SARS-CoV-2-specific T cell responses: a comparative analysis between QuantiFERON SARS-CoV-2, T-SPOT.COVID, and an in-house Omicron ELISpot.

BACKGROUND: T cell immunity plays a pivotal role in mitigating the severity of coronavirus disease 2019 (COVID-19). Therefore, reliable functional T cell assays are required to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell immunity in specific patient populations. METHODS: We recruited a cohort of 23 healthcare workers who received their bivalent Omicron BA.1 / ancestral mRNA booster vaccination or were infected with the Omicron variant at a median of 144 days and 227 days before blood collection, respectively. In this cohort, we compared the performances of two widely utilized commercial SARS-CoV-2 interferon-gamma release assays (IGRAs), i.e., QuantiFERON SARS-CoV-2 and T-SPOT.COVID, and an in-house designed Omicron enzyme-linked immunospot (ELISpot). RESULTS: The QuantiFERON SARS-CoV-2 and T-SPOT.COVID assays detected SARS-CoV-2 spike-specific T cells in 34.8 % and 21.7 % of participants, respectively. Moreover, our in-house designed ELISpot that included Omicron BA.4 and BA.5 full-spike peptides detected T cell responses in 47.8 % of participants and was strongly associated with the T-SPOT.COVID. CONCLUSION: The evaluation of SARS-CoV-2 T cell immunity using commercially accessible assays may yield disparate outcomes as results from different assays are not directly comparable. A specific Omicron ELISpot should be considered to assess Omicron-specific T cell immunity.

Correction: COVID-19 Vaccine-Induced Myocarditis and Pericarditis: Towards Identification of Risk Factors.

[This corrects the article DOI: 10.5334/gh.1252.].

Evaluation of a New Standardized Nasal Sampling Method for Detection of SARS-CoV-2 RNA via RT-PCR.

The aim of this study was to compare the diagnostic accuracy of nasal sampling using a novel anterior nasal swab (ANS) (Rhinoswab) versus combined oro-nasopharyngeal (OP/NP) sampling in COVID-19 suspected patients. This prospective observational study was performed from 11 November to 2 December 2021 (part 1), and from 16 January to 22 February 2022 (part 2). Adult patients who attended the emergency room with suspected COVID-19 were asked to participate. One ANS and one OP/NP sample were consecutively collected, and both were analyzed via reverse transcription polymerase chain reaction (RT-PCR). The result of the OP/NP sample was considered to be the reference standard. A total of 412 patients were included, of whom 171 (41.5%) had a positive RT-PCR of the OP/NP swab, whereas 139 (33.7%) were positive on the ANS sample. The overall diagnostic accuracy for ANS sampling in terms of sensitivity, specificity, positive predictive value, and negative predictive value was 80.7% (95% CI 73.8-86.2), 99.6% (95% CI 97.3-100), 99.3% (95% CI 95.5-100), and 87.9% (95% CI 83.3-91.4), respectively. In conclusion, ANS sampling with the Rhinoswab identified 80.7% of all presented COVID-19 patients in an emergency department. Future studies should investigate if nasal Rhinoswab self-sampling is suitable for reliable diagnosis of COVID-19 in an outpatient setting.

An absence of imperfections: A proposed framework for defining, assessing, and achieving skin glow.

BACKGROUND: Skin glow is a subcomponent of skin quality. It has become entrenched in the cosmeceuticals and aesthetics lexicons as a synonym for health and youth, but is not well-defined as a scientific metric. AIMS: To examine the concept of skin glow and determine if it is an objective concept that can be defined and quantified. METHODS: Literature review was used to develop a survey on current concepts relating to skin quality. The survey results were analyzed descriptively and presented to a focus group comprising five dermatologists and four aesthetic physicians. This group then discussed the concept of skin glow, how to define it and what metrics could be used to assess it. RESULTS: Surveyed practitioners (n = 38) ranked skin quality as the fourth most important factor related to a person's overall aesthetic first impression. Almost all (95%) respondents reported routinely assessing skin quality, citing serial photography (83%), and visual inspection (67%) as the main means of achieving this. The focus group defined skin glow as even reflectance from an unaffected papillary and reticular dermal collagen layer, which is created only when skin does not exhibit any characteristics that detract from this even reflectance. Due to its complexity, the focus group proposed a hierarchal framework for assessment, encompassing patient self-rating, practitioner severity rating, and supplemental use of validated measurement devices. CONCLUSIONS: Skin glow can be defined and quantified. More work is warranted to develop a practical skin glow assessment tool suitable for use in the clinic setting.

Consensus recommendations on the use of injectable poly-l-lactic acid in Asian patients.

BACKGROUND: Injectable poly-L-lactic acid (PLLA) has been proven safe and effective with numerous medical applications for more than 25 years. The product has been approved in over 40 countries and is being used for soft tissue augmentation in the face and certain body parts. With the increased demand for subtle and natural-looking aesthetic treatments in the Asia-Pacific region, there is also a heightened need for consistent preparation and effective treatment methodologies to optimize outcomes for Asian patients. METHODS: The body of evidence in medical literature, clinical data of presented case reports, and the collective experience of the authors are reflected in these consensus recommendations, which also take under consideration the availability of biostimulators in the Asia-Pacific region. RESULTS: The resulting consensus recommendations include patient selection and assessment, management of treatment expectations, appropriate preparation and storage, proper injection techniques and treatment plans, management of adverse effects, PLLA combination with other facial rejuvenation procedures, and other constructive considerations. CONCLUSIONS: In the above consensus recommendations, the authors shared their best practices in accordance with the updated preparation and treatment protocols of PLLA. These recommendations represent the clinical and real-world techniques utilized by authors in providing PLLA treatments for Asian patients.

Ancestral SARS-CoV-2 and Omicron BA.5-specific neutralizing antibody and T-cell responses after Omicron bivalent booster vaccination in previously infected and infection-naive individuals.

Coronavirus disease-2019 (COVID-19) bivalent ancestral/Omicron messenger RNA (mRNA) booster vaccinations became available to boost and expand the immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron infections. In a prospective cohort study including 59 healthcare workers, we assessed SARS-CoV-2 ancestral and Omicron BA.5-specific neutralizing antibody and T-cell responses in previously infected and infection-naive individuals. Also, we assessed the effect of an ancestral/Omicron BA.1 bivalent mRNA booster vaccination on these immune responses. 10 months after previous monovalent mRNA vaccinations, ancestral SARS-CoV-2 S1-specific T-cell and anti-RBD IgG responses remained detectable in most individuals and a previous SARS-CoV-2 infection was associated with increased T-cell responses. T-cell responses, anti-RBD IgG, and Omicron BA.5 neutralization activity increased after receiving an ancestral/Omicron BA.1 bivalent booster mRNA vaccination. An Omicron BA.5 infection in addition to bivalent vaccination, led to a higher ratio of Omicron BA.5 to ancestral strain neutralization activity compared to no bivalent vaccination and no recent SARS-CoV-2 infection. In conclusion, SARS-CoV-2 T-cell and antibody responses persist for up to 10 months after a monovalent booster mRNA vaccination. An ancestral/Omicron BA.1 bivalent booster mRNA vaccination increases these immune responses and also induces Omicron BA.5 cross-neutralization antibody activity. Finally, our data indicate that hybrid immunity is associated with improved preservation of T-cell immunity.

Airborne virus shedding of the alpha, delta, omicron SARS-CoV-2 variants and influenza virus in hospitalized patients.

Airborne transmission is an important transmission route for the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological data indicate that certain SARS-CoV-2 variants, like the omicron variant, are associated with higher transmissibility. We compared virus detection in air samples between hospitalized patients infected with different SARS-CoV-2 variants or influenza virus. The study was performed during three separate time periods in which subsequently the alpha, delta, and omicron SARS-CoV-2 variants were predominant. In total, 79 patients with coronavirus disease 2019 (COVID-19) and 22 patients with influenza A virus infection were included. Collected air samples were positive in 55% of patients infected with the omicron variant in comparison to 15% of those infected with the delta variant (p < 0.01). In multivariable analysis, the SARS-CoV-2 omicron BA.1/BA.2 variant (as compared to the delta variant) and the viral load in nasopharynx were both independently associated with air sample positivity, but the alpha variant and COVID-19 vaccination were not. The proportion of positive air samples patients infected with the influenza A virus was 18%. In conclusion, the higher air sample positivity rate of the omicron variant compared to previous SARS-CoV-2 variants may partially explain the higher transmission rates seen in epidemiological trends.

Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19.

BACKGROUND: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. METHODS: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). RESULTS: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. CONCLUSIONS: Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death.

After-hours radiology reporting in an Australian tertiary hospital: Factors influencing the rate of discrepancy for computed tomography reporting.

INTRODUCTION: Demand for after-hours radiology services across Australia has been rapidly increasing for many years. Public hospital radiology departments are generally staffed by trainees after hours, often 1-2 doctors. This study reviewed 1 year of after-hours data at a tertiary hospital in Sydney, to determine overall discrepancy rates and factors which influenced the rate of discrepancy after hours. Overall radiology and after-hours case volumes are increasing, and the goal was to ensure that our department practices are within safe limits at current staffing levels. METHODS: After-hours computed tomography scan reports issued by registrars were reviewed over 1 year between 01 January 2019 and 01 January 2020. Data recorded included overall case numbers on each shift, discrepancy rates and rates of clinically significant discrepancy. Caseload was measured by equivalent ascribed reporting time as described by Pitman et al. (2018). RESULTS: There were 10,886 cases reported after hours during the study period and 1,412 discrepancies (13% cases). Of these, 300 (3.7%) were clinically significant. Factors that increased the rate of significant discrepancy included shifts with caseloads greater than 3 h of equivalent consultant reporting time per 8-h shift and the radiology trainee's level of training. The frequency of discrepancy for trauma cases was similar to non-trauma after adjusting for study type; however, the frequency of significant discrepancy was higher. CONCLUSION: In all instances, the rates of discrepancy and clinically significant discrepancy remained well within ranges previously described.

Performance of point-of care molecular and antigen-based tests for SARS-CoV-2: a living systematic review and meta-analysis.

BACKGROUND: Molecular and antigen point-of-care tests (POCTs) have augmented our ability to rapidly identify and manage SARS-CoV-2 infection. However, their clinical performance varies among individual studies. OBJECTIVES: The evaluation of the performance of molecular and antigen-based POCTs in confirmed, suspected, or probable COVID-19 cases compared with that of laboratory-based RT-PCR in real-life settings. DATA SOURCES: MEDLINE/PubMed, Scopus, Embase, Web of Science, Cochrane Library, Cochrane COVID-19 study register, and COVID-19 Living Evidence Database from the University of Bern. STUDY ELIGIBILITY CRITERIA: Peer-reviewed or preprint observational studies or randomized controlled trials that evaluated any type of commercially available antigen and/or molecular POCTs for SARS-CoV-2, including multiplex PCR panels, approved by the United States Food and Drug Administration, with Emergency Use Authorization, and/or marked with Conformitè Europëenne from European Commission/European Union. PARTICIPANTS: Close contacts and/or patients with symptomatic and/or asymptomatic confirmed, suspected, or probable COVID-19 infection of any age. TEST/S: Molecular and/or antigen-based SARS-CoV-2 POCTs. REFERENCE STANDARD: Laboratory-based SARS-CoV-2 RT-PCR. ASSESSMENT OF RISK OF BIAS: Eligible studies were subjected to quality-control and risk-of-bias assessment using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. METHODS OF DATA SYNTHESIS: Summary sensitivities and specificities with their 95% CIs were estimated using a bivariate model. Subgroup analysis was performed when at least three studies informed the outcome. RESULTS: A total of 123 eligible publications (97 and 26 studies assessing antigen-based and molecular POCTs, respectively) were retrieved from 4674 initial records. The pooled sensitivity and specificity for 13 molecular-based POCTs were 92.8% (95% CI, 88.9-95.4%) and 97.6% (95% CI, 96.6-98.3%), respectively. The sensitivity of antigen-based POCTs pooled from 138 individual evaluations was considerably lower than that of molecular POCTs; the pooled sensitivity and specificity rates were 70.6% (95% CI, 67.2-73.8%) and 98.9% (95% CI, 98.5-99.2%), respectively. DISCUSSION: Further studies are needed to evaluate the performance of molecular and antigen-based POCTs in underrepresented patient subgroups and different respiratory samples.

Dynamics of Antibody and T Cell Immunity against SARS-CoV-2 Variants of Concern and the Impact of Booster Vaccinations in Previously Infected and Infection-Naïve Individuals.

Despite previous coronavirus disease 2019 (COVID-19) vaccinations and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, SARS-CoV-2 still causes a substantial number of infections due to the waning of immunity and the emergence of new variants. Here, we assessed the SARS-CoV-2 spike subunit 1 (S1)-specific T cell responses, anti-SARS-CoV-2 receptor-binding domain (RBD) IgG serum concentrations, and the neutralizing activity of serum antibodies before and one, four, and seven months after the BNT162b2 or mRNA-1273 booster vaccination in a cohort of previously infected and infection-naïve healthcare workers (HCWs). Additionally, we assessed T cell responses against the spike protein of the SARS-CoV-2 Delta, Omicron BA.1 and BA.2 variants of concern (VOC). We found that S1-specific T cell responses, anti-RBD IgG concentrations, and neutralizing activity significantly increased one month after booster vaccination. Four months after booster vaccination, T cell and antibody responses significantly decreased but levels remained steady thereafter until seven months after booster vaccination. After a similar number of vaccinations, previously infected individuals had significantly higher S1-specific T cell, anti-RBD IgG, and neutralizing IgG responses than infection-naïve HCWs. Strikingly, we observed overall cross-reactive T cell responses against different SARS-CoV-2 VOC in both previously infected and infection-naïve HCWs. In summary, COVID-19 booster vaccinations induce strong T cell and neutralizing antibody responses and the presence of T cell responses against SARS-CoV-2 VOC suggest that vaccine-induced T cell immunity offers cross-reactive protection against different VOC.

An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients.

Background: Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings. Methods: Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. Results: Our analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61-0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population. Conclusions: Although clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome. Funding: Bronner P. Gonçalves, Peter Horby, Gail Carson, Piero L. Olliaro, Valeria Balan, Barbara Wanjiru Citarella, and research costs were supported by the UK Foreign, Commonwealth and Development Office (FCDO) and Wellcome [215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z]; and Janice Caoili and Madiha Hashmi were supported by the UK FCDO and Wellcome [222048/Z/20/Z]. Peter Horby, Gail Carson, Piero L. Olliaro, Kalynn Kennon and Joaquin Baruch were supported by the Bill & Melinda Gates Foundation [OPP1209135]; Laura Merson was supported by University of Oxford's COVID-19 Research Response Fund - with thanks to its donors for their philanthropic support. Matthew Hall was supported by a Li Ka Shing Foundation award to Christophe Fraser. Moritz U.G. Kraemer was supported by the Branco Weiss Fellowship, Google.org, the Oxford Martin School, the Rockefeller Foundation, and the European Union Horizon 2020 project MOOD (#874850). The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views of the European Commission. Contributions from Srinivas Murthy, Asgar Rishu, Rob Fowler, James Joshua Douglas, François Martin Carrier were supported by CIHR Coronavirus Rapid Research Funding Opportunity OV2170359 and coordinated out of Sunnybrook Research Institute. Contributions from Evert-Jan Wils and David S.Y. Ong were supported by a grant from foundation Bevordering Onderzoek Franciscus; and Andrea Angheben by the Italian Ministry of Health "Fondi Ricerca corrente-L1P6" to IRCCS Ospedale Sacro Cuore-Don Calabria. The data contributions of J.Kenneth Baillie, Malcolm G. Semple, and Ewen M. Harrison were supported by grants from the National Institute for Health Research (NIHR; award CO-CIN-01), the Medical Research Council (MRC; grant MC_PC_19059), and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE) (award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award IS-BRC-1215-20013), and NIHR Clinical Research Network providing infrastructure support. All funders of the ISARIC Clinical Characterisation Group are listed in the appendix.

Comparative clinical manifestations and immune effects of cytomegalovirus infections following distinct types of immunosuppression.

BACKGROUND: Cytomegalovirus (CMV) infection is a well-recognised complication of solid organ and hematopoietic cell transplantation. However, CMV infection also occurs in patients with human immunodeficiency virus infection, previously immunocompetent intensive care unit patients, and individuals on immunosuppressive medications for various underlying diseases. OBJECTIVES: This review describes the comparative effects of CMV infection in distinct types of acquired immunosuppression. SOURCES: Selected peer-reviewed publications on CMV infections published until December 2021. CONTENT: CMV infection affects various organ systems through direct cytolytic mechanisms but may also exert indirect effects by promoting pro-inflammatory and immunosuppressive responses. This has been well studied in transplant recipients, for whom antiviral prophylaxis and pre-emptive therapy have now become standard practice. These strategies not only prevent direct CMV disease manifestations but also mitigate various immunopathological processes to reduce graft-vs.-host disease, graft rejection, and the occurrence of secondary bacterial and fungal infections. The efficacy of neither prophylactic nor pre-emptive treatment of CMV infection has been demonstrated for patients with critical illness- or medication-induced immunosuppression. Many observational studies have shown an independent association between CMV reactivation and a prolonged duration of mechanical ventilation or increased mortality in the intensive care unit. Furthermore, data suggest that CMV reactivation may increase pulmonary inflammation and prolong the duration of mechanical ventilation. IMPLICATIONS: A large number of observational and experimental studies suggest attributable morbidity and mortality related to CMV infection, not only in transplant recipients and patients with human immunodeficiency virus infection but also in patients with critically illness- or medication-induced immunosuppression. Adequately powered randomised controlled trials investigating the efficacy of prophylaxis or pre-emptive treatment of CMV infection in these patients are lacking, with a notable exception for transplant recipients.

Oral Microbiome of Crohn's Disease Patients With and Without Oral Manifestations.

BACKGROUND AND AIMS: Microbiome dysbiosis is associated with inflammatory destruction in Crohn's disease [CD]. Although gut microbiome dysbiosis is well established in CD, the oral microbiome is comparatively under-studied. This study aims to characterize the oral microbiome of CD patients with/without oral manifestations. METHODS: Patients with CD were recruited with age-, gender- and race-matched controls. Potential confounders such as dental caries and periodontal condition were recorded. The oral microbiome was collected using saliva samples. Microbial DNA was extracted and sequenced using shotgun sequencing. Metagenomic taxonomic and functional profiles were generated and analysed. RESULTS: The study recruited 41 patients with CD and 24 healthy controls. Within the CD subjects, 39.0% had oral manifestations with the majority presenting with cobblestoning and/or oral ulcers. Principal coordinate analysis demonstrated distinct oral microbiome profiles between subjects with and without CD, with four key variables responsible for overall oral microbiome variance: [1] diagnosis of CD, [2] concomitant use of steroids, [3] concomitant use of azathioprine and 4] presence of oral ulcers. Thirty-two significant differentially abundant microbial species were identified, with the majority associated with the diagnosis of CD. A predictive model based on differences in the oral microbiome found that the oral microbiome has strong discriminatory function to distinguish subjects with and without CD [AUROC 0.84]. Functional analysis found that an increased representation of microbial enzymes [n = 5] in the butyrate pathway was positively associated with the presence of oral ulcers. CONCLUSIONS: The oral microbiome can aid in the diagnosis of CD and its composition was associated with oral manifestations.

ESCMID guidelines on testing for SARS-CoV-2 in asymptomatic individuals to prevent transmission in the health care setting.

SCOPE: This guideline addresses the indications for direct testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic individuals in health care facilities, with the aim to prevent SARS-CoV-2 transmissions in these settings. The benefit of testing asymptomatic individuals to create a safe environment for patients and health care workers must be weighed against potential unintended consequences, including delaying necessary treatments owing to false positive results and lower quality of care owing to strict isolation measures. METHODS: A total of nine PICOs (population, intervention, comparison, outcome) on the topic of testing asymptomatic individuals was selected by the panel members. Subsequently, a literature search for existing guidelines and systematic reviews was performed on PubMed, Epistemonikos, and RecMap using relevant filters available in each database. Data on article/recommendation type, setting, target population, intervention, and quality of the evidence were extracted. Credibility of the systematic reviews was evaluated using the AMSTAR tool, and level of agreement with available recommendation was evaluated with the AGREE II score. Because the evidence available from systematic reviews was deemed insufficiently updated to formulate relevant recommendations, an additional search targeting relevant guidance documents from major public health institutions and original studies was performed. Provisional recommendations were discussed via web conferences until agreement was reached, and final recommendations were formulated according to the GRADE approach. RECOMMENDATIONS: Recommendations were formulated regarding systematic testing in asymptomatic individuals upon admission to a health care setting, during hospital stay, before elective procedures, and before scheduled nonsurgical procedures. Moreover, recommendations regarding testing of asymptomatic visitors, personal caregivers, and health care workers in health care facilities were presented. Recommendations also were given on contact tracing in asymptomatic patients or health care workers and the possibility of a negative screening test to shorten the quarantine period. Furthermore, if applicable, recommendations were specified to transmission rate and vaccination coverage.

Development of an in-house SARS-CoV-2 interferon-gamma ELISpot and plate reader-free spot detection method.

Coronavirus disease 2019 (COVID-19) vaccination programs rolled out in an attempt to stop the COVID-19 pandemic. Besides neutralising antibodies, effective T cell responses are also crucial for protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 disease severity. To assess SARS-CoV-2-specific T cell immunity, we developed an interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) that can be deployed in research and diagnostic settings. We optimised our ELISpot by testing multiple antigen concentrations to stimulate peripheral blood mononuclear cells of SARS-CoV-2-unexposed, COVID-19 convalescent and COVID-19 vaccinated volunteers. Also, we developed an ELISpot plate reader-free method to detect and quantify spots, which we compared to manual spot counting and automated analysis by an ELISpot plate reader. We observed strong SARS-CoV-2-reactive T cell responses in COVID-19 convalescent, and COVID-19 vaccinated volunteers but absent or only weak responses in unexposed volunteers. Overall, antigens with concentrations from 0.1 to 5.0 µg/mL per peptide elicited similar T cell responses. Also, our plate reader-free detection method reliably detected and quantified SARS-CoV-2-specific T cells, demonstrated by an excellent reliability when compared to manual analysis and automated analysis by an ELISpot plate reader.

Two vs One Forward View Examination of Right Colon on Adenoma Detection: An International Multicenter Randomized Trial.

BACKGROUND & AIMS: Second forward view (SFV) examination of the right colon (RC) in colonoscopy was suggested to improve the adenoma detection rate (ADR), but multicenter data to inform its routine use remain limited. We performed an international multicenter randomized trial comparing SFV vs a standard single forward view examination of the RC on adenoma detection. METHODS: Asymptomatic individuals undergoing screening or surveillance colonoscopies from 6 Asia Pacific regions were invited for study. A forward view examination of the RC was first performed in all patients, followed by randomization at the hepatic flexure to either SFV examination of the RC and standard withdrawal examination from the hepatic flexure to rectum, or a standard withdrawal colonoscopy (SWC) examination from the hepatic flexure to rectum. The primary outcome was RC ADR. RESULTS: Between 2016 and 2019, there were 1011 patients randomized (SFV group, 502 patients; SWC group, 509 patients). Forty-five endoscopists performed the colonoscopies. The RC ADR was significantly higher in the SFV group than in the SWC group (27.1% vs 21.6%; P = .042). The whole-colon ADR was high in both groups (49.0% vs 45.0%; P =.201). The SFV examination identified 58 additional adenomas in 49 patients (9.8%), leading to a change in surveillance recommendations in 15 patients (3.0%). The median overall withdrawal time was 1.5 minutes longer in the SFV group (12.0 vs 10.5 min; P < .001). Older age, male sex, ever smoking, and longer RC withdrawal time were independent predictors of right-sided adenoma detection. CONCLUSIONS: In this multicenter trial, SFV examination significantly increased the RC ADR in screening and surveillance colonoscopies. Routine RC SFV examination should be considered. ClinicalTrials.gov ID: NCT03121495.