key: cord-0723264-mnkos147
authors: Loconsole, Daniela; Sallustio, Anna; Accogli, Marisa; Leaci, Angela; Sanguedolce, Antonio; Parisi, Antonio; Chironna, Maria
title: Outbreak investigation of symptomatic SARS-COV-2 VOC 202012/01-lineage B.1.1.7 infection in healthcare workers, Italy
date: 2021-05-10
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2021.05.007
sha: 7eb7f75f03b92b91459088d29a97c60c005e59dc
doc_id: 723264
cord_uid: mnkos147

OBJECTIVES: In December 2020, Italy began a national immunization campaign using the BNT162b2 mRNA COVID-19 vaccine, prioritizing healthcare workers (HCWs). Immune serum from vaccinated subjects seems to (largely) retain titres of neutralizing antibodies, even against SARS-CoV-2 VOC 202012/01-lineage B.1.1.7. Here, we describe an outbreak of SARS-CoV-2 lineage B.1.1.7 infection in three HCWs in a hospital setting; two of the HCWs were fully vaccinated (i.e., had received two doses). METHODS: Two physicians and one nurse working on the same shift on February 20, 2021, were involved in the outbreak. Real-time PCR, antigen tests, and serological tests for the IgG anti-spike protein of SARS-CoV-2 were performed, along with whole-genome sequencing (WGS). RESULTS: SARS-CoV-2 infection was confirmed in all three HCWs; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE). CONCLUSIONS: This mini-outbreak highlights some important issues about the efficacy of vaccines against transmission of SARS-CoV-2 variants, the high risk of exposure among HCWs, and the need for optimized implementation of PPE in hospitals. The wide circulation of VOC 202012/01 in Europe and Italy highlights the need to improve surveillance and genetic sequencing.

In December 2020, Italy began a national immunization campaign, prioritizing healthcare workers 27 (HCWs) [1] . Initially, the campaign used the BNT162b2 mRNA COVID-19 vaccine. Clinical trial 28 data demonstrate that two doses of the BNT162b2 vaccine confer 95% protection against COVID-29 19 caused by wild-type SARS-CoV-2 [2]. A recent study shows that immune serum from subjects Samples were subjected to molecular test using a three-target commercial multiplex real-time PCR 47 assay targeting the N, ORF1ab, and S genes (TaqPath RT-PCR COVID-19 Assay; Thermo Fisher 48 Scientific). An antigen test was also performed using the Lumipulse SARS-CoV-2 Ag kit 49 (Fujirebio, Tokyo, Japan). Moreover, to assess responses to vaccination, serological tests for IgG Quant assay; Abbott Architect iSystem, Abbott Diagnostics, Chicago, USA). Whole-genome 52 sequencing (WGS) was performed using the Ion Torrent platform (Thermo Fisher Scientific). The 53 aligned reads were used for both reference-guided assembly and variant calling. Assembly was 54 performed using the Iterative Refinement Meta-Assembler (IRMA) v.1.3.0.2. 55

Approval by a research ethics committee was not required since the activities described here were 57 conducted as part of the national and regional COVID-19 surveillance effort. All procedures were 58 carried out in accordance with the Declaration of Helsinki, as revised in 2013, for research on 59 human subjects. Informed written consent for publication was obtained from the subjects who 60 provided samples. 61

The first case was a healthy 41-year-old male physician. The date of symptom onset (conjunctivitis) 63 was February 23, 2021. On February 25, he presented with strong asthenia, low-grade fever (T max, 64 37.2°C), and coryza. On the following day, he developed anosmia and ageusia. A molecular test of 65 a nasopharyngeal swab collected on February 27 was positive for SARS-CoV-2. The second case 66 was a healthy 34-year-old female physician who presented with a cough on February 28. The 67 diagnosis was confirmed by a molecular test on a nasopharyngeal swab collected on March 2. 68

Serological tests were performed on both patients on the day of diagnosis. Antibody titres in the 69 male and female patient were 1,774 AU/mL and 2,500 AU/mL, respectively. The third case was a 70 51-year-old male nurse who developed a fever (T max, 38°C) on February 25; there were no 71 respiratory symptoms. The diagnosis was confirmed on February 27. This case showed high-grade 72 fever for 8 days from symptom onset. The clinical presentation of the three cases was classified as 73 mild (Table) . 74

The two physicians had been fully vaccinated with the BNT162b2 mRNA COVID-19 vaccine, 75 having received two doses; the second dose was administered 21 days after the first, in accordance 76 with the recommended schedule. The second dose was administered 1 month before symptom onset 77 J o u r n a l P r e -p r o o f (Table) . The nurse refused the vaccination. The multiplex real-time PCR assay performed on 78 nasopharyngeal swabs from all three HCWs identified an S gene dropout, a good proxy for VOC 79 202012/01 (Table) . All three samples tested positive in the antigen test. Whole genome sequencing 80 confirmed that all strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of 81 exposure ( Figure) . Epidemiological investigation revealed that it is likely that the three HCWs were 82 infected by exposure to aerosols while conducting an invasive procedure on a patient with COVID- 

COVID-19 vaccination and 138 prioritisation strategies in the EU/EEA

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus 150 by BNT162b2 vaccine-elicited human sera

Chironna Collaboration Vaccine-associated Enhanced Disease Working Group. Vaccine-associated 179 enhanced disease: Case definition and guidelines for data collection, analysis, and 180 presentation of immunization safety data

Rapid COVID-19 vaccine development