Memory T Cell Responses Targeting the SARS Coronavirus Persist up to 11 Years Post-Infection

10.1016/j.vaccine.2016.02.063Vaccine34172008–201

Understanding the super-spreading events of SARS in Singapore.

INTRODUCTION: It has been noted that SARS transmission is characterised by a few super-spreading events (SSEs) giving rise to a disproportionate number of secondary cases. Clinical and environmental features surrounding the index cases involved were compared with cases in non- SSEs. MATERIALS AND METHODS: Data on 231 cases of probable SARS admitted to Tan Tock Seng Hospital (TTSH) were used. Index cases directly causing 10 or more secondary cases were classified as having been involved in SSEs; all others were defined as non-SSEs. RESULTS: Only 5 cases were involved in SSEs; all 5 were isolated on day 5 of illness or later, and spent at least a brief period in a non-isolation ward; in contrast, amongst the 226 non-SSE cases, only 40.7% and 4.0% were isolated late and admitted to non-isolation wards respectively, and only 3.1% had both these environmental features present; the differences were highly significant (P = 0.012, P <0.001 and P <0.001 by Fisher's Exact test). When compared to 7 non-SSE cases with delayed isolation and an admission to non-isolation wards, SSEs were more likely to have co-morbid disease or require ICU care at time of isolation (P = 0.045 for both factors). CONCLUSION: SSEs were likely due to a conglomeration of environmental factors of delayed isolation and admission to a non-isolation ward, coupled with severe disease stage at time of isolation

SARS in Singapore--predictors of disease severity.

INTRODUCTION: Severe acute respiratory syndrome (SARS) affected 8096 individuals in 29 countries, with 774 deaths. In Singapore, there were 238 cases of SARS with 33 deaths. A retrospective analysis was performed to identify predictors of poor outcome in patients with SARS locally. MATERIALS AND METHODS: Clinical, laboratory and outcome data of 234 patients admitted to Tan Tock Seng Hospital and Singapore General Hospital were collected and analysed. Only data collected at the time of admission were used in the analysis for predictors of poor outcome. Adverse events were defined as admission to the intensive care unit or death. RESULTS: Clinical (temperature, FiO2) and laboratory [leukocyte, lymphocyte, neutrophil, platelet, lactate dehydrogenase (LDH), albumin] trends in groups with and without an adversarial event were presented. Fifty patients experienced an adverse event. On univariate analysis, male gender, advanced age, presence of comorbidities, neutrophilia, lymphopaenia, hyponatraemia, hypoalbuminaemia, transaminitis and elevated LDH or C-reactive protein were found to be significant predictors. On multivariate analysis, predictors of poor outcome were increased age [odds ratio (OR) 1.73 for every 10-year increase; 95% CI, 1.35 to 2.21], neutrophilia (OR 1.06 for every 1 x 10(9)/L increase; 95% CI, 1.02 to 1.11) and high LDH (OR 1.17 for every 100 U/L increase; 95% CI, 1.02 to 1.34). None of the 12 paediatric patients had an adverse event. CONCLUSION: Advanced age, neutrophilia and high LDH predict poor outcomes in patients with SARS

Human herpesvirus 6 integrates within telomeric regions as evidenced by five different chromosomal Sites

Fluorescent in situ hybridization (FISH) was used to investigate the chromosomal integration sites of human herpesvirus 6 (HHV-6) in phytohemagglutinin-stimulated leukocytes and B lymphocytes from Epstein–Barr virus transformed lymphoblastoid cell lines (LCLs). Five different chromosomal integration sites were found in nine individuals. Only one site was identified in each individual, each site was in the vicinity of the telomeric region and was on either the p or q arm of only one of the two chromosome homologues. The sites were 9q34.3, 10q26.3, 11p15.5, 17p13.3, and 19q 13.4, of which three have not been previously identified. For 9q34.3 the site of integration was further mapped using a locus-specific probe for 9q34.3 together with a pan-telomeric probe and both co-localized with the HHV-6 signal. Similarly an arm-specific telomeric probe for 19q co-localized with the HHV-6 signal. It was therefore concluded that the site of integration is actually within the telomere. The number of viral DNA copies/cell was calculated in blood, LCL cells and hair follicles and was one or more in every case for each of the nine individuals. This result was confirmed by FISH where 100% of cells gave an HHV-6 signal. These findings add to previous reports suggesting that integrated HHV-6 DNA is found in every cell in the body and transmitted vertically. Finally, including our data, worldwide seven different chromosomal sites of HHV-6 integration have now been identified. Large epidemiological studies of chromosomal integration are required to identify further telomeric sites, geographical or racial variation and possible clinical consequences

Chronic Hepatitis E Infection Resulting in Graft Failure in a Liver Transplant Tourist

Hepatitis E, usually an acute hepatitis in the immunocompetent, has a chronic form described in immunocompromised hosts. We report the clinical course and outcome of an adult liver transplant recipient whose posttransplant period was complicated by chronic hepatitis E, Epstein-Barr virus infection, and cellular rejection of the graft

Human Herpesvirus 6 Chromosomal Integration in Immunocompetent Patients Results in High Levels of Viral DNA in Blood, Sera, and Hair Follicles

Six immunocompetent patients with human herpesvirus 6 (HHV-6) chromosomal integration had HHV-6 and β-globin DNA quantified in various samples by PCR. The mean HHV-6 DNA concentration (log(10) copies/milliliter) in blood was 7.0 (≥1 HHV-6 DNA copies/leukocyte), and in serum it was 5.3 (≥1 HHV-6 DNA copies/lysed cell). The mean HHV-6 DNA load (log(10) copies)/hair follicle was 4.2 (≥1 copies/hair follicle cell), demonstrating that viral integration is not confined to blood cells. The characteristically high HHV-6 DNA levels in chromosomal integration may confound laboratory diagnosis of HHV-6 infection and should be given due consideration

Clinical and epidemiological predictors of transmission in Severe Acute Respiratory Syndrome (SARS).

BACKGROUND: Only a minority of probable SARS cases caused transmission. We assess if any epidemiological or clinical factors in SARS index patients were associated with increased probability of transmission. METHODS: We used epidemiological and clinical data on probable SARS patients admitted to Tan Tock Seng Hospital. Using a case-control approach, index patients who had probable SARS who subsequently transmitted the disease to at least one other patient were analysed as "cases" against patients with no transmission as "controls", using multivariate logistic regression analysis. RESULTS: 98 index patients were available for analysis (22 with transmission, 76 with no transmission). Covariates positively associated with transmission in univariate analysis at p 650 IU/L (OR 6.4, 23.8 and 4.7 respectively). CONCLUSION: Clinical and epidemiological factors can help us to explain why transmission was observed in some instances but not in others