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      Rapid antigen testing as a reactive response to surges in nosocomial SARS-CoV-2 outbreak risk

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      1 , 2 , 3 , , 1 , 2 , 4 , 4 , 5 , the EMAE-MESuRS Working Group on Nosocomial SARS-CoV-2 Modelling, 1 , 2 , 3 , 6
      Nature Communications
      Nature Publishing Group UK
      Viral infection, Computational models, Population screening

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          Abstract

          Healthcare facilities are vulnerable to SARS-CoV-2 introductions and subsequent nosocomial outbreaks. Antigen rapid diagnostic testing (Ag-RDT) is widely used for population screening, but its health and economic benefits as a reactive response to local surges in outbreak risk are unclear. We simulate SARS-CoV-2 transmission in a long-term care hospital with varying COVID-19 containment measures in place (social distancing, face masks, vaccination). Across scenarios, nosocomial incidence is reduced by up to 40-47% (range of means) with routine symptomatic RT-PCR testing, 59-63% with the addition of a timely round of Ag-RDT screening, and 69-75% with well-timed two-round screening. For the latter, a delay of 4-5 days between the two screening rounds is optimal for transmission prevention. Screening efficacy varies depending on test sensitivity, test type, subpopulations targeted, and community incidence. Efficiency, however, varies primarily depending on underlying outbreak risk, with health-economic benefits scaling by orders of magnitude depending on the COVID-19 containment measures in place.

          Abstract

          Healthcare facilities are vulnerable to SARS-CoV-2 introductions and subsequent nosocomial outbreaks. Here, the authors simulate transmission in a long-term care facility with varying containment measures in place and evaluate reactive response with antigen rapid diagnostic testing.

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          BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting

          Abstract Background As mass vaccination campaigns against coronavirus disease 2019 (Covid-19) commence worldwide, vaccine effectiveness needs to be assessed for a range of outcomes across diverse populations in a noncontrolled setting. In this study, data from Israel’s largest health care organization were used to evaluate the effectiveness of the BNT162b2 mRNA vaccine. Methods All persons who were newly vaccinated during the period from December 20, 2020, to February 1, 2021, were matched to unvaccinated controls in a 1:1 ratio according to demographic and clinical characteristics. Study outcomes included documented infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), symptomatic Covid-19, Covid-19–related hospitalization, severe illness, and death. We estimated vaccine effectiveness for each outcome as one minus the risk ratio, using the Kaplan–Meier estimator. Results Each study group included 596,618 persons. Estimated vaccine effectiveness for the study outcomes at days 14 through 20 after the first dose and at 7 or more days after the second dose was as follows: for documented infection, 46% (95% confidence interval [CI], 40 to 51) and 92% (95% CI, 88 to 95); for symptomatic Covid-19, 57% (95% CI, 50 to 63) and 94% (95% CI, 87 to 98); for hospitalization, 74% (95% CI, 56 to 86) and 87% (95% CI, 55 to 100); and for severe disease, 62% (95% CI, 39 to 80) and 92% (95% CI, 75 to 100), respectively. Estimated effectiveness in preventing death from Covid-19 was 72% (95% CI, 19 to 100) for days 14 through 20 after the first dose. Estimated effectiveness in specific subpopulations assessed for documented infection and symptomatic Covid-19 was consistent across age groups, with potentially slightly lower effectiveness in persons with multiple coexisting conditions. Conclusions This study in a nationwide mass vaccination setting suggests that the BNT162b2 mRNA vaccine is effective for a wide range of Covid-19–related outcomes, a finding consistent with that of the randomized trial.
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            Covid-19 Breakthrough Infections in Vaccinated Health Care Workers

            Background Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare breakthrough infections have been reported, including infections among health care workers. Data are needed to characterize these infections and define correlates of breakthrough and infectivity. Methods At the largest medical center in Israel, we identified breakthrough infections by performing extensive evaluations of health care workers who were symptomatic (including mild symptoms) or had known infection exposure. These evaluations included epidemiologic investigations, repeat reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays, antigen-detecting rapid diagnostic testing (Ag-RDT), serologic assays, and genomic sequencing. Correlates of breakthrough infection were assessed in a case–control analysis. We matched patients with breakthrough infection who had antibody titers obtained within a week before SARS-CoV-2 detection (peri-infection period) with four to five uninfected controls and used generalized estimating equations to predict the geometric mean titers among cases and controls and the ratio between the titers in the two groups. We also assessed the correlation between neutralizing antibody titers and N gene cycle threshold (Ct) values with respect to infectivity. Results Among 1497 fully vaccinated health care workers for whom RT-PCR data were available, 39 SARS-CoV-2 breakthrough infections were documented. Neutralizing antibody titers in case patients during the peri-infection period were lower than those in matched uninfected controls (case-to-control ratio, 0.361; 95% confidence interval, 0.165 to 0.787). Higher peri-infection neutralizing antibody titers were associated with lower infectivity (higher Ct values). Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks). The B.1.1.7 (alpha) variant was found in 85% of samples tested. A total of 74% of case patients had a high viral load (Ct value, <30) at some point during their infection; however, of these patients, only 17 (59%) had a positive result on concurrent Ag-RDT. No secondary infections were documented. Conclusions Among fully vaccinated health care workers, the occurrence of breakthrough infections with SARS-CoV-2 was correlated with neutralizing antibody titers during the peri-infection period. Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur.
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              Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study

              Background Vaccine effectiveness studies have not differentiated the effect of the delta (B.1.617.2) variant and potential waning immunity in observed reductions in effectiveness against SARS-CoV-2 infections. We aimed to evaluate overall and variant-specific effectiveness of BNT162b2 (tozinameran, Pfizer–BioNTech) against SARS-CoV-2 infections and COVID-19-related hospital admissions by time since vaccination among members of a large US health-care system. Methods In this retrospective cohort study, we analysed electronic health records of individuals (≥12 years) who were members of the health-care organisation Kaiser Permanente Southern California (CA, USA), to assess BNT162b2 vaccine effectiveness against SARS-CoV-2 infections and COVID-19-related hospital admissions for up to 6 months. Participants were required to have 1 year or more previous membership of the organisation. Outcomes comprised SARS-CoV-2 PCR-positive tests and COVID-19-related hospital admissions. Effectiveness calculations were based on hazard ratios from adjusted Cox models. This study was registered with ClinicalTrials.gov , NCT04848584. Findings Between Dec 14, 2020, and Aug 8, 2021, of 4 920 549 individuals assessed for eligibility, we included 3 436 957 (median age 45 years [IQR 29–61]; 1 799 395 [52·4%] female and 1 637 394 [47·6%] male). For fully vaccinated individuals, effectiveness against SARS-CoV-2 infections was 73% (95% CI 72–74) and against COVID-19-related hospital admissions was 90% (89–92). Effectiveness against infections declined from 88% (95% CI 86–89) during the first month after full vaccination to 47% (43–51) after 5 months. Among sequenced infections, vaccine effectiveness against infections of the delta variant was high during the first month after full vaccination (93% [95% CI 85–97]) but declined to 53% [39–65] after 4 months. Effectiveness against other (non-delta) variants the first month after full vaccination was also high at 97% (95% CI 95–99), but waned to 67% (45–80) at 4–5 months. Vaccine effectiveness against hospital admissions for infections with the delta variant for all ages was high overall (93% [95% CI 84–96]) up to 6 months. Interpretation Our results provide support for high effectiveness of BNT162b2 against hospital admissions up until around 6 months after being fully vaccinated, even in the face of widespread dissemination of the delta variant. Reduction in vaccine effectiveness against SARS-CoV-2 infections over time is probably primarily due to waning immunity with time rather than the delta variant escaping vaccine protection. Funding Pfizer.
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                Author and article information

                Contributors
                david.smith@pasteur.fr
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                11 January 2022
                11 January 2022
                2022
                : 13
                : 236
                Affiliations
                [1 ]GRID grid.428999.7, ISNI 0000 0001 2353 6535, Institut Pasteur, , Epidemiology and Modelling of Antibiotic Evasion (EMAE), ; Paris, France
                [2 ]GRID grid.463845.8, ISNI 0000 0004 0638 6872, Université Paris-Saclay, UVSQ, Inserm, CESP, , Anti-infective evasion and pharmacoepidemiology team, ; Montigny-Le-Bretonneux, France
                [3 ]GRID grid.36823.3c, ISNI 0000 0001 2185 090X, Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), , Conservatoire national des arts et métiers, ; Paris, France
                [4 ]GRID grid.469994.f, ISNI 0000 0004 1788 6194, IAME, UMR 1137, Université Paris 13, Sorbonne Paris Cité, ; Paris, France
                [5 ]GRID grid.50550.35, ISNI 0000 0001 2175 4109, Service de Microbiologie Clinique et Unité de Contrôle et de Prévention du Risque Infectieux, , Groupe Hospitalier Paris Seine Saint-Denis, AP-HP, ; Bobigny, France
                [6 ]GRID grid.36823.3c, ISNI 0000 0001 2185 090X, PACRI unit, Institut Pasteur, , Conservatoire national des arts et métiers, ; Paris, France
                [7 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, , Imperial College London, ; London, UK
                Author information
                http://orcid.org/0000-0002-7330-4262
                Article
                27845
                10.1038/s41467-021-27845-w
                8752617
                35017499
                3236f700-f3f5-4093-a757-f08cdb3b8d93
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 16 August 2021
                : 7 December 2021
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                viral infection,computational models,population screening
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                viral infection, computational models, population screening

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