Coronavirus COVID19: A couple self isolate in a small hotel room. Video / Supplied
Cristian Guaman Benítez, a 33-year-old electrician who moved to Spain from Ecuador, had been sick for a week with a cough, a terrible headache and a fever as high as $40C.
He saw three doctors who treated his illness like a cold, prescribing medicines and sending him back to work. Finally, he called the number for Covid-19 information, and a doctor came to his home to examine him - and sent him by ambulance to Madrid's 12 de Octubre Hospital.
Which was where he discovered he was an outlier.
"I looked around and all I saw [were] very old people," Benítez remembered. Struggling to breathe by that point, he ended up in the intensive care unit, and only then, fortunately, was able to recover.
Benítez's story, of an ICU admission for Covid-19 at age 33, remains rare. However, based on detailed epidemiological data from the advancing epidemic in Spain, even young men are not risk free. And as men in the country get older, their cases of severe disease, including pneumonia, trips to the ICU, and deaths, become far more numerous than those for women.
Doctors work on a Covid-19 patient in the intensive care unit of San Matteo Hospital, in Pavia, northern Italy. Photo / AP
The data arriving from Spain, combined with similar findings from other countries with large outbreaks, such as Italy, China and France, are increasingly suggesting that the top risk group for the novel coronavirus is not simply older adults, but older men. A Washington Post analysis of US deaths so far also found that nearly 60 per cent of deaths, in cases where a gender could be identified, were male.
The Spain data, based on an analysis of 20,648 cases so far and 722 deaths by the country's Institute of Health Carlos III, a national public health agency, delivers a new level of detail. It shows that men are faring worse on multiple metrics for the disease.
Among gender-identified disease cases, men have 60 per cent of those that progress to the dangerous pneumonia stage. They have 59 per cent of the hospitalisations, 72 per cent of the intensive care unit admissions and 65 per cent of the deaths.
The gender divide shows up early, according to Spanish health officials. Men exhibit more of the initial symptoms: fever, cough and trouble breathing. And that carries through the course of sickness: Men progress more often to pneumonia, have more cases of acute respiratory distress syndrome, and more kidney failures.
One prominent hypothesis to explain higher male deaths from the disease in other countries is that men tend to smoke more. And yet in Spain, the gender-based smoking gap is small.
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Thirty-one per cent of males ages 15 and older smoke in the country, according to the World Health Organisation, and so do 27 per cent of women. So it seems unlikely that smoking alone would explain the disparities above.
"The discrepancy between rates of smoking in men and women are less pronounced in Spain and Italy than in China, yet the sex difference in Covid-19 outcomes are more pronounced in Spain and Italy, than in China," said Sabra Klein, an expert on how men and women experience disease, especially viral infections, at Johns Hopkins's Bloomberg School of Public Health. "Smoking cannot be the primary cause."
That's true of Benítez. He doesn't smoke or have any health issues, and he was stunned that he could get so sick.
"It was strange," he said of his hospitalisation, "because I was so much younger than everyone else. When I left, the doctor told me I was very strong because I had been very sick and a lot of people wouldn't have made it."
Experts trying to parse the meaning of the gender-based data out there say that, while behaviours play some role, it's also hard to rule out biological explanations. That's especially true because the additional X chromosome that women have plays a role in immune response, so much so that one recent study asserted that "it is clear that sex-specific effects contribute to infectious disease susceptibility and females have a major immunological advantage over males".
"The data from Spain and Italy supports the hypothesis that there is a biological basis for the sex bias observed in Covid-19 disease severity," said Angela Rasmussen, a virologist at Columbia University. "As the data continues to be analysed, it's possible we may find a behavioural or cultural basis for these disparities, but this is now emerging as a global trend, suggesting that this is rooted in the biological underpinnings of sex."
Klein agrees. At the same time, she also suspects a role for behavioural differences, such as less of a tendency toward hand-washing and less willingness to go to the doctor.
"I realise that everyone wants answers for the question of 'why,' but the truth is that we don't know and will not likely know until controlled research studies can be conducted to better understand these mechanisms," she said. "I think it is fair to say that being a male is a risk factor for more severe outcomes at this stage in the pandemic and should be taken seriously."
More data trickling in from other countries confirms the picture presented in Spain. Take, for example, admissions into critical or intensive care units for Covid-19, which Benítez experienced.
In France, 73 per cent of intensive care unit admissions for Covid-19 have been for men. In Norway that figure is 75 per cent. In Britain, it is 71 cent.
Granted, there is a great deal of uncertainty about why these statistics are turning out this way, and experts in Spain said there are theories but few clear answers.
Two Spanish experts agreed that whatever is going on, it does not seem to involve men contracting more cases. Rather, it's that their cases are worse once they do get the disease.
"Among men, severe disease appears more frequently than among women, and yet when we talk about the disease as a whole, both the serious and the mildest cases, the difference is not as stark," said Carlos A. Jiménez-Ruiz, pulmonologist and president of the Spanish Society of Pneumology and Thoracic Surgery (SEPAR).
While many countries show that men are also getting more infected with the novel coronavirus than women, the difference in Spain is slight. Men have 51 per cent of cases and women have 49 per cent.
One possible explanation for Jiménez-Ruiz, is that patients who have severe Covid-19 cases are more likely to have suffered previous diseases that are typically more common among Spanish men, such as chronic obstructive pulmonary disease and hypertension. According to data released by the Spanish government, 58 per cent of ICU or fatal Covid-19 cases involved previous cardiovascular diseases.
Jordi Vila Estape, president of Sociedad Española de Enfermedades Infecciosas y Microbiología (SEIMC) and head of the Department of Clinical Microbiology at Barcelona's Hospital Clinic, said that when it comes to severe disease, men are showing more cases, but "what isn't known is the reason for that".
He speculates that there could be a role for genetics. He also pointed out, as did Jiménez-Ruiz, that men have health conditions that complicate the disease at a younger age.
"And of course these basic diseases are creating a worse scenario, because if you already have a disease, if in addition you have an infection, the probability of mortality is very high."
For now, Benítez is at home in Madrid, where he lives with his mother, sister and girlfriend, but in quarantine by himself. He is recovering, but his main concern is whether he may have infected someone.
"My girlfriend has a fever and a headache," he said, "but when she went out to go to the doctor, they told her she can't go out on the street. She has to call the phone number. So she's waiting to see if it goes away by itself."
