The humoral and cellular response to mRNA SARS-CoV-2 vaccine is influenced by HLA polymorphisms.

Host genetic variability contributes to susceptibility to SARS-CoV-2 infection and COVID-19 evolution and the role of HLA system has not clearly emerged, suggesting the involvement of other factors. Studying response to vaccination with Spyke protein mRNA represents an ideal model to highlight whether the humoral or cellular responses are influenced by HLA. Four hundred and sixteen workers, vaccinated with Comirnaty beginning 2021, were selected within the Azienda Ospedaliera Universitaria "Città della Salute e della Scienza di Torino." The humoral response was determined with the LIAISON® kit, while the analysis of the cellular response was performed with the Quantiferon SARS-CoV-2 assay, for the S1 (receptor-binding domain; Ag1) and S1 and S2 (Ag2) subunits of the Spyke protein. Six HLA loci were typed by next-generation sequencing. Associations between HLA and vaccine response were performed with univariate and multivariate analyses. An association was found between A*03:01, B*40:02 and DPB1*06:01 and high antibody concentration and between A*24:02, B*08:01 and C*07:01 and low humoral responses. The haplotype HLA-A*01:01 ~ B1*08:01 ~ C*07:01 ~ DRB1*03:01 ~ DQB1*02:01 conferred an increased risk of low humoral response. Considering cellular responses, 50% of the vaccinated subjects responded against Ag1 and 59% against Ag2. Carriers of DRB1*15:01 displayed a higher cellular response both to Ag1 and Ag2 compared to the rest of the cohort. Similarly, DRB1*13:02 predisposed to a robust cellular response to Ag1 and Ag2, while DRB1*11:04 showed an opposite trend. Cellular and humoral responses to Comirnaty are influenced by HLA. Humoral response is mainly associated to class I alleles, with A*03:01, previously associated to protection against severe COVID-19, and response to vaccination, standing out. Cellular response predominantly involves class II alleles, with DRB1*15:01 and DPB1*13:01 prevailing. Affinity analysis for Spyke peptides is generally in line with the association results.

Feasibility of Self-Performed Lung Ultrasound with Remote Teleguidance for Monitoring at Home COVID-19 Patients.

During the COVID-19 pandemic, use of telemedicine with the aim of reducing the rate of viral transmission increased. This proof-of-concept observational study was planned to test the feasibility of a home-based lung ultrasound (LUS) follow-up performed by patients with mild COVID-19 infection on themselves. We enrolled patients presenting to the emergency department with SARS-CoV-2 infection without signs of pneumonia and indication to discharge. Each patient received a brief training on how to perform LUS and a handheld ultrasound probe. Then, patients were contacted on a daily basis, and LUS images were acquired by the patients themselves under "teleguidance" by the investigator. Twenty-one patients were enrolled with a median age of 44 years. All evaluations were of sufficient quality for a follow up. Probability of a better LUS quality was related to higher degree (odds ratio, OR, 1.42, 95% CI 0.5-3.99) and a lower quality to evaluation time (from 0.71, 95% CI 0.55-0.92 for less than 7 min, to 0.52, 95% CI 0.38-0.7, between 7 and 10 min, and to 0.29, 95% CI 0.2-0.43, for evaluations longer than 10 min). No effect related to gender or age was detected. LUS performed by patients and remotely overseen by expert providers seems to be a feasible and reliable telemedicine tool.

Cellular Immune Response to BNT162b2 mRNA COVID-19 Vaccine in a Large Cohort of Healthcare Workers in a Tertiary Care University Hospital.

We describe the results of a T-cell immunity evaluation performed after a median elapsed time of 7 months from second-dose BNT162b2 vaccine administration, in a representative sample of 419 subjects from a large cohort of hospital workers. Overall, the Quantiferon SARS-CoV-2 assay detected a responsive pattern in 49.9%, 59.2% and 68.3% of subjects to three different antigenic stimuli from SARS-CoV-2, respectively, with 72.3% of positivity to at least one antigenic stimulus. Potential predictors of cellular response were explored by multivariable analyses; factors associated with positivity to cellular response (to Ag1 antigenic stimulus) were a previous SARS-CoV-2 infection (OR = 4.24, 95% CI 2.34-7.67, p < 0.001), increasing age (per year: OR = 1.03 95% CI 1.01-1.06, p = 0.019 and currently smoking (compared to never smoking) (OR = 1.93, 95% CI 1.11-3.36, p = 0.010). Increasing time interval between vaccine administration and T-cell test was associated with decreasing cellular response (per week of time: OR = 0.94, 95% CI 0.91-0.98, p = 0.003). A blood group A/AB/B (compared to group O) was associated with higher levels of cellular immunity, especially when measured as Ag2 antigenic stimulus. Levels of cellular immunity tended to be lower among subjects that self-reported an autoimmune disorder or an immunodeficiency and among males. Further studies to assess the protective significance of different serological and cellular responses to the vaccine toward the risk of reinfection and the severity of COVID-19 are needed to better understand these findings.

Factors Influencing Level and Persistence of Anti SARS-CoV-2 IgG after BNT162b2 Vaccine: Evidence from a Large Cohort of Healthcare Workers.

We aimed at evaluating quantitative IgG response to BNT162b2 COVID-19 vaccine among health care workers (HCW), and exploring the role of demographic, clinical, and occupational factors as predictors of IgG levels. On May 2021, among 6687 HCW at the largest tertiary care University-Hospital of Northwestern Italy, at a median of 15 weeks (Interquartile range-IQR 13.6-16.0) after second-dose, serological response was present in 99.8%. Seropositivity was >97% in all the subgroups, except those self-reporting immunodeficiency (94.9%). Overall, the median serological IgG value was 990 BAU/mL (IQR 551-1870), with most of subjects with previous SARS-CoV-2 infection or with shorter time lapse (2-8 weeks) between vaccination and serology with values in the highest quintile (>2080). At multivariable analysis, significant predictors of lower values were increasing age, male, current smoking, immunodeficiency, recent occupational contacts, and increasing time lapse from vaccination; conversely, previous infection and recent household contacts were significantly associated with higher IgG levels. Subjects with previous infection kept a very high level (around 2000 BAU/mL) up to 120 days. These results, besides supporting a high serological response up to 4-5 months, suggest predictive factors of faster decay of IgG levels that could be useful in tailoring vaccination strategies.

SARS-CoV-2 infection: use and effectiveness of antigenic swab for the health surveillance of healthcare workers.

BACKGROUND:  The gold standard to identify SARS-CoV-2 infections is the Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) on rhino-pharyngeal swabs, but faster and cheaper methods such as antigenic swabs have been developed. A retrospective observational study on antigenic swabs included in the extraordinary health surveillance protocol of a large Hospital in Turin was aimed to assess their performance validity. Methods: From 30 October 2020 to 4 May 2021, 4000 antigenic swabs were carried out in three groups of healthcare workers (HCWs), respectively (i) asymptomatic, (ii) cohabiting with a positive case, and (iii) not recently exposed to the virus.  Results: Overall sensitivity and specificity associated with a prevalence of 1.30% were 26.9%, 97.2%, respectively, the corresponding positive (PPV) and negative predictive value (NPV) being 11.29% and 99.02% [95% IC (99.00 - 99.04)] respectively; a prevalence of 0.29% was observed in the asymptomatic group, among whom sensitivity and specificity were 25.0% and 98.9%, respectively, the corresponding PPV and NPV being 6.25% and 99.78% [95% IC (99.76 - 99.81)], respectively; the cohabitant group showed a prevalence of 21.11%, sensitivity and specificity were 47.4%, 81.7%, respectively, giving rise to a PPV of 40.91% and NPV of 85.29% [95% IC (85.18 - 85.41)] respectively. The prevalence in the not exposed group was 0.77%, sensitivity and specificity were 29.2%, 97.4%, respectively, and PPV and NPV 8.05% and 99.44% [95% IC (99.42 - 99.46)] respectively. Conclusions: Antigenic swabs reduced costs and provided reliable diagnostic results. In the cohabitant group, the higher-prevalence groups showed poor test performances, likely because of the high prevalence of pre-symptomatic illness in this group. Owing to the relatively low NPV, a negative result would still require confirmation with a molecular test to be acceptable for a surveillance program that effectively reduces the virus's intra-hospital spread.

The Adverse Impact of the COVID-19 Pandemic on Abdominal Emergencies: A Retrospective Clinico-Pathological Analysis.

The COVID-19 pandemic has caused a worldwide significant drop of admissions to the emergency department (ED). The aim of the study was to retrospectively investigate the pandemic impact on ED admissions, management, and severity of three abdominal emergencies (appendicitis, diverticulitis, and cholecystitis) during the COVID-19 pandemic using 2017-2019 data as a control. The difference in clinical and pathological disease severity was the primary outcome measure while differences in (i) ED admissions, (ii) triage urgency codes, and (iii) surgical rates were the second ones. Overall, ED admissions for the selected conditions decreased by 34.9% during the pandemic (control: 996, 2020: 648) and lower triage urgency codes were assigned for cholecystitis (control: 170/556, 2020: 66/356, p < 0.001) and appendicitis (control: 40/178, 2020: 21/157, p = 0.031). Less surgical procedures were performed in 2020 (control: 447, 2020: 309), but the surgical rate was stable (47.7% in 2020 vs. 44.8% in 2017-2019). Considering the clinical and pathological assessments, a higher percentage of severe cases was observed in the four pandemic peak months of 2020 (control: 98/192, 2020: 87/109; p < 0.001 and control: 105/192, 2020: 87/109; p < 0.001). For the first time in this study, pathological findings objectively demonstrated an increased disease severity of the analyzed conditions during the early COVID-19 pandemic.

Prevalence, Persistence, and Factors Associated with SARS-CoV-2 IgG Seropositivity in a Large Cohort of Healthcare Workers in a Tertiary Care University Hospital in Northern Italy.

This observational study evaluated SARS-CoV-2 IgG seroprevalence and related clinical, demographic, and occupational factors among workers at the largest tertiary care University-Hospital of Northwestern Italy and the University of Turin after the first pandemic wave of March-April 2020. Overall, about 10,000 individuals were tested; seropositive subjects were retested after 5 months to evaluate antibodies waning. Among 8769 hospital workers, seroprevalence was 7.6%, without significant differences related to job profile; among 1185 University workers, 3.3%. Self-reporting of COVID-19 suspected symptoms was significantly associated with positivity (Odds Ratio (OR) 2.07, 95%CI: 1.76-2.44), although 27% of seropositive subjects reported no previous symptom. At multivariable analysis, contacts at work resulted in an increased risk of 69%, or 24% for working in a COVID ward; contacts in the household evidenced the highest risk, up to more than five-fold (OR 5.31, 95%CI: 4.12-6.85). Compared to never smokers, being active smokers was inversely associated with seroprevalence (OR 0.60, 95%CI: 0.48-0.76). After 5 months, 85% of previously positive subjects still tested positive. The frequency of SARS-COV-2 infection among Health Care Workers was comparable with that observed in surveys performed in Northern Italy and Europe after the first pandemic wave. This study confirms that infection frequently occurred as asymptomatic and underlines the importance of household exposure, seroprevalence (OR 0.60, 95%CI: 0.48-0.76).

Evaluation of an antigen-based test for hospital point-of-care diagnosis of SARS-CoV-2 infection.

BACKGROUND: An accurate diagnosis is essential to identify and manage SARS-CoV-2 infected patients and implement infection control measures. Although real-time reverse transcription polymerase chain reaction (RT-PCR) is the current recommended laboratory method, several rapid antigen point-of-care tests (POCTs) were developed as frontline testing for SARS-CoV-2 infection diagnosis. OBJECTIVES: The aim of this study was to assess a recently CE-approved POCT, SARS-CoV-2 Ag Test on the LumiraDx™ Platform (LumiraDx GmbH, Cologne, Germany) for the identification of SARS-COV-2 infected subjects at hospital setting. METHODS: LumiraDx POCT was implemented in three hospital settings: adult and pediatric emergency departments and occupational medicine department along two-month period during the second peak of Italian SARS-CoV-2 pandemic. Rapid antigen testing was performed on direct nasal swabs and results were compared with those obtained by Xpert Xpress SARS-CoV-2 assay. RESULTS: Overall sensitivity, specificity, NPV and PPV were 90.3%, 92.1%, 95.1%, and 84.9%, respectively, compared to reference method. Sensitivity, specificity, PPV and NPV for symptomatic group were 89.3% [95% IC 84.2-93.3], 88.2% [95% IC 72.5-96.7], 97.8% [95% IC 94.6-99.1], and 58.8% [95% IC 48.4-68.5], respectively. Sensitivity, specificity, PPV and NPV for asymptomatic group were 92.1% [95% IC 85-96.5], 92.3% [95% IC 89.9-94.4], 67.9% [95% IC 61.3-73.8], and 98.5% [95% IC 97.1-99.2], respectively. False positive and negative antigen testing results in both symptomatic and asymptomatic group were observed. CONCLUSION: SARS-CoV-2 Ag POCT may represent an interesting tool to rapidly identify symptomatic or asymptomatic infected subjects. However, in hospital setting in which false negative or false positive results may have relevant implications, confirmatory NAAT always remains necessary for the appropriate management of patients.

Clinical and epidemiological characteristics associated with pneumonia at disease onset in patients admitted for COVID-19 to the Emergency Department of a large Hospital in Piedmont (North-Western Italy).

OBJECTIVES: to explore clinical and epidemiological characteristics associated with an imaging feature of COVID-19 pneumonia at disease onset, in order to identify factors that may be evaluable by general practitioners at patient's home, and which may lead to identify a more severe disease, needing hospitalization. DESIGN: this is a retrospective/prospective observational hospital cohort. SETTING AND PARTICIPANTS: the study population includes all patients consecutively admitted to the emergency department of Città della salute e della scienza University Hospital from 01.03 to 31.05.2020 with a confirmed diagnosis of SARS-CoV-2 infection. MAIN OUTCOME MEASURES: patients were classified in two groups according to the findings of X-ray imaging, lung ultrasound and chest computer tomography, as pneumonia or not pneumonia patients. RESULTS: in multivariable analysis, factors most strongly associated with emergency department admission with pneumonia were age, oxygen saturation <90% (adj OR 4.16 ;95%CI 1.44-12.07), respiratory rate >24 breaths/min (adj OR 6.50; 95%CI 2.36-17.87), fever ≥38° (adj OR 3.05; 95%CI 1.53-6.08) and the presence of gastroenteric symptoms (vomiting and diarrhea). A delay (> 7 days) between the appearance of the initial lung symptoms (cough and dyspnea) and the admission to the emergency department was also related to a higher probability of receiving a positive imaging report (OR 4.99; 95%CI 2,02-12,34). CONCLUSIONS: in order to reorganize the management of COVID-19 patients in Italy, in view of the risk of a second wave of epidemic or of local outbreaks, it would be desirable to relocate the triage, and possibly the patient's care, from hospital to home. In this scenario it is important to identify all symptoms and signs associated with COVID-19 pneumonia that would facilitate the decision-making process of GPs leading to patients hospitalization.

[Audit and Feedback approach in the CoViD-19 emergency: adaptation of the EASY-NET project in the AOU Città della Salute e della Scienza of Turin.] / Audit e Feedback nell'emergenza CoViD-19: adattamento del progetto EASY-NET nell'AOU Città della Salute e della Scienza di Torino.

CoViD-19 pandemic heavily impacted most on-going research activities, causing delays and need of re-programming. EASY-NET (NET-2016-02364191) is a network project, started in April 2019, co-funded by the Italian Ministry of Health and the participating regions. Within the general project, centred on the evaluation of Audit and Feedback (A&F) strategies in improving quality and equity in different health care contexts, the Piedmont region is responsible of the work package 3 (WP3) on specific oncology pathways and procedures. After a thorough evaluation of the impact of the CoViD-19 emergency on the WP3 activities, at the beginning of March 2020, the decision was to continue, with some adaptations, the audits already started, and to delay those in the early planning phase. The provisional availability of part of the time-persons involved in EASY-NET on one side, and the urgency of acquiring data on the management of the large number of CoViD-19 patients admitted to the study coordinator hospital on the other side, determined the personnel responsible of the WP3, in accordance with the hospital management, to invest these resources in monitoring the CoViD-19 hospitalized patients with both A&F activity and research objectives. Besides periodic reports, a web site, with restricted access to the involved health care personnel, was developed to allow a direct and timely consultation of graphics describing the flow of the patients, their management, and outcomes. This experience was made possible thanks to a favourable combination of different factors: the presence within the hospital of a group of experienced epidemiologists in A&F, the availability of extra resources, the strong support and collaboration by the hospital management and the readiness for authorisation by the Ethics Committee. We underline the need to provide a certain degree of flexibility in the long-term projects funded by the Ministry of Health, the extraordinary adaptability of the A&F approach also to emergency situations and the possibility of combining audit activities and research objectives in the same project.