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      Viral load dynamics of SARS-CoV-2 Delta and Omicron variants following multiple vaccine doses and previous infection

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          Abstract

          An important aspect of vaccine effectiveness is its impact on pathogen transmissibility, harboring major implications for public health policies. As viral load is a prominent factor affecting infectivity, its laboratory surrogate, qRT-PCR cycle threshold (Ct), can be used to investigate the infectivity-related component of vaccine effectiveness. While vaccine waning has previously been observed for viral load during the Delta wave, less is known regarding how Omicron viral load is affected by vaccination status, and whether vaccine-derived and natural infection protection are sustained. By analyzing results of more than 460,000 individuals, we show that while recent vaccination reduces Omicron viral load, its effect wanes rapidly. In contrast, a significantly slower waning rate is demonstrated for recovered COVID-19 individuals. Thus, while the vaccine is effective in decreasing morbidity and mortality, its relatively small effect on transmissibility of Omicron (as measured here by Ct) and its rapid waning call for reassessment of future booster campaigns.

          Abstract

          COVID vaccination can reduce virus levels in breakthrough infections, which in turn may reduce transmission of the virus. By using qRT-PCR cycle threshold as a surrogate of virus levels, the authors here show that this positive effect of vaccination wanes relatively quickly for Omicron breakthrough infection.

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          BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting

          Noa Dagan, Noam Barda, Eldad Kepten … (2021)
          Abstract Background As mass vaccination campaigns against coronavirus disease 2019 (Covid-19) commence worldwide, vaccine effectiveness needs to be assessed for a range of outcomes across diverse populations in a noncontrolled setting. In this study, data from Israel’s largest health care organization were used to evaluate the effectiveness of the BNT162b2 mRNA vaccine. Methods All persons who were newly vaccinated during the period from December 20, 2020, to February 1, 2021, were matched to unvaccinated controls in a 1:1 ratio according to demographic and clinical characteristics. Study outcomes included documented infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), symptomatic Covid-19, Covid-19–related hospitalization, severe illness, and death. We estimated vaccine effectiveness for each outcome as one minus the risk ratio, using the Kaplan–Meier estimator. Results Each study group included 596,618 persons. Estimated vaccine effectiveness for the study outcomes at days 14 through 20 after the first dose and at 7 or more days after the second dose was as follows: for documented infection, 46% (95% confidence interval [CI], 40 to 51) and 92% (95% CI, 88 to 95); for symptomatic Covid-19, 57% (95% CI, 50 to 63) and 94% (95% CI, 87 to 98); for hospitalization, 74% (95% CI, 56 to 86) and 87% (95% CI, 55 to 100); and for severe disease, 62% (95% CI, 39 to 80) and 92% (95% CI, 75 to 100), respectively. Estimated effectiveness in preventing death from Covid-19 was 72% (95% CI, 19 to 100) for days 14 through 20 after the first dose. Estimated effectiveness in specific subpopulations assessed for documented infection and symptomatic Covid-19 was consistent across age groups, with potentially slightly lower effectiveness in persons with multiple coexisting conditions. Conclusions This study in a nationwide mass vaccination setting suggests that the BNT162b2 mRNA vaccine is effective for a wide range of Covid-19–related outcomes, a finding consistent with that of the randomized trial.
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            Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months

            Einav Levin, Yaniv Lustig, Carmit Cohen … (2021)
            Background Despite high vaccine coverage and effectiveness, the incidence of symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been increasing in Israel. Whether the increasing incidence of infection is due to waning immunity after the receipt of two doses of the BNT162b2 vaccine is unclear. Methods We conducted a 6-month longitudinal prospective study involving vaccinated health care workers who were tested monthly for the presence of anti-spike IgG and neutralizing antibodies. Linear mixed models were used to assess the dynamics of antibody levels and to determine predictors of antibody levels at 6 months. Results The study included 4868 participants, with 3808 being included in the linear mixed-model analyses. The level of IgG antibodies decreased at a consistent rate, whereas the neutralizing antibody level decreased rapidly for the first 3 months with a relatively slow decrease thereafter. Although IgG antibody levels were highly correlated with neutralizing antibody titers (Spearman’s rank correlation between 0.68 and 0.75), the regression relationship between the IgG and neutralizing antibody levels depended on the time since receipt of the second vaccine dose. Six months after receipt of the second dose, neutralizing antibody titers were substantially lower among men than among women (ratio of means, 0.64; 95% confidence interval [CI], 0.55 to 0.75), lower among persons 65 years of age or older than among those 18 to less than 45 years of age (ratio of means, 0.58; 95% CI, 0.48 to 0.70), and lower among participants with immunosuppression than among those without immunosuppression (ratio of means, 0.30; 95% CI, 0.20 to 0.46). Conclusions Six months after receipt of the second dose of the BNT162b2 vaccine, humoral response was substantially decreased, especially among men, among persons 65 years of age or older, and among persons with immunosuppression.
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              Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel

              Yinon Bar-On, Yair Goldberg, Micha Mandel … (2021)
              Background On July 30, 2021, the administration of a third (booster) dose of the BNT162b2 messenger RNA vaccine (Pfizer–BioNTech) was approved in Israel for persons who were 60 years of age or older and who had received a second dose of vaccine at least 5 months earlier. Data are needed regarding the effect of the booster dose on the rate of confirmed coronavirus 2019 disease (Covid-19) and the rate of severe illness. Methods We extracted data for the period from July 30 through August 31, 2021, from the Israeli Ministry of Health database regarding 1,137,804 persons who were 60 years of age or older and had been fully vaccinated (i.e., had received two doses of BNT162b2) at least 5 months earlier. In the primary analysis, we compared the rate of confirmed Covid-19 and the rate of severe illness between those who had received a booster injection at least 12 days earlier (booster group) and those who had not received a booster injection (nonbooster group). In a secondary analysis, we evaluated the rate of infection 4 to 6 days after the booster dose as compared with the rate at least 12 days after the booster. In all the analyses, we used Poisson regression after adjusting for possible confounding factors. Results At least 12 days after the booster dose, the rate of confirmed infection was lower in the booster group than in the nonbooster group by a factor of 11.3 (95% confidence interval [CI], 10.4 to 12.3); the rate of severe illness was lower by a factor of 19.5 (95% CI, 12.9 to 29.5). In a secondary analysis, the rate of confirmed infection at least 12 days after vaccination was lower than the rate after 4 to 6 days by a factor of 5.4 (95% CI, 4.8 to 6.1). Conclusions In this study involving participants who were 60 years of age or older and had received two doses of the BNT162b2 vaccine at least 5 months earlier, we found that the rates of confirmed Covid-19 and severe illness were substantially lower among those who received a booster (third) dose of the BNT162b2 vaccine.
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                Author and article information

                Contributors
                Naama M. Kopelman:
                ORCID: http://orcid.org/0000-0002-9091-9517
                naamako@hit.ac.il
                Journal
                Journal ID (nlm-ta): Nat Commun
                Journal ID (iso-abbrev): Nat Commun
                Title: Nature Communications
                Publisher: Nature Publishing Group UK (London )
                ISSN (Electronic): 2041-1723
                Publication date (Electronic): 7 November 2022
                Publication date PMC-release: 7 November 2022
                Publication date Collection: 2022
                Volume: 13
                Electronic Location Identifier: 6706
                Affiliations
                [1 ]GRID grid.413795.d, ISNI 0000 0001 2107 2845, The Gertner Institute for Epidemiology & Health Policy Research, , Sheba Medical Center, ; Ramat Gan, Israel
                [2 ]GRID grid.417597.9, ISNI 0000 0000 9534 2791, Department of Computer Science, , Holon Institute of Technology, ; Holon, Israel
                [3 ]GRID grid.413795.d, ISNI 0000 0001 2107 2845, Clinical Microbiology, , Sheba Medical Center, ; Ramat Gan, Israel
                [4 ]GRID grid.12136.37, ISNI 0000 0004 1937 0546, Sackler Faculty of Medicine, Tel-Aviv University, ; Tel-Aviv, Israel
                Author information
                http://orcid.org/0000-0002-9091-9517
                Article
                Publisher ID: 33096
                DOI: 10.1038/s41467-022-33096-0
                PMC ID: 9640564
                PubMed ID: 36344489
                SO-VID: 17866e99-119f-4ed6-bc31-a2fc010c4f38
                Copyright © © The Author(s) 2022
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 2 March 2022
                Date accepted : 1 September 2022
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100003977, Israel Science Foundation (ISF);
                Award ID: 3663/19
                Award ID: 3963/19
                Award Recipient :
                Categories
                Subject: Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2022

                ScienceOpen disciplines: Uncategorized
                Keywords: viral infection,sars-cov-2,rna vaccines,epidemiology
                Data availability:
                ScienceOpen disciplines: Uncategorized
                Keywords: viral infection, sars-cov-2, rna vaccines, epidemiology

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