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Recurrent COVID-19 including evidence of reinfection and enhanced severity in thirty Brazilian healthcare workers - 18/03/21

Doi : 10.1016/j.jinf.2021.01.020 
Letícia Adrielle dos Santos a, 1, Pedro Germano de Góis Filho a, 1, Ana Maria Fantini Silva a, João Victor Gomes Santos a, Douglas Siqueira Santos a, Marília Marques Aquino a, Rafaela Mota de Jesus b, Maria Luiza Dória Almeida a, João Santana da Silva c, Daniel M. Altmann d, , Rosemary J. Boyton d, Cliomar Alves dos Santos e, Camilla Natália Oliveira Santos f, Juliana Cardoso Alves f, Ianaline Lima Santos f, Lucas Sousa Magalhães f, Emilia M.M.A. Belitardo g, Danilo J.P.G. Rocha g, João P.P. Almeida h, Luis G.C. Pacheco g, Eric R.G.R. Aguiar i, Gubio Soares Campos j, Silvia Inês Sardi j, Rejane Hughes Carvalho j, Amélia Ribeiro de Jesus a, f, 2, Karla Freire Rezende a, 2, Roque Pacheco de Almeida a, f, 2,
a Department of Medicine, Federal University of Sergipe, Immunology Investigative Institute (III), INCT, CNPq, Aracaju, Sergipe 49060-100, Brazil 
b Division of Pulmonology, Institute of Health Promotion and Assistance for Employees of the State of Sergipe (IPESAÚDE), Sergipe, Brazil 
c Fiocruz - Bi-Institutional Translational Medicine Project, Ribeirao Preto Medical School, Department of Biochemistry and Immunology, 14049-900 Ribeirao Preto, SP, Brazil 
d Department of Immunology and Inflammation, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, W12 ONN, United Kingdom 
e Health Foundation Parreiras Horta, Central Laboratory of Public Health (LACEN/SE), State Secretary for Health, Sergipe, Brazil 
f Division of Immunology and Molecular Biology Laboratory, University Hospital/EBSERH, Federal University of Sergipe, Sergipe CEP 49.060-025, Brazil 
g Institute of Health Sciences, Federal University of Bahia, Salvador-BA, Brazil 
h Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte-MG, Brazil 
i Department of Biological Sciences, Center of Biotechnology and Genetics, State University of Santa Cruz (UESC), Ilhéus-BA, Brazil 
j Virology Laboratory, Institute of Health Sciences, Federal University of Bahia, Salvador-BA, Brazil 

Corresponding authors.

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Highlights

We describe 33 patients with recurrent COVID19 and a positive PCR.
Recurrence is associated with working as a healthcare professional, blood-group A, and low IgG response to infection.
Evidence from differential virus sequencing between the first and second episode supports de novo reinfection.
Recurrent episodes tended to be more severe, with one fatal infection.

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Summary

Background

There is growing concern about individuals reported to suffer repeat COVID-19 disease episodes, these in a small number of cases characterised as de novo infections with distinct sequences, indicative of insufficient protective immunity even in the short term.

Methods

Observational case series and case-control studies reporting 33 cases of recurrent, symptomatic, qRT-PCR positive COVID-19. Recurrent disease was defined as symptomatic recurrence after symptom-free clinical recovery, with release from isolation >14 days from the beginning of symptoms confirmed by qRT-PCR. The case control study-design compared this group of patients with a control group of 62 patients randomly selected from the same COVID-19 database.

Results

Of 33 recurrent COVID-19 patients, 26 were female and 30 were HCW. Mean time to recurrence was 50.5 days which was associated with being a HCW (OR 36.4 (p <0.0001)), and blood type A (OR 4.8 (p = 0.002)). SARS-CoV-2 antibodies were signifcantly lower in recurrent patients after initial COVID-19  (2.4 ± 0.610; p<0.0001) and after recurrence (6.4 ± 11.34; p = 0.007).  Virus genome sequencing identified reinfection by a different isolate in one patient.

Conclusions

This is the first detailed case series showing COVID-19 recurrence with qRT-PCR positivity. For one individual detection of phylogenetically distinct genomic sequences in the first and second episodes confirmed bona fide renfection, but in most cases the data do not formally distinguish between reinfection and re-emergence of a chronic infection reservoir. These episodes were significantly associated with reduced Ab response during initial disease and argue the need for ongoing vigilance without an assumption of protection after a first episode.

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Keywords : COVID-19, Recurrence, Reinfection, SARS-CoV-2, Antibodies


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Vol 82 - N° 3

P. 399-406 - mars 2021 Retour au numéro
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