Viral Dynamics of SARS-CoV-2 Variants in Vaccinated and Unvaccinated Persons

Kissler, Stephen M; Fauver, Joseph R.; Mack, Christina; Tai, Caroline G.; Breban, Mallery I.; Watkins, Anne E.; Samant, Radhika M; Anderson, Deverick J.; Metti, Jessica; Khullar, Gaurav; Baits, Rachel; MacKay, Matthew; Salgado, Daisy; Baker, Tim; Dudley, Joel T.; Mason, Christopher E.; Ho, David D.; Grubaugh, Nathan D.; Grad, Yonatan H.

doi:10.1056/nejmc2102507

Cited by 253 publications

(294 citation statements)

References 4 publications

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“…The proliferation phase (day 0 to 7), where the viral load increases, does not seem to substantially differ neither between asymptomatic and symptomatic individuals nor between vaccinated and unvaccinated individuals. The peak viral concentration is reached in about 7 days after the infection [ 2 , [8] , [9] , [10] ]. The viral load declines slower, on average, in symptomatic individuals [2] , with more severe infections taking significantly longer to clear [8] .…”

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confidence: 99%

“…Conversely, in vaccinated individuals, the clearance is faster than in unvaccinated individuals, regardless of the presence of symptoms. The faster clearance time of asymptomatic or vaccinated individuals [ 2 , 9 , 11 ] may explain the reported lower peak C t values in studies with less dense sampling of the asymptomatic individuals [ 12 , 13 ].…”

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confidence: 99%

“…The “infectious period” is shown in orange in Figure 1 and usually lasts 5 to 8 days [8] , [9] , [10] . The majority of new infections occur before or soon after the peak viral load is reached [ 14 , 15 ].…”

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confidence: 99%

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SARS-CoV-2 rapid antigen tests provide benefits for epidemic control – observations from Austrian schools

Polechová¹,

Johnson²,

Payne³

et al. 2022

Journal of Clinical Epidemiology

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Objective : This paper motivates and justifies the use of antigen tests for epidemic control as distinct from a diagnostic test. Study Design and Setting : We discuss the relative advantages of antigen and PCR tests, summarising evidence from both the literature as well as Austrian schools, which conducted frequent, mass rapid antigen testing during the spring of 2021. While our report on testing predates Delta, we have updated the review with recent data on viral loads in breakthrough infections and more information about testing efficacy, especially in children. Results : Rapid antigen tests detect proteins at the surface of virus particles, identifying the disease during its infectious phase. In contrast, PCR tests detect viral genomes: they can thus diagnose COVID-19 before the infectious phase but also react to remnants of the virus genome, even weeks after live virus ceases to be detectable in the respiratory tract. Furthermore, the logistics for administering the tests are different. Large-scale rapid antigen testing in Austrian schools showed low false-positive rates along with an approximately 10% lower effective reproduction number in the tested cohort. Conclusion : Using antigen tests at least 2-3 times per week could become a powerful tool to suppress the COVID-19 pandemic.

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SARS-CoV-2 rapid antigen tests provide benefits for epidemic control – observations from Austrian schools

Polechová¹,

Johnson²,

Payne³

et al. 2022

Journal of Clinical Epidemiology

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“…Previous studies show viral growth rates and peak viral loads are comparable between vaccinated and unvaccinated individuals following SARS-CoV-2 infection, although vaccinated subjects show a faster viral clearance after the peak ( 8, 9 ). A major question is to identify which immune responses mediate rapid viral clearance and if this is mechanistically linked to protection from severe infection in vaccinated subjects.…”

Section: Figurementioning

confidence: 87%

“…Studies of intranasal SARS-CoV-2 challenge after intramuscular vaccination of non-human primates ( 27, 28 ) indicate a temporal disconnect in recall kinetics between anatomical compartments, with both SARS-CoV-2 specific and non-specific IgG levels increasing in the bronchoalveolar lavage fluid (although this may reflect inflammation-induced exudation) prior to antibody recall in the serum. Additionally, the accelerated viral clearance observed in vaccinated individuals ( 8, 9 ) is based on analysis of nasopharyngeal samples, which may not necessarily reflect the viral loads or kinetics of the lower respiratory tract.…”

Section: Figurementioning

confidence: 99%

Dynamics of immune recall following SARS-CoV-2 vaccination or breakthrough infection

Koutsakos

Lee

Reynaldi

et al. 2021

Preprint

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Vaccination against SARS-CoV-2 results in protection from acquisition of infection as well as improved clinical outcomes even if infection occurs, likely reflecting a combination of residual vaccine-elicited immunity and the recall of immunological memory. Here, we define the early kinetics of spike-specific humoral and T cell immunity after vaccination of seropositive individuals, and after breakthrough infection in vaccinated individuals. Intensive and early longitudinal sampling reveals the timing and magnitude of recall, with the phenotypic activation of B cells preceding an increase in neutralizing antibody titres. In breakthrough infections, the delayed kinetics of humoral immune recall provides a mechanism for the lack of early control of viral replication but likely underpins accelerated viral clearance and the protective effects of vaccination against severe COVID-19.

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Association Between 3 Doses of mRNA COVID-19 Vaccine and Symptomatic Infection Caused by the SARS-CoV-2 Omicron and Delta Variants

Accorsi

Britton

Fleming-Dutra

et al. 2022

JAMA

625

576

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IMPORTANCEAssessing COVID-19 vaccine performance against the rapidly spreading SARS-CoV-2 Omicron variant is critical to inform public health guidance.OBJECTIVE To estimate the association between receipt of 3 doses of Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 vaccine and symptomatic SARS-CoV-2 infection, stratified by variant (Omicron and Delta). DESIGN, SETTING, AND PARTICIPANTSA test-negative case-control analysis among adults 18 years or older with COVID-like illness tested December 10, 2021, through January 1, 2022, by a national pharmacy-based testing program (4666 COVID-19 testing sites across 49 US states).EXPOSURES Three doses of mRNA COVID-19 vaccine (third dose Ն14 days before test and Ն6 months after second dose) vs unvaccinated and vs 2 doses 6 months or more before test (ie, eligible for a booster dose). MAIN OUTCOMES AND MEASURESAssociation between symptomatic SARS-CoV-2 infection (stratified by Omicron or Delta variants defined using S-gene target failure) and vaccination (3 doses vs unvaccinated and 3 doses vs 2 doses). Associations were measured with multivariable multinomial regression. Among cases, a secondary outcome was median cycle threshold values (inversely proportional to the amount of target nucleic acid present) for 3 viral genes, stratified by variant and vaccination status.RESULTS Overall, 23 391 cases (13 098 Omicron; 10 293 Delta) and 46 764 controls were included (mean age, 40.3 [SD, 15.6] years; 42 050 [60.1%] women). Prior receipt of 3 mRNA vaccine doses was reported for 18.6% (n = 2441) of Omicron cases, 6.6% (n = 679) of Delta cases, and 39.7% (n = 18 587) of controls; prior receipt of 2 mRNA vaccine doses was reported for 55.3% (n = 7245), 44.4% (n = 4570), and 41.6% (n = 19 456), respectively; and being unvaccinated was reported for 26.0% (n = 3412), 49.0% (n = 5044), and 18.6% (n = 8721), respectively. The adjusted odds ratio for 3 doses vs unvaccinated was 0.33 (95% CI, 0.31-0.35) for Omicron and 0.065 (95% CI, 0.059-0.071) for Delta; for 3 vaccine doses vs 2 doses the adjusted odds ratio was 0.34 (95% CI, 0.32-0.36) for Omicron and 0.16 (95% CI, 0.14-0.17) for Delta. Median cycle threshold values were significantly higher in cases with 3 doses vs 2 doses for both Omicron and Delta (

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Viral Dynamics of SARS-CoV-2 Variants in Vaccinated and Unvaccinated Persons

Cited by 253 publications

References 4 publications

SARS-CoV-2 rapid antigen tests provide benefits for epidemic control – observations from Austrian schools

SARS-CoV-2 rapid antigen tests provide benefits for epidemic control – observations from Austrian schools

Dynamics of immune recall following SARS-CoV-2 vaccination or breakthrough infection

Association Between 3 Doses of mRNA COVID-19 Vaccine and Symptomatic Infection Caused by the SARS-CoV-2 Omicron and Delta Variants

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