Treatment of severe H1N1 2009 infection with convalescent plasma reduced respiratory tract viral load, serum cytokine response, and mortality.

Background: In late 2019, a novel human coronavirus e severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) e emerged in Wuhan, China. This virus has caused a global pandemic involving more than 200 countries. SARS-CoV-2 is highly adapted to humans and readily transmits from person-to-person. Aim: To investigate the infectivity of SARS-CoV-2 under various environmental and pH conditions. The efficacies of various laboratory virus inactivation methods and home disinfectants against SARS-CoV-2 were investigated. Methods: The residual virus in dried form or in solution was titrated on to Vero E6 cells on days 0, 1, 3, 5 and 7 after incubation at different temperatures. Viral viability was determined after treatment with various disinfectants and pH solutions at room temperature (20e25 o C). Findings: SARS-CoV-2 was able to retain viability for 3e5 days in dried form or 7 days in solution at room temperature. SARS-CoV-2 could be detected under a wide range of pH conditions from pH 4 to pH 11 for several days, and for 1e2 days in stool at room temperature but lost 5 logs of infectivity. A variety of commonly used disinfectants and laboratory inactivation procedures were found to reduce viral viability effectively. Conclusion:This study demonstrated the stability of SARS-CoV-2 on environmental surfaces, and raises the possibility of faecaleoral transmission. Commonly used fixatives, nucleic acid extraction methods and heat inactivation were found to reduce viral infectivity significantly, which could ensure hospital and laboratory safety during the SARS-CoV-2 pandemic.

Background Serial cross-sectional data on antibody levels to 2009 pandemic influenza A (H1N1) virus from a population can be used to estimate the infection attack rates and immunity against future infection in the community. Methods Between April and December 2009, we obtained 12,217 serum specimens from blood donors (16–59 yo), 2,520 from hospital outpatients (5–59yo), and 917 from subjects of a community pediatric cohort study (5–14yo). We estimated infection attack rates by comparing the proportions of specimens with antibody titers ≥1:40 by viral microneutralization before and after the first wave of the pandemic. Estimates were validated using paired sera from 324 individuals that spanned the first wave. Combining these estimates with epidemiologic surveillance data, we calculated the proportion of infections that led to hospitalization, intensive care admission, and death. Results We found that 3.3% and 14% of 5–59 yo had antibody titers ≥1:40 before and after the first wave. The overall attack rate was 10.7% with the following age-stratification: 43.4% in 5–14 yo, 15.8% in 15–19 yo, 11.8% in 20–29 yo, and 4–4.6% in 30–59 yo. Case-hospitalization rates were 0.47%–0.87% among 5–59 yo. Case-ICU and case-fatality rates increased from 7.9 and 0.4 per 100,000 infections in 5–14 yo to 75 and 26.5 per 100,000 infections in 50–59 yo. Conclusions Almost half of all school-children in Hong Kong were infected during the first wave. Compared to school-children aged 5–14, older adults aged 50–59 had 9.5 and 66 times higher risk of ICU admission and death if infected.

Emerging infectious diseases in humans are often caused by respiratory viruses such as pandemic or avian influenza viruses and novel coronaviruses. Microbiological testing for respiratory viruses is important for patient management, infection control and epidemiological studies. Nasopharyngeal specimens are frequently tested, but their sensitivity is suboptimal. This study evaluated the incremental benefit of testing respiratory viruses in expectorated saliva using molecular assays. A total of 258 hospitalized adult patients with suspected respiratory infections were included. Their expectorated saliva was collected without the use of any special devices. In the first cohort of 159 patients whose nasopharyngeal aspirates (NPAs) tested positive for respiratory viruses during routine testing, the viral load was measured using quantitative reverse transcription PCR. Seventeen percent of the patients (27/159) had higher viral loads in the saliva than in the NPA. The second cohort consisted of 99 patients whose NPAs tested negative for respiratory viruses using a direct immunofluorescence assay. Their NPA and saliva specimens were additionally tested using multiplex PCR. In these patients, the concordance rate by multiplex PCR between NPA and saliva was 83.8%. Multiplex PCR detected viruses in saliva samples from 16 patients, of which nine (56.3%) had at least one virus that was not detected in the NPA. Decisions on antiviral or isolation precautions would be affected by salivary testing in six patients. Although NPAs have high viral loads and remain the specimen of choice for most patients with respiratory virus infections, supplementary molecular testing of saliva can improve the clinical management of these patients.

Elderly-onset UC patients are increasing in number. These patients have higher risk of opportunistic infections, hospitalisation, colorectal cancer, and mortality than non-elderly-onset patients. Management and therapeutic strategies in this special group need careful attention.

ABSTRACTThe importance of neutralizing antibody in protection against influenza virus is well established, but the role of the early antibody response during the initial stage of infection in affecting the severity of disease is unknown. The 2009 influenza pandemic provided a unique opportunity for study because most patients lacked preexisting neutralizing antibody. In this study, we compared the antibody responses of 52 patients with severe or mild disease, using sera collected at admission. A microneutralization (MN) assay was used to detect neutralizing antibody. We also developed an enzyme-linked immunosorbent assay (ELISA) which detects both neutralizing and nonneutralizing antibodies against viral antigens from a split-virion inactivated monovalent influenza virus vaccine. While the MN titers were not significantly different between the two groups (P= 0.764), the ELISA titer and ELISA/MN titer ratio were significantly higher for patients with severe disease than for those with mild disease (P= 0.004 andP= 0.011, respectively). This finding suggested that in patients with severe disease, a larger proportion of serum antibodies were antibodies with no detectable neutralizing activity. The antibody avidity was also significantly higher in patients with severe disease than in those with mild disease (P< 0.05). Among patients with severe disease, those who required positive pressure ventilation (PPV) had significantly higher ELISA titers than those who did not require PPV (P< 0.05). Multivariate analysis showed that the ELISA titer and antibody avidity were independently associated with severe disease. Higher titers of nonneutralizing antibody with higher avidity at the early stage of influenza virus infection may be associated with worse clinical severity and poorer outcomes.

The differential antibody response measured by the commonly used hemagglutination inhibition (HI) and microneutralization (MN) assays in patients with natural infection and vaccination has not been fully assessed. HI and conventional MN (CMN) assays were performed on sera from 651 patients with natural infection by pandemic H1N1 2009 influenza virus and on sera from 567 recipients of the corresponding vaccine. Surprisingly, the overall seroprotection rates determined by CMN and HI assays in vaccine recipients were only 44.8 and 35.1%, respectively. Antibody titers measured by the CMN assay was significantly higher than that obtained by HI assay in vaccine recipients aged >50 years, but these titers were not significantly different among younger vaccine recipients. In contrast, the HI titer was greater than the CMN titer for the age group from 16 to 29 years but was not significantly different in other age groups for natural infection. Lower antibody levels were found in both naturally infected patients and immunized recipients in the older than in the younger age groups, but naturally infected patients exhibited higher HI and CMN titers than did the corresponding vaccine recipients. In addition, we developed a rapid fluorescent focus microneutralization (FFMN) assay to test sera from naturally infected patients. The FFMN assay has a better correlation with CMN than with HI ( ‫؍‬ 0.810 versus 0.684), which is expected of neutralizing antibody mainly targeted toward the inhibition of viral entry into cells. The higher antibody level elicited by natural infection than by vaccination may be related to differences between antigen presentation by the intramuscular route of vaccination and mucosal viral replication in mucosal cells of the respiratory tract.

h Although tuberculosis (TB) is a reemerging disease that affects people in developing countries and immunocompromised populations in developed countries, the current diagnostic methods are far from optimal. Metabolomics is increasingly being used for studies on infectious diseases. We performed metabolome profiling of plasma samples to identify potential biomarkers for diagnosing TB. We compared the plasma metabolome profiles of TB patients (n ‫؍‬ 46) with those of community-acquired pneumonia (CAP) patients (n ‫؍‬ 30) and controls without active infection (n ‫؍‬ 30) using ultrahigh-performance liquid chromatographyelectrospray ionization-quadrupole time of flight mass spectrometry (UHPLC-ESI-QTOFMS). Using multivariate and univariate analyses, four metabolites, 12R-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid [12(R)-HETE], ceramide (d18:1/16:0), cholesterol sulfate, and 4␣-formyl-4␤-methyl-5␣-cholesta-8-en-3␤-ol, were identified and found to have significantly higher levels in TB patients than those in CAP patients and controls. In a comparison of TB patients and controls, the four metabolites demonstrated area under the receiver operating characteristic curve ( T uberculosis (TB) is a disease caused by the bacterium Mycobacterium tuberculosis. Although it is a well-known disease that has been around for much of human history, there are still millions of new TB cases occurring per year worldwide, and TB remains a leading cause of deaths worldwide, especially in developing countries. Since the 1980s, TB has reemerged as a result of the AIDS epidemic and increasing use of immunosuppressants. In recent years, a higher incidence of extrapulmonary disease in immunocompromised hosts and the emergence of multidrug-resistant strains have further complicated diagnosis and treatment (1-3). Despite the medical importance of TB, diagnosis is still associated with many unresolved problems. The traditional gold standard methods are smear and culture for acid-fast bacilli from clinical specimens. Although culture offers higher sensitivity and specificity than those of smears, it is not useful for culture-negative cases, especially in early, disseminated, or extrapulmonary disease (4, 5). Moreover, it often takes 2 to 6 weeks before culture is positive and even longer for definitive species identification. While newer diagnostic modalities, such as adenosine deaminase levels in pleural fluid, lipoarabinomannan levels in urine, PCR, and Xpert MTB/RIF assays, have been developed (6-12), there are still limitations in terms of their sensitivity and/or specificity.Metabolomics is an emerging platform for studies of infectious diseases or pathogens (13)(14)(15)(16)(17)(18)(19). For TB, the technique has been applied on cultured isolates for differentiation from other Mycobacterium species and studies on the biology and virulence of tuberculosis (14,15,(20)(21)(22). For example, lipidomics studies have revealed novel metabolites potentially associated with growth and virulence of M. tuberculosis (23,24). We also recently identified ...