Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

It is unclear whether prior endemic coronavirus infections affect COVID-19 severity. Here, we show that in cases of fatal COVID-19, antibody responses to the SARS-COV-2 spike are directed against epitopes shared with endemic beta-coronaviruses in the S2 subunit of the SARS-CoV-2 spike protein. This immune response is associated with the compromised production of a de novo SARS-CoV-2 spike response among individuals with fatal COVID-19 outcomes.

T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses

A major issue in identification of protective T cell responses against SARS-CoV-2 lies in distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity generated by exposure to other coronaviruses. We characterised SARS-CoV-2 T cell immune responses in 168 PCR-confirmed SARS-CoV-2 infected subjects and 118 seronegative subjects without known SARS-CoV-2 exposure using a range of T cell assays that differentially capture immune cell function. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) were found in those who had been infected by SARS-CoV-2 but were rare in pre-pandemic and unexposed seronegative subjects. However, seronegative doctors with high occupational exposure and recent COVID-19 compatible illness showed patterns of T cell responses characteristic of infection, indicating that these readouts are highly sensitive. By contrast, over 90% of convalescent or unexposed people showed proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on the choice of assay and antigen. Memory responses to specific non-spike proteins provides a method to distinguish recent infection from pre-existing immunity in exposed populations.

Prevalence of abnormal liver function tests and comorbid psychiatric disorders among patients with anorexia nervosa and eating disorders not otherwise specified in the anorexia nervosa DSM-IV criteria

<p><b>INTRODUCTION</b>Anorexia nervosa (AN) and eating disorders not otherwise specified (EDNOS) are on the rise in Singapore. Abnormal liver function tests have been reported for up to 12.2% of patients with AN. These patients are also known to present with comorbid psychiatric disorders. This study aims to investigate the correlation between body mass index (BMI) and the severity of abnormal liver function tests, and between BMI and the presence of comorbid psychiatric disorders.</p><p><b>METHODS</b>A retrospective cohort analysis of 373 patients diagnosed with AN or EDNOS at a tertiary hospital was performed. The clinical course of transaminitis and comorbid psychiatric disorders was correlated with the patient's BMI.</p><p><b>RESULTS</b>Patients with a BMI of ≥ 16.6 kg/m(2) at their first consult had a significantly lower risk of having comorbid psychiatric disorders (χ(2) = 32.08, p < 0.001). These patients were five times less likely to have comorbid psychiatric disorders as compared to patients from the other BMI groups (odds ratio [OR] 0.21). On the other hand, patients with a BMI of < 14.6 kg/m(2) had a significantly higher risk of having transaminitis (χ(2) = 72.5, p < 0.001). They were 11.1 times more likely to develop transaminitis as compared to patients with a BMI of ≥ 14.6 kg/m(2) (OR 11.05).</p><p><b>CONCLUSION</b>Severity of BMI can be used by clinicians as an indicator to assess for secondary psychiatric comorbidities and/or transaminitis during the first consultation. This could help reduce the morbidity and mortality rates in patients with AN or EDNOS.</p>

Antibiotic prophylaxis in elective colorectal surgery.

BACKGROUND: Antibiotics are often administered in elective colorectal surgery to prevent wound infection. The tendency for surgeons to prolong the administration of prophylactic antibiotic therapy in the postoperative period is a well-known fact. The aim of this study was to elucidate the pattern of prophylactic antibiotic utilization in elective colorectal surgery and to determine if evidence-based medicine is employed in relation to this practice. METHODS: A cross-sectional study encompassing general surgeons performing elective colorectal surgery was performed. Questionnaires were distributed to 144 surgeons (national, academic and private health care). Questions pertaining to the type, timing and duration of antibiotic administration were asked. The prevalence of wound infection audit rate and whether or not there were specific guidelines related to antibiotic administration were also determined. RESULTS: The response rate obtained was 67% (n = 96). Although evidence from the current medical literature and recommended national guidelines support the use of single-dose prophylactic antibiotics, 72% of the respondents used more than a single dose. Forty surgeons (42%) claimed that their prescribing practice was supported by the medical literature, 31 respondents (32%) based their practice on hospital guidelines and personal preference was cited as a reason by 21 surgeons (22%). The remaining four respondents (4%) used a similar scheduling policy to that practiced by their colleagues in relation to antibiotic administration. There was no significant difference in antibiotic dose scheduling between national, private and university academic institutions (P = 0.85). CONCLUSIONS: These results suggest that a significant proportion of surgeons administer excessive and unnecessary doses of antibiotics in elective colorectal surgery. Further studies are required to uncover the reasons but lack of appropriate guidelines and failure to exercise evidence-based medicine are major factors that account for this practice.