Developments Concerning Coronavirus Disease 2019 (COVID-2019)
Last Revised: 3/1/2020
Media attention concerning the outbreak of a novel coronavirus in December of 2019 has steadily increased over preceding weeks, and at the time of writing there is early evidence of community spread in the United States. The World Health Organization (WHO) has declared the coronavirus disease 2019 (COVID-2019) outbreak to be a Public Health Emergency of International Concern, and significant efforts are underway to better understand the disease’s clinical features, transmissibility, and potential treatment options. Simultaneously, organizations with purviews ranging from international to hyperlocal are faced with decisions concerning optimal approaches to patient screening, diagnosis, exposure mitigation, and resource allocation. The potential for severe respiratory failure prompting need for intensive care has come to the attention of critical care physicians worldwide, and optimal preparatory steps can be better informed by reviewing our current state of understanding. As an important note, and similar to any new disease, the global healthcare community’s conception of COVID-2019 is in a rapid state of flux. Over the coming weeks to months, gaps in understanding will gradually close, and current understandings will be retrospectively recognized as misunderstandings.
What is a coronavirus?
Broadly speaking, coronaviruses (CoVs) are large, enveloped single-stranded RNA viruses with the potential for zoonosis. CoVs lead to respiratory infection in humans, which can range in severity – based on the pathogenicity of the causative virus and frailty of the host – from the common cold to life-threatening acute respiratory distress syndrome (ARDS).
Has the nomenclature surrounding this particular CoV changed?
As with any new disease, some time was required to establish a definitive nomenclature. The CoV itself, previously termed 2019 novel coronavirus (2019-nCOV) has more recently been named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The resulting infection and clinical disease state has also been recently termed COVID-2019.
Have we seen coronavirus outbreaks before?
Both the Severe Acute Respiratory Syndrome (SARS) epidemic circa 2002–2003 and Middle East Respiratory Syndrome (MERS) epidemic circa 2012–2013 highlight the potential impacts of a CoV outbreak. (To again draw a parallel, MERS was originally termed novel coronavirus 2012.) While CoVs, broadly speaking, may be pathogens of little clinical consequence, MERS-CoV and SARS-CoV were associated with significant worldwide morbidity and mortality. As suggested by the name SARS-CoV-2, the virus itself appears closely related to SARS-CoV with about 80% genetic similarity and the same cell entry receptor (i.e., angiotensin converting enzyme 2 [ACE2] receptors). SARS-related CoV (SARSr-CoV) was previously identified by the WHO as a potential cause of future epidemics.
Are lessons from SARS and MERS applicable to COVID-2019?
There appear to both similarities to, and differences from, SARS and MERS. As with prior CoV outbreaks, an animal reservoir has again been implicated. In SARS and MERS, as with other respiratory infections, hosts with risk factors such as advanced age, numerous comorbid conditions, and/or severe comorbid disease were more likely to develop frank ARDS and succumb to the disease. Evidence suggests that the same may be true for COVID-2019. Early clinical data about COVID-2019 supported human-human transmission, and in SARS and MERS viral shedding from symptomatic patients was a significant contributor to hospital environmental contamination and nosocomial transmission, including that to healthcare workers. With SARS-CoV infection, it has been posited that high ACE2 receptor density in the lower airways may account for the predominantly lower respiratory symptomatology and delayed viral shedding. However, a recent study of SARS-CoV-2 upper respiratory viral loads has suggested that viral shedding patterns may more closely resemble those of patients infected with influenza than SARS-CoV, as viral loads in asymptomatic patients were similar to those in symptomatic patients. Additional evidence continues to mount suggesting the potential for transmissibility by asymptomatic carriers. As reviewed below, isolation, environmental decontamination, and personal protective equipment (PPE) are important to mitigate these risks.
Variable adherence to the foundational principles of public health were credited both for the initial spread of SARS and its eventual containment. Steps to contain COVID-2019 have likely been informed by those lessons; however, aggressive state-supported quarantine and travel restrictions have been controversial. Basic measures, such as hand hygiene, respiratory etiquette, and staying home when sick form the foundation of public health best practice when dealing with respiratory viruses.
SARS was highly pathogenic with an estimated 20-30% of patients requiring intensive care unit admission, and of those approximately 75% required mechanical ventilation in some case series. The overall mortality rate of SARS has been estimated at about 10% amongst all infected persons, but for patients with ARDS mortality rates generally approximated those of ARDS at the time. As reviewed below, SARS-2-CoV appears more readily transmissible but potentially less fatal.
How can we screen for and recognize cases of COVID-2019?
Screening recommendations have been the subject of substantial attention and revision over the prior weeks. In the United States, the Centers for Disease Control and Prevention (CDC) provides continuously updated screening recommendations online (see Selected Resources). At the time of writing, screening recommendations are based on the combination of clinical features (i.e., symptomatology) and epidemiologic risk factors.
Early symptoms are nonspecific can include fever, dry cough, and shortness of breath anywhere between 2 and 14 days after potential exposure. Other constitutional symptoms are possible. Epidemiologic risk factors could include potential travel-related exposure or exposure to sick contacts. Travel to Hubei Province, China is considered to be highest risk followed by travel to mainland China excluding Hubei Province. South Korea, Italy, Iran, and Japan are additional areas of disease activity at the time of writing, and screening recommendations are likely to remain dynamic as the disease spreads further. Exposure to sick contacts and/or persons under investigation (PUIs) is complex and again stratified by potential severity.
How should patients with suspected or known COVID-2019 be triaged?
CDC guidelines remain dynamic and may change over time; as such, updated online recommendations should be referenced when developing local policies and procedures. Options based on symptomatology and epidemiologic risk include ordered quarantine, voluntary quarantine, isolation for evaluation or treatment in a healthcare setting, routine medical care, and home monitoring with or without oversight. Clinicians suspecting COVID-2019 should consider those individuals as PUIs and notify their facility’s infection prevention team and local/state public health authorities. Early identification of a PUI is critical to prevent unrecognized and/or unprotected exposures. Plans exist to expand the capability of diagnostic testing beyond the CDC alone.
What is known about the clinical course of COVID-2019?
Information is still being gathered about COVID-2019; however, it has been argued that COVID-2019 appears to have a greater infectivity rate but lower mortality rate compared to SARS and MERS. As with any outbreak, the infection and mortality statistics are dynamic. At the time of writing, the WHO estimates that 80% of patients will have mild disease, 14% of patients will have severe disease with significant respiratory symptomatology, and 5% of patients will be critically ill. The overall mortality rate, again at the time of writing, appears to be no more than approximately 2% based on epidemiologic estimates. Care should be taken when interpreting small case series of hospitalized and/or critically ill patients as their outcomes are not representative of population-level outcomes.
The reported median incubation period ranges from approximately 4 to 7 days, but incubation periods stretching out to 14 days, and as long as 24 days, have been suggested. This potential 14 day window is reflected in the approach to screening delineated above. Initial symptomatology is variable and outlined above. As with SARS, older patients with comorbid disease appear to be at higher risk for progression to overt respiratory failure. Patients requiring hospitalization have variably demonstrated radiographic evidence of pneumonia, including infiltrates on plain film and ground glass on computed tomographic imaging.
What treatment options are available?
Although antiviral medications are being trialed, care is largely supportive, as with other viral respiratory pathogens. It was historically felt that non-invasive positive pressure ventilation and/or heated high flow nasal canula conferred substantial risks of aerosolization, and therefore tracheal intubation may be deemed by care teams to confer less risk. However, there is some evidence to suggest that modern systems with well-fitting interfaces do not create wide dispersion of exhaled air. Having said that, guidance from the WHO at the time of writing calls for additional caution with non-invasive respiratory support given a tendency toward treatment failure with MERS. As such, clinicians may still choose to initiate invasive positive pressure ventilation quickly. Interim guidance from the WHO for clinical management also currently carries recommendations for close attention to fluid resuscitation to avoid respiratory trespass, lung protective mechanical ventilation, and prone positioning in patients with ARDS.
What type of personal protective equipment is needed?
The CDC has released detailed guidance about infection control measures, including PPE, which are linked below. Training in the proper donning, use, and doffing of PPE should be an institutional priority when undertaking preparatory steps, and critical care leaders will need to partner with their facilities and infection prevention colleagues to ensure adequate clinician competency. Isolation measures include recommendations for airborne infection isolation rooms. Current PPE recommendations include use of a N95 (or equivalent), or better, respirator; gown; gloves; and eye protection. Relevant to anesthesiologists, the CDC also calls for caution when performing aerosol-generating procedures, such as endotracheal intubation, open suctioning, bronchoscopy, and cardiopulmonary resuscitation. A serious respiratory pandemic may limit available supplies of PPE due to both increased utilization and supply chain challenges, and the CDC has issued guidance about optimizing the supply of N95 respirators, again linked below. In a recently-published large case series, 3.8% (N=1,716/44,672) of healthcare personnel contracted COVID-2019, of which 14.8% of cases were severe or critical, and there were five reported deaths. At the time of writing, standard, contact, and airborne precautions are recommended.
Where can I find more information?
COVID-2019 has clearly demonstrated the evolving nature of biomedical information dissemination. As highlighted by the conventional press, social media played an important role in raising the level of global awareness and concern about clinical suspicion for a novel respiratory pathogen, which we now know to be SARS-CoV-2. Major biomedical publishers have accelerated their review and acceptance processes to aid in information dissemination and made content available free of charge. Twitter and other avenues for free open access medical education are also potential resources. In exchange for increased timeliness and access to information must come a measure of caution and balance. For example, under-recognition of less severe COVID-2019 cases may have initially contributed to the perception that SARS-2-CoV was highly fatal. This highlights the importance of staying current as additional developments unfold.
Selected Online Resources
SOCCA Member-Only Online Resources: https://socca.memberclicks.net/
CDC Resource Hub: https://www.cdc.gov/coronavirus/2019-ncov/index.html
CDC Respiratory Conservation Strategies: https://www.cdc.gov/coronavirus/2019-ncov/hcp/respirator-supply-strategies.html
CDC Infection Control: https://www.cdc.gov/coronavirus/2019-nCoV/hcp/infection-control.html
WHO Resource Hub: https://www.who.int/health-topics/coronavirus
WHO Patient Management Guidance: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/patient-management
Dynamic COVID-2019 Tracking (John’s Hopkins): https://systems.jhu.edu/research/public-health/ncov/
Selected Peer-Reviewed References
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- Bouadma L, Lescure FX, Lucet JC, Yazdanpanah Y, Timsit JF. Severe SARS-CoV-2 infections: practical considerations and management strategy for intensivists. Intensive Care Med. 2020.
- Chang, Lin M, Wei L, Xie L, Zhu G, Dela Cruz CS, et al. Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China. JAMA. 2020.
- Del Rio C, Malani PN. 2019 Novel Coronavirus-Important Information for Clinicians. JAMA. 2020.
- Del Rio C, Malani PN. COVID-19-New Insights on a Rapidly Changing Epidemic. JAMA. 2020.
- Gostin LO, Hodge JG, Jr. US Emergency Legal Responses to Novel Coronavirus: Balancing Public Health and Civil Liberties. JAMA. 2020.
- Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, et al. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020.
- Hui DS, Chow BK, Lo T, Tsang OTY, Ko FW, Ng SS, et al. Exhaled air dispersion during high-flow nasal cannula therapy versus CPAP via different masks. Eur Respir J. 2019;53(4).
- Lee EYP, Ng MY, Khong PL. COVID-19 pneumonia: what has CT taught us? Lancet Infect Dis. 2020.
- Leung CCH, Joynt GM, Gomersall CD, Wong WT, Lee A, Ling L, et al. Comparison of high-flow nasal cannula versus oxygen face mask for environmental bacterial contamination in critically ill pneumonia patients: a randomized controlled crossover trial. J Hosp Infect. 2019;101(1):84-87.
- Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020.
- Paules CI, Marston HD, Fauci AS. Coronavirus Infections-More Than Just the Common Cold. JAMA. 2020.
- Rothe C, Schunk M, Sothmann P, Bretzel G, Froeschl G, Wallrauch C, et al. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. N Engl J Med. 2020.
- Swerdlow DL, Finelli L. Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus: Lessons From Previous Epidemics. JAMA. 2020.
- Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020:10.1001/JAMA.2020.648.
- Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020.
- Yang X, Yu Y, Xu J, Shu H, Xia Ja, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020.
- Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-33.
- Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, et al. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med. 2020.