By Gary Evans, Medical Writer

Given the deadly precedents of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses, a rapidly emerging similar virus out of Wuhan, China, could pose a grave threat to healthcare workers in the United States. As of Jan. 21, the World Health Organization (WHO) reported that 16 healthcare workers had been infected by the 2019 novel coronavirus (2019- nCoV), and none have died. However, those numbers were considered conservative amid a dramatically accelerating situation as this report was filed.

“I am sure it is more than that,” says Daniel Lucey, MD, MPH, FIDSA, FACP, an infectious diseases physician at Georgetown University Medical Center, who is closely following the 2019-nCoV epidemic in China for the Infectious Diseases Society of America. “I don’t know about the numbers. There are rumors of a lot more healthcare workers infected in the incredibly overstretched hospitals throughout Wuhan and other cities in Hubei province.”

As this story was filed, no U.S. healthcare workers had been infected. There were six infected American patients, five of whom had returned from Wuhan to Illinois, Washington, California, and Arizona, the CDC reported. The case in Illinois transmitted the virus to her husband, bringing the total to six. (See related story in this issue.) The patients were hospitalized in these respective states, and no transmission had been reported to any other contacts. In addition to the six cases, 68 possible U.S. cases have tested negative, and 92 people are still under investigation in 36 states.

“We expect to find more cases of 2019-nCoV in the U.S.,” Nancy Messonnier, MD, director of CDC’s National Center for Immunization and Respiratory Diseases, said at a January press conference. “We have had multiple states and clinicians reach out to us to establish potential cases, with their labs following up and sending samples if warranted.”

In a widely anticipated move, the WHO declared the coronavirus outbreak a Public Health Emergency of International Concern on Jan. 30. (See related story in this issue.)

The rapidly emerging 2019-nCoV follows the SARS coronavirus outbreak in 2002-2003, which also emerged from China, resulting in 8,098 infections globally, and 774 deaths. Some of the SARS infections and deaths, particularly in hospitals in Toronto, were in healthcare workers. The ongoing MERS outbreak centered in Saudi Arabia has been deadly to healthcare workers but has not shown the ability to sustain spread to other countries. A recently published analysis of reported MERS cases between December 2016 and January 2019 revealed that 26% of 403 cases in the region were healthcare workers. The case fatality rate was 16% among healthcare workers, compared to 34% among patients.1 The threat of 2019-nCoV to healthcare workers was a point of emphasis at a recent CDC press conference.

“This is a hugely important issue, and the health of our healthcare workers is very important to all of us,” Messonnier said. “We are being proactive at all levels to make sure that as much as possible the people taking care of [these patients] are careful and cautious.”

In a snapshot of rapidly changing numbers, as of Jan. 30, China reported 9,692 cases, including 1,527 people in serious condition, and 213 deaths. Although Wuhan remains ground zero, cases were reported from many other cities in China, including 139 in Beijing, the second most populous city in the world. Including the United States, there were at least 129 cases scattered among many other countries, with at least one case in Taiwan, Japan, Korea, Thailand, Singapore, Vietnam, Nepal, Malaysia, Australia, France, Canada, Germany, Cambodia, United Arab Emirates, Finland, Philippines, India, and Italy.2

In a particularly concerning development, several media outlets reported that a Chinese health minister said the 2019-nCoV may be transmissible before symptoms are present, which would considerably complicate infection control efforts. SARS and MERS primarily spread through respiratory droplets dispersed when an infected person coughs or sneezes. However, both coronaviruses could contaminate hospital surfaces, linger in the environment, and spread via aerosols produced by medical procedures.

“We also have seen reports coming out of China regarding spread of disease. We at CDC do not have any clear evidence of patients being infectious before symptom onset,” Messonnier said. “We are actively investigating that possibility. That is part of the reason we are working with our state health partners to aggressively evaluate close contacts. We certainly would want to pick up a close contact who got ill, and it might even change our guidance.”

Another ominous sign is in the emerging research on the epidemiologic measure of viral reproductive ratio, called r-naught. The conventional wisdom is that an r-naught of less than 1 means viral spread will fade out.

“R-naught is how many infected people come from a single infected person,” Messonnier explained. “Most of the research [on 2019-nCoV] has the r-naught between 1.5 and 3. In general, you want to see an r-naught below 1, and that’s how you get the disease controlled.”

Case Identification, PPE

The CDC originally recommended considering 2019-nCoV in a patient with fever, respiratory illness, and coughing who has traveled to Wuhan city in the last 14 days or has been in contact with a confirmed case of the coronavirus. With China closing down travel out of Wuhan, and the virus reported in other cities throughout the country, the CDC was expected to expand screening of travelers from China.

“If they come in with fever and respiratory symptoms, we are asking whether they have recently been in China or have been in contact with someone from China,” says William Schaffner, MD, an infectious disease physician at Vanderbilt University Medical Center. “We may have to update that very quickly because we know already that this virus has been exported to Singapore, Japan, and Thailand. We might have to include all of Southeast Asia.”

EDs will bear the brunt if suspect cases descend on hospitals. “Previous outbreaks have forced us to be more forward-thinking,” says Shannon Sovndal, MD, of Boulder (CO) Emergency Physicians. “New processes, such as updated triage questions and isolation techniques, have better prepared the ED to face new threats. We have a foundation in place that should aid us in addressing threats such as coronavirus from China, but vigilance, aggressive intervention, and constant modification will be needed.”

Suspect patients should don a surgical mask and undergo evaluation in a private room with the door closed, ideally an airborne infection isolation room, the CDC recommends. “Healthcare personnel entering the room should use standard precautions, contact precautions, airborne precautions, and use eye protection (e.g., goggles or a face shield),” the CDC states.3

Airborne precautions call for use of an N95 or equivalent. The mask vs. respirator issue has caused some controversy in the past, but the emergence of several epidemics and pandemic flu in the first 20 years of this century should translate to preparedness in many hospitals.

“We have a robust respiratory protection program. Our healthcare workers are fit-tested annually with N95s,” says Lydia Crutchfield, MA, BSN, RN, CLC, director of corporate teammate health at Atrium Health in Charlotte, NC. “I don’t anticipate any challenges with that; it is hardwired into our safety program.”

Likewise, the facility is proactive about personal protective equipment (PPE) supplies, and is ready to replenish stock as needed. “We’re always mindful of these emerging infectious diseases,” says Crutchfield, president of the Association of Occupational Health Professionals in Healthcare. “This is a novel disease, and we emphasize respiratory etiquette like covering your cough. To report back to work, [employees] have to be fever-free for 24 hours after taking an antipyretic.”

Employee health works very closely with infection control in these types of situations, she says. “We actually have an infectious disease team of nurses within occupational health,” she said.

Given the many documented instances and studies of healthcare workers contaminating themselves while doffing PPE, it may be helpful to have someone observe workers removing gear after treating a patient.

“If they have a confirmed or suspect case, make sure there are observers who are watching as they don and doff PPE going in and out of the room to ensure the healthcare workers’ safety,” says Connie Steed, MSN, RN, CIC, FAPIC, president-elect of the Association for Professionals in Infection Control and Epidemiology. “I have talked with our infection prevention team about doing just-in-time-reminder competencies for frontline healthcare workers on how to put on and take off respirators. That seems to be the biggest issue, as the hands [touch] the face.”

Infection control and PPE are critical because there is no antiviral treatment or vaccine for 2019-nCoV. “Infection prevention is the best thing we have, and that worked after a while with SARS,” says Lucey. “It’s not just about the equipment. Like with Ebola, it is knowing how to use it safely every single time, especially when you are taking it off, and the virus is on your gown, gloves, or goggles.”

On Dec. 30, China reported an outbreak of respiratory disease in Wuhan City. Reports indicate some of the first patients in China were at a Wuhan seafood market that also sold chickens, bats, snakes, marmots, and other wild animals. However, in reviewing case reports, Lucey theorizes the virus may have been circulating under the radar for weeks or months before the first cases were linked to the food market. (For more information, see related story in this issue.)

“It didn’t just suddenly appear in December and somehow mutate and become very contagious,” he says. “My hypothesis is it has been around for several months, and it has been sort of accelerating and developing the ability to spread quickly.”

The scientific consensus is that both SARS and MERS coronaviruses arose in bats before transferring to palm civet cats in China and camels in Saudi Arabia, respectively. The animal reservoir of 2019-nCoV has not been determined definitively, but China has closed all live animal markets in the wake of the outbreak.

A recently published genetic analysis by Chinese scientists revealed that the 2019-nCoV may be of snake origin via bats. “Results obtained from our analyses suggest that the 2019‐nCoV appears to be a recombinant virus between the bat coronavirus and an origin‐unknown coronavirus,” the researchers reported.4 “The recombination occurred within the viral spike glycoprotein, which recognizes cell surface receptors. [O]ur findings suggest that snake is the most probable wildlife animal reservoir for the 2019‐nCoV.”

Identifying that the palm civet cat was the intermediary host for SARS led to a mass culling of the animals from markets where they were sold live as food. In addition to that and other aggressive actions, the SARS outbreak ended relatively quickly, and the virus has not been seen again. In contrast, the Saudis have resisted culling camels, an animal central to their culture. Thus, MERS remains in the region, although it has not shown the ability to sustain transmission to other parts of the world.

“Each of these rogue coronaviruses that jump species from animals to humans has its own characteristics and personality,” Schaffner says. “From a scientific point of view and a better comprehensive understanding, we would like to figure out what the animal source is for the people in China. If snakes are indeed the source, then it is important for the local public health people to take that into account.”

Coronaviruses can possibly mutate, and “although there was some mutational change in both the SARS and the MERS virus, all in all they were pretty stable viruses,” Schaffner says. “Given that this new virus has just recently adapted to humans, there is a concern that it may become more readily transmissible. That’s the big issue.”

The CDC reports that genetic sequencing of the virus in the U.S. cases matches those in China, suggesting no mutation has taken place thus far. The CDC first alerted clinicians on Jan. 8 to be on the lookout for patients with respiratory symptoms and a history of travel to Wuhan. The agency has activated it Emergency Operations Center and developed a diagnostic polymerase chain reaction (PCR) test to detect the virus in clinical specimens. Currently, testing must take place at CDC, but the agency was expected to distribute test kits to state health departments in the near term.

“Once the sample is prepared at CDC, the time it takes to actually do the test is four to six hours, which is a very typical time for a real-time PCR,” Messonnier said. “Part of the delay is the sample getting to CDC, and that’s one of the reasons we are focusing on getting these tests out closer to the patients so the results can become available more quickly.” The CDC also has posted a blueprint of how to make the test for other countries.

Initially, travelers from Wuhan were routed to one of five major U.S. airports for screening in Atlanta, Chicago, New York, Los Angeles, and San Francisco. However, since China moved to shut down travel out of Wuhan, this screen approach was subject to change, and may include more cities in China.

“We have seen a fairly dramatic change in the situation in China with the government’s announcement of travel bans and restrictions out of Wuhan. Those are extending to additional cities as we speak,” said Martin Cetron, MD, director of CDC’s Division of Global Migration and Quarantine.

The virus has a 14-day incubation period, so the CDC was focusing on arriving flights in the two weeks following the Chinese travel ban, he said. For planes with suspect cases, other passengers are advised to check symptoms for two weeks.

The Chinese took the extraordinary step of quarantining Wuhan, a city of 11 million people. However, a large portion of the city’s population reportedly left before the measures went into effect. The real-time spectacle played out somewhat cinematically, with some comparing the outbreak to the movie Contagion, which was based in part on the rapid emergence of SARS.

“Can you imagine trying to semi-quarantine a city of 11 million people? What does that mean in real life?” Schaffner says. “The first three things I thought of were food, medicine, and fuel. How do they get that into a quarantined city?”

The efforts to rapidly build new hospitals in the area also were unsettling. All signs indicate that the case numbers out of China will continue to escalate before 2019-nCoV is brought under control.

REFERENCES

  1. Al-Tawfiq JA, Memish ZA. Middle East respiratory syndrome coronavirus in the last two years: Health care workers still at risk. Am J Infect Control 2019;47:1167-1170.
  2. Centre for Health Protection of the Department of Health, Hong Kong. Severe respiratory disease associated with a novel infectious agent, Jan. 24, 2020. Available at: https://bit.ly/2uE2yg7.
  3. Centers for Disease Control and Prevention. Interim infection prevention and control recommendations for patients with known or patients under investigation for 2019 novel coronavirus (2019-nCoV) in a healthcare setting, Jan. 28, 2020. Available at: https://bit.ly/2t3D6QS.
  4. Wang WJW, Zhao X, Zai J, et al. Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross-species transmission from snake to human. J Med Virol 2020; Jan 22. doi: 10.1002/jmv.25682. [Epub ahead of print].