SARS-CoV Attack (Severe Acute Respiratory Syndrome)

Description of event

As you are completing a patient’s chart in the emergency department (ED), the emergency medical service(s) (EMS) telephone rings. You pick up the phone and introduce yourself. In a muffled tone, the paramedic begins to provide a thorough report. He states that he is wearing an N-95 mask due to concern that the patient onboard may have a communicable disease. Your sympathetic tone kicks in as you listen to the report. The paramedic provides you with the following information:

• •Middle-aged woman complaining of high fever, neck stiffness, shortness of breath, and nonproductive cough, and who had visited the same ED 2 days prior, for similar symptoms, and was sent home with instructions for flu-like syndrome. Patient denies chest pain.
• •History: Hypertension
• •Allergies: No known allergies
• •Medications: Metoprolol
• •Vital signs: Blood pressure 148/90. Heart rate 120. Sinus tachycardia, respiratory rate 26 and diminished bilaterally. Blood oxygen saturation 93% on room air. Unable to obtain temperature in the ambulance.
• •Physical assessment: Limited assessment in the ambulance reveals a patient that is diaphoretic, tachycardic, and tachypneic. Nuchal rigidity is noted. Patient is only alert and oriented to person and place (not to time) and appears fatigued. Pupils are equally round and reactive to light.

Based on this report, what is the possible ailment? Could this be meningitis? Pneumonia? Severe acute respiratory syndrome (SARS)? You advise the staff caring for the patient in the ED to wear N-95 masks. You assess the patient while labs are drawn. You quickly perform a lumbar puncture while antibiotics are started for meningitis. You are shocked, however, when the lumbar puncture results come back normal. Her chest x-ray shows a severe bilateral pneumonia. You recall that there was a SARS outbreak two weeks prior in a local suburb. What if this patient had SARS? How would you have provided medical care to this patient without exposing yourself and others? Have you received training and preparation in managing a patient infected with SARS?

Our recent history and current events (at the time of this publication) have shown that SARS is a formidable, evolving virus, able to withstand changing environmental and human-made conditions, with the potential of infecting hundreds or even thousands of people. The SARS pandemic, beginning in late 2002 through mid-2003, proved that the world was not ready for such a biological catastrophe. On November 16, 2002, a patient in Guangdong, China, presented with an atypical pneumonia. Over the next several weeks and into early 2003, this atypical pneumonia spread throughout the southern border of China to Hong Kong and Vietnam, and across the Atlantic Ocean into Canada. On March 17, 2003, the Centers for Disease Control and Prevention (CDC) conducted its first briefing showing that this new virus had landed in the United States. In June 2003, the outbreak was finally contained, and the CDC removed air travel alerts from Hong Kong. During the outbreak, more than 8000 individuals became infected with SARS. Approximately 774 died in 26 countries over 5 continents. This pandemic demonstrated that the world and the medical community had not been prepared for such an event. Nevertheless, the international medical community showed its resiliency and the ability to join together for one cause.

In May 2012, a new respiratory virus related to SARS, MERS-CoV (Middle East respiratory syndrome or MERS), evolved in the Middle East. Saudi Arabian officials detected this new virus causing flu-like symptoms that rapidly evolved into respiratory distress, similar to SARS. To date, 808 people have become infected with MERS, and 311 of those individuals have died. This virus has spread to 21 countries, including the United States, France, Germany, Italy, Tunisia, and Great Britain. Investigations are currently under way. A recently published study in The Journal of American Medical Association (JAMA) shows that transmission of MERS to humans originated from dromedary camels.¹ Even though MERS-CoV is considered to be distinct from SARS-CoV,² individuals who have contracted the virus in the Middle East have died from respiratory and/or kidney failure.³

Terrorist attacks using biological agents such as SARS can be described as a type of asymmetric warfare. In asymmetric warfare, a single individual or group can cause damage and destruction to massive numbers of objects and/or people, with a small amount of ammunition, such as a biological agent.⁴ However, using biological agents in a terrorist attack is highly expensive and sophisticated, and it takes many years to develop. When a terrorist decides to develop a biological agent, the individual or group must first locate scientists who are willing and able to conduct the development of the agent without exposure to themselves, exposure to the terrorist organization, or others. Second, the terrorist(s) must acquire the equipment needed to facilitate the development of the agent in a safe manner. Third, the development of the agent in mass quantities requires many years. Finally, synthesized agents require certain environmental conditions that must be met for appropriate dissemination. Because of these conditions, the world has been fortunate to not have fallen victim to such a terrorist attack to date.

The origin, its transmission mechanisms, effective treatment modality, and the full extent of SARS have yet to be fully understood; however, much information about SARS has been discovered. SARS is caused by SARS-CoV, which belongs to the Coronaviridae family. Coronaviruses are a family of enveloped, single-stranded ribonucleic acid (RNA) viruses with the ability to affect humans and animals. SARS-CoV is a polyadenylated, single-stranded virus, containing 29,727 nucleotides, making their genome the largest of any RNA virus.⁵ Within the SARS-CoV genome, there are four major open reading frames (ORFs) that encode the structural proteins such as the nucleocapsid protein (N), envelope (E), spike (S), and membrane glycoproteins (M) that all contribute to replication. At each proximal end of the virus, there is 5′ methylated cap on one end, and the 3′ polyadenylated tail that enables the virus to attach to ribosomes for translation. SARS-CoV genome also contains a replicase gene (rep gene) that enables the virus to be transcribed into new RNA copies. Once the virus enters its host, the virus has high affinity to and it uses angiotensin-converting enzyme 2 (ACE2) receptors to infect cells.⁶ These receptors are predominantly found in the lungs, kidneys, and gastrointestinal (GI) tract.

SARS-CoV is a virus that is disseminated from person to person through respiratory droplets and is able to infect hosts through the mucous membranes of the mouth, nose, or eyes. Once the virus is inside the host, the virus will bind to the ACE2 receptors using the spike (S). Through endocytosis, the virus will enter the cell. Once in the cytoplasm, the virus is translated and then transcribed into immature virions. These immature particles will progress to become mature, icosahedral-shaped viruses. Within vesicles, the newly formed viruses are released via exocytosis, to begin the replication cycle again while infecting the host.

SARS can affect individuals of any age, gender, race, and socioeconomic status. Even though the clinical manifestation of the SARS-CoV virus is nonspecific, the manifestations present similar to influenza. Once infected, signs and symptoms may appear within 2 to 14 days. Patients begin to develop a high fever (> 100.4 °F [> 38 °C]), followed by body aches, headache, and a mild lower-respiratory infection. In the lungs, the virus causes atelectasis, gross edema, desquamation of epithelial cells on the respiratory tract, and the development of fibrous tissues within alveolar spaces.⁷ Many patients may develop pneumonia and hypoxia, which may progress rapidly, within hours to several days, into respiratory failure secondary to acute respiratory distress syndrome (ARDS). These respiratory symptoms may appear rapidly, within hours or over several days. Within the central nervous system (CNS), neural edema and degeneration have been seen. In the kidneys, necrotic tubular epithelial cells may result in renal dysfunction or failure. There is evidence attained through immunohistochemistry that SARS increases IgG precipitation, causing an immune response and increasing temperature, resulting in orchitis and the destruction of germ cells within the testes.⁸ The immune system may also suffer damage. There may be extensive splenic necrosis, atrophy of the lymph nodes, and lymphopenia. SARS also affects the cardiovascular system as patients may develop vasculitis, pericarditis, and coagulopathy. Coagulopathy may result in disseminated intravascular coagulopathy (DIC). Gastrointestinal symptoms involve a range from nausea and vomiting to diarrhea from inflammation caused by infected epithelial cells. Hepatic steatosis and centrilobular necrosis may also be seen.⁹ Box 152-1 summarizes the signs and symptoms of SARS.

Box 152-1. Summary of Signs and Symptoms of SARS*.

General

• High fever (> 100.4 °F [> 38 °C])

• Body aches

• Headache

Cardiovasular

• Vasculitis

• Coagulopathy

• Pericarditis

Respiratory

• Mild lower-respiratory infection

• Atelectasis

• Pulmonary edema

• Dry cough

• Hypoxia

Immunological

• Lymphopenia

• Necrosis of the spleen

• Lymph node atrophy

Gastrointestinal

• Nausea

• Vomiting

• Diarrhea

Urinary

• Renal dysfunction or failure

Reproductive (Males)

• Hepatic steatosis

• Orchitis

• Centrilobular necrosis

• Destruction of germ cells

Pre-incident actions

Preparation is of utmost importance, and it begins with information sharing. Throughout history, many of the failures and shortcomings in mitigating catastrophes involve the lack of information sharing among all parties. This lack of sharing originates from egos of an individual or a group of individuals wanting to be the “hero.” To prevent this, all health care providers must first acknowledge that they are part of a national and international team united by medicine, having a duty not only to themselves, their peers, and colleagues, but also to all patients, especially when a contagious and communicable virus is involved. Information sharing is best achieved through education. This education begins with prioritizing the development of a disaster plan addressing outbreaks or biological attacks. The disaster plan should be a “living” document, able to be edited on a yearly basis to include surveillance for communicable and contagious diseases; notification of and joint efforts with outside agencies; and personal protective equipment (PPE)/universal precautions guidelines for all health care providers. Terminology within the disaster plan should be a universal language that is shared among police departments, fire departments, EMS, and state, local, and federal government personnel. This universal language can be achieved through using documents such as the National Incident Management System (NIMS) and the National Response Framework (NRF) from the Federal Emergency Management Agency (FEMA). Using these documents will assist in creating a disaster plan with interoperable communications, as well as in defining leadership, chain of command, roles and responsibilities, and interdepartmental efforts. The disaster plan should be made available to all personnel, and frequent mock evolutions should be performed on a bi-yearly or yearly basis. Hospitals and outpatient facilities should perform frequent mock evolutions individually and with outside agencies. With each evolution, debriefing sessions should occur to learn the strengths and weakness, so that changes and enhancements to the plan can be made. Many fire, police, and EMS departments require personnel to complete online FEMA courses through its Independent Study Program (ISP), which covers these topics in more detail. These courses are free of charge; each course takes 3 to 8 hours to complete, and the health care provider will receive a certificate of completion. Hospital administration may also require their health care employees to complete these courses. When all parties involved in patient treatment and mitigation can work together systematically, more time and more patients will be saved. The FEMA ISP website address and the courses designed specifically for hospitals and health care providers are listed in Box 152-2 .

Box 152-2. FEMA ISP Courses for Health Care Personnel*^,†.

• •IS-100.b Introduction to Incident Command System
• •IS-100.HCb Introduction to the ICS (100) for Healthcare/Hospitals
• •IS-200.b ICS for Single Resources and Initial Action Incidents
• •IS-200.HCa Applying ICS to Healthcare Organizations
• •IS-700.a NIMS: An Introduction
• •IS-701.a NIMS MACS Course
• •IS-703.a NIMS Resource Management
• •IS-704 NIMS Communications and Information Management
• •IS-800.b National Response Framework: An Introduction

In syndromic surveillance, hospitals and outpatient centers will need to allocate resources to monitor a possible influx of respiratory illnesses, especially those accompanied by a high fever. When a suspicion of a communicable disease is confirmed, the disaster plan should include policies and procedures in contacting outside agencies. The plan should also contain the contact information of agencies and individuals who will be involved in the investigation and mitigation process. Immediate notification is a priority upon confirmation.

Policies and procedures for PPE and universal precautions guidelines for all health care providers should exist and be strictly enforced. Hand washing is paramount and is a basic skill to lessen the possibility of exposure to SARS-CoV. All necessary equipment and supplies to mitigate a possible exposure should be accrued prior to patient arrival or an outbreak. The equipment to mitigate SARS-CoV exposures includes N-95 masks, gloves, gowns, eye protection, shoe covers, and disinfectant such as sodium hypochlorite. All health care providers should be properly fitted for N-95 masks prior to any exposure.¹⁰ Hospitals also should have ventilation and filtration systems tested, repaired, or updated to be fully operational in the event of a SARS outbreak.

Health care providers who conduct patient assessments and provide treatment should incorporate additional questions while assessing the history of present illness, to develop an earlier working diagnosis. Questions should include inquiring about any recent international travel to countries prior to declaring a SARS outbreak, or any exposure to people who may have recently traveled to those countries. Asking patients about their employment history and personal relationships could also provide invaluable information. Patients who work in a facility containing SARS-CoV, or a patient who lives with a person who is employed in a SARS-CoV-containing laboratory could also provide the etiology for the outbreak. Since the first SARS outbreak involved animal-to-human transmission, it may also be beneficial to inquire about exposures to any infected animals. If a health care provider or hospital has evaluated an influx of patients suffering from atypical pneumonia, notification of the proper personnel should begin. A summary of these questions is given in Box 152-3 .

Box 152-3. Summary of Patient Assessment Questions*: Important Questions to Ask Regarding Possible SARS-CoV Exposure.

• 1.Has the patient traveled internationally to countries that have a SARS outbreak?
• 2.Has the patient been exposed to people who have returned from international travel?
• 3.Has the patient had possible exposure to SARS-CoV within the workplace?
• 4.Is the patient living with a person who works in a facility containing SARS-CoV?
• 5.Has the patient been exposed to infected animals?
• 6.Have health care facilities seen an influx of patients suffering from atypical pneumonia?

Post-incident actions

If there is a high index of suspicion that a SARS exposure is imminent or has already occurred, immediate notification of hospital infection-control personnel should occur to notify proper authorities and agencies, beginning the information sharing and mitigation process. The earlier the notification, the faster and more efficient the mitigation of the outbreak can occur. Infection-control personnel should notify agencies such as the CDC and local police, fire, and EMS agencies. The public should be notified immediately. Hospital personnel should be used to disseminate the correct message to the public. This will assure that the public receives the necessary information, and minimize panic. All healthcare personnel should adhere to the strictest universal precautions, such as mucous membrane protection with N-95 mask and eye protection. Gowns and scrubs should be used and then discarded upon completion of a shift, and they should not be removed from the building because that could cause contamination to others. Shoes should be covered with shoe covers. Rooms, equipment, and supplies that may have had exposure to SARS-CoV should be disinfected prior to being placed back into service or properly disposed of based on disaster plans. If invasive procedures are required for patient survival, the most-experienced providers should perform these procedures, using strict, aseptic technique. Infected patients who are admitted should be placed into quarantine rooms. Health care employees who have become exposed and are showing signs and symptoms of a SARS-CoV infection should be placed off duty until resolution of the infection. Procedures should be created, ensuring that these employees receive treatment and monitoring as their symptoms persist. Hospital personnel should use ventilation and filtration systems to minimize or prevent additional exposures. Patients who have become infected with SARS should be quarantined and not allowed to have visitors until resolution of symptoms.

EMS providers should also practice strict universal precautions because their risk of exposure and contraction of SARS-CoV is high because they are the first providers to render medical treatment to infected individuals who use prehospital emergency services. In a prospective observational study of an Asian metropolitan EMS system that was involved in the transport of patients during the SARS outbreak, EMS providers who transported patients with SARS were at higher risk of contracting SARS in comparison with the general population.¹¹ Proper medical evaluation and treatment of EMS providers are also recommended when a fever of over 38 °C is present. Within days of Ontario’s declaring a provincial emergency due to the 2003 SARS outbreak, Toronto fire and police departments created a medical unit that was designed to support, educate, and evaluate EMS providers regarding the SARS outbreak. In this collaboration with a hospital-based medical director, EMS providers received daily medical support and evaluation to determine the extent of their infection and whether further treatment was needed.¹²

Medical treatment of casualties

Unlike hurricanes, earthquakes, and other natural disasters, biological attacks and outbreaks bring about a unique dynamic to patient treatment. In such natural disasters, traumatic injuries are primarily seen. During an outbreak or biological attack, physicians may see a combination of traumatic injuries and medical and psychological complications. Similar to first responders who must properly allocate limited resources to facilitate the initial, high volume of patient triage and treatment, hospitals may also be faced with the same dilemmas. One of the major goals is to treat as many patients as possible in the quickest amount of time without exposure to health care personnel. However, many lessons were learned from the SARS outbreak in 2003. For example, because many health care workers had to work under extreme conditions, staff suffered from infections secondary to physical and mental exhaustion.¹³

Hospital personnel must effectively and rapidly triage patients, provide treatment, and request assistance early when resources begin to become scarce. There are several reasons why there could be an influx of hospital visits during an outbreak. First, many patients who are ill will still come for medical treatment. Many patients who have flu-like symptoms during an outbreak will wonder if they have been infected by the SARS-CoV and seek out medical treatment. Second, many asymptomatic people may panic and seek out medical evaluations. The media will play a significant role in peoples’ perceptions. Many people may not be aware of the outbreak, and the tone of the reporters can influence the actions of others. However, the opposite could occur in the ED. In the 2003 outbreak, Toronto-based community hospitals saw a decrease in ED visits during the SARS outbreak. Even though many people considered the ED as a place of safety, many viewed the ED as the etiology for the outbreak and therefore avoided the ED.¹⁴ It was determined that human-to-human transmission in Toronto originated in hospitals and households of infected individuals.¹⁵ In the current MERS-CoV outbreak in the Middle East, the human-to-human transmission has been originating primarily in hospital settings. Saudi Arabian hospital surveillance in 2013 demonstrated that the etiology for the majority of transmissions occurred in the ICU, dialysis centers, and hospital wards.¹⁶

Treatment of individual patients during a SARS-CoV outbreak also brings about unique obstacles. Therefore treatment of SARS-infected patients should be patient-centered. To date, there are no effective antivirals or anti-inflammatory medications for the treatment of SARS-CoV.^{17 , 18} However, experiments have been performed in attempts to produce a vaccination. One experiment used a portion of the S glycoprotein from the virus, as the foundation of the vaccine, and it was injected into mice. Addressing the glycoprotein as foreign, the immune system of the mice created a cell-mediated response through the creation of T cells and antibodies. When the immunized mice received the virus, replication of the virus within the nostrils and lungs was reduced.¹⁸

As many SARS-infected patients will develop respiratory complications secondary to pneumonia, emphasis must focus on airway management, the treatment of hypoxemia, and the prevention of multiple organ failure. This encompasses the early recognition of disease and aggressive resuscitation of the patient. As emphasized earlier, because of the high-stress, low-resource atmosphere, it is imperative that the most-experienced health care providers perform invasive procedures such as endotracheal intubation.¹⁹ Endotracheal intubation should be considered for patients with respiratory distress, using the recommended ventilatory support with low-tidal volume settings.²⁰ Postintubation management should include continued resuscitation, pain management, and consideration of the broad differential diagnosis of a patient with rapid-onset respiratory distress.

Unique considerations

Unfortunately, in the event of an outbreak or biological attack, most of the actions performed to mitigate the catastrophe will be reactive, even though preparedness may be emphasized. This reactive mitigation results from the incubation time of the virus and the time required for investigational and epidemiological reports to declare such an event. Because of its complex and resilient structure, SARS-CoV has the ability to adapt to adverse environments. This resiliency enables SARS-CoV to spread across various types of environments with the capability to quickly infect hosts. As the presenting signs and symptoms are nonspecific, many health care providers may treat the virus as an isolated infection, such as pneumonia, and release the patient to recover at home or admit the patient to the hospital floor without isolation. Similar to the Tokyo Sarin subway attack in 1995, terrorists may use an aerosolized form of the SARS-CoV virus to disseminate into a highly populated area. To lessen the effects of an outbreak or biological attack, health care providers must continually “think outside the box,” and remember to keep their differential diagnosis for a patient with rapidly progressing flu symptoms broad, considering viruses such as SARS-CoV and other potential agents of biological warfare.

Pitfalls

• •Failure to focus on preparation through the design of a comprehensive, “living” disaster plan that is modifiable based on up-to-date information
• •Failure to practice disaster plans through training evolutions to evaluate interoperability, communications, and the integration of resources among agencies
• •Failure to provide early notification and updates to public health agencies when there is a possible SARS outbreak
• •Failure to notify the public of an outbreak or attack or failure to provide thorough and proper notification to guide the future actions of the mitigation process²¹
• •Failure to assess resources prior to a SARS outbreak or biological attack
• •Failure to quarantine patients who present with possible SARS-CoV infection: remember, one person with the infection can cause a major spread of the disease²²
• •Failure to educate health care providers on the clinical manifestations of SARS-CoV
• •Failure to perform a comprehensive medical history including travel, living, and workplace arrangements
• •Failure to adhere to strict universal precautions anytime while performing physical examinations and providing medical treatment
• •Failure to sterilize or dispose of equipment used in the treatment of infected patients
• •Ultimately, failure of health care providers to “think outside the box”