Sars-Cov Research Paper

Introduction of SARS

Severe acute respiratory syndrome (SARS) is an upper respiratory infection caused by a coronavirus. The etiological agent responsible for SARS is called SARS-associated coronavirus (SARS-CoV). SARS-CoV is a relatively novel mutated form of coronavirus, resulting in a virus capable of becoming infectious in a human host. Typically, coronaviruses express themselves much like a common cold. However, SARS-CoV can cause complications uncommon in other coronavirus strains. A host infected with SARS-CoV may develop additional infections, like pneumonia or respiratory failure6,7. According to the World Health Organization (WHO),37 SARS-CoV presents itself as an atypical cold but with similar symptoms, resulting in a virulent pathogen

capable of infecting multiple people. Reportedly,6,7,26 patients diagnosed with SARS presented with a high grade fever (>38.0ºC), myalgia, chills, loss of appetite, headaches, non-productive coughs, and shortness of breath, or dyspnea. Approximately 10-20% of patients also experience diarrhea associated with SARS. Most patients go on to develop pneumonia as a result of the viral infection.
The first suspected case of SARS-CoV infection occurred on November 16, 2002 in Foshan City, China.8 However, at this time the coronavirus was unknown and did not come to the attention of the Chinese government until early 2003 when the spread of the disease surpassed 300, resulting in 5 deaths by March of 2003. Officials at the WHO37 first began testing for a new strain of influenza because of the symptomatology associated with SARS-CoV. Further testing for other pathogens like anthrax, hemorrhagic fever, and leptospirosis were conducted and ruled out as caused for an outbreak. The WHO37 finally discovered in mid-March that the causative agent of the outbreak was a mutated coronavirus. Over the course of the year, more than two dozen countries had one or more cases of SARS, including the United States and Canada due to international travel. In total, 8,098 contracted the virus and 774 died from the infection.6 The exact origin of the SARS-CoV mutagen has not been thoroughly established. Epidemiologists8 suspect it began as a zoonotic pathogen that jumped to human hosts.
The public health importance of SARS extends beyond initial acquisition of viral infection. According to recent research,30 SARS survivors have experienced chronic complications long after viral shedding. Certain patients who survive the initial infection have impaired physical, mental, and functional abilities. Most of the chronic conditions experienced by affected patients post-infection include chronic respiratory complications, myocardial issues, anxiety, depression, and post-traumatic stress disorder (PTSD).23,27 Furthermore, SARS is a highly transmissible disease and could easily cause a global pandemic if left uncontrolled (see Figure 7 for viral spread).
Basic Biology of SARS
According to genomic research over coronaviruses,9 the family of viruses possesses one of the most complex genomic structures among all RNA viruses.

In general, coronaviruses are positive-stranded and are enveloped in a lipoprotein outer layer. Before the SARS outbreak in 2002, coronaviruses were atypical in the human population and common among animals.3,21 The SARS-CoV genetic expression is nearly identical to other coronaviruses.4,9 However, SARS-CoV lacks the gene to produce hemagglutin-esterase (HE), a protein found in the envelope of some viruses to help it bind to the mucosal layer of the intestines. The lack of the HE-protein may be a possible explanation for why the pathogenesis of SARS-CoV is different from other coronaviruses. The lifecycle of SARS begins at the point of inoculation. The incubation period of SARS is between 2-10 days.37,38 Once the virus has infected a human host, it immediately begins to replicate by un-coating the lipoprotein outer layer, replicating and translating a single, positive RNA strand. The protein responsible for apoptosis in cells is the SARS-CoV U122 protein. Upon infection, healthy cells undergo pro-apoptotic (MAPK) or anti- apoptotic activation (Akt), causing either cell survival or programmed cell death. This mechanism remains unknown in SARS-CoV. Once SARS-CoV infects a cell and activates pro-apoptosis, the virus is destroyed along with the

cell.12
SARS-CoV is a zoonotic disease, indicating that a human host can become infected by an animal host. Looking at the history of SARS-CoV outbreaks, the virus seems to spread primarily through close person-to-person contact via respiratory droplets from sneezing and coughing. The virus attaches itself to the mucosal lining of the nose, eyes, or mouth of a nearby host. The virus can also live on surfaces for a short period of time and potentially infect anyone who touches fomites. Research speculates that SARS-CoV could become airborne, but the evidence for airborne evolution remains unclear.5,38
Immediately, SARS-CoV was suspected of emerging from an animal reservoir since coronaviruses are most typical an animals and birds, not humans. Reports3 show that live-animal markets in China may have provided the perfect incubator for viral evolution and disease transmission. SARS-CoV was identified in masked palm civets and raccoon dogs. However, civets and raccoon dogs are not accepted as the source of SARS-CoV and instead may be an asymptomatic vehicle. Bats11,18 have also been suspected as potential reservoirs and the true source of the virus, passing the virus directly or indirectly to humans (see Figure 3).
Clinically, of the patients who present with SARS-CoV, 85% are admitted with a high-grade fever. Patients also develop a non-productive cough (70%), muscle ache or pain (>50%), shortness of breath (>50%) and a headache. Diarrhea is also a common symptoms associated with SARS.29 Patients who present with SARS-CoV are nearly identical to patients who develop pneumonia or lower respiratory infections.26
According to clinical research,20 white blood cell (WBC) counts may remain normal or decrease depending on the immune function of the patient. Immunodeficient patients are at a higher risk of becoming infected and have a lower survival rate. The overall lymphocyte count at the start of infection is usually low. Additional laboratory testing demonstrates high levels of creatine phosphokinase (CPK) and hepatic transaminases, indicative of stress to the muscular system. Other common trends in lab results include high levels of lactate dehydrogenase (LD) from muscle damage, hypocalcemia from low Ca levels, and lymphopenia, or low lymphocyte count. The virus can also be isolated via a blood, stool, or respiratory secretion from a suspected SARS patient.
There are no widely accepted treatments or vaccinations for SARS-CoV. Vaccination options are still under clinical trial.15,19 To treat the inflammation in the lung tissue, most doctors prescribe corticosteroids to try and prevent chronic lung damage. Some pharmaceutical approaches involve a combination therapy of antibacterials (Levofloxacin or clarithromycin, 500 mg) and ribavirin and methylprednisolone.15,26 The combination therapy worked well in some patients and had no effect in others. Patients who progress to more serious lung symptoms sometimes require mechanical ventilation. Plasma therapy has also been attempted as a form of treatment and seemed to be effective in reducing recovery time and length of hospital stay among SARS patients. Nutritionally, maintaining Ca levels in SARS patients may help reduce muscle damage but may not be effective as a treatment option. Research6,7,26,37 demonstrates little evidence that behavior plays a role in a patient’s health once infected, but patients can avoid becoming infected by limiting close contact with infected individuals and by engaging in frequent hand washing.
Epidemiology of SARS
The longstanding 2003 SARS outbreak spread to 29 countries, infected over 8,000 people and killed 774 . According to the WHO,37 the overall global case-fatality rate was 9.6/100,000. SARS22 had an overall incidence and mortality rate of 18.57 per 100,000 and 1.41 per 100,000 respectively with a fatality rate of 7.6%. The group with the highest incidence rate of SARS was young people between 20-29 years (30.85/100,000), and the lowest incidence occurred between 0-14 years (2.54/100,000). Men and women between 20-49 made up 72.3% of all SARS-CoV cases during the 2003 epidemic. Researchers also calculated incidence rates based on geographical distribution. The three regions identified were urban (32.25/100,000), suburban (20.57/100,000), and rural residencies (8.90/100,000) (see Figures 4 & 6 for epidemiological curves). The incidence had a decreasing trend consistent with decreasing population density. Noscomonial rates were also calculated among heathcare providers and other hospital staff. The incidence rate was highest among physicians and nurses (17.3%) and less than 13% among general workers (see Figure 5). The case fatality rate was highest among populations older than 65 years. Ontario, Canada24 had a total of 351 suspect and probable cases of SARS-CoV and a peak incidence rate of 12.1/100,000. Canada had 44 SARS-related deaths and an overall case-fatality rate of 12.5%.
The young, old, and immunocompromised were most at-risk of infection and had lower survival rates.

The highest risk group was among comorbid patients aged 65 or older. In Canada,24 the highest SARS frequency group, based on probable/suspected cases, occurred in adults aged 40 and above (62.7% of cases). Type of exposure also played a pivotal role in who was most at-risk of infection. Based on the Ontario, Canada study,24 people in healthcare were most vulnerable to infection, followed by: members of a household, social gathering, and those who traveled among infected

persons.
SARS-CoV was of great concern because of its transmissibility factor.5,38 SARS has the ability to infect individuals through a few different routes. Nosocomial infections were the most common because patients were most virulent and health workers would often come into close contact with bodily fluids. Aerosol (air droplets), usually saliva, can pass through the air with the virus and adhere to the mucosal membrane of the alveoli in the lungs and cause infection. Close person-to-person was, therefore, established as a major form of transmission. Infection may also occur through physical contact of infected surfaces. For instance,29 urine, stool samples, and saliva have all shown samples of SARS in an infected individual and could be passed along through bodily waste. Finally,38 close contact with animal reservoirs could also transmit SARS-CoV.
Patients who had other comorbidities recovered poorly, if they recovered at all, compared to their healthier counterparts. The most frequent comorbidities included renal failure, cardiovascular-related diseases, pulmonary disease, and diabetes.38 The SARS outbreak was cause for concern for older patients already in a hospital setting who were infected with hospital-acquired SARS-CoV (<50% mortality rate) (Varia, 2003). Patients who were younger and had healthier immune systems recovered most quickly.24
One study in particular29 stood out among other published material. A prospective cohort study published by The Lancet during the 2003 outbreak provided interesting insights into the epidemiology of the novel virus. Age-adjusted odds ratio were provided to determine the overall risk of acquiring the infection based on age (21-40 OR=1.0, 41-60 OR=4.3, over 61 OR=28.0). Individuals aged 61 and older had 28 times the odds of acquiring SARS than any other age group. Also, chronic hepatitis B (HBV) turned out to be one of the most significant risk factors in the clinical progression of SARS-CoV. In addition to comorbidities, viral load significantly determines how the SARS virus progresses in a human host and is most present in the respiratory tract instead of the upper airways.
Prevention and Intervention Programs/Strategies of SARS
The WHO36,37 developed an initial case definition of SARS during the first outbreak of the virus. Later,31 a more extensive case definition was developed to identify as many cases as possible, especially with the risk of global travel (see Figures 1 & 2). Case definitions also vary depending on the surveillance system. For instance, SARS case definition is different in China than in the US system.
The WHO36,37 case definition of SARS is classified “as being disease in a person with a documented fever (temperature >38 Cº), lower respiratory tract symptoms, and contact with a person believed to have had SARS or a history of travel to a geographic area where there has been documented transmission of the illness.” A probable case has a more clinical definition that includes pneumonia in the chest cavity, found via chest radiographic tools, SARS-CoV syndrome, and death that follows a pattern consistent with the SARS virus.
Infection of SARS requires close person-to-person contact with another infected person. Hence, the primary prevention strategy recommended1 to the general population is avoiding close contact with persons’ suspected of being infected. This recommendation was not followed at first during the 2003 outbreak because of the difficulty in distinguishing between pneumonia and SARS cases, especially for healthcare workers. Secondary prevention of SARS involves detecting the virus in its early stages and immediately starting a course of anti-bacterial and anti-viral medications. SARS survivors often experience long-term debilitating effects. Tertiary prevention of SARS comprises of rehabilitation strategy and long-term care for conditions like chronic respiratory disease.
Looking back on all of the efforts to contain the 2003 outbreak, there was significant confusion at the start, but strategies to control the spread of the virus were quickly implemented and the threat of a larger SARS pandemic was minimized. The majority of studies documenting SARS were retrospective and published post-outbreak. However, one study published by The Lancet29 was prospective and provided interesting insights into the progression of SARS-CoV. Investigators documented the temporal sequence of events as well as the clinical vicissitudes in a community outbreak of SARS. There is strength in the number of studies completed surrounding the 2003 SARS epidemic. However, a major setback to in-depth investigation into SARS is the lack of current research. That leaves considerable gaps in knowledge concerning the epidemiology, progression, and other etiological factors of SARS-CoV, like the affect seasons have on the infection rate; temperature fluctuations in particular may play a vital role in transmission33 (see Figures 8 & 9). The most current research8-10,12,16,19 into SARS focuses on detailed descriptions of the biological nature of SARS.
Surveillance of SARS-CoV
The novel nature of SARS-CoV challenged public health experts initially when attempting to track and control the outbreak. Because there were no systems in place to rapidly respond to the SARS outbreak, the Chinese government improvised by using their SCAP34 (severe community acquired pneumonia) program to find suspected and probable cases of SARS. Although SCAP was designed to detect pneumonia cases, the program was useful in distinguishing certain patterns among SARS patients that set them apart from the true pneumonia cases. SCAP was used in China, Hong Kong, and Canada for rapid global detection of SARS.
The United States also initiated a rapid response to the SARS outbreak in case it crossed the border17. The SARS Surveillance Project (SARS-SP) implemented protocols to quickly receive emergency department (ED) information on suspected or probable cases of SARS, particularly among citizens who recently traveled from affected areas. Surveillance of SARS was possible through the EMSystem because it already had 26 communication lines across the US (see Figure 10). Fortunately, the 2003 outbreak did not spread to the US.31
Current monitoring of SARS occurs across the globe. China has heavy surveillance over SARS because they were the epicenter of the initial outbreak. Under International Health Regulations (IHR; revised 2005),2 SARS-CoV falls under a “public health emergency of international concern” and must immediately be reported to the WHO Global Alert and Response Network (GOARN) surveillance system.18,36 SARS was the first international biological threat GOARN responded to in the history of disease outbreaks18. There have been no new cases of SARS-CoV since 2004.
Frankly, ascertaining the current level of effectiveness in any of the SARS reporting systems is difficult. Almost an entire decade has passed since the first and last outbreak. However, the systems that responded to the initial SARS threat, particularly the SCAP system34, were well-prepared to respond to the new infectious agent. After the initial outbreak and revisions to IHR, China expanded their surveillance response system to include 441 laboratories (14% increase) and 556 surveillance hospitals (35% increase). Each province is responsible and equipped to detect and identify a suspected SARS case. The data is reported through chains of command up to the Health Ministry of China. Again, there is little information to support the responsiveness and effectiveness of their surveillance system.
Conclusion
The memory of SARS could quickly fade in the minds of the public. SARS-CoV is a highly infectious agent capable of spreading across the globe with a case-fatality rate of 9.6/100,00037. The disease took over a year to contain. However, SARS-CoV has not re-emerged in nearly a decade. Nevertheless, a lack of viral presence is not indicative of lax vigilance. The possibility of SARS resurging is enough to maintain diligence in detecting future outbreaks. Frequent testing and drilling of outbreak scenarios, like a SARS outbreak, is necessary for public health preparedness training and maintenance of surveillance networks. If anything, the SARS outbreak of 2003 taught public health experts that a disease can emerge at any time and being prepared is vital to efforts to controlling future epidemics.