Correlates of protection, viral load trajectories and symptoms in BA.1, BA.1.1 and BA.2 breakthrough infections in triple vaccinated healthcare workers

This article has been Reviewed by the following groups

Read the full article See related articles

Abstract

Background

Booster vaccine doses offer protection against severe COVID-19 caused by omicron but are less effective against infection. Characteristics such as serological correlates of protection, viral abundance, and clearance of omicron infection in triple vaccinated individuals are scarce.

Methods

We conducted a 4-week twice-weekly SARS-CoV-2 qPCR screening shortly after an mRNA vaccine booster in 368 healthcare workers. Spike-specific IgG levels and neutralization titers were determined at study start. qPCR-positive participants were sampled repeatedly for two weeks and monitored for symptoms.

Result

In total 81 (cumulative incidence 22%) omicron infections were detected, divided between BA.1, BA.1.1 and BA.2. Increasing post-booster antibody titers were protective against infection (p<0.05), linked to reduced viral load (p<0.01) and time to viral clearance (p<0.05). Only 10% of infected participants remained asymptomatic through the course of their infection. Viral load peaked at day 3 and live virus could be detected for up to 9 days after first PCR-positive sample. Presence of symptoms correlated to elevated viral load (p<0.0001), but despite resolution of symptoms most participants showed Ct levels <30 at day 9. No significant differences were observed for viral load and time to viral clearance between BA.1, BA.1.1 and BA.2 infected individuals.

Conclusion

We report a high incidence of omicron infection despite recent booster vaccination in triple vaccinated individuals. Increasing levels of vaccine-induced spike-specific WT antibodies entail increased protection against infection and reduce viral load if infected. High viral load and secretion of live virus for up to nine days may facilitate transmission in a triple vaccinated population.

Article activity feed

  1. SciScore for 10.1101/2022.04.02.22273333: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: Written informed consent was obtained from all study participants.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibody titers are expressed as arbitrary units (AU)/ml, except for anti-WT IgG, which are expressed in the WHO-standard binding antibody units (BAU)/ml.
    anti-WT IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Briefly, heat-inactivated serum was 3-fold serially diluted, mixed with virus, incubated for 1 hour and finally added, in duplicates, to confluent Vero E6 cells in 96-well plates.
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    PCR, whole genome sequencing (WGS) and virus isolation was performed as previously described [19].
    WGS
    suggested: None
    Mann-Whitney U test was performed for comparisons of antibody titers between groups, peak Ct levels and number of positive days between groups, using GraphPad Prism version 9.2.0 (GraphPad Software, San Diego, California, USA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Further, post booster antibody titers were similar in participants with and without subsequent breakthrough infection, exemplifying limitations of vaccine induced antibody titres as a marker of protection against omicron breakthrough infection. Although identification of SARS-CoV-2 RNA through qPCR is not equivalent to the detection of infectious virus, low Ct values have repeatedly been shown to correspond to viable virus in cell cultures for both omicron [11 ,13] and other SARS-CoV-2 variants [27 ,28]. Consequently, Ct values are often used as a proxy of viral load. Fall et al., reported presence of infectious omicron virus in samples obtained up to eight days after symptom onset, and that the presence of infectious omicron virus was similar in non vaccinated, vaccinated and boosted individuals, implying that vaccine has little effect on viral load once infected [11]. In line with this, we here demonstrate high viral RNA levels up to nine days after first qPCR positive sample, including after symptom resolution, in the majority of omicron breakthrough infections occurring shortly after a vaccine booster dose. Together, this suggests that recently vaccinated omicron-infected individuals may transmit the virus for a longer time period than the five days quarantine from symptom onset recommended by current guidelines [29]. This is of particular importance in vulnerable environments such as healthcare settings. Our data are furthermore in line with a recent report demonstrating...

    Results from TrialIdentifier: No clinical trial numbers were referenced.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.


    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.