mufson in Washington contributed to this report.
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