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2.
Front Immunol ; 13: 827306, 2022.
Article in English | MEDLINE | ID: covidwho-1789384

ABSTRACT

Background: Effective vaccines against coronavirus disease 2019 (COVID-19) are available worldwide; however, the longevity of vaccine effectiveness is not known. Objective: We performed a prospective observational study to assess the antibody response of healthcare workers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after BNT162b2 mRNA COVID-19 vaccination. Methods: SARS-CoV-2 neutralizing antibody (nAb) and spike (S) protein-IgG (S-IgG) antibody titers were examined in participants who received two doses of the BNT162b2 mRNA COVID-19 vaccine in a single center between March 1, 2021, and October 11, 2021. Antibody levels were analyzed at four times: before vaccination (visit 1), 4 weeks after the first vaccination (visit 2), 3 months after the second vaccination (visit 3), and 6 months after the second vaccination (visit 4). Results: A total of 249 healthcare workers at Jeju National University Hospital were enrolled in this study, and 982 blood samples were analyzed. The mean age was 38.1 ± 9.5 years, and 145 (58.2%) participants were females. Positive nAbs (inhibition rates ≥ 20%) were measured in 166/249 (66.7%) subjects at visit 2, 237/243 (97.5%) subjects at visit 3, and 150/237 (63.3%) subjects at visit 4. A S-IgG (≥50 AU/mL) positivity was detected in 246/249 (98.8%) subjects at visit 1, and all participants had positive S-IgG antibody levels at visits 3 and 4 after being fully vaccinated. Further analysis of S-IgG levels revealed a median quantitative antibody level of 1275.1 AU/mL (interquartile range [IQR] 755.5-2119.0) at visit 2, 2765.9 AU/mL (IQR 1809.8-4138.4) at visit 3, and 970.1 AU/mL (IQR 606.0-1495.9) at visit 4. Patient characteristics, such as age, body mass index, and comorbidity, had no relationship with nAb or S-IgG levels at any of the visits. Considering the change in antibody levels over time, both nAb and S-IgG levels at visit 4 decreased compared with the corresponding levels at visit 3. No evidence of SARS-CoV-2 infection was found among any of the participants throughout the study. Conclusions: The BNT162b2 mRNA vaccine was effective in protecting healthcare personnel working in COVID-19-related departments. While the level of S-IgG antibodies was maintained for 6 months after the second vaccination, nAb levels waned over this 6-month period, indicating the need for a booster vaccination in some healthcare workers 6 months after full vaccination. Herein, we suggest that further studies are needed to evaluate the need for an interval of booster vaccination after full vaccination.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , SARS-CoV-2/immunology , /statistics & numerical data , Adult , Aged , Antibody Formation/immunology , COVID-19/prevention & control , Female , Health Personnel/statistics & numerical data , Humans , Immunization, Secondary , Immunoglobulin G/blood , Immunologic Tests , Male , Middle Aged , Prospective Studies , Republic of Korea , Spike Glycoprotein, Coronavirus/immunology , Young Adult
3.
Nat Commun ; 13(1): 1971, 2022 Apr 13.
Article in English | MEDLINE | ID: covidwho-1788288

ABSTRACT

Israel began administering a BNT162b2 booster dose to restore protection following the waning of the 2-dose vaccine. Biological studies have shown that a "fresh" booster dose leads to increased antibody levels compared to a fresh 2-dose vaccine, which may suggest increased effectiveness. To compare the real-world effectiveness of a fresh (up to 60 days) booster dose with that of a fresh 2-dose vaccine, we took advantage of a quasi-experimental study that compares populations that were eligible to receive the vaccine at different times due to age-dependent policies. Specifically, we compared the confirmed infection rates in adolescents aged 12-14 (215,653 individuals) who received the 2-dose vaccine and in adolescents aged 16-18 (103,454 individuals) who received the booster dose. Our analysis shows that the confirmed infection rate was lower by a factor of 3.7 (95% CI: 2.7 to 5.2) in the booster group.


Subject(s)
COVID-19 , Adolescent , COVID-19/prevention & control , Humans , Immunization, Secondary , Israel , SARS-CoV-2
4.
Int J Environ Res Public Health ; 19(7)2022 Mar 29.
Article in English | MEDLINE | ID: covidwho-1785635

ABSTRACT

BACKGROUND: While the effectiveness of tetanus-diphtheria-pertussis childhood immunization programs is unquestionable, the actual need for a periodic boosting vaccination in adults is controversial. In Italy, the Ministry of Health recommends a Tdap booster vaccination every 10 years. The aim of this study is to assess the real-world adherence of Italian regional healthcare services to national recommendations and to evaluate two alternative strategies. METHODS: Annual Tdap vaccine requirements by the 21 Italian regions were retrieved from related tender announcements, and regional and national vaccination coverage rates (VCRs) were estimated for three scenarios, namely the currently recommended 10-year booster vaccination, a single booster shot at age 50 and at age 65. RESULTS: In Scenario 1, no region reached a VCR > 30%, and the national VCR was 10.6%; in Scenario 2, five regions achieved the optimal vaccination coverage of ≥95%, but the vast majority continued to have inadequate VCRs, with a national VCR of 54.4%; in Scenario 3, five regions reached VCRs exceeding 100%, with VCRs from other regions significantly improving and a national VCR of 74.8%. CONCLUSIONS: A substantial lack of adherence by Italian regional healthcare services to current national recommendations on tetanus-diphtheria-pertussis adult vaccination was shown. Scenario 3 is the most feasible, i.e., a single booster shot at age 65, possibly administrable along with other already-recommended, age-specific vaccines.


Subject(s)
Diphtheria-Tetanus-acellular Pertussis Vaccines , Diphtheria , Tetanus , Whooping Cough , Aged , Child , Diphtheria/prevention & control , Diphtheria-Tetanus Vaccine , Diphtheria-Tetanus-acellular Pertussis Vaccines/therapeutic use , Humans , Immunization, Secondary , Italy , Middle Aged , Tetanus/prevention & control , Vaccination , Whooping Cough/prevention & control
5.
Front Immunol ; 13: 841868, 2022.
Article in English | MEDLINE | ID: covidwho-1785344

ABSTRACT

The Bacillus Calmette-Guérin (BCG) vaccine, which is widely used to protect children against tuberculosis, can also improve immune response against viral infections. This unicentric, randomized-controlled clinical trial assessed the efficacy and safety of revaccination with BCG Moscow in reducing the positivity and symptoms of COVID-19 in health care workers (HCWs) during the COVID-19 pandemic. HCWs who had negative COVID-19 IgM and IgG and who dedicated at least eight hours per week in facilities that attended to individuals suspected of having COVID-19 were included in the study and were followed for 7, 15, 30, 60, and 180 days by telemedicine. The HCWs were randomly allocated to a revaccinated with BCG group, which received the BCG vaccine, or an unvaccinated group. Revaccination with BCG Moscow was found to be safe, and its efficacy ranged from 30.0% (95.0%CI -78.0 to 72.0%) to 31.0% (95.0%CI -74.0 to 74.0%). Mycobacterium bovis BCG Moscow did not induce NK cell activation at 15-20 days post-revaccination. As hypothesized, revaccination with BCG Moscow was associated with a lower incidence of COVID-19 positivity, though the results did not reach statistical significance. Further studies should be carried out to assess whether revaccination with BCG is able to protect HCWs against COVID-19. The protocol of this clinical trial was registered on August 5th, 2020, at REBEC (Registro Brasileiro de Ensaios Clínicos, RBR-4kjqtg - ensaiosclinicos.gov.br/rg/RBR-4kjqtg/1) and the WHO (# U1111-1256-3892). The clinical trial protocol was approved by the Comissão Nacional de ética de pesquisa- CONEP (CAAE 31783720.0.0000.5078).


Subject(s)
COVID-19 , Mycobacterium bovis , BCG Vaccine , COVID-19/prevention & control , Child , Health Personnel , Humans , Immunization, Secondary/methods , Moscow , Pandemics/prevention & control
6.
CMAJ ; 194(14): E532-E533, 2022 Apr 11.
Article in English | MEDLINE | ID: covidwho-1785221
7.
Indian J Pediatr ; 89(5): 490-496, 2022 May.
Article in English | MEDLINE | ID: covidwho-1782955

ABSTRACT

COVID-19 has been reported to have caused more than 286 million cases and 5.4 million deaths till date. COVID variants have appeared at regular intervals-alpha, beta, gamma, delta and now omicron. 'Omicron' is driving the current surge of cases in most countries including India and is poised to replace 'delta' the world over. This variant with more than 50 mutations is phylogenetically very different from other variants. The omicron variant spreads rapidly with an average doubling time of two days. The disease so far has been mild as compared with delta. Though previous infection and vaccination offer little or no protection against infection with omicron, they do seem to partially protect against hospitalization and severe disease. Booster vaccinations have not made any notable impact on the spread of omicron and have further worsened global vaccine equity. The indirect consequences of omicron from lockdowns, restrictions, travel bans, economic losses, health care worker infections and overwhelming of health care facilities are likely to be enormous. The direct effects of omicron on children are expected to be mild like with the previous variants. However, the indirect effects on child mental, physical, and social health may be considerable owing to school closures, missed vaccinations, neglect of other diseases, etc. It is, therefore, imperative that governments take rational decisions to navigate the world through this latest crisis.


Subject(s)
COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , Child , Communicable Disease Control , Humans , Immunization, Secondary , SARS-CoV-2
10.
Epidemiol Prev ; 46(1-2): 34-46, 2022.
Article in English | MEDLINE | ID: covidwho-1771985

ABSTRACT

BACKGROUND: the levels of anti-SARS-CoV-2 antibodies after the second vaccine dose decline in the following months; the administration of an additional vaccine dose (booster) is able to restore the immune system in the short period significantly reducing the risk of a severe disease. In the winter of 2021, a new particularly infectious variant caused the urgent need to increase the coverage of the booster dose. OBJECTIVES: to present, using real data, an evaluation of the efficacy of the booster dose in reducing the severe disease of SARS-CoV-2 infection in terms of hospital admissions, intensive care and death from all causes. DESIGN: descriptive study of vaccine adherence; associative study of the factors linked with adherence of vaccination and COVID-19 symptoms; associative study of vaccine effectiveness against hospital admission and mortality. SETTING AND PARTICIPANTS: population-based study in the Milan and Lodi provinces (Lombardy Region, Northern Italy) with subjects aged >=19 years alive at 01.10.2021, not residing in a nursery home, followed up to 31.12.2021. MAIN OUTCOME MEASURES: COVID-19 symptoms, hospitalization for COVID-19, intensive care hospitalization, and all-cause mortality in the period 01.10.2021-31.12.2021. RESULTS: the cohort included 2,936,193 patients at 01.10.2021: at the end of the follow-up period (31.12.2021), 378,616 (12.9%) had no vaccine, 128,879 (4.3%) had only 1 dose, 412,227 (14.0%) had a 2nd dose given since less than 4 months, 725. 806 (25%) had a 2nd dose given since 4-7 months, 74,152 (2.5%) had a 2nd dose given since 7+ months, 62,614 (2.1%) had a 2nd dose and have had the disease, and 1,153,899 (39.3%) received the booster. In the study period (01.10.2021-31.12.2021), characterized by a very high prevalence of the omicron variant, 121,620 cases (antigenic/molecular buffer positive), 3,661 hospitalizations for COVID-19, 162 ICU hospitalizations, and 7,508 deaths from all causes were identified. Compared to unvaccinated people, subjects who had the booster dose had half the risk of being symptomatic, in particular for asthenia, muscle pain, and dyspnoea which are the most commons COVID-19 symptoms. In comparison with the subjects who had the booster dose, the unvaccinated had a 10-fold risk of hospitalization for COVID-19, a 9-fold risk of intensive care, and a 3-fold risk of dying. CONCLUSIONS: this work highlights the vaccination efficacy in reducing serious adverse events for those who undergo the booster and the need to implement specific engagement policies to bring to a booster those who had taken the second dose since the longest time.


Subject(s)
COVID-19 , Public Health , Adult , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunization, Secondary , Italy/epidemiology , SARS-CoV-2 , Young Adult
11.
MMWR Morb Mortal Wkly Rep ; 71(13): 495-502, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1771891

ABSTRACT

CDC recommends that all persons aged ≥18 years receive a single COVID-19 vaccine booster dose ≥2 months after receipt of an Ad.26.COV2.S (Janssen [Johnson & Johnson]) adenovirus vector-based primary series vaccine; a heterologous COVID-19 mRNA vaccine is preferred over a homologous (matching) Janssen vaccine for booster vaccination. This recommendation was made in light of the risks for rare but serious adverse events following receipt of a Janssen vaccine, including thrombosis with thrombocytopenia syndrome and Guillain-Barré syndrome† (1), and clinical trial data indicating similar or higher neutralizing antibody response following heterologous boosting compared with homologous boosting (2). Data on real-world vaccine effectiveness (VE) of different booster strategies following a primary Janssen vaccine dose are limited, particularly during the period of Omicron variant predominance. The VISION Network§ determined real-world VE of 1 Janssen vaccine dose and 2 alternative booster dose strategies: 1) a homologous booster (i.e., 2 Janssen doses) and 2) a heterologous mRNA booster (i.e., 1 Janssen dose/1 mRNA dose). In addition, VE of these booster strategies was compared with VE of a homologous booster following mRNA primary series vaccination (i.e., 3 mRNA doses). The study examined 80,287 emergency department/urgent care (ED/UC) visits¶ and 25,244 hospitalizations across 10 states during December 16, 2021-March 7, 2022, when Omicron was the predominant circulating variant.** VE against laboratory-confirmed COVID-19-associated ED/UC encounters was 24% after 1 Janssen dose, 54% after 2 Janssen doses, 79% after 1 Janssen/1 mRNA dose, and 83% after 3 mRNA doses. VE for the same vaccination strategies against laboratory-confirmed COVID-19-associated hospitalizations were 31%, 67%, 78%, and 90%, respectively. All booster strategies provided higher protection than a single Janssen dose against ED/UC visits and hospitalizations during Omicron variant predominance. Vaccination with 1 Janssen/1 mRNA dose provided higher protection than did 2 Janssen doses against COVID-19-associated ED/UC visits and was comparable to protection provided by 3 mRNA doses during the first 120 days after a booster dose. However, 3 mRNA doses provided higher protection against COVID-19-associated hospitalizations than did other booster strategies during the same time interval since booster dose. All adults who have received mRNA vaccines for their COVID-19 primary series vaccination should receive an mRNA booster dose when eligible. Adults who received a primary Janssen vaccine dose should preferentially receive a heterologous mRNA vaccine booster dose ≥2 months later, or a homologous Janssen vaccine booster dose if mRNA vaccine is contraindicated or unavailable. Further investigation of the durability of protection afforded by different booster strategies is warranted.


Subject(s)
COVID-19 , Influenza Vaccines , Adolescent , Adult , Ambulatory Care , COVID-19/prevention & control , COVID-19 Vaccines , Emergency Service, Hospital , Hospitalization , Humans , Immunization, Secondary , SARS-CoV-2 , Vaccines, Synthetic
13.
Lancet ; 399(10328): 924-944, 2022 03 05.
Article in English | MEDLINE | ID: covidwho-1768606

ABSTRACT

BACKGROUND: Knowing whether COVID-19 vaccine effectiveness wanes is crucial for informing vaccine policy, such as the need for and timing of booster doses. We aimed to systematically review the evidence for the duration of protection of COVID-19 vaccines against various clinical outcomes, and to assess changes in the rates of breakthrough infection caused by the delta variant with increasing time since vaccination. METHODS: This study was designed as a systematic review and meta-regression. We did a systematic review of preprint and peer-reviewed published article databases from June 17, 2021, to Dec 2, 2021. Randomised controlled trials of COVID-19 vaccine efficacy and observational studies of COVID-19 vaccine effectiveness were eligible. Studies with vaccine efficacy or effectiveness estimates at discrete time intervals of people who had received full vaccination and that met predefined screening criteria underwent full-text review. We used random-effects meta-regression to estimate the average change in vaccine efficacy or effectiveness 1-6 months after full vaccination. FINDINGS: Of 13 744 studies screened, 310 underwent full-text review, and 18 studies were included (all studies were carried out before the omicron variant began to circulate widely). Risk of bias, established using the risk of bias 2 tool for randomised controlled trials or the risk of bias in non-randomised studies of interventions tool was low for three studies, moderate for eight studies, and serious for seven studies. We included 78 vaccine-specific vaccine efficacy or effectiveness evaluations (Pfizer-BioNTech-Comirnaty, n=38; Moderna-mRNA-1273, n=23; Janssen-Ad26.COV2.S, n=9; and AstraZeneca-Vaxzevria, n=8). On average, vaccine efficacy or effectiveness against SARS-CoV-2 infection decreased from 1 month to 6 months after full vaccination by 21·0 percentage points (95% CI 13·9-29·8) among people of all ages and 20·7 percentage points (10·2-36·6) among older people (as defined by each study, who were at least 50 years old). For symptomatic COVID-19 disease, vaccine efficacy or effectiveness decreased by 24·9 percentage points (95% CI 13·4-41·6) in people of all ages and 32·0 percentage points (11·0-69·0) in older people. For severe COVID-19 disease, vaccine efficacy or effectiveness decreased by 10·0 percentage points (95% CI 6·1-15·4) in people of all ages and 9·5 percentage points (5·7-14·6) in older people. Most (81%) vaccine efficacy or effectiveness estimates against severe disease remained greater than 70% over time. INTERPRETATION: COVID-19 vaccine efficacy or effectiveness against severe disease remained high, although it did decrease somewhat by 6 months after full vaccination. By contrast, vaccine efficacy or effectiveness against infection and symptomatic disease decreased approximately 20-30 percentage points by 6 months. The decrease in vaccine efficacy or effectiveness is likely caused by, at least in part, waning immunity, although an effect of bias cannot be ruled out. Evaluating vaccine efficacy or effectiveness beyond 6 months will be crucial for updating COVID-19 vaccine policy. FUNDING: Coalition for Epidemic Preparedness Innovations.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Immunization Schedule , Immunization, Secondary , /therapeutic use , Humans , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Time Factors
14.
BMJ Case Rep ; 15(3)2022 Mar 24.
Article in English | MEDLINE | ID: covidwho-1765101

ABSTRACT

Thrombotic thrombocytopenic purpura (TTP) is a type of thrombotic microangiopathy that is characterized by microangiopathic haemolytic anaemia, consumption thrombocytopenia and organ injury. It is caused by a severe deficiency of ADAMTS13, which can be either congenital or acquired. There is a plethora of things that can cause the acquired form, including medications and infections. Vaccines have also been shown to cause TTP. In the midst of the COVID-19 pandemic, with multiple new vaccines being developed and distributed to the masses, the medical community needs to be aware of adverse events associated with these new vaccines. We present a case of TTP following administration of the Moderna booster vaccine.


Subject(s)
Anemia, Hemolytic , COVID-19 , Purpura, Thrombotic Thrombocytopenic , Anemia, Hemolytic/complications , COVID-19/prevention & control , Humans , Immunization, Secondary/adverse effects , Pandemics , Purpura, Thrombotic Thrombocytopenic/chemically induced , Purpura, Thrombotic Thrombocytopenic/complications
16.
MMWR Morb Mortal Wkly Rep ; 71(12): 466-473, 2022 Mar 25.
Article in English | MEDLINE | ID: covidwho-1761303

ABSTRACT

Beginning the week of December 19-25, 2021, the B.1.1.529 (Omicron) variant of SARS-CoV-2 (the virus that causes COVID-19) became the predominant circulating variant in the United States (i.e., accounted for >50% of sequenced isolates).* Information on the impact that booster or additional doses of COVID-19 vaccines have on preventing hospitalizations during Omicron predominance is limited. Data from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET)† were analyzed to compare COVID-19-associated hospitalization rates among adults aged ≥18 years during B.1.617.2 (Delta; July 1-December 18, 2021) and Omicron (December 19, 2021-January 31, 2022) variant predominance, overall and by race/ethnicity and vaccination status. During the Omicron-predominant period, weekly COVID-19-associated hospitalization rates (hospitalizations per 100,000 adults) peaked at 38.4, compared with 15.5 during Delta predominance. Hospitalizations rates increased among all adults irrespective of vaccination status (unvaccinated, primary series only, or primary series plus a booster or additional dose). Hospitalization rates during peak Omicron circulation (January 2022) among unvaccinated adults remained 12 times the rates among vaccinated adults who received booster or additional doses and four times the rates among adults who received a primary series, but no booster or additional dose. The rate among adults who received a primary series, but no booster or additional dose, was three times the rate among adults who received a booster or additional dose. During the Omicron-predominant period, peak hospitalization rates among non-Hispanic Black (Black) adults were nearly four times the rate of non-Hispanic White (White) adults and was the highest rate observed among any racial and ethnic group during the pandemic. Compared with the Delta-predominant period, the proportion of unvaccinated hospitalized Black adults increased during the Omicron-predominant period. All adults should stay up to date (1) with COVID-19 vaccination to reduce their risk for COVID-19-associated hospitalization. Implementing strategies that result in the equitable receipt of COVID-19 vaccinations, through building vaccine confidence, raising awareness of the benefits of vaccination, and removing barriers to vaccination access among persons with disproportionately higher hospitalizations rates from COVID-19, including Black adults, is an urgent public health priority.


Subject(s)
COVID-19 Vaccines , COVID-19/ethnology , Hospitalization/statistics & numerical data , SARS-CoV-2 , Vaccination/statistics & numerical data , Adult , Humans , Immunization, Secondary , United States/epidemiology
17.
BMJ ; 376: e069052, 2022 02 10.
Article in English | MEDLINE | ID: covidwho-1759321

ABSTRACT

OBJECTIVES: To estimate the effectiveness of mRNA vaccines against SARS-CoV-2 infection and severe covid-19 at different time after vaccination. DESIGN: Retrospective cohort study. SETTING: Italy, 27 December 2020 to 7 November 2021. PARTICIPANTS: 33 250 344 people aged ≥16 years who received a first dose of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine and did not have a previous diagnosis of SARS-CoV-2 infection. MAIN OUTCOME MEASURES: SARS-CoV-2 infection and severe covid-19 (admission to hospital or death). Data were divided by weekly time intervals after vaccination. Incidence rate ratios at different time intervals were estimated by multilevel negative binomial models with robust variance estimator. Sex, age group, brand of vaccine, priority risk category, and regional weekly incidence in the general population were included as covariates. Geographic region was included as a random effect. Adjusted vaccine effectiveness was calculated as (1-IRR)×100, where IRR=incidence rate ratio, with the time interval 0-14 days after the first dose of vaccine as the reference. RESULTS: During the epidemic phase when the delta variant was the predominant strain of the SARS-CoV-2 virus, vaccine effectiveness against SARS-CoV-2 infection significantly decreased (P<0.001) from 82% (95% confidence interval 80% to 84%) at 3-4 weeks after the second dose of vaccine to 33% (27% to 39%) at 27-30 weeks after the second dose. In the same time intervals, vaccine effectiveness against severe covid-19 also decreased (P<0.001), although to a lesser extent, from 96% (95% to 97%) to 80% (76% to 83%). High risk people (vaccine effectiveness -6%, -28% to 12%), those aged ≥80 years (11%, -15% to 31%), and those aged 60-79 years (2%, -11% to 14%) did not seem to be protected against infection at 27-30 weeks after the second dose of vaccine. CONCLUSIONS: The results support the vaccination campaigns targeting high risk people, those aged ≥60 years, and healthcare workers to receive a booster dose of vaccine six months after the primary vaccination cycle. The results also suggest that timing the booster dose earlier than six months after the primary vaccination cycle and extending the offer of the booster dose to the wider eligible population might be warranted.


Subject(s)
/immunology , COVID-19/epidemiology , Immunization, Secondary/statistics & numerical data , SARS-CoV-2/pathogenicity , /administration & dosage , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/immunology , COVID-19/prevention & control , Female , Follow-Up Studies , Humans , Immunogenicity, Vaccine , Incidence , Italy/epidemiology , Male , Middle Aged , SARS-CoV-2/isolation & purification , Severity of Illness Index , Time Factors , Treatment Outcome , Vaccination/statistics & numerical data , Young Adult
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