SARS-CoV-2 Infections in mRNA Vaccinated Individuals are Biased for Viruses Encoding Spike E484K and Associated with Reduced Infectious Virus Loads that Correlate with Respiratory Antiviral IgG levels

Mostafa, Heba H.; Luo, Chun; Morris, C. Paul; Li, Maggie; Swanson, Nicholas J; Amadi, Adannaya; Gallagher, Nicholas; Pekosz, Andrew

doi:10.1101/2021.07.05.21259105

Cited by 11 publications

(9 citation statements)

References 30 publications

(17 reference statements)

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“…For example, virus isolated from vaccinated individuals may have vaccine-induced antibodies bound to it, reducing its infectivity. This is consistent with a recent report showing that messenger RNA-vaccinated individuals have reduced infectious VLs that correlate with respiratory antiviral IgG levels (45).…”

Section: Discussionsupporting

confidence: 93%

In vivo kinetics of SARS-CoV-2 infection and its relationship with a person’s infectiousness

Zitzmann

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

137

210

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The within-host viral kinetics of SARS-CoV-2 infection and how they relate to a person’s infectiousness are not well understood. This limits our ability to quantify the impact of interventions on viral transmission. Here, we develop viral dynamic models of SARS-CoV-2 infection and fit them to data to estimate key within-host parameters such as the infected cell half-life and the within-host reproductive number. We then develop a model linking viral load (VL) to infectiousness and show a person’s infectiousness increases sublinearly with VL and that the logarithm of the VL in the upper respiratory tract is a better surrogate of infectiousness than the VL itself. Using data on VL and the predicted infectiousness, we further incorporated data on antigen and RT-PCR tests and compared their usefulness in detecting infection and preventing transmission. We found that RT-PCR tests perform better than antigen tests assuming equal testing frequency; however, more frequent antigen testing may perform equally well with RT-PCR tests at a lower cost but with many more false-negative tests. Overall, our models provide a quantitative framework for inferring the impact of therapeutics and vaccines that lower VL on the infectiousness of individuals and for evaluating rapid testing strategies.

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Section: Discussionsupporting

confidence: 93%

In vivo kinetics of SARS-CoV-2 infection and its relationship with a person’s infectiousness

Zitzmann

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

137

210

View full text Add to dashboard Cite

show abstract

“…One important factor that has not been carefully addressed to date is the level of mucosal antibodies present after vaccination, as these antibodies are critical for protection from infection in the upper respiratory tract ( 19 ). The presence of anti–SARS-CoV-2 IgG in the nasal tract of infected individuals is inversely correlated with the presence of infectious virus ( 20 , 21 ) emphasizing the importance of mucosal antibody response for rapid neutralization of SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 99%

“…Automated nucleic acid extraction was performed as described previously ( 20 , 21 ) using the chemagic 360 (PerkinElmer) following the manufacturer’s protocol. Whole genome sequencing and analysis were performed as previously described ( 23 ).…”

Section: Methodsmentioning

confidence: 99%

Adaptive immune responses in vaccinated patients with symptomatic SARS-CoV-2 Alpha infection

Park¹,

Shapiro²,

Sitaras³

et al. 2022

JCI Insight

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Benchmarks for protective immunity from infection or severe disease after SARS-CoV-2 vaccination are still being defined. Here we characterized virus neutralizing and ELISA antibody levels, cellular immune responses, and viral variants in 4 separate groups: Healthy control participants weeks (early) or months (late) following vaccination in comparison to symptomatic SARS-CoV-2 infections after partial or full mRNA vaccination. During the study time, most symptomatic breakthrough infections were caused by the SARS-CoV-2 Alpha variant. Neutralizing antibody levels in the healthy controls were sustained over time against the vaccine parent virus, but decreased against the Alpha variant, whereas IgG titers and T cell responses against the parent virus and Alpha variant declined over time in healthy controls. Both partially and fully vaccinated patients with symptomatic infections had lower virus neutralizing antibody levels against parent virus than the healthy controls, similar IgG antibody titers and similar virus-specific T cell responses measured by IFN-g. Compared to healthy controls, neutralization activity against the Alpha variant was lower in the partially vaccinated infected patients and tended toward lower in the fully vaccinated infected patients. In this cohort of breakthrough infections, parent virus neutralization was the superior predictor of breakthrough infections with the Alpha variant of SARS-CoV-2. Summary: Despite similar antibody titers and T-cell responses to vaccinated noninfected healthy controls, neutralizing capacity was reduced in those with breakthrough infection.

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“…A main finding in our study was the correlation between vaccination and a lower likelihood of prolonged shedding or recovery of good quality genomes after the first 20 days of the initial positive result. Even though, vaccine breakthrough infections correlated with a bias to genomes carrying the S: E484K ( Feder et al., 2021 ; Mostafa et al., 2021 ), a limited infectious virus shedding was notable when samples from patients were longitudinally analyzed ( Ke et al., 2021 ). SARS-CoV-2 genomic diversity was also shown to decline after widespread vaccination ( Niesen et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Large Scale SARS-CoV-2 Molecular Testing and Genomic Surveillance Reveal Prolonged Infections, Protracted RNA shedding, and Viral Reinfections

Morris

Luo²,

Sachithanandham

et al. 2022

Front. Cell. Infect. Microbiol.

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Large-scale SARS-CoV-2 molecular testing coupled with whole genome sequencing in the diagnostic laboratories is instrumental for real-time genomic surveillance. The extensive genomic, laboratory, and clinical data provide a valuable resource for understanding cases of reinfection versus prolonged RNA shedding and protracted infections. In this study, data from a total of 22,292 clinical specimens, positive by SARS-CoV-2 molecular diagnosis at Johns Hopkins clinical virology laboratory between March 11th 2020 to September 23rd 2021, were used to identify patients with two or more positive results. A total of 3,650 samples collected from 1,529 patients who had between 2 and 20 positive results were identified in a time frame that extended up to 403 days from the first positive. Cycle threshold values (Ct) were available for 1,622 samples, the median of which was over 30 by 11 days after the first positive. Extended recovery of infectious virus on cell culture was notable for up to 70 days after the first positive in immunocompromised patients. Whole genome sequencing data generated as a part of our SARS-CoV-2 genomic surveillance was available for 1,027 samples from patients that had multiple positive tests. Positive samples collected more than 10 days after initial positive with high quality sequences (coverage >90% and mean depth >100), were more likely to be from unvaccinated, or immunosuppressed patients. Reinfections with viral variants of concern were found in 3 patients more than 130 days from prior infections with a different viral clade. In 75 patients that had 2 or more high quality sequences, the acquisition of more substitutions or deletions was associated with lack of vaccination and longer time between the recovered viruses. Our study highlights the value of integrating genomic, laboratory, and clinical data for understanding the biology of SARS-CoV-2 as well as for setting a precedent for future epidemics and pandemics.

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SARS-CoV-2 Infections in mRNA Vaccinated Individuals are Biased for Viruses Encoding Spike E484K and Associated with Reduced Infectious Virus Loads that Correlate with Respiratory Antiviral IgG levels

Cited by 11 publications

References 30 publications

In vivo kinetics of SARS-CoV-2 infection and its relationship with a person’s infectiousness

In vivo kinetics of SARS-CoV-2 infection and its relationship with a person’s infectiousness

Adaptive immune responses in vaccinated patients with symptomatic SARS-CoV-2 Alpha infection

Large Scale SARS-CoV-2 Molecular Testing and Genomic Surveillance Reveal Prolonged Infections, Protracted RNA shedding, and Viral Reinfections

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