Until the 21st century, the worst a coronavirus, a large family of viruses capable of infecting humans and animals, could do to humans was to deliver the common cold—annoying but hardly sinister. But three times so far in the 21st century, novel coronaviruses have emerged that could potentially cause a deadly pandemic—SARS (severe acute respiratory syndrome) in 2003, MERS (Middle East respiratory syndrome) in 2012, and now 2019-nCoV emanating from Wuhan, China. As of Jan. 26, the new coronavirus has reportedly infected at least 2,463 people and caused at least 80 deaths. Those numbers are certain to mushroom.
Controlling the spread of the virus requires both public health and medical measures—and for that we need a clear clinical profile. At this stage, that information is only just being put together, but what we do have is disturbing.
So far, the limited clinical information coming out of China means we know only about the mid-to-worst-case outcomes—from moderate to life-threatening pneumonia. Two studies released on Jan. 24—one about 41 infected patients and the other on a family cluster of six separate from those 41—provide both clues and concerns.
The official story is that this new coronavirus emerged from a Wuhan wet market, where live animals that would never normally meet in the wild live side by side, facilitating trans-species mutation of pathogens. Yet the first three known cases from Dec. 1 and 2 were not linked to the market. Neither were 11 more cases of the 41 reviewed in the recent study. This early data suggests an evolving virus that surfaced considerably earlier. Undetected among the plethora of similar chest infections and common symptoms, it honed its capacity to spread from human to human. As happened with SARS, new corona may be mutating along the way, gradually becoming more virulent.
The coronavirus is a physically large virus—in relative terms, at just 125 nanometers with a surface of spike projections, too big to survive or stay suspended in the air for hours or travel more than a few feet. Like influenza, this coronavirus spreads through both direct and indirect contact. Direct contact occurs through the physical transfer of the microorganism among friends and family through close contact with oral secretions. Indirect contact results when an infected person coughs or sneezes, spreading coronavirus droplets on nearby surfaces, including knobs, bedrails, and smartphones.
As with SARS, droplets generated during medical procedures such as bronchoscopy and respiratory treatment may be aerosolized, infecting multiple medical staff and enabling super-spreading. Hand hygiene and personal protective barriers—gowns, gloves, masks, and goggles—reduce droplet transmission. The incubation period, however, is unknown but currently very roughly estimated as between one and 14 days.
To complicate matters further, we do not know how easily the new coronavirus spreads. Can transmission take place before the onset of symptoms? (Measles, one of the most contagious diseases on Earth, is infectious two to four days beforehand.) Do people who never become symptomatic nonetheless spread the disease? Do symptomatic people become less contagious over time, like SARS, or is it like Ebola, which becomes increasingly contagious as the disease progresses? These are all unanswered questions.
In fact, it probably causes a spectrum of disease, from asymptomatic to lethal. Even in deadly cases, new coronavirus infections start off much like many other less dangerous diseases. Initial symptoms are fever, dry cough, myalgia (muscle pain), and fatigue. Productive cough (a cough that produces phlegm) and headache are infrequent, hemoptysis (coughing up blood) and diarrhea occasional. It can take about a week before an infected person feels sick enough to seek medical care.
After this deceptively slow start, the disease progresses rapidly during the second week—in a similar fashion to SARS. Hypoxemia caused by increasing lung injury leads to difficulty breathing and the need for oxygen therapy. ARDS (acute respiratory distress syndrome) is a common complication. Between 25 and 32 percent of cases are admitted to the intensive care unit (ICU) for mechanical ventilation and sometimes ECMO (pumping blood through an artificial lung for oxygenation).
Other complications include septic shock, acute kidney injury, and virus-induced cardiac injury. The extensive lung damage also sets the lung up for secondary bacterial pneumonia, which occurs in 10 percent of ICU admissions. (This may also be the case for the Spanish flu of 1918, which killed 50 million people; the fatalities attributed to the viral influenza may be more because of the bacterial pneumonia that followed.)
Pneumonia from any cause severe enough to require ICU admission is associated with high morbidity and mortality. Defined as an infection of one or both lungs, it was already considered an ancient disease in Hippocrates’s time. In 1881, pneumococcus—the main cause of bacterial pneumonia—was finally identified. Over the next century, medical advances and the development of antibiotics made treatment possible, honed by intensivists to reduce the mortality rate to single figures.
In contrast, because few respiratory viruses cause more than mild infection, adult intensive care physicians generally have relatively little experience with viral pneumonia. Yet infection by SARS, H1N1, and MERS can lead to severe pneumonitis, ARDS, and respiratory failure, possibly because of an exaggerated inflammatory reaction. (Corticosteroids, the go-to anti-inflammatory drug, are ineffective and not recommended by the World Health Organization, or WHO.) The lack of effective antivirals and treatment options means viral pneumonia has a high mortality rate.
We do not know how lethal the new coronavirus is. While the single figures of deaths in early January seemed reassuring, the death toll has now climbed to above 3 percent. This may indicate better reporting—or the lethal lag time (the time for those infected to die). Another big unknown is the risk factors that would lead infection in a deadly direction. Certainly, some adults have compromised immune systems due to chronic illnesses. Of these, 15 percent have died, with higher fatality rates among older patients and those with co-morbidities of diabetes, hypertension, or coronary artery disease. However, most patients with severe illness were healthy to begin with, including a 30-year-old man who recently died.
Even trickier than treatment is detecting the virus. In quarantined Wuhan, dozens of fever clinics are singling out anyone with a fever of 99.1 degrees Fahrenheit or above—the cardinal sign for 98 percent of pneumonia cases—and then interviewing them about possible exposure to the coronavirus. In theory, this sounds reasonable.
In practice, it is the screening from hell. Early symptoms of fever and cough are clinically indistinguishable from the usual winter suspects, such as influenza, while fever is an undifferentiated sign, common to hundreds of noninfective diseases from allergies to arthritis. Even pregnancy elevates body temperature.
Because 110,000 people (about 1 percent of the population) in Wuhan might have a febrile illness at any given time, clinics, hospitals, and medical personnel are overwhelmed, short on lab tests and personal protective equipment. And as all those with a fever are detained until lab tests are back, nosocomial infection—transmission of disease in crowded clinics—becomes more likely.
Exit and entry screenings at international airports have been successful in picking up cases in Thailand and South Korea but have missed cases still incubating in the United States and Australia that were later detected in hospital after symptoms manifested.
More worrying is that several cases have been identified without a fever. This includes detection of coronavirus in a 10-year-old girl who exhibited no symptoms at all. If the coronavirus can be spread before symptoms appear, it will greatly complicate screening efforts even beyond the inadequacies of the fever test.
One puzzling aspect so far is the thankful lack of child victims. Usually, children, with less developed immune systems than adults, come down with one illness after another. A particularly severe example is RSV viral pneumonia, which results in an estimated 118,200 child deaths annually. (Adults are not seriously affected.)
Yet few children have yet been reported with coronavirus symptoms. That does not mean that no children have been infected. A similar pattern of benign disease in children, with increasing severity and mortality with age, was seen in SARS and MERS. SARS had a mortality rate averaging 10 percent. Yet no children, and just 1 percent of youths under 24, died, while those older than 50 had a 65 percent risk of dying. Is being an adult a risk factor per se? If so, what is it about childhood that confers protection? It may be the nonspecific effects of live vaccines such as for measles and rubella, which already have been found to provide protection from diseases beyond their immediate target. That may also explain why more men than women have been infected by the coronavirus, because women routinely are given a rubella vaccine booster in their teens to guard against the dangers of having rubella while pregnant. While we wait for an accelerated coronavirus vaccine to be ready, could innate immunity in adults be boosted by giving measles vaccines?
The virus itself is not the only risk. Fewer than half the patients hospitalized so far for the coronavirus ended up having the underlying disease. As hundreds more cases, many of them likely to be false positives, are picked up during aggressive screening, fewer patients can receive adequate support care. This compounds the clinical and ethical burden on medics working 24-hour shifts, working alongside colleagues who then become patients and living in hospitals because they are unwilling to risk infecting their families by going home.
This compounds the clinical and ethical burden on medics working 24-hour shifts, working alongside colleagues who then become patients and living in hospitals because they are unwilling to risk infecting their families by going home.
The risk of hospitals themselves becoming sites of infection is considerable: In March 2003, it was the infection of scores of medical staff that led the WHO to declare a global alert for SARS. This time, while only 16 medics are reported to have been infected, this is a likely underestimate—and the first case of a doctor dying from the virus has just been reported.
Fever clinics and screening are an exercise in clinical insanity, attempting to discern corona patients from every other common winter illness. Because there is no rapid diagnostic test, screening has focused on whether people have a fever, quickly overwhelming medical facilities until more time-consuming laboratory tests can be performed. Moreover, if nonsymptomatic people can spread the coronavirus, the focus on symptoms may be causing dangerous oversights.
The most powerful measures may be public education about the best ways to avoid infection, such as avoiding physical contact with people known to be infected, and to minimize spread from unidentified infections, wearing masks and hand hygiene. China is taking these measures, with public health information broadcast through multiple means, from state-run television to the village loudspeakers that usually blare propaganda. These steps can protect everyone, including families as they care for members who come down with typical flulike symptoms and may not seem to require more intensive treatment for several days. A more targeted approach can also ensure that medical facilities can focus on the people who really need intensive care rather than the far greater numbers who may simply have a fever but are kept in effective detention until laboratory tests can clear them.
Any new deadly pathogen inevitably gives rise to panic. But experience with other epidemics has shown us that a targeted approach can contain and arrest the spread of a virus—even more effectively than sweeping quarantines.
is an assistant professor of population
health science and policy at
Icahn School of Medicine at Mount Sinai in New York
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