Psychological distress and negative appraisals in survivors of severe acute respiratory syndrome (SARS)

BACKGROUND: Severe acute respiratory syndrome (SARS) is a novel disease. The authors have limited knowledge of its impact on mental health. The present study aimed to examine the level and extent of psychological distress of SARS survivors following 1-month recovery, to explore patients' negative appraisals of the impact of SARS, and to evaluate the associations between psychological distress and negative appraisals. METHOD: The Beck Anxiety Inventory, the Beck Depression Inventory, and a newly developed measure, the SARS Impact Scale (SIS), were mailed to 453 Hong Kong Chinese SARS survivors discharged from hospital for 4 weeks or more. RESULTS: A total of 425 patients received the questionnaires and 180 (mean age 36.9 years; 120 women) gave valid replies. The response rate was 42.4 %. The participants also represented 13.6 % of all adult survivors in Hong Kong. About 35 % of respondents reported 'moderate to severe' or 'severe' ranges of anxiety and/or depressive symptoms. It was found that those working as healthcare workers or having family members killed by SARS were more prone to develop subsequent high levels of distress. Factor analyses extracted three meaningful factors of the SIS, namely 'survival threat', 'physical impact', and 'social impact'. Negative appraisals at the acute phase and 1-month recovery significantly accounted for substantial portions of variances for anxiety and depressive symptoms, after the effects of other psychosocial variables were controlled. CONCLUSIONS: Psychological distress of SARS survivors at 1-month recovery is real and significant. Negative appraisals may play a pivotal role in the development of psychological distress for SARS survivors, at least in the short term.     

Human immunopathogenesis of severe acute respiratory syndrome (SARS)

Progressive immune-associated injury is a hallmark of severe acute respiratory syndrome (SARS). Viral evasion of innate immunity, hypercytokinemia and systemic immunopathology in the SARS coronavirus (SARS CoV) infected host have been suggested as possible mechanisms for the cause of severe pathology and morbidity in SARS patients. The molecular and cellular basis for how SARS CoV impacts the host immune system resulting in severe SARS, however, has not been elucidated. The variable clinical course of SARS may be the result of complex programs of host responses against the infectious agent. Therefore, the systematic analysis of innate and adaptive immune responses to SARS CoV is imperative in building as complete an immunological model as possible of host immunity and inflammatory responses during illness. Here we review recent advances in SARS immunopathogenesis research and present a summary of our findings regarding host responses in SARS patients. We contend that dysregulated type I and II interferon (IFN) responses during SARS may culminate in a failure of the switch from hyper-innate immunity to protective adaptive immune responses in the human host.     

严重急性呼吸综合征的病理改变

目的 探讨严重急性呼吸综合征(SARS)的主要脏器的病理改变特点及发病机制。方法 详细检查7例SARS患者的肺、心、脾、肝、肾等标本的大体特点及用常规方法研究光镜下SARS累及各脏器的病变特点。结果 7例中,病程短(5d)的患者肺部表现以肺水肿为主。与通常的肺水肿相比,其水肿液中纤维素成分多,可见透明膜形成。5例病程超过3周的患者出现肺泡内机化及肺泡间隔内的纤维母细胞增生,造成肺泡的实变和闭塞。6例可见到肺小血管内的微血栓。7例均可见到散在的肺出血、小叶性肺炎、肺泡上皮脱落、增生等病变。2例可见真菌感染,1例累及左全肺及右肺部分区域,还累及心脏和肾脏,1例出现在肺门淋巴结。肺门淋巴结多表现为充血、出血及淋巴组织减少,窦组织细胞增多。5例心脏有明显的肥大,2例有心内血栓,1例有灶性心肌炎,1例为真菌性心肌炎。7例中有1例为结节性肝硬化,另1例出现广泛的肝细胞带状坏死。脾内均有白髓变小或消失,红髓明显充血和出血。1例腹腔内淋巴结肿大,但其内淋巴滤泡亦减少,有明显充血和出血及窦组织细胞增生。结论 SARS的主要病变为肺,以各期弥漫性肺泡损伤的病变为基本特征。发病机制可能为病毒造成肺泡上皮及毛细血管的严重损伤导致肺水肿及肺泡及细支气管的纤维素性渗出性炎,出现透明膜,继而出现肺泡内机化及肺泡间隔的纤维化,导致肺泡萎陷,最终形成纤维化、实变。脾和淋巴结的淋巴组织减少是此病影响免疫系统的形态学表现。     

Sputum cytology of patients with severe acute respiratory syndrome (SARS)

BACKGROUND: Severe acute respiratory syndrome (SARS) is a newly described form of atypical pneumonia linked to a novel coronavirus. AIMS: To review the sputum cytology of 15 patients who fulfilled the World Health Organisation clinical criteria for SARS in an attempt to evaluate whether early diagnosis is feasible with routine sputum examination. METHODS: All sputum samples from patients with SARS from the four major hospitals in Hong Kong were reviewed; abnormalities were sought in the cellular component, including abnormal numbers and morphology of the component cells compared with those from age matched controls taken over the same period one year ago. RESULTS: Fifteen sputum samples from patients were compared with 25 control samples. In the patients with SARS, loose aggregates of macrophages were seen more frequently in the sputum. These macrophages frequently showed morphological changes, such as cytoplasmic foaminess, vacuole formation, and nuclear changes (including multinucleation and a ground glass appearance) when compared with the control samples. CONCLUSIONS: The cytological features of SARS are non-specific, but the observation of any of the described features should prompt further investigations, especially in patients with suspicious clinical features.     

The clinical pathology of severe acute respiratory syndrome (SARS): a report from China

In order to investigate the clinical pathology of severe acute respiratory syndrome (SARS), the autopsies of three patients who died from SARS in Nan Fang Hospital Guangdong, China were studied retrospectively. Routine haematoxylin and eosin (H&E) staining was used to study all of the tissues from the three cases. The lung tissue specimens were studied further with Macchiavello staining, viral inclusion body staining, reticulin staining, PAS staining, immunohistochemistry, ultrathin sectioning and staining, light microscopy, and transmission electron microscopy. The first symptom was hyperpyrexia in all three cases, followed by progressive dyspnoea and lung field shadowing. The pulmonary lesions included bilateral extensive consolidation, localized haemorrhage and necrosis, desquamative pulmonary alveolitis and bronchitis, proliferation and desquamation of alveolar epithelial cells, exudation of protein and monocytes, lymphocytes and plasma cells in alveoli, hyaline membrane formation, and viral inclusion bodies in alveolar epithelial cells. There was also massive necrosis of splenic lymphoid tissue and localized necrosis in lymph nodes. Systemic vasculitis included oedema, localized fibrinoid necrosis, and infiltration of monocytes, lymphocytes, and plasma cells into vessel walls in the heart, lung, liver, kidney, adrenal gland, and the stroma of striated muscles. Thrombosis was present in small veins. Systemic toxic changes included degeneration and necrosis of the parenchyma cells in the lung, liver, kidney, heart, and adrenal gland. Electron microscopy demonstrated clusters of viral particles, consistent with coronavirus, in lung tissue. SARS is a systemic disease that injures many organs. The lungs, immune organs, and systemic small vessels are the main targets of virus attack, so that extensive consolidation of the lung, diffuse alveolar damage with hyaline membrane formation, respiratory distress, and decreased immune function are the main causes of death.     

Pulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS)

BACKGROUND: Severe acute respiratory syndrome (SARS) became a worldwide outbreak with a mortality of 9.2%. This new human emergent infectious disease is dominated by severe lower respiratory illness and is aetiologically linked to a new coronavirus (SARS-CoV). METHODS: Pulmonary pathology and clinical correlates were investigated in seven patients who died of SARS in whom there was a strong epidemiological link. Investigations include a review of clinical features, morphological assessment, histochemical and immunohistochemical stainings, ultrastructural study, and virological investigations in postmortem tissue. RESULTS: Positive viral culture for coronavirus was detected in most premortem nasopharyngeal aspirate specimens (five of six) and postmortem lung tissues (two of seven). Viral particles, consistent with coronavirus, could be detected in lung pneumocytes in most of the patients. These features suggested that pneumocytes are probably the primary target of infection. The pathological features were dominated by diffuse alveolar damage, with the presence of multinucleated pneumocytes. Fibrogranulation tissue proliferation in small airways and airspaces (bronchiolitis obliterans organising pneumonia-like lesions) in subpleural locations was also seen in some patients. CONCLUSIONS: Viable SARS-CoV could be isolated from postmortem tissues. Postmortem examination allows tissue to be sampled for virological investigations and ultrastructural examination, and when coupled with the appropriate lung morphological changes, is valuable to confirm the diagnosis of SARS-CoV, particularly in clinically unapparent or suspicious but unconfirmed cases.     

Fear of severe acute respiratory syndrome (SARS) among health care workers

In this study, the authors examined fear related to severe acute respiratory syndrome (SARS) among 2 samples of hospital staff in Hong Kong. Sample 1 included health care workers (n=82) and was assessed during the peak of the SARS epidemic. Sample 2 included hospital staff who recovered from SARS (n=97). The results show that participants in both samples had equal, if not more, concern about infecting others (especially family members) than being self-infected. Sample 1 participants had stronger fear related to infection than Sample 2 participants, who seemed to be concerned more about other health problems and discrimination. Participants with lower self-efficacy tended to have higher fear related to SARS. Fear related to SARS was also correlated positively with posttraumatic stress symptoms among respondents of Sample 2 (recovered staff). Interventions based on these findings are described.     

The spectrum of pathological changes in severe acute respiratory syndrome (SARS)

AIMS: To analyse the lung pathology of severe acute respiratory syndrome (SARS) and correlate the findings with the time sequence of the disease. METHODS AND RESULTS: Ten patients with a clinical diagnosis of SARS, and virological confirmation of SARS coronavirus infection were identified. Histology in most cases showed diffuse alveolar damage, from early to late phases, and the changes corresponded to the time sequence. Other variable features include multinucleated giant cells, pneumocytes with cytomegaly and variable amounts of inflammatory cells and foamy macrophages. One case showed superimposed bronchopneumonia. No viral inclusions were found. Coronavirus particles were identified in pneumocytes by electron microscopy. CONCLUSIONS: The predominant pathological process of SARS is diffuse alveolar damage and, in patients who die from the disease, there is evidence of organization and fibrosis. There are apparently no histological features specific for this disease, and the aetiological diagnosis depends on virological and ultrastructural studies.     

从SARS患者肺部病变的病理特点探讨SARS的损伤机理

目的 根据严重急性呼吸道综合征(severe acute respiratory syndrome，SARS)患者肺部病变的病理特点探讨SARS的损伤机理。方法 在3500例尸体解剖材料中，找出死亡时有肺部炎症的共842例。对其中病毒性肺炎16例、Good-Pasture综合征2例、自身免疫疾病2例、SARS1例，共21例进行肺部病变的病理组织学的比较观察。结果 病毒性肺炎的肺部病变主要的病理变化表现为间质性肺炎；自身免疫性疾病病人的肺部病理变化有肺泡表面透明膜形成，肺泡腔内脱落的细胞团，肺泡腔内机化等；SARS病人尸体解剖的肺部病变主要为肺泡腔内细颗粒样或泡状肺水肿，脱屑性肺炎以及机化性肺炎的表现。同时，肺间质内的小动脉出现明显的结构改变，形态学上与自身免疫性疾病的肺损伤相似。结论 机体的变态反应可能是SARS的损伤机理之一。     

Identification of N-linked carbohydrates from severe acute respiratory syndrome (SARS) spike glycoprotein

N-glycans were released from the SARS coronavirus (SARS-CoV) spike glycoprotein produced in Vero E6 cells and their structures were determined by a combination of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry, negative ion electrospray collision-induced dissociation time-of-flight mass spectrometry and normal-phase high-performance liquid chromatography with exoglycosidase digestion. Major glycans were high-mannose (Man_5-9GlcNAc₂), hybrid and bi-, tri- and tetra-antennary complex with and without bisecting GlcNAc and core fucose. Complex glycans with fewer than the full complement of galactose residues were present and sialylation was negligible. Treatment with the glucosidase inhibitor N-butyl-deoxynojirimycin (NB-DNJ) inhibited N-glycan processing as evidenced by the appearance of glycans of composition Glc₃Man_7-9GlcNAc₂. However, some complex glycans remained suggesting the presence of an α-endomannosidase. Our data in tissue culture indicate that inhibition of N-glycan processing may be considered as a therapeutic strategy against SARS CoV infections.     

Kinetics of severe acute respiratory syndrome (SARS) coronavirus-specific antibodies in 271 laboratory-confirmed cases of SARS

The sensitivities and specificities of an immunofluorescence assay and an enzyme immunoassay for detection of antibodies specific for severe acute respiratory syndrome coronavirus (SARS-CoV) were compared for 148 laboratory-confirmed SARS cases. The appearance and persistence of SARS-CoV-specific antibodies were assessed, with immunoglobulin G detected in 59% of samples collected within 14 days and persisting for 60 to 95 days after the onset of illness.     

9例严重急性呼吸综合征死亡病例分析

了解严重急性呼吸综合征死亡患者的危险因素。回顾性分析9例死亡患者的临床资料。6男，3女，大于65岁的6例，平均年龄61．66岁，从发病到死亡平均10．78天。5例患者有基础疾病其中2例为晚期肿瘤，1例糖尿病，1例高血压，1例慢支。8例患者有发热、咳嗽、全身不适，腹泻1例，8例淋巴细胞计数低于正常，5例患者血氧分压在入院时低于60mmHg，死亡前有肝功能异常和血小板降低分别有4例和5例。2例死于恶性肿瘤，3例突然死亡，4例死于呼吸衰竭。因此，年龄大于60岁，伴有基础疾病者死亡率较高；加强基础疾病治疗和护理以及强调卧床休息可能降低死亡率。     

Identification of a critical neutralization determinant of severe acute respiratory syndrome (SARS)-associated coronavirus: importance for designing SARS vaccines

The spike (S) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is not only responsible for receptor binding, but also a major antigenic determinant capable of inducing protective immunity. In this study, we demonstrated that the receptor-binding domain (RBD) of S protein is an important immunogenic site in patients with SARS and rabbits immunized with inactivated SARS-CoV. Serum samples from convalescent SARS patients and immunized rabbits had potent neutralizing activities against infection by pseudovirus expressing SARS-CoV S protein. Depletion of RBD-specific antibodies from patient or rabbit immune sera by immunoadsorption significantly reduced serum-mediated neutralizing activity, while affinity-purified anti-RBD antibodies had relatively higher potency neutralizing infectivity of SARS pseudovirus, indicating that the RBD of S protein is a critical neutralization determinant of SARS-CoV during viral infection and immunization. Two monoclonal antibodies (1A5 and 2C5) targeting at the RBD of S protein were isolated from mice immunized with inactivated SARS-CoV. Both 1A5 and 2C5 possessed potent neutralizing activities, although they directed against distinct conformation-dependant epitopes as shown by ELISA and binding competition assay. We further demonstrated that 2C5, but not 1A5, was able to block binding of the RBD to angiotensin-converting enzyme 2 (ACE2), the functional receptor on targeted cells. These data provide important information for understanding the antigenicity and immunogenicity of SARS-CoV and for designing SARS vaccines.