Shedding of infectious SARS-CoV-2 despite vaccination

The SARS-CoV-2 Delta Variant of Concern is highly transmissible and contains mutations that confer partial immune escape. The emergence of Delta in North America caused the first surge in COVID-19 cases after SARS-CoV-2 vaccines became widely available. To determine whether individuals infected despite vaccination might be capable of transmitting SARS-CoV-2, we compared RT-PCR cycle threshold (Ct) data from 20,431 test-positive anterior nasal swab specimens from fully vaccinated (n = 9,347) or unvaccinated (n = 11,084) individuals tested at a single commercial laboratory during the interval 28 June– 1 December 2021 when Delta variants were predominant. We observed no significant effect of vaccine status alone on Ct value, nor when controlling for vaccine product or sex. Testing a subset of low-Ct (<25) samples, we detected infectious virus at similar rates, and at similar titers, in specimens from vaccinated and unvaccinated individuals. These data indicate that vaccinated individuals infected with Delta variants are capable of shedding infectious SARS-CoV-2 and could play a role in spreading COVID-19.

[1]  Amy L Riegelman.  Research Square , 2022, The Charleston Advisor.

[2]  D. McManus,et al.  Daily longitudinal sampling of SARS-CoV-2 infection reveals substantial heterogeneity in infectiousness , 2022, Nature Microbiology.

[3]  Cory C. Funk,et al.  Risk factors for severe COVID-19 differ by age for hospitalized adults , 2022, Scientific Reports.

[4]  S. Crovella,et al.  Comparison between nucleic acid amplification tests, antigen immunofluorescence assay, and in vitro infectivity in SARS-CoV-2 diagnosis , 2022, Brazilian Journal of Microbiology.

[5]  N. Peek,et al.  Mortality in People with Type 2 Diabetes Following SARS-CoV-2 Infection: A Population Level Analysis of Potential Risk Factors , 2022, Diabetes Therapy.

[6]  J. McLaughlin,et al.  Durability of BNT162b2 vaccine against hospital and emergency department admissions due to the omicron and delta variants in a large health system in the USA: a test-negative case–control study , 2022, The Lancet Respiratory Medicine.

[7]  M. Sughayer,et al.  Comparison of the effectiveness and duration of anti-RBD SARS-CoV-2 IgG antibody response between different types of vaccines: Implications for vaccine strategies , 2022, Vaccine.

[8]  S. Doron,et al.  Cycle threshold values and SARS‐CoV‐2: Relationship to demographic characteristics and disease severity , 2022, Journal of medical virology.

[9]  F. Meloni,et al.  Neutralizing Antibodies Responses against SARS-CoV-2 in a Sardinian Cohort Group Up to 9 Months after BNT162b2 Vaccination , 2022, Vaccines.

[10]  A. Riva,et al.  Low‐frequency variants in mildly symptomatic vaccine breakthrough infections presents a doubled‐edged sword , 2022, Journal of medical virology.

[11]  S. Cramer,et al.  Association of frailty, age, and biological sex with SARS-CoV-2 mRNA vaccine-induced immunity in older adults , 2022, medRxiv.

[12]  M. Exline,et al.  Clinical severity of, and effectiveness of mRNA vaccines against, covid-19 from omicron, delta, and alpha SARS-CoV-2 variants in the United States: prospective observational study , 2022, BMJ.

[13]  K. Nilgiriwala,et al.  Impact of Delta and Vaccination on SARS-CoV-2 transmission risk: Lessons for Emerging Breakthrough infections , 2022, medRxiv.

[14]  C. Lambert,et al.  Decline of Humoral and Cellular Immune Responses Against SARS-CoV-2 6 Months After Full BNT162b2 Vaccination in Hospital Healthcare Workers , 2022, Frontiers in Immunology.

[15]  R. Irizarry,et al.  Effectiveness estimates of three COVID-19 vaccines based on observational data from Puerto Rico , 2022, The Lancet Regional Health - Americas.

[16]  B. Nunes,et al.  Comparative complete scheme and booster effectiveness of COVID‐19 vaccines in preventing SARS‐CoV‐2 infections with SARS‐CoV‐2 Omicron (BA.1) and Delta (B.1.617.2) variants: A case–case study based on electronic health records , 2022, medRxiv.

[17]  J. Kim,et al.  The Safety of mRNA-1273, BNT162b2 and JNJ-78436735 COVID-19 Vaccines: Safety Monitoring for Adverse Events Using Real-World Data , 2022, Vaccines.

[18]  M. Dimopoulos,et al.  Comparison of Neutralizing Antibody Responses at 6 Months Post Vaccination with BNT162b2 and AZD1222 , 2022, Biomedicines.

[19]  S. Zeger,et al.  Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression , 2022, The Lancet.

[20]  D. Zeng,et al.  Effectiveness of Covid-19 Vaccines over a 9-Month Period in North Carolina , 2022, The New England journal of medicine.

[21]  G. Alter,et al.  Durability and cross-reactivity of SARS-CoV-2 mRNA vaccine in adolescent children , 2022, medRxiv.

[22]  T. Peto,et al.  Effect of Covid-19 Vaccination on Transmission of Alpha and Delta Variants , 2022, The New England journal of medicine.

[23]  Xiaoqian Jiang,et al.  Factors Associated With COVID-19 Death in the United States: Cohort Study , 2021, JMIR public health and surveillance.

[24]  S. Haneuse,et al.  Duration of viral shedding and culture positivity with postvaccination SARS-CoV-2 delta variant infections , 2021, JCI insight.

[25]  S. Kissler,et al.  Viral Dynamics of SARS-CoV-2 Variants in Vaccinated and Unvaccinated Persons , 2021, The New England journal of medicine.

[26]  Lindsay N. Carpp,et al.  Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial , 2021, Science.

[27]  R. Lin,et al.  Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine breakthrough infections: a multicentre cohort study , 2021, Clinical Microbiology and Infection.

[28]  I. Diamond,et al.  Effect of Delta variant on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK , 2021, Nature Medicine.

[29]  A. Fasano,et al.  Virologic features of SARS-CoV-2 infection in children. , 2021, The Journal of infectious diseases.

[30]  T. Peto,et al.  The impact of SARS-CoV-2 vaccination on Alpha and Delta variant transmission , 2021, medRxiv.

[31]  M. Holodniy,et al.  COVID-19 Vaccine Breakthrough Infections in the Veterans Health Administration. , 2021, medRxiv.

[32]  Michael I. Mandel,et al.  Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel , 2021, The New England journal of medicine.

[33]  O. Mor,et al.  Nosocomial outbreak caused by the SARS-CoV-2 Delta variant in a highly vaccinated population, Israel, July 2021 , 2021, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[34]  I. Diamond,et al.  Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK , 2021, medRxiv.

[35]  Catherine M. Brown,et al.  Outbreak of SARS-CoV-2 Infections, Including COVID-19 Vaccine Breakthrough Infections, Associated with Large Public Gatherings — Barnstable County, Massachusetts, July 2021 , 2021, MMWR. Morbidity and mortality weekly report.

[36]  V. Lee,et al.  Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine breakthrough infections: a multicentre cohort study , 2021, Clinical Microbiology and Infection.

[37]  M. Lipsitch,et al.  Covid-19 Breakthrough Infections in Vaccinated Health Care Workers , 2021, The New England journal of medicine.

[38]  R. Myers,et al.  Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant , 2021, The New England journal of medicine.

[39]  M. Churpek,et al.  The impact of vaccination to control COVID-19 burden in the United States: A simulation modeling approach , 2021, PloS one.

[40]  F. Rey,et al.  Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization , 2021, Nature.

[41]  N. Ikonen,et al.  An outbreak caused by the SARS-CoV-2 Delta variant (B.1.617.2) in a secondary care hospital in Finland, May 2021 , 2021, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[42]  A. Lansky,et al.  Decreases in COVID-19 Cases, Emergency Department Visits, Hospital Admissions, and Deaths Among Older Adults Following the Introduction of COVID-19 Vaccine — United States, September 6, 2020–May 1, 2021 , 2021, MMWR. Morbidity and mortality weekly report.

[43]  Hannah R. Meredith,et al.  Modeling of Future COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Rates and Nonpharmaceutical Intervention Scenarios — United States, April–September 2021 , 2021, MMWR. Morbidity and mortality weekly report.

[44]  William L. Hamilton,et al.  SARS-CoV-2 B.1.617.2 Delta variant replication, sensitivity to neutralising antibodies and vaccine breakthrough , 2021 .

[45]  A. Al-Zalabani,et al.  Association of Viral Load in SARS-CoV-2 Patients With Age and Gender , 2021, Frontiers in Medicine.

[46]  H. Schuitemaker,et al.  Interim Results of a Phase 1–2a Trial of Ad26.COV2.S Covid-19 Vaccine , 2021, The New England journal of medicine.

[47]  Kathryn Brillinger,et al.  Felis catus System : Terrestrial Kingdom Phylum Class Order Family Animalia Chordata Mammalia Carnivora Felidae , 2022 .

[48]  OUP accepted manuscript , 2021, International Journal Of Epidemiology.

[49]  Aditya Sharma,et al.  COVID-19 Infections Among Healthcare Personnel in the United States Veterans Health Administration, March - August, 2020. , 2020, Journal of occupational and environmental medicine.

[50]  E. Walsh,et al.  Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates , 2020, The New England journal of medicine.

[51]  E. Petinaki,et al.  Children and Adolescents With SARS-CoV-2 Infection , 2020, The Pediatric infectious disease journal.

[52]  P. Shi,et al.  In vivo antiviral host transcriptional response to SARS-CoV-2 by viral load, sex, and age , 2020, PLoS biology.

[53]  A. Charlett,et al.  Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020 , 2020, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[54]  T. Heald-Sargent,et al.  Age-Related Differences in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Levels in Patients With Mild to Moderate Coronavirus Disease 2019 (COVID-19). , 2020, JAMA pediatrics.

[55]  J. Mascola,et al.  An mRNA Vaccine against SARS-CoV-2 — Preliminary Report , 2020, The New England journal of medicine.

[56]  G. Biele,et al.  An analysis of SARS-CoV-2 viral load by patient age , 2020, medRxiv.

[57]  Anne Kimball,et al.  Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility , 2020, The New England journal of medicine.

[58]  P. Vollmar,et al.  Virological assessment of hospitalized patients with COVID-2019 , 2020, Nature.

[59]  R. Irizarry.  ggplot2 , 2019, Introduction to Data Science.

[60]  Hadley Wickham,et al.  ggplot2 - Elegant Graphics for Data Analysis (2nd Edition) , 2017 .