The second case of person-to-person spread of the emerging 2019 novel coronavirus (2019-nCoV) in the United States has occurred, raising concern that the community spread could continue, even as travel from China is being checked aggressively.
As of Feb. 13, 2020, there were 15 cases of the new coronavirus in the United States, with 13 of them infected travelers returning from Wuhan, China. The Centers for Disease Control and Prevention (CDC) updated the numbers in describing new cases at a recent press conference.
“One patient in California is a close household contact of another patient in California,” said Nancy Messonnier, MD, director of the CDC National Center for Respiratory Diseases. “This is the second instance of person-to-person spread in the United States. We expect to find additional cases of novel coronavirus infection in the United States. We expect to see more cases of person-to-person spread among close contacts.”
The reasons for this expectation are twofold: the continuing explosive outbreak in China and the aggressive testing and contact tracing being done in the United States. As the CDC tracks down contacts of confirmed cases, 347 people have tested negative and 66 are awaiting results. Investigations have been conducted in 41 states and territories.
The first confirmed person-to-person transmission also involved close contacts, as a woman returning to Illinois from Wuhan infected her husband. The other U.S. patients live in Washington state, Arizona, and Wisconsin.
“We have seen a spectrum of illness among cases in the United States. Some of them seem pretty mild,” Messonnier said. “At least a few at some point in the course of their illness have been more severely ill. There are no deaths in the United States. Some of our patients have had oxygen requirements during the course of their illness.”
The CDC has cautioned against overreaction, like wearing surgical masks in public, as the number of cases in the United States is still only at 15.
Limited person-to-person spread also has been seen in at least nine other countries, as people traveling from China infect their close contacts.
Although it was soon followed by other cases in the United States, the first case of 2019-nCoV in the United States was unusual in that a self-aware patient who became ill after traveling from Wuhan essentially self-diagnosed and reported for care.
The man returned from Wuhan on a connecting flight into Seattle-Tacoma International Airport in Washington, the CDC reported at a Jan. 21, 2020, press conference.
He had no symptoms of illness since leaving China, but was closely following his vital signs for the fever and cough that mark the onset of the coronavirus infection.
“This was a very astute gentleman who was looking at internet activity, had actually researched this, and shared this information with his provider on Jan. 19,” says Scott Lindquist, MD, epidemiologist for Washington state.
“We were in communication with the CDC Emergency Operations Center coordinating specimens that were shipped overnight and had the results the following day, incredibly fast,” he says.
The first patient has recovered and been discharged from the hospital, officials report.
Tests, Treatments, Vaccine
In a move that will greatly improve case identification, public officials have distributed a polymerase chain reaction (PCR) test to state labs for 2019-nCoV.
Heretofore, testing of specimens was being done at the CDC, but the agency requested Emergency Use Authorization to distribute the tests. “Once approved, this will allow public health labs across the United States to use the CDC-developed diagnostic assay,” Messonnier said. “This will greatly enhance our national capacity to test for this virus.”
The CDC also has posted a “blueprint” of how to make the test for other countries.
Two widely available molecular viral respiratory panels are used in the United States to detect the four common human coronaviruses that usually cause mild illness and colds.
“Those assays do not detect this new coronavirus. There is no cross reaction,” says Timothy Uyeki, MD, MPH, MPP, Clinical Team Lead for the CDC response to the outbreak.
Better diagnostics can improve case identification and infection control, but there are no established treatment options for the novel coronavirus.
“Clinical management is really supportive care for any kind of complications,” he says. “At this time, there is no specific treatment for novel coronavirus infection. There is no approved or demonstrated antiviral treatment that is efficacious for this virus.”
Corticosteroids should be avoided for treatment of this virus, including for respiratory failure, he says. “With MERS [Middle East respiratory syndrome] and seasonal influenza, corticosteroids can actually prolong viral replication. There are antiviral drugs that have been used for other infectious diseases that are under investigation for potential treatment for patients with the new virus, but at this time there are no recommendations that can be made,” he says.
“In China, one clinical trial has been instigated of investigational therapeutics,” says Uyeki. “Other clinical trials are planned. When one uses investigational therapeutics for compassionate use that is uncontrolled — it is basically impossible to draw conclusions about that clinical treatment. We really need randomized, controlled clinical trials. Unfortunately, in the absence of in vitro data, we can’t make any comments about what drugs appear to be beneficial.”
The National Institutes of Health (NIH) have fast-tracked vaccine development to stop 2019-nCoV, but it will be months before it could be safely administered to an anxious public. Anthony Fauci, MD, director of the NIH National Institute of Allergy and Infectious Diseases, described the ongoing research at a Jan. 28, 2020, press conference.
“We already started at the NIH, with many of our collaborators, the development of a vaccine,” he said. “One [vaccine] has a messenger-RNA platform. When the Chinese isolated the coronavirus, they put the sequence on a public database. Given the technology of the 21st century, we are able to use that sequence, pull out the gene of the glycoprotein spike of this particular virus, and make that the immunogen to be used in a vaccine. Right now, it is being prepared.”
While promising, vaccine development and testing is a time-consuming process, both to ensure that it works and that it is safe in humans.
“I anticipate with some cautious optimism that we will be in a Phase I trial within the next three months,” he said. “I want to emphasize that does not mean that you have a vaccine that is ready for development. It will take three months to get it into the trial, then three months to get safety and immunogenicity data. Then, you move into Phase II. What we do from that point on will be determined by what is happening with the outbreak over that time.”
Considering that current trends find 2019-nCoV expanding rapidly in China and reaching other nations near and far, the general consensus is that the vaccine will be needed. “We are proceeding as if we will have to deploy a vaccine,” Fauci said. “We are looking at the worst-case scenario: that this becomes a bigger outbreak.”
Diagnostics and therapeutics also are in development, promising treatment until there is a vaccine to prevent infection.
“With regard to diagnostics, the CDC has rapidly developed [a test] based on the published sequence of the virus,” Fauci said. “The NIH, along with the CDC, will be working on next-generation diagnostics more at the point of care so we can get them to more people throughout the world.”
Despite the prior emergence of severe acute respiratory syndrome (SARS) and MERS, there currently is no therapeutic treatment for coronavirus infection. Ongoing studies were initiated because of those outbreaks, but treatment remains elusive. “Between those outbreaks and the current one, a number of antiviral drugs have been tested in vitro, in animal models, and even in the field anecdotally with historic controls,” he said.
One of them is the antiviral remdesivir, which once was used in a clinical trial against Ebola, he said. Another that is now being used by some clinicians in China is a combination of two antivirals, lopinavir and ritonavir, Fauci said.
“I must emphasize there is no proven efficacy of these, but they are being pursued together with a number of agents,” he said. “That is why it is so important that we get isolates of the virus, which we will soon have from the individuals in this country who have been infected.”
During the SARS outbreak, researchers developed monoclonal antibodies as a potential therapeutic. “They were only used in vitro and in animal models,” he said.
“Given the somewhat close homology between SARS and the new coronavirus, that could be utilized. However, what we are really trying to do — and it will happen soon, as we get specimens from individuals who are infected — is to clone their cells and make specific monoclonal antibodies against this new coronavirus.”