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Academic papers

Most Recent




  • Omicron-associated changes in SARS-CoV-2 symptoms in the United Kingdom [Clinical Infectious Diseases, 3 August 2022] [MedrXiv, 11 January 2022]

    • Key findings: in this study of predominantly mild community-based infection, Omicron was associated with fewer lower and more upper respiratory tract symptoms.
    • Increases in sore throat (also common in symptomatic PCR-negative participants), and the marked reduction in the previously highest specificity symptoms, namely loss of taste/smell, mean Omicron is harder to detect with symptom-based testing algorithms.

    Effectiveness of vaccines in preventing new infections and effects on behaviours

      • Correlates of protection against SARS-CoV-2 Omicron variant and anti-spike antibody responses after a third/booster vaccination or breakthrough infection in the UK general population [Nature Communications, May 2023; MedrXiv, 30 November 2022]
        • Key findings: higher anti-spike IgG antibody levels were associated with increased protection against Omicron BA.4/5 infection - breakthrough infections were associated with higher levels of protection at any given antibody level than booster vaccinations.
        • Breakthrough infections generated similar antibody levels to third/booster vaccinations, and the subsequent declines in antibody levels were similar to or slightly slower than those after third/booster vaccinations.
        • Taken together our findings show that breakthrough infection provides longer lasting protection against further infections than booster vaccinations.
          • For example, considering antibody levels associated with 67% protection against infection, a third/booster vaccination did not provide long-lasting protection, while a Delta/Omicron BA.1 breakthrough infection could provide 5-10 months of protection against Omicron BA.4/5 reinfection.
          • 50-60% of the vaccinated UK population with a breakthrough infection would still be protected by the end of 2022, compared to <15% of the triple-vaccinated UK population without previous infection
        Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK [Nature Medicine, 15 October 2021] [MedrXiv, 24 August 2021] [preliminary data for SAGE, 22 July 2021]
        • Key findings: With Delta, two doses of Pfizer-BioNTech and Oxford-AstraZeneca vaccines still offer good protection against new infections, but effectiveness is reduced compared with Alpha.
        • People who had been vaccinated after already being infected with COVID-19 had even more protection than vaccinated individuals who had not had COVID-19 before and those who had had COVID-19 but not been vaccinated. 
        • Two doses of Pfizer-BioNTech have greater initial effectiveness against new COVID-19 infections, but this declines faster compared with two doses of Oxford-AstraZeneca.
        • Although vaccination reduced the chance of getting COVID-19, the smaller number of Delta infections after two vaccine doses had similar peak levels of virus to those in unvaccinated people; with the Alpha variant, peak virus levels in those infected post-vaccination were much lower.
        • Also see our press release  and blog.

      Changes in antibody levels after vaccination and natural infection

      • The challenge of limited vaccine supplies: impact of prior infection on anti-spike IgG antibody trajectories after a single COVID-19 vaccination [MedrXiv, 8 December 2021; accepted by Nature Communications] 

        • A single vaccination in previously infected individuals generates similar initial and subsequent antibody responses to two vaccinations in those without prior infection.
        • Prior infection significantly boosted antibody responses for all three vaccines, producing a higher peak level and longer half-life, and a response comparable to those without prior infection receiving two vaccinations.
        • In those with prior infection, median time above the positivity threshold was estimated to last for >1 year after the first dose.
        • Single-dose vaccination targeted to those previously infected may provide protection in populations with high rates of previous infection faced with limited vaccine supply, as an interim measure while vaccine campaigns are scaled up.
      • Antibody responses and correlates of protection in the general population after two doses of the ChAdOx1 or BNT162b2 vaccines [Nature Medicine, 14 February 2022; MedrXiv, 15 November 2021; previous version 16 September 2021; preliminary data for SAGE, 22 July 2021]
        • Key findingsIn 222,493 individuals, we found significant boosting of anti-spike IgG by second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2.
        • After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Antibody levels declined faster at older ages and in males with BNT162b2, but declines were similar across ages and sexes with ChAdOX1. Prior infection significantly increased antibody half-life with both vaccines.
        • Anti-spike IgG levels were associated with protection from infection after vaccination and, to an even greater degree, after prior infection. At least 67% protection against infection was estimated to last for 2-3 months after two ChAdOx1 doses and 6-15 months after two BNT162b2 doses in those without prior infection, and 1-2 years for those unvaccinated after natural infection. 
      • Anti-spike antibody response to natural SARS-CoV-2 infection in the general population [Nature Communications 29 October 2021, MedrXiv, 5 July 2021]

        • Key findings24% of 7,256 participants who had positive swab SARS-CoV-2 PCR tests were ‘non-responders’, not developing anti-spike antibodies. These seronegative non-responders were older, had higher SARS-CoV-2 cycle threshold values during infection (i.e. lower viral burden), and less frequently reported any symptoms.
        • Among those who seroconverted, the estimated anti-spike IgG peak level was 7.3-fold higher than the level previously associated with 50% protection against reinfection, with higher peak levels in older participants and those of non-white ethnicity. The estimated anti-spike IgG half-life was 184 days, being longer in females and those of white ethnicity. Antibody levels associated with protection against reinfection likely last 1.5-2 years on average, with levels associated with protection from severe infection present for several years. 
      • Antibody responses to SARS-CoV-2 vaccines in 45,965 adults from the general population of the United Kingdom [Nature Microbiology, 22 July 2021] [Original MedrXiv preprint, 23 April 2021]

      Characteristics of those testing positive and symptoms

      Variants and trends over calendar time