Update of European Society of Clinical Microbiology and Infectious Diseases coronavirus disease 2019 guidelines: diagnostic testing for severe acute respiratory syndrome coronavirus 2.

SCOPE: Since the onset of COVID-19, several assays have been deployed for the diagnosis of SARS-CoV-2. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published the first set of guidelines on SARS-CoV-2 in vitro diagnosis in February 2022. Because the COVID-19 landscape is rapidly evolving, the relevant ESCMID guidelines panel releases an update of the previously published recommendations on diagnostic testing for SARS-CoV-2. This update aims to delineate the best diagnostic approach for SARS-CoV-2 in different populations based on current evidence. METHODS: An ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair, and the remaining selected with an open call. The panel met virtually once a week. For all decisions, a simple majority vote was used. A list of clinical questions using the population, intervention, comparison, and outcome (PICO) format was developed at the beginning of the process. For each PICO, 2 panel members performed a literature search focusing on systematic reviews with a third panellist involved in case of inconsistent results. The panel reassessed the PICOs previously defined as priority in the first set of guidelines and decided to address 49 PICO questions, because 6 of them were discarded as outdated/non-clinically relevant. The 'Grading of Recommendations Assessment, Development and Evaluation (GRADE)-adoption, adaptation, and de novo development of recommendations (ADOLOPMENT)' evidence-to-decision framework was used to produce the guidelines. QUESTIONS ADDRESSED BY THE GUIDELINES AND RECOMMENDATIONS: After literature search, we updated 16 PICO questions; these PICOs address the use of antigen-based assays among symptomatic and asymptomatic patients with different ages, COVID-19 severity status or risk for severe COVID-19, time since the onset of symptoms/contact with an infectious case, and finally, types of biomaterials used.

Appropriateness of frequent use of emergency departments: A retrospective analysis in Rome, Italy.

Background: Frequent users (FUs) are patients who repeatedly and inappropriately visit the emergency department (ED) for low-grade symptoms that could be treated outside the hospital setting. This study aimed to investigate the phenomenon of the FU in Rome by profiling such users and analyzing ED attendance by FUs. Methods: The analysis was carried out for attendance in 2021 at 15 EDs in the Local Health Authority Roma 1 geographical area. A digital app collected data, including information on the following variables: number of attendance, demographic characteristics, emergency medical service (EMS) usage, triage code, and appropriateness of attendance. COVID-19 diagnosis was also studied to analyze any possible influence on ED attendance. Differences between FUs and non-FUs were investigated statistically by t-test and chi-square test. Univariate analysis and multivariable logistic regression were performed to analyze the associated factors. Results: A total of 122,762 ED attendance and 89,036 users were registered. The FU category represented 2.9% of all users, comprising 11.9% of total ED attendance. There was a three times higher frequency of non-urgent codes in attendance of FU patients (FU: 9.7%; non-FU: 3.2%). FUs were slightly more likely to have used the EMS (13.6% vs. 11.4%) and had a lower frequency of appropriate ED attendance (23.8% vs. 27.0%). Multivariate logistic analysis confirmed a significant effect of triage code, gender, age, EMS usage, and COVID-19 diagnosis for the appropriateness of attendance. The results were statistically significant (p < 0.001). Conclusion: The FU profile describes mostly non-urgent and inappropriate attendance at the ED, including during the COVID-19 pandemic. This study represents an important tool for strengthening preventive policies outside the hospital setting. The Italian National Recovery and Resilience Plan represents an excellent opportunity for the development of new strategies to mitigate the phenomenon of FUs.

Risk of Infection and Duration of Protection after the Booster Dose of the Anti-SARS-CoV-2 Vaccine BNT162b2 among Healthcare Workers in a Large Teaching Hospital in Italy: Results of an Observational Study.

The efficacy of the first schedule of COVID-19 mRNA vaccines has decreased after the surge of the Delta variant, posing the need to administer a booster dose to enhance the neutralising immune response. This study aims at evaluating the duration of protection given by the booster dose of Pfizer-BioNTech BNT162b2 mRNA vaccine in healthcare workers (HCWs) of a large teaching hospital in Rome and to analyse the factors associated with post-booster vaccination infections. Data about vaccinations of HCWs with the BNT162b2 vaccine and nasal swabs positive for SARS-CoV-2 were extracted from the digital archives of the hospital from 27 September 2021 to 31 May 2022. In total, 5770 HCWs were observed. The cumulative risk of becoming infected by SARS-CoV-2 increased with time (2.5% at 4 weeks, 17% at 12 weeks and 40% at 24 weeks) and was significantly higher for females, younger classes of patients and for those who had developed a hybrid immunity (natural infection plus one dose, namely the primary schedule, added to the booster dose) compared to those who had completed the three doses. This study describes the duration and the determinants of the protection against infections after the booster dose of COVID-19 vaccine, highlighting the need for continuous monitoring of vaccine-induced immunogenicity.

Coordinated innate and T-cell immune responses in mild COVID-19 patients from household contacts of COVID-19 cases during the first pandemic wave.

Objective: To better define the immunopathogenesis of COVID-19, the present study aims to characterize the early immune responses to SARS-CoV-2 infection in household contacts of COVID-19 cases. In particular, innate, T- and B-cell specific responses were evaluated over time. Methods: Household contacts of COVID-19 cases screened for SARS-CoV-2 infection by nasopharyngeal swab for surveillance purposes were enrolled (T0, n=42). Of these, 28 subjects returned for a follow-up test (T1). The innate response was assessed by detecting a panel of soluble factors by multiplex-technology in plasma samples. Cell-mediated response was evaluated by measuring interferon (IFN)-γ levels by ELISA in plasma harvested from whole-blood stimulated with SARS-CoV-2 peptide pools, including spike (S), nucleocapsid (N) and membrane (M) proteins. The serological response was assessed by quantifying anti-Receptor-Binding-Domain (RBD), anti-Nucleocapsid (N), whole virus indirect immunofluorescence, and neutralizing antibodies. Results: At T0, higher levels of plasmatic IFN-α, IL-1ra, MCP-1 and IP-10, and lower levels of IL-1ß, IL-9, MIP-1ß and RANTES were observed in subjects with positive swab compared to individuals with a negative one (p<0.05). Plasmatic IFN-α was the only cytokine detectable in subjects with positive SARS-CoV-2 swabs with high accuracy for swab score positivity (0.93, p<0.0001). Among subjects with positive swabs, significant negative correlations were found among the RT-PCR cycle threshold values reported for genes S and N and IFN-α or IP-10 levels. At T0, the IFN-γ T-cell specific response was detected in 50% (5/10) of subjects with positive swab, while anti-RBD/anti-N antibodies showed a positivity rate of 10% (1/10). At T1, the IFN-γ T-cell specific response was detected in most of the confirmed-infection subjects (77.8%, 7/9), whereas the serological response was still observed in a minority of them (44.4%, 4/9). Overall, the swab test showed a moderate concordance with the T-cell response (78.6%, k=0.467), and a scarce concordance with the serological one (72.9%, k=0.194). Conclusions: Plasmatic IFN-α and the IFN-γ T-cell specific response appear early even in the absence of seroconversion, and show a greater positivity rate than the serological response in household contacts with positive swab.

Ensuring Equitable Access to the COVID-19 Vaccine: The Experience of A Local Health Unit in Rome, Italy.

Growing evidence is emerging on the higher risk of infection and adverse outcomes for the most disadvantaged groups of the population, and COVID-19 vaccination campaigns worldwide are struggling to ensure equitable access to immunization for all. From 21 June 2021 to 15 October 2021, the Local Health Unit ASL Roma 1 adopted a tailored immunization strategy to reach socially vulnerable groups of the population with the primary vaccination course. This strategy was developed with a step-by-step, participatory approach. Through engagement with internal and external stakeholders, target groups were identified, potential barriers analyzed, solutions discussed, and tailored interventions designed. Over nine thousand individuals from among irregular migrants, homeless people and hard-to-reach communities were contacted and vaccinated.

Coordinated innate and T-cell immune responses in mild COVID-19 patients from household contacts of COVID-19 cases during the first pandemic wave

Objective To better define the immunopathogenesis of COVID-19, the present study aims to characterize the early immune responses to SARS-CoV-2 infection in household contacts of COVID-19 cases. In particular, innate, T- and B-cell specific responses were evaluated over time. Methods Household contacts of COVID-19 cases screened for SARS−CoV−2 infection by nasopharyngeal swab for surveillance purposes were enrolled (T0, n=42). Of these, 28 subjects returned for a follow-up test (T1). The innate response was assessed by detecting a panel of soluble factors by multiplex-technology in plasma samples. Cell-mediated response was evaluated by measuring interferon (IFN)-γ levels by ELISA in plasma harvested from whole-blood stimulated with SARS−CoV−2 peptide pools, including spike (S), nucleocapsid (N) and membrane (M) proteins. The serological response was assessed by quantifying anti-Receptor-Binding-Domain (RBD), anti-Nucleocapsid (N), whole virus indirect immunofluorescence, and neutralizing antibodies. Results At T0, higher levels of plasmatic IFN-α, IL-1ra, MCP-1 and IP-10, and lower levels of IL-1β, IL-9, MIP-1β and RANTES were observed in subjects with positive swab compared to individuals with a negative one (p<0.05). Plasmatic IFN-α was the only cytokine detectable in subjects with positive SARS-CoV-2 swabs with high accuracy for swab score positivity (0.93, p<0.0001). Among subjects with positive swabs, significant negative correlations were found among the RT-PCR cycle threshold values reported for genes S and N and IFN-α or IP-10 levels. At T0, the IFN-γ T-cell specific response was detected in 50% (5/10) of subjects with positive swab, while anti-RBD/anti-N antibodies showed a positivity rate of 10% (1/10). At T1, the IFN-γ T-cell specific response was detected in most of the confirmed-infection subjects (77.8%, 7/9), whereas the serological response was still observed in a minority of them (44.4%, 4/9). Overall, the swab test showed a moderate concordance with the T-cell response (78.6%, k=0.467), and a scarce concordance with the serological one (72.9%, k=0.194). Conclusions Plasmatic IFN-α and the IFN-γ T-cell specific response appear early even in the absence of seroconversion, and show a greater positivity rate than the serological response in household contacts with positive swab.

ESCMID COVID-19 guidelines: diagnostic testing for SARS-CoV-2.

SCOPE: The objective of these guidelines is to identify the most appropriate diagnostic test and/or diagnostic approach for SARS-CoV-2. The recommendations are intended to provide guidance to clinicians, clinical microbiologists, other health care personnel, and decision makers. METHODS: An ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair and the remaining selected with an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A list of clinical questions using the PICO (population, intervention, comparison, outcome) format was developed at the beginning of the process. For each PICO, two panel members performed a literature search focusing on systematic reviews, with a third panellist involved in case of inconsistent results. Quality of evidence assessment was based on the GRADE-ADOLOPMENT (Grading of Recommendations Assessment, Development and Evaluation - adoption, adaptation, and de novo development of recommendations) approach. RECOMMENDATIONS: A total of 43 PICO questions were selected that involve the following types of populations: (a) patients with signs and symptoms of COVID-19; (b) travellers, healthcare workers, and other individuals at risk for exposure to SARS-CoV-2; (c) asymptomatic individuals, and (d) close contacts of patients infected with SARS-CoV-2. The type of diagnostic test (commercial rapid nucleic acid amplification tests and rapid antigen detection), biomaterial, time since onset of symptoms/contact with an infectious case, age, disease severity, and risk of developing severe disease are also taken into consideration.

Are vaccine shortages a relevant public health issue in Europe? Results from a survey conducted in the framework of the EU Joint Action on Vaccination.

National immunisation programmes require an adequate supply of vaccines to function properly but many countries, globally and in Europe, have reported vaccine shortages. A comprehensive view of vaccine shortages and stockouts in the EU/EEA is missing in the published literature. This study was conducted in the framework of the European Joint Action on Vaccination (EU-JAV). Twenty-eight countries, including 20 EU-JAV consortium member states and an additional 8 EU/EEA countries, were invited to participate in a survey aimed at collecting information on vaccine shortages and stock-outs experienced from 2016 to 2019, their main causes, actions taken, and other aspects of vaccine supply. Twenty-one countries completed the survey (response rate 75%), of which 19 reported at least one shortage/stock-out event. Overall, 115 events were reported, 28 of which led to a change in the national immunisation programme. The most frequently involved vaccines were DT- and dT-containing combination vaccines, hepatitis B, hepatitis A, and BCG vaccines. The median duration of shortages/stock-outs was five months (range <1 month-39 months). Interruption in supply and global shortage were the most frequently indicated causes. Only about half of countries reported having an immunization supply chain improvement plan. Similarly, only about half of countries had recommendations or procedures in place to address shortages/stockouts. The survey also identified the occurrence of shortages/stockouts of other biological products (e.g. diphtheria antitoxin in 12 countries). Public health strategies to assure a stable and adequate vaccine supply for immunization programmes require coordinated actions from all stakeholders, harmonized definitions, strengthening of reporting and monitoring systems, the presence of an immunization supply chain improvement plan in all countries, and procedures or recommendations in place regarding the use of alternative vaccines or vaccination schedules in case of shortages/stockouts.

Organisational Model and Coverage of At-Home COVID-19 Vaccination in an Italian Urban Context.

The COVID-19 pandemic called for a reorganisation of the methods for providing health services. The aim of this paper is to describe the organisational model implemented by one of Rome's Local Health Units (LHU), ASL Roma 1, for the "at-home COVID-19 vaccination campaign" dedicated to a target population and to outline data related to vaccination coverage stratified by health districts. A cross-sectional study was designed to describe the strategies implemented by LHU to deliver at-home vaccination programmes. People eligible for the at-home vaccination programme included patients living in the area of the LHU, being assisted by the district home care centre or not transportable or individuals with social situations that make traveling difficult. Priority for vaccination was given to (I) age > 80 years, (II) ventilated patients with no age limit, (III) very seriously disabled people with no age limit. Patients' data were acquired from regional and LHU databases. From 5 February until the 16 May, 6127 people got at least one dose of Pfizer-Biontech Comirnaty® vaccine, while 5278 (86.14%) completed the necessary two doses. The highest number of vaccines was administered during the first week of April, reaching 1296 doses overall. The number of vaccines administered were similar across the districts. The average number of people vaccinated at home was 6 per 1000 inhabitants in the LHU. This model proved to be extremely complex but effective, reaching satisfying results in terms of vaccination coverage.

Evaluation of the Effectiveness and Safety of the BNT162b2 COVID-19 Vaccine in the Vaccination Campaign among the Health Workers of Fondazione Policlinico Universitario Agostino Gemelli IRCCS.

Health workers, especially those in patient-facing roles, had a significantly increased risk of COVID-19 infection, having serious outcomes, and risking spreading the virus to patients and staff. Vaccination campaign planning suggests allocating initial supplies of BNT162b2 vaccine to health workers given the importance of early protection to safeguard the continuity of care to patients. The aim of the study is to assess the effectiveness and safety of BNT162b2 vaccine among the health workers of Fondazione Policlinico Universitario Agostino Gemelli IRCCS (FPG). The retrospective cohort study was conducted among health staff working at the FPG. Vaccination data were collected from hospital records. The primary end points were vaccine effectiveness and safety. A total of 6649 health workers were included, of whom 5162 received injections. There were 14 cases of COVID-19 with onset at least 14 days after the second dose among vaccinated health workers and 45 cases among unvaccinated ones. BNT162b2 was 91.5% effective against COVID-19 (95% credible interval, 84.7% to 95.3%). The safety profile of BNT162b2 vaccine consisted of short-term, non-serious events. The promotion and boost of the COVID-19 vaccination campaign represents a key public health measure useful to curb the spread of the pandemic especially in vulnerable contexts, such as hospitals, where health workers carry out a paramount role for the entire community, and requires further protection with a possible booster dose in view of autumn-winter 2021.

Hand hygiene and facemask use to prevent droplet-transmitted viral diseases during air travel: a systematic literature review.

BACKGROUND: Transmission of viral diseases (e.g., influenza A H1N1) via respiratory droplets takes place mainly in confined spaces, including in aircraft during commercial air travel. The adoption of hygiene measures may help to prevent disease spread aboard aircraft. This review summarizes the evidence on hand hygiene and the use of facemasks as viral disease prevention measures in aircraft. METHODS: A literature search was performed in the PubMed, Scopus, and Web of Science databases up to 10 June 2020, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. A population, intervention, comparison, outcomes, and study design (PICOS) approach was used to define the review question. RESULTS: We included four studies published between 2007 and 2020, all targeting influenza virus disease, in the qualitative synthesis. Three studies used mathematical models to simulate single- or multiple-direction flights, and two of them showed that facemask (e.g., N95 respirator) use considerably reduced infection probability. In the third study, hand cleaning by 20 to 60% of people at any time in all airports (including on aircraft) reduced the measure of airports' power to spread the disease across the globe by ~ 24 to 69%. The fourth study was a case-control study designed to trace an influenza outbreak in two flights during the 2009 influenza A H1N1 pandemic. The study showed that none (0%) of nine infected passengers compared to 15 (47%) of 32 healthy control passengers in the aircraft cabin during one of these flights wore a facemask (odds ratio, 0.0; 95% confidence interval, 0.0-0.7). In contrast, both case and control passengers appeared to be equally compliant in self-assessed hand hygiene. CONCLUSIONS: Facemask use combined with hand hygiene may minimize the chance of droplet-transmitted virus spread by air travelers. Thus, it is necessary that hygiene measures become an integral part of standard procedures in commercial air travel.

Safety of hydroxychloroquine for treatment or prevention of SARS-CoV-2 infection: A rapid systematic review and meta-analysis of randomized clinical trials.

INTRODUCTION: Hydroxycloroquine (HCQ) has been extensively studied for treatment and prevention of coronavirus diseases 2019 (COVID-19) from the start of the pandemic. Conflicting evidence about its usefulness has begun to accrue. METHODS: In the face of controversial results about clinical efficacy of HCQ, we performed a rapid systematic review to assess its safety in the framework of COVID-19 randomized clinical trials. RESULTS: Five studies investigating 2291 subjects were included. The use of HCQ was associated with higher risk of adverse event compared with placebo or standard of care: odds ratio 4.57, 95% confidence interval 2.14-9.45. CONCLUSION: Safety profile of HCQ appears to be unsatisfactory when used to treat or prevent COVID-19, especially in the light of unproved clinical benefit.