An observational study of breakthrough SARS-CoV-2 Delta variant infections among vaccinated healthcare workers in Vietnam

Abstract

Background: Data on breakthrough SARS-CoV-2 Delta variant infections in vaccinated individuals are limited.

Methods: We studied breakthrough infections among Oxford-AstraZeneca vaccinated healthcare workers in an infectious diseases hospital in Vietnam. We collected demographic and clinical data alongside serial PCR testing, measurement of SARS-CoV-2 antibodies, and viral whole-genome sequencing.

Findings: Between 11^th-25^th June 2021 (7-8 weeks after the second dose), 69 staff tested positive for SARS-CoV-2. 62 participated in the study. Most were asymptomatic or mildly symptomatic and all recovered. Twenty-two complete-genome sequences were obtained; all were Delta variant and were phylogenetically distinct from contemporary viruses obtained from the community or from hospital patients admitted prior to the outbreak. Viral loads inferred from Ct values were 251 times higher than in cases infected with the original strain in March/April 2020. Median time from diagnosis to negative PCR was 21 days (range 8-33). Neutralizing antibodies (expressed as percentage of inhibition) measured after the second vaccine dose, or at diagnosis, were lower in cases than in uninfected, fully vaccinated controls (median (IQR): 69.4 (50.7-89.1) vs. 91.3 (79.6-94.9), p=0.005 and 59.4 (32.5-73.1) vs. 91.1 (77.3-94.2), p=0.002). There was no correlation between vaccine-induced neutralizing antibody levels and peak viral loads or the development of symptoms.

Interpretation: Breakthrough Delta variant infections following Oxford-AstraZeneca vaccination may cause asymptomatic or mild disease, but are associated with high viral loads, prolonged PCR positivity and low levels of vaccine-induced neutralizing antibodies. Epidemiological and sequence data suggested ongoing transmission had occurred between fully vaccinated individuals.

Funding: Wellcome and NIH/NIAID.

Keywords: COVID-19; Delta variant; Oxford-AstraZeneca; Vietnam; vaccine breakthrough.

Figure 1

Flowchart showing timelines and results of SARS-CoV-2 RT-PCR screening before and during the lockdown (11-25 June 2021). Notes toFigure 1: *The remaining members of staff were working from home.

Figure 2

Viral load analyses, A) plot outlining kinetics of viral loads in relation to illness onset of the 49 symptomatic participants, B) comparison between peak viral loads of breakthrough infections (cases) and those (controls) infected with old SARS-CoV-2 strains detected between March and April 2020 in Vietnam. Notes toFigure 2: Vertical dashed line indicates the time point of illness onset. Horizontal dashed line indicates detection limit of PCR assay. A) Black lines indicates median viral loads, B) black dots represent for whole groups, red dots represent for symptomatic cases and blue dots represent for asymptomatic cases.

Figure 3

Maximum likelihood tree illustrating the relatedness between SARS-CoV-2 Delta variant strains obtained from cases of vaccine breakthrough infection (red) and contemporary Delta variant sequences obtained from cases of community transmission in Ho Chi Minh City (blue) and from COVID-19 patients admitted to HTD prior to the outbreaks (in blue marked with dots).

Figure 4

Correlation between neutralizing antibodies at diagnosis and peak viral loads during the course of infection

Figure 5

Comparison between neutralizing antibody levels of the 10 case patients (red) and 30 uninfected, fully vaccinated controls (grey green)