Correlates of protection, viral load trajectories and symptoms in BA.1, BA.1.1 and BA.2 breakthrough infections in triple vaccinated healthcare workers
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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.
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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
Ethics Consent: Written informed consent was obtained from all study participants. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources 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 IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources 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 E6suggested: …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
Ethics Consent: Written informed consent was obtained from all study participants. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources 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 IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources 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 E6suggested: NoneSoftware and Algorithms Sentences Resources PCR, whole genome sequencing (WGS) and virus isolation was performed as previously described [19]. WGSsuggested: NoneMann-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 Prismsuggested: (GraphPad Prism, RRID:SCR_002798)GraphPadsuggested: (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.
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Results from scite Reference Check: We found no unreliable references.
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