key: cord-0932703-8mwjrimz authors: Mattiuzzi, Camilla; Lippi, Giuseppe title: Primary COVID-19 vaccine cycle and booster doses efficacy: analysis of Italian nationwide vaccination campaign date: 2022-01-03 journal: Eur J Public Health DOI: 10.1093/eurpub/ckab220 sha: 76da28355b8972479f3ab887090878cac6ffd97e doc_id: 932703 cord_uid: 8mwjrimz We provide here an updated analysis of primary COVID-19 vaccination and vaccine booster doses efficacy, emerging from the ongoing Italian nationwide COVID-19 vaccination campaign. Primary COVID-19 vaccination efficacy was 76-92% within 6 months, decreasing to 34-80% after 6 months. Administration of vaccine booster doses decreased SARS-CoV-2 infections by 65%, COVID-19 related hospitalizations and deaths by 69% and 97% compared to vaccine efficacy after 6 months, but also decreased SARS-CoV-2 infections by 39% compared to vaccine efficacy within 6 months. These results suggest that COVID-19 vaccine booster doses are important for restoring vaccine efficacy and further limiting virus circulation. As brilliantly highlighted in many articles, such as that published by Zeegers Paget et al., 1 many important things have been learned nearly 2 years after the emergence of the coronavirus disease (COVID-19) pandemic outbreak, though several aspects remained unrevealed. Several lines of evidence now attest that physical measures (e.g., social distancing, face masking, and so forth) are only partially effective for preventing SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection and complications, 2 so that widespread COVID-19 vaccination shall be considered the most effective strategy for decreasing virus circulation and preventing or limiting the risk of developing severe COVID-19 illness. 3 Despite the efficacy of COVID-19 vaccines is now straightforward and unquestionable, even higher than that of vaccines used for preventing other respiratory infectious diseases such as Influenza, 4 waning immunity against SARS-CoV-2 has been widely reported, especially 4 to 6 months after completing the primary COVID-19 vaccination cycle, 5 so that there is ongoing debate as to whether additional vaccine booster doses may be necessary to restore the immune response to levels similar to or even greater than those achievable immediately after completing a primary COVID-19 vaccination. 5 This article is hence aimed at providing an updated analysis of primary COVID-19 vaccination and vaccine booster doses efficacy by analyzing data emerging from the ongoing Italian nationwide COVID-19 vaccination campaign. We downloaded and analytically reviewed the official statistics of the COVID-19 national integrated surveillance program, published and regularly updated by the Italian National Institute of Health (Istituto Superiore di Sanità, ISS; Last available update, November 19, 2021). 6 This bulletin contains comprehensive nationwide Software Ltd., Ostend, Belgium). Statistical significance was set at p<0.05. The study was carried out in accordance with Helsinki Declaration, under terms of relevant local legislation. The research was based on public ISS data, 6 so that Ethical Committee approval was unnecessary. As shown in table 1 (and Supplementary Figure 1 ), the cumulative primary COVID-19 vaccine cycle efficacy within 6 months from administration was effective to 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 reduce all SARS-CoV-2 infections by 76%, COVID-19 related hospitalizations by 87%, ICU admissions by 92% and deaths by 84%, respectively. After 6 months from completing the primary COVID-19 vaccine cycle the protection declined to 59% against the risk of developing SARS-CoV-2 infections, 52% against COVID-19 related hospitalizations and 34% against deaths, but remained considerably high, up to 80%, for preventing COVID-19 related ICU admissions. The cumulative efficacy of COVID-19 vaccine booster dose is summarized in Table 1 (and Supplementary Figure 1 ). Compared to COVID-19 vaccine efficacy recorded 6 months after completing the primary vaccination cycle, the administration of COVID-19 vaccine booster doses was effective to reduce SARS-CoV-2 infections by 65%, COVID-19 related hospitalizations by 69% and deaths by 97%. A trend towards reduction of COVID-19 related ICU admissions could also be observed (i.e., -67%), though failing to reach statistical significance. Notably, the efficacy of COVID-19 vaccine booster doses did not significantly differ from that recorded within 6 months after completing the primary COVID-19 vaccination (Table 1) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 confirmed to be over 84%, and is also associated with a remarkable 76% reduced risk of developing SARS-CoV-2 infection. Despite primary vaccine efficacy at 6 months after completing the primary vaccination cycle remains sizeable, a substantial decline could be observed when all endpoints were compared to those observed within 6 months after primary vaccination (Table 1) . Such reduction seems however completely reversible by administering COVID-19 vaccine booster doses, which are seemingly effective to generate a cumulative protection very similar (or even better) than that achievable immediately after completing primary COVID-19 vaccination. Notably, the administration of additional COVID-19 vaccine booster doses seems also effective to substantially diminish the risk of developing SARS-CoV-2 infection compared to immediate (i.e., within 6 months) primary vaccination efficacy, with such efficacy further increasing to 65% in people who had received a primary COVID-19 vaccination over 6 months before. This aspect is of paramount importance, since reducing the circulation of the virus in the community not only remains a primary target of SARS-CoV-2 eradication campaigns, but may also generate additional advantages such as reducing the likelihood of emergence of new variants and the risk of mandating social limitations such as lockdowns or partial closures. 9 Finally, adjunctive vaccine doses will probably become almost unavoidable for restoring COVID-19 vaccine efficacy against emerging and highly mutated SARS-CoV-2 variants, such as Conflicts of interest: None declared. This article received no funding. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 http://mc.manuscriptcentral.com/ejph Manuscripts submitted to European Journal of Public Health 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Table 1 . Efficacy of primary COVID-19 vaccine cycle and vaccine boosters from the ongoing Italian nationwide COVID-19 vaccination campaign. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Manuscripts submitted to European Journal of Public Health 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 COVID-19: What have we learned? What are the public health challenges? Social distancing measures: barriers to their implementation and how they can be overcome -a systematic review COVID-19 vaccines a global public good? Moving past the rhetoric and making work of sharing intellectual property rights, know-how and technology The Future of SARS-CoV-2 Vaccination -Lessons from Influenza Waning Immunity after the BNT162b2 Vaccine in Israel Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe outcomes in Israel: an observational study SARS-CoV-2 variants, spike mutations and immune escape Plasma neutralization properties of the SARS-CoV-2 Omicron variant Reduced Neutralization of SARS-CoV-2 Omicron Variant by Vaccine Sera and monoclonal antibodies