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Observational Study
. 2021 Mar;82(3):399-406.
doi: 10.1016/j.jinf.2021.01.020. Epub 2021 Feb 13.

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

Letícia Adrielle Dos Santos  1 , Pedro Germano de Góis Filho  1 , Ana Maria Fantini Silva  1 , João Victor Gomes Santos  1 , Douglas Siqueira Santos  1 , Marília Marques Aquino  1 , Rafaela Mota de Jesus  2 , Maria Luiza Dória Almeida  1 , João Santana da Silva  3 , Daniel M Altmann  4 , Rosemary J Boyton  5 , Cliomar Alves Dos Santos  6 , Camilla Natália Oliveira Santos  7 , Juliana Cardoso Alves  7 , Ianaline Lima Santos  7 , Lucas Sousa Magalhães  7 , Emilia M M A Belitardo  8 , Danilo J P G Rocha  8 , João P P Almeida  9 , Luis G C Pacheco  8 , Eric R G R Aguiar  10 , Gubio Soares Campos  11 , Silvia Inês Sardi  11 , Rejane Hughes Carvalho  11 , Amélia Ribeiro de Jesus  12 , Karla Freire Rezende  1 , Roque Pacheco de Almeida  13
Affiliations
Observational Study

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

Letícia Adrielle Dos Santos et al. J Infect. 2021 Mar.

Abstract

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.

Keywords: Antibodies; COVID-19; Recurrence; Reinfection; SARS-CoV-2.

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Conflict of interest statement

Declaration of Competing Interests All authors report there are no conflicts of interest.

Figures

Image, graphical abstract
Graphical abstract
Fig 1
Fig. 1
Characterization of SARS-CoV-2 viral genomes in patients with recurrent COVID-19. Phylogenetic (A) and genomic variant (B) analysis of viral genomes recovered from individuals with recurrent COVID-19. In the phylogenetic tree, strains derived from Brazilian individuals are shown in orange. E1 and E2 represent samples of the patient E at first and second event of COVID-19, respectively. K2 represent the sample of patient K during the second episode of COVID-19. Vertical lines indicate the genomic position of the high-confidence mutation in SARS-CoV-2 genomic sequence. Only variants with frequency higher than 90% were considered in the analysis. Text above the vertical lines indicates the base transition from reference genomes to newly assembled genomes in this work. Genomic structure of SARS-CoV-2 is also plotted.
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