Severe Acute Respiratory Syndrome Cases Research Articles

The SARS-coronavirus-host interactome

Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated human vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B) as interaction partners of the CoV non-structural protein 1 (Nsp1). These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA) blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad-range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock.

Acute renal failure in patients with severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is caused by a new coronavirus, and results in respiratory failure. Acute renal failure (ARF) may also occur and/or complicate the disease course, however, its incidence, causes and impact in SARS patients are not known. ARF patients were identified from a total of 78 (33 men and 45 women) probable SARS cases admitted to a single hospital. The clinical features of patients with ARF were characterized, and the etiologies analyzed. Patients were assigned to ARF (n = 13; 17%) and non-ARF groups (n = 65). Patients with ARF were older than their non-ARF counterparts. ARF developed 7.2 +/- 4.3 days after admission. The incidence of ARF was higher in males (77% vs 35%; p < 0.05). Comorbidities of diabetes and heart failure were more common in patients who developed ARF (38% vs 6%, p < 0.01 and 38% vs 2%, p < 0.001, respectively) and the incidence of respiratory failure (85% vs 26%, p < 0.001) and mortality (77% vs 8%, p < 0.001) were also higher. Multiple organ system failure usually accompanied ARF. Hypotension (77%) caused by nosocomial infections, gastrointestinal bleeding, or SARS per se, and rhabdomyolysis (43%) was associated with ARF in addition to pre-renal factors. Five patients in the ARF group and 1 female patient with end-stage renal failure underwent renal replacement therapy during hospitalization; however, both eventually died. Of the 16 medical staff performing renal replacement therapy, none was subsequently infected with SARS coronavirus. Development of ARF during the disease course in SARS patients is associated with catastrophic outcome. The cause of ARF in SARS patients is often associated with pre-renal factors, hypotension, rhabdomyolysis, and previous comorbidities including diabetes and old age. Universal precautions to prevent viral transmission are mandatory for medical staff performing renal replacement therapy.

Evolution of pulmonary pathology in severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is characterized by fever with rapid progression to acute respiratory distress and it is associated with substantial morbidity and mortality. Transmission patterns suggest spread by respiratory droplet or close person-to-person contact. To elucidate the correlation of clinical presentation to the pathogenesis and course of the disease, we reviewed the pulmonary pathologic specimens of SARS patients taken at different stages of the disease. Four "probable" cases of SARS were studied. SARS-associated coronavirus (SARS-CoV) infection was demonstrated using reverse transcriptase-polymerase chain reaction in all 4 patients. The pulmonary specimens were taken on day 7 after symptom onset in patient 1, day 11 in patient 2, day 17 in patient 3, and day 21 in patient 4. The autopsy lung tissue from patient 1, who died 7 days after symptoms onset due to the complication of acute myocardial infarction, revealed mild histologic change in the lung. Only focal pulmonary edema or hemorrhage was seen. In the second patient, who died 11 days after symptom onset, severe acute alveolar damage was characterized by patchy or diffuse lung edema, hyaline membrane formation, and scarce lymphocytic infiltration. The lymphocytes were mostly CD3-positive and CD20-negative. In the third patient, biopsy specimen taken 17 days after symptom onset showed patches of organizing pneumonia with reactive fibroblastic proliferation, more abundant type II pneumocytes and clustering of CD68-positive macrophages within the alveolar spaces. Few CD68-positive syncytial multinucleated giant cells were also seen in the specimens but no viral inclusion body could be identified in these cells. The lung biopsy specimen from patient 4 taken 21 days after symptom onset showed characteristics of the fibrotic stage, with significant myofibroblastic proliferation in the alveolar space and interstitium resulting in loss of pulmonary architecture. The number of CD3-positive lymphocytes and of CD68-positive macrophages in this specimen from a patient in the fibrotic phase of diffuse alveolar damage (DAD) whose condition deteriorated was less than in the specimen from case 3 who was in the early proliferative phase of DAD and eventually recovered. The histologic evolution of SARS coincided with the different stages of DAD: acute, proliferative organizing, and fibrotic stages. SARS cannot be differentiated from the other etiologies of DAD by morphologic examination alone. The absence of DAD does not rule out the possibility of SARS-CoV infection, particularly in the early stage of the disease.

Effects of underlying cerebrocardiovascular diseases on the incidence of critical conditions and multiple organs dysfunction syndrome in severe acute respiratory syndrome cases

To investigate the effects of underlying cerebrocardiovascular diseases on the incidence of critical conditions and multiple organs dysfunction syndrome (MODS) among the severe acute respiratory syndrome (SARS) cases. A database of all SARS cases in Beijing in 2003 was established and the data of 1291 cases whose data were complete among them was analyzed. The effects of cerebrocardiovascular diseases, other comorbid diseases and absence of underlying diseases on the incidence of critical conditions and MODS in SARS cases were compared with chi-square test and logistic regression analysis. The incidence rates of critical conditions and MODS in SARS cases were 34.86% and 13.71% respectively. The incidence rates of critical conditions and MODS among the SARS cases without underlying diseases, with other comorbid diseases, and with cerebrocardiovascular diseases were 28.10%, 43.70%, and 58.18%, and 9.83%, 18.52%, and 27.27% respectively. The differences among the three groups were all statistically significant (all P < 0.0001). Logistic regression analysis showed that presence of cerebrocardiovascular diseases in SARS patients was independently associated with the risks of critical conditions and MODS in comparison with those without underlying diseases after adjusting for age and occupation. [odds ratio (OR) = 1.819, 95% CI = 1.276 approximately 2.592, and OR = 1.974, 95% CI = 1.273 approximately 3.060 respectively]. The SARS cases with cerebrocardiovascular diseases have the highest incidence rate of critical conditions and MODS. Presence of Cerebrocardiovascular diseases is an important risk factor for critical conditions and MODS in the SARS cases.

China kills 10 000 civet cats in “patriotic” campaign against SARS

A cull of thousands of civet cats, badgers, racoons, dogs, and cockroaches has been started in response to China's first new case of SARS (severe acute respiratory syndrome) in six months. The infected man, from the city of Guangzhou, in the southern province of Guangdong, has made a full recovery. He had caught a similar strain of SARS to one found in civet cats but said that he had never eaten nor even seen the animals. In Guangdong, civets--weasel-like members of the mongoose family--are an expensive delicacy. “We …

Atypical SARS -- Spread Enhanced by Patient Transfer

With new diseases, atypical case presentations are recognized only as experience with the conditions increases. This report from Singapore chronicles the spread of severe acute respiratory syndrome (SARS) through a tertiary care facility after a patient with atypical disease arrived from a hospital where probable SARS cases were being …

Severe acute respiratory syndrome (SARS) - an emerging infection of the 21st century.

Severe acute respiratory syndrome (SARS) is an emerging infection caused by a novel coronavirus known as SARS-CoV. The disease has a high propensity to spread to household members and healthcare workers and may be associated with transmission and outbreaks in the community. Severe illness in immunocompromised patients, sophisticated hospital facilities and treatment procedures, particularly those that generate aerosols, and lack of adequate isolation and control measures, can amplify transmission and contribute to so-called "super-spreading" events. The presence of non-specific clinical manifestations at presentation and a lack of validated early diagnostic methods and effective management pose great difficulty for frontline physicians in the containment of this disease. The mortality of SARS is in the region of 10 to 15%; the presence of underlying disease, high initial C-reactive protein levels, and positive SARS-CoV in nasopharyngeal aspirate samples are associated with a higher risk of respiratory failure and mortality. Despite the disappearance of SARS cases worldwide, the potential evolution of SARS-CoV in animals suggests the disease may re-emerge in the future. Heightened levels of clinical suspicion, rapid case detection and isolation, and contact tracing are essential to effective management of future outbreaks. Further ongoing requirements for successful management include research on the immunopathogenesis of SARS and the development of timely and reliable diagnostic tests, effective antiviral and immunomodulatory agents, and vaccines for the disease.

Characterization of a novel coronavirus associated with severe acute respiratory syndrome.

In March 2003, a novel coronavirus (SARS-CoV) was discovered in association with cases of severe acute respiratory syndrome (SARS). The sequence of the complete genome of SARS-CoV was determined, and the initial characterization of the viral genome is presented in this report. The genome of SARS-CoV is 29,727 nucleotides in length and has 11 open reading frames, and its genome organization is similar to that of other coronaviruses. Phylogenetic analyses and sequence comparisons showed that SARS-CoV is not closely related to any of the previously characterized coronaviruses.