Novel coronavirus summary and literature update – as of 8 May 2013

As of 8 May 2013, 30 laboratory-confirmed cases of human infection with novel coronavirus (nCoV) have been reported to WHO: two from Jordan, two from Qatar, 23 cases from Saudi Arabia, two from the United Kingdom (UK), and one from the United Arab Emirates. Most patients are male (79.3%; 23 of 29 cases with sex reported) and range in age from 24 to 94 years (median 56 years). The first cases had onset of illness in late March or early April 2012; the most recent cases reported had onset on 1 May 2013 (13 cases with onset 14 April - 1 May 2013). Most patients presented with severe acute respiratory disease requiring hospitalization and eventually required mechanical ventilation or other advanced respiratory support. Eighteen patients have died.

Several cases have occurred in clusters, including in a health care setting in Jordan in April 2012 (of 2 confirmed and 11 probable cases, 10 were health care workers) and in the UK among family members of an infected patient who had recently arrived from Saudi Arabia. The Jordanian outbreak illustrated the potential of this virus to spread through health care facilities and the UK outbreak confirmed the potential of the virus to transmit between humans with close contact. In neither instance did transmission appear to go beyond the immediate outbreak into the community.

Since 14 April 2013, 13 new cases of infection have been confirmed and reported in Saudi Arabia (10 males and 3 females, median age 58 years). Seven of these have died, four remain critically ill in intensive care and two are hospitalized but clinically improved. All patients were reported to have at least one comorbid medical condition and most had more than one. Most of the cases were patients at a single health care facility. Two were family members of two patients from that facility; no health care workers have been affected. Although investigations are still ongoing into the source of this outbreak, early information indicated that only a small minority of these cases had contact with animals in the time leading up to their illness.

Five viruses from the United Kingdom (n=2), Saudi Arabia (n=1), Jordan (n=1), and Germany (n=1) have been cultured and genome sequences have been made publicly available. No sequence data are yet available from the latest cluster. All five of the sequenced viruses have a high degree of genetic similarity. Preliminary analyses show that the viruses are genetically somewhat similar to bat viruses. It should be noted, however, that the similarity does not necessarily imply that bats are the reservoir for the human virus or that direct exposure to bats or bat excreta were responsible for infection. The nCoV itself has not yet been found in an animal.

An international network of clinical experts has been convened to discuss therapeutic options. It concluded that in the absence of clinical evidence for disease-specific interventions, convalescent plasma is the most promising therapy. A memo containing advice for setting up international or regional serum centers, to obtain and share convalescent plasma, has been circulated by WHO to ministries of health in affected countries. WHO and the International Severe Acute Respiratory and Emerging Infection Consortium have developed and shared a set of research protocols and case report forms to help clinical investigators establish studies of pathogenesis and pharmacology. These are available at http://www.prognosis.org/isaric/.

WHO has developed interim guidance document Infection prevention and control during health care for probable or confirmed cases of nCoV infection. The recommendations have been reviewed by members of the WHO Global Infection Prevention and Control Network (GIPCN) and other international experts. The interim guidance document is available at: http://www.who.int/csr/disease/coronavirus_infections/IPCnCoVguidance_06May13.pdf.

Recent peer-reviewed papers published since the last update

The United States of America’s National Institutes of Health has found that a combination of two licensed antiviral drugs, ribavirin and interferon-alpha 2b, can inhibit replication of the virus in cell cultures. Reference: Falzarano et al. Inhibition of novel human coronavirus-EMC replication by a combination of interferon-alpha2b and ribavirin. Scientific Reports 2013, doi: 10.1038/srep01686.

Areas of ongoing research and epidemiological investigation

There a number of areas of ongoing research related to nCoV, including:

Further development of nCoV serologic assays using known and novel approaches. Defining the serological response to different viral proteins and the kinetics of antibody response.

Further development of PCR-based diagnostic tests to verify acutely nCoV-infected persons .

Work related to the binding sites of the virus and the pathogenic potential of nCoV in human respiratory tissues.

Pathogenesis and testing of intervention strategies in animal models, including antiviral medications and candidate vaccines.

Studies of the response of human lung cells in culture to nCoV.

Further work evaluating genetic sequences as viral isolates become available to better understand the evolution of the virus, its relationship to other coronaviruses, and to identify any adaptive mutations in the viral genome.

Contact testing of individuals, including health care workers, exposed to known cases to determine transmissibility.

Testing samples from patients with severe acute respiratory infections from the affected region.

Field work to determine the presumed animal reservoir of the virus.

Summary

The reappearance of this virus and the pattern of transmission currently being observed in Saudi Arabia increase the level of concern regarding this novel pathogen. The questions of the exposures that result in human infection, the mode of transmission, the source of the virus, and the extent of infection in the community urgently need to be answered and are being actively pursued by the Ministry of Health of Saudi Arabia. The association of this outbreak with a single health care facility suggests nosocomial transmission. The patients may have had increased susceptibility to infection or severe disease because of their multiple comorbidities. However, the presence of infection in two family members not associated with the facility itself raises a concern about potential broader transmission in the community. Some features of the cases, such as the predominance of males and the age distribution among confirmed cases, may provide important clues to exposures. In addition to the key epidemiological questions, more work is needed to determine the optimal management strategy for patients infected with nCoV and to evaluate potential pharmaceutical interventions.

Evidence suggests that the virus may have its origin in bat species, though the evidence is largely circumstantial and will remain so until the virus is demonstrated in an animal species. However, experience with Nipah virus in Malaysia and Severe Acute Respiratory Syndrome (SARS) in China both illustrate that intermediate hosts may sometimes play an important role in transmission to humans and that direct exposure to reservoir specie(s) is not needed for infection. Therefore, the work to identify the source, the exposure and the mode of transmission should be multisectoral and involve veterinary services, food safety authorities, environmental health agencies in addition to public health authorities.

Vigilance and enhanced surveillance are needed within the affected area and for unusual clusters of respiratory disease in the rest of the world, particularly clusters associated with health care environments. WHO requests that confirmed and probable cases be reported within 24 hours of being classified as such, through the regional Contact Point for International Health Regulations at the appropriate WHO Regional Office.