The importance of anosmia,ageusia and age in community presentation of symptomatic and asymptomatic SARS-CoV-2 infection in Louisiana,USA; a cross-sectional prevalence study

ObjectiveWhile many seroprevalence studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been performed, few are demographically representative. This investigation focused on defining the nature and frequency of symptomatic and asymptomatic SARS-CoV-2 infection in a representative, cross-sectional sample of communities in Louisiana, USA.MethodsA sample of 4778 adults from New Orleans and Baton Rouge, Louisiana were given a survey of symptoms and co-morbidities, nasopharyngeal swab to test for active infection (PCR), and blood draw to test for past infection (IgG). Odds ratios, cluster analysis, quantification of virus and antibody, and linear modelling were used to understand whether certain symptoms were associated with a positive test, how symptoms grouped together, whether virus or antibody varied by symptom status, and whether being symptomatic was different across the age span.ResultsReported anosmia/ageusia was strongly associated with a positive test; 40.6% (93/229) tested positive versus 4.8% (218/4549) positivity in those who did not report anosmia/ageusia (OR 13.6, 95% CI 10.1–18.3). Of the people who tested positive, 47.3% (147/311) were completely asymptomatic. Symptom presentation clustered into three groups; low/no symptoms (0.4 ± 0.9, mean ± SD), highly symptomatic (7.5 ± 1.9) or moderately symptomatic (4.0 ± 1.5). Quantity of virus was lower in the asymptomatic versus symptomatic group (cycle number 23.3 ± 8.3 versus 17.3 ± 9.0; p < 0.001). Modelling the probability of symptoms showed changes with age; the highest probability of reporting symptoms was 64.6% (95% CI 50.4–76.5) at age 29 years, which decreased to a probability of 49.3% (95% CI 36.6–62.0) at age 60 years and only 25.1% (95% CI 5.0–68.1) at age 80 years.ConclusionAnosmia/ageusia can be used to differentiate SARS-CoV-2 infection from other illnesses, and, given the high ratio of asymptomatic individuals, contact tracing should include those without symptoms. Regular testing in congregant settings of those over age 60 years may help mitigate asymptomatic spread.     

Postvaccination infections among staff of a tertiary care hospital after vaccination with severe acute respiratory syndrome coronavirus 2 vector and mRNA-based vaccines

ObjectivesThe identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen or RNA in respiratory specimens ≥14 days after administration of all recommended doses of authorized coronavirus disease 2019 (COVID-19) vaccines is defined as breakthrough infection. In the present investigation, mRNA and vector-based SARS-CoV-2 vaccines were analysed with respect to postvaccination infections in vaccinated hospital employees.MethodsA total of 8553 staff members were vaccinated with BNT162b2 (47%) or ChAdOx1-S (53%) between January and May 2021. In a retrospective observational cohort study, incidence of SARS-CoV-2 postvaccination infections was analysed in relation to demographic data, viral load, virus variants, vaccine brand and vaccination status at time of positive PCR test (fully vaccinated: ≥14 days since second dose; partially vaccinated: >21 days since first, but <14 days after second dose; insufficiently vaccinated: <22 days since first dose).ResultsWithin the follow-up period, ending on 31 July 2021, person-time at risk-adjusted monthly rates for SARS-CoV-2 postvaccination infections were 0.18% (BNT162b2) and 0.57% (ChAdOx1-S) for insufficiently vaccinated, 0.34% (BNT162b2) and 0.32% (ChAdOx1-S) for partially vaccinated and 0.06% (BNT162b2) and 0.04% (ChAdOx1-S) for fully vaccinated participants. The two vaccine types did not differ with respect to hazard ratios for any of the respective postvaccination infection types. No cases of COVID-19-related hospitalizations or deaths were reported. Genotyping of positive PCR specimens revealed 42 variants of concern: B.1.1.7 (Alpha variant; n = 34); B.1.351 (Beta variant; n = 2), B.1.617.2 (Delta variant; n = 6).ConclusionsBNT162b2 and ChAdOx1-S are both effective in preventing breakthrough infections; however, it seems important, that all recommended vaccine doses are administered.     

Development and validation of a prediction model for severe respiratory failure in hospitalized patients with SARS-CoV-2 infection: a multicentre cohort study (PREDI-CO study)

ObjectivesWe aimed to develop and validate a risk score to predict severe respiratory failure (SRF) among patients hospitalized with coronavirus disease-2019 (COVID-19).MethodsWe performed a multicentre cohort study among hospitalized (>24 hours) patients diagnosed with COVID-19 from 22 February to 3 April 2020, at 11 Italian hospitals. Patients were divided into derivation and validation cohorts according to random sorting of hospitals. SRF was assessed from admission to hospital discharge and was defined as: Spo₂ <93% with 100% Fio₂, respiratory rate >30 breaths/min or respiratory distress. Multivariable logistic regression models were built to identify predictors of SRF, β-coefficients were used to develop a risk score. Trial Registration NCT04316949.ResultsWe analysed 1113 patients (644 derivation, 469 validation cohort). Mean (±SD) age was 65.7 (±15) years, 704 (63.3%) were male. SRF occurred in 189/644 (29%) and 187/469 (40%) patients in the derivation and validation cohorts, respectively. At multivariate analysis, risk factors for SRF in the derivation cohort assessed at hospitalization were age ≥70 years (OR 2.74; 95% CI 1.66–4.50), obesity (OR 4.62; 95% CI 2.78–7.70), body temperature ≥38°C (OR 1.73; 95% CI 1.30–2.29), respiratory rate ≥22 breaths/min (OR 3.75; 95% CI 2.01–7.01), lymphocytes ≤900 cells/mm³ (OR 2.69; 95% CI 1.60–4.51), creatinine ≥1 mg/dL (OR 2.38; 95% CI 1.59–3.56), C-reactive protein ≥10 mg/dL (OR 5.91; 95% CI 4.88–7.17) and lactate dehydrogenase ≥350 IU/L (OR 2.39; 95% CI 1.11–5.11). Assigning points to each variable, an individual risk score (PREDI-CO score) was obtained. Area under the receiver-operator curve was 0.89 (0.86–0.92). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 71.6% (65%–79%), 89.1% (86%–92%), 74% (67%–80%) and 89% (85%–91%), respectively. PREDI-CO score showed similar prognostic ability in the validation cohort: area under the receiver-operator curve 0.85 (0.81–0.88). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 80% (73%–85%), 76% (70%–81%), 69% (60%–74%) and 85% (80%–89%), respectively.ConclusionPREDI-CO score can be useful to allocate resources and prioritize treatments during the COVID-19 pandemic.     

Seroprevalence of severe acute respiratory syndrome coronavirus 2 in Slovenia: results of two rounds of a nationwide population study on a probability-based sample,challenges and lessons learned

ObjectivesSeroprevalence surveys provide crucial information on cumulative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure. This Slovenian nationwide population study is the first longitudinal 6-month serosurvey using probability-based samples across all age categories.MethodsEach participant supplied two blood samples: 1316 samples in April 2020 (first round) and 1211 in October/November 2020 (second round). The first-round sera were tested using Euroimmun Anti-SARS-CoV-2 ELISA IgG (ELISA) and, because of uncertain estimates, were retested using Elecsys Anti-SARS-CoV-2 (Elecsys-N) and Elecsys Anti-SARS-CoV-2 S (Elecsys-S). The second-round sera were concomitantly tested using Elecsys-N/Elecsys-S.ResultsThe populations of both rounds matched the overall population (n = 3000), with minor settlement type and age differences. The first-round seroprevalence corrected for the ELISA manufacturer's specificity was 2.78% (95% highest density interval [HDI] 1.81%–3.80%), corrected using pooled ELISA specificity calculated from published data 0.93% (95% CI 0.00%–2.65%), and based on Elecsys-N/Elecsys-S results 0.87% (95% HDI 0.40%–1.38%). The second-round unadjusted lower limit of seroprevalence on 11 November 2020 was 4.06% (95% HDI 2.97%–5.16%) and on 3 October 2020, unadjusted upper limit was 4.29% (95% HDI 3.18%–5.47%).ConclusionsSARS-CoV-2 seroprevalence in Slovenia increased four-fold from late April to October/November 2020, mainly due to a devastating second wave. Significant logistic/methodological challenges accompanied both rounds. The main lessons learned were a need for caution when relying on manufacturer-generated assay evaluation data, the importance of multiple manufacturer-independent assay performance assessments, the need for concomitant use of highly-specific serological assays targeting different SARS-CoV-2 proteins in serosurveys conducted in low-prevalence settings or during epidemic exponential growth and the usefulness of a Bayesian approach for overcoming complex methodological challenges.     

Detection of severe acute respiratory syndrome coronavirus 2 in nasopharynx according to clinical phenotype of affected patients

ObjectivesDuration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the upper respiratory tract is extremely variable, but its relation to disease severity is unknown. We investigated this relation in the 530 000 inhabitants of the northeastern Italian province of Udine.MethodsWe analysed real-time RT-PCR tests for SARS-CoV-2 in upper respiratory specimens conducted at the Virology Laboratory of the University Hospital of Udine, Italy (which serves the whole province) from 1 March to 30 April 2020 Specimens were from positive individuals in four groups characterized by different disease severity (critically ill patients admitted to intensive care units, patients admitted to infectious disease units, symptomatic patients visiting the emergency department and not hospitalized, and asymptomatic individuals tested during contact tracing or screening activities). Duration of viral positivity was assessed from the first positive test to the day of the first of two consecutive negative tests. Univariate and multivariate analyses were conducted to investigate differences in the four groups.ResultsFrom 1 March to 30 April, 39 483 RT-PCR tests for SARS-CoV-2 were conducted on 23 778 individuals, and 974 individuals had a positive test result. Among those with multiple tests (n = 878), mean time to negativity was 23.7 days (standard error 0.3639; median 23, interquartile range 16–30 days). Mean time to negativity was longer in the group admitted to the intensive care unit than in the others, whereas no difference was observed between asymptomatic patients and those with mild disease.ConclusionsDisease control measures should not be adjusted to account for differences in viral shedding according to symptomatic status.     

Severe acute respiratory syndrome coronavirus 2 causes lung inflammation and injury

BackgroundAs of 14 October 2021, coronavirus disease 2019 (COVID-19) has affected more than 246 million individuals and caused more than 4.9 million deaths worldwide. COVID-19 has caused significant damage to the health, economy and lives of people worldwide. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not as lethal as SARS coronavirus or Middle East respiratory syndrome coronavirus, its high transmissibility has had disastrous consequences for public health and health-care systems worldwide given the lack of effective treatment at present.ObjectivesTo clarify the mechanisms by which SARS-CoV-2 caused lung inflammation and injury, from the molecular mechanism to lung damage and tissue repair, from research to clinical practice, and then presented clinical requirements.SourcesReferences for this review were identified through searches ‘(COVID-19 [Title]) OR (SARS-CoV-2 [Title])’ on PubMed, and focused on the pathological damage and clinical practice of COVID-19.ContentWe comprehensively reviewed the process of lung inflammation and injury during SARS-CoV-2 infection, including pyroptosis of alveolar epithelial cells, cytokine storm and thrombotic inflammatory mechanisms.ImplicationsThis review describes SARS-CoV-2 in comparison to SARS and explores why most people have mild inflammatory responses, even asymptomatic infections, and only a few develop severe disease. It suggests that future therapeutic strategies may be targeted antiviral therapy, the pathogenic pathways in the lung inflammatory response, and enhancing repair and regeneration in lung injury.     

Tissue and cellular tropism of the coronavirus associated with severe acute respiratory syndrome: an in-situ hybridization study of fatal cases

Severe acute respiratory syndrome (SARS) is a new human infectious disease with significant morbidity and mortality. The disease has been shown to be associated with a new coronavirus (SARS-CoV). The clinical and epidemiological aspects of SARS have been described. Moreover, the viral genome of SARS-CoV has been fully sequenced. However, much of the biological behaviour of the virus is not known and data on the tissue and cellular tropism of SARS-CoV are limited. In this study, six fatal cases of SARS were investigated for the tissue and cellular tropism of SARS-CoV using an in-situ hybridization (ISH) technique. Among all the tissues studied, positive signals were seen in pneumocytes in the lungs and surface enterocytes in the small bowel. Infected pneumocytes were further confirmed by immunofluorescence-fluorescence in-situ hybridization (FISH) analysis. These results provide important information concerning the tissue tropism of SARS-CoV, which is distinct from previously identified human coronaviruses, and suggest the possible involvement of novel receptors in this infection. Whereas the lung pathology was dominated by diffuse alveolar damage, the gut was relatively intact. These findings indicated that tissue responses to SARS-CoV infection are distinct in different organs.     

The potential clinical utility of measuring severe acute respiratory syndrome coronavirus 2-specific T-cell responses

BackgroundBoth humoral and cell-mediated responses are associated with immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although our understanding of the potential role of T-cell responses in the context of coronavirus disease 2019 (COVID-19) is rapidly increasing, more information is still needed.ObjectivesTo provide an overview of the role of T-cell immunity in COVID-19, in the context of natural infection and post-vaccination, and discuss the potential utility of measuring SARS-CoV-2-specific T-cell responses, drawing on experience of the use of interferon-γ release assays (IGRAs) in tuberculosis (TB).SourcesPubMed articles up to 16 April 2021.ContentT-cell responses can be detected very early in the course of COVID-19, earlier than the detection of antibody responses, and are correlated with COVID-19 outcome. Lower CD4⁺ and CD8⁺ T-cell counts are markers of more severe disease, longer duration of viral RNA positivity and increased mortality. In line with natural infection, SARS-CoV-2 vaccination stimulates robust T-cell responses, which probably play an important role in protection; data on long-term T-cell responses are currently limited. The utility of measuring T-cell responses is already well established in both aiding the diagnosis of TB infection using IGRAs, and evaluation of T-cell responses to TB vaccine candidates. A variety of assays have already been developed to measure SARS-CoV-2-specific T-cell responses, including IGRAs, intracellular cytokine staining and activation-induced markers. IGRAs based on SARS-CoV-2 antigens can distinguish between convalescent and uninfected healthy blood donors.ImplicationsSimple assays for measuring the quantity and function of T-cell responses may have utility in the prognostication of COVID-19, and for monitoring immune responses to SARS-CoV-2 vaccination and population-based immunity to SARS-CoV-2 variants of interest.     

Effective use of an advanced isolation unit during the COVID-19 pandemic: A retrospective cohort study

We described a strategy for preventing virus transmission within hospitals through screening and advanced isolation during the coronavirus pandemic. Patients were screened and admitted to the adult advanced isolation unit from February to April 2020. Our process minimized exposure without delaying proper treatment and prevented virus transmission within the hospital.     

严重急性呼吸综合征血细胞动态变化及预测意义

目的探讨严重急性呼吸综合征(SARS)患者血细胞的变化规律,分析SARS预后的临床指征。方法 对43例SAP6患者动态观察血细胞变化规律,做出趋势图,并比较SARS组与正常对照组、SAPS康复组与病死组之间的区别。结果初诊时SARS组白细胞、淋巴细胞、红细胞均低于对照组(P<0.01)差异有显著意义。SARS病死组淋巴细胞和血小板持续降低,康复组则无降低,据此可提示SARS预后。结论动态观察血细胞变化有利于SARS早期诊断及病情预警,从而提示治疗方法,降低病死率。     

质粒介导的RNAi抑制SARS-CoV复制和感染

目的研究RNAi作为治疗SARS-CoV感染新策略的可能性。方法选择并克隆针对SARS-CoV编码基因的共同前导序列非结构蛋白-1(Non-structureprotein1,NSP1)的siRNAs;RT-PCR和FACS法检测所选取的siRNAs对NSP1基因抑制的特异性和有效性;利用MTT法检测选取的siRNAs对病毒感染的细胞生存率的影响;空斑形成实验证实在siRNAs存在下病毒量减少情况;RT-PCR和Western-blot法进一步证实感染细胞中S和N基因在mRNA和蛋白水平的表达情况。结果结果显示重组质粒衍生的靶向SARS-CoVNSP1的siRNAs能特异地抑制靶序列表达;在体外培养的VeroE6细胞中能显著抑制SARS-CoV的复制与繁殖。感染1d后,RT-PCR和Western-blot结果显示,同对照组相比,SARS-CoV的S和N基因的mRNA和蛋白质表达均显著减少。结论NSP1序列是SARS-CoV的RNAi策略的有效靶标,这些siRNAs很可能广泛地抑制了SARS-CoV亚基因组的合成及随后的蛋白质表达。     

Effect of hydroxychloroquine pre-exposure on infection with SARS-CoV-2 in rheumatic disease patients: a population-based cohort study

ObjectivesEarly in vitro studies have suggested that hydroxychloroquine (HCQ) is a potentially useful drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. This study was conducted to determine whether HCQ had a preventive effect on coronavirus disease 2019 (COVID-19) in rheumatic disease patients who were taking HCQ.MethodsWe conducted a population-based retrospective cohort study using the records of the Korean Health Insurance Review and Assessment (HIRA) claim records. The clinical data of patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) who were tested for SARS-CoV-2 were investigated. We compared the attack rate of COVID-19 between those who underwent HCQ therapy within 14 days before the test for SARS-CoV-2 (HCQ users) and HCQ non-users. Data were analysed using logistic regression models, χ², and Student's t-tests.ResultsAs of 15th May 2020, 2066 patients with RA or SLE were tested for COVID-19. Among them, 31.4% (649/2066) were treated with HCQ. Most HCQ users (93.7%, 608/649) were taking 200–400 mg/day recommended for the treatment of rheumatic diseases. The attack rate of COVID-19 in the HCQ users (2.3%, 15/649) did not differ from that in the HCQ non-users (2.2%, 31/1417) (p 0.86).ConclusionsHCQ prophylactic use at a usual dose did not prevent COVID-19 in patients with rheumatic disease.     

Severe acute respiratory syndrome coronavirus 2 may cause liver injury via Na+/H+ exchanger

The liver has many significant functions, such as detoxification, the urea cycle, gluconeogenesis, and protein synthesis. Systemic diseases, hypoxia, infections, drugs, and toxins can easily affect the liver, which is extremely sensitive to injury. Systemic infection of severe acute respiratory syndrome coronavirus 2 can cause liver damage. The primary regulator of intracellular p H in the liver is the Na⁺/H⁺ exchanger(NHE). Physiologically, NHE protects hepatocytes from ap...     

Immunization with an attenuated severe acute respiratory syndrome coronavirus deleted in E protein protects against lethal respiratory disease

The severe acute respiratory syndrome coronavirus (SARS-CoV) caused substantial morbidity and mortality in 2002-2003. Deletion of the envelope (E) protein modestly diminished virus growth in tissue culture but abrogated virulence in animals. Here, we show that immunization with rSARS-CoV-ΔE or SARS-CoV-Δ[E,6-9b] (deleted in accessory proteins (6, 7a, 7b, 8a, 8b, 9b) in addition to E) nearly completely protected BALB/c mice from fatal respiratory disease caused by mouse-adapted SARS-CoV and partly protected hACE2 Tg mice from lethal disease. hACE2 Tg mice, which express the human SARS-CoV receptor, are extremely susceptible to infection. We also show that rSARS-CoV-ΔE and rSARS-CoV-Δ[E,6-9b] induced anti-virus T cell and antibody responses. Further, the E-deleted viruses were stable after 16 blind passages through tissue culture cells, with only a single mutation in the surface glycoprotein detected. The passaged virus remained avirulent in mice. These results suggest that rSARS-CoV-ΔE is an efficacious vaccine candidate that might be useful if SARS recurred.     

The impact of laryngopharyngeal reflux disease on 95 hospitalized patients with COVID-19 in Wuhan,China: A retrospective study

Studies have demonstrated that comorbidities, especially cardiovascular and endocrine diseases, correlated with poorer clinical outcomes. However, the impact of digestive system diseases has not been issued. The aim of this study is to determine the impact of laryngopharyngeal reflux disease (LPRD) on hospitalized patients with coronavirus disease 2019 (COVID-19). We extracted clinical data regarding 95 patients in Wuhan Jinyintan Hospital, Wuhan, China, between 26 January and 21 February 2020. The Reflux Symptom Index (RSI) was used to assess the presence and severity of LPRD. An RSI greater than 13 is considered to be abnormal. A total of 95 patients with COVID-19 were enrolled, with 61.1% (58/95), 32.6% (31/95), and 6.3% (6/95) being moderately ill, severely ill, and critically ill, respectively. In this study, 38.9% (37/95) of the patient had an RSI score over 13, which was indicative of LPRD. In univariable analysis, the age and RSI scores of severely or critically ill patients were statistically significantly higher than patients with moderate disease (P = .026 and P = .005, respectively). After controlling for age difference in a multivariable model, the RSI greater than 13, compared to RSI equal to 0, was associated with significantly higher risk of severe infection (P < .001; odds ratio [OR] = 11.411; 95% confidence interval [CI], 2.95-42.09) and critical infection (P = .028; OR= 19.61; 95% CI, 1.38-277.99). Among hospitalized patients with COVID-19, RSI scores greater than 13, indicative of LPRD, correlated with poorer clinical outcomes. The prevalence of LPRD may be higher than the general population, which indicated that COVID-19 can impair the upper esophageal sphincter and aggravate reflux.     

SARS尸检组织的病理变化和超微结构观察

目的 研究严重急性呼吸综合征(SARS)尸检组织的临床病理和超微结构特征。方法 对1例SARS死亡患者做即刻肺穿刺和12h后尸检,进行病理形态和超微结构的观察;用Macchiavello法做病毒包涵体染色;并对淋巴结、脾脏、结肠、小肠及骨髓组织行CD20、CD45RO(UCHL-1)、CD4、CD8、CD68、CD34免疫组织化学标记。结果 SARS肺的主要病变为急性弥漫性全小叶性间质性炎,可见肺泡腔内透明膜形成和增生及脱落的肺泡上皮,偶见胞质内病毒包涵体样结构,病毒包涵体染色阳性,肺内小血管增生、扩张,呈血管炎性改变。淋巴结、脾脏结构破坏,淋巴滤泡消失,脾小体萎缩,淋巴细胞明显减少,组织细胞增生;结肠、小肠孤立和集合淋巴结淋巴滤泡消失;骨髓增生减低,巨核细胞增多。免疫组织化学染色：淋巴结、脾脏B细胞CD20弥漫散在阳性,CD45RO(UCHL-1)散在阳性,CD4辅助T细胞显著减少,CD8毒性T细胞稍增加,CD4／CD8比例明显小于0．5。电镜观察：肺泡内的单核巨噬细胞、肺泡上皮胞质内可见病毒样颗粒,大小80～160nm,有光晕或花环状包膜。结论 肺部明显急性弥漫性全小叶性间质性炎,肺泡腔透明膜形成,肺外淋巴造血系统明显损害,尤T细胞明显;内脏器官出血、坏死和血管炎改变等为急性SARS的形态特征;肺内所见病毒样颗粒可能为新型冠状病毒,推测其为此次SARS流行的主要病原体。     

Immune responses against severe acute respiratory syndrome coronavirus induced by virus-like particles in mice

Virus-like particles (VLPs) represent a promising vaccine against severe acute respiratory syndrome coronavirus (SARS CoV). In this study, recombinant baculovirus vAcS and vAcME were constructed to express the S protein and the M and E proteins of SARS CoV, respectively. Electron microscope analysis demonstrated the formation of VLPs in vAcME and vAcS coinfected insect cells. Mice immunized four times with VLPs developed high antibody titres against SARS CoV. In addition, VLPs elicited cell-mediated immunity as demonstrated by enhanced interferon-gamma and interleukin-4 production. VLPs also conferred protective immunity against the infection of Spike protein pseudotyped murine leukaemia virus. Our findings demonstrate that SARS CoV VLPs are immunogenic and can elicit strong SARS CoV-specific humoral and cellular immune responses in mice. This is the first study describing the immunogenicity of SARS CoV VLPs, providing valuable data for developing a protective vaccine against SARS CoV infection.     

严重急性呼吸综合征患者尸解肺标本的病理改变和致病机制研究

目的研究严重急性呼吸综合征（SARS）患者尸解肺标本的病理改变和致病机制。方法观察了2003年4-7月期间死于SARS的6例患者的肺标本,并采用光镜、电镜、Masson三色染色和免疫组织化学染色方法（EnVision法）进行研究。结果肺标本的病理形态改变：（1）6例的双肺均可见到弥漫性实变病灶,肺重量明显增加;（2）6例均可见到弥漫性肺泡损伤,包括透明膜形成、肺泡腔内水肿／出血、纤维素沉积和肺泡上皮细胞脱屑,AE1／AE3免疫组织化学染色显示肺泡上皮细胞的完整性明显破坏;（3）Ⅱ型肺泡上皮细胞轻度增生,有一定异型性,细胞体积增大,胞质呈双染性和颗粒状,胞质内可见小脂肪空泡聚集（5／6）;（4）6例中有5例可见巨细胞在肺泡内浸润,巨细胞大多AEl／AE3阳性（5／6）,少数CD68阳性（2／6）;（5）组织学形态和免疫组织化学染色证实肺泡腔内和肺泡间隔内有多量巨噬细胞浸润（6／6）;（6）6例中有5例可见巨噬细胞噬红细胞象;（7）6例中有5例可见肺纤维化,包括肺泡间隔和肺间质增宽（5／6）、肺泡腔内渗出物机化（6／6）和胸膜增厚（4／6）。Masson三色染色证实胶原纤维明显增生,免疫组织化学染色显示大多数为Ⅲ型胶原。光镜和免疫组织化学染色显示5例有明显的成纤维细胞／肌纤维母细胞增生灶;（8）5例可见支气管黏膜鳞状上皮化生;（9）6例患者均可见血栓;（10）2例同时合并其他感染,1例合并细菌感染,另1例合并真菌感染。此外,电镜发现在肺泡上皮细胞和肺血管内皮细胞的胞质内有冠状病毒样颗粒。结论SARS冠状病毒直接损伤肺泡上皮细胞、巨噬细胞明显浸润和成纤维细胞／肌纤维母细胞显著增生在SARS的致病机制中起重要作用。