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1.
Cell Host Microbe ; 30(3): 400-408.e4, 2022 03 09.
Article in English | MEDLINE | ID: covidwho-1650182

ABSTRACT

Breakthrough SARS-CoV-2 infections in fully vaccinated individuals are considered a consequence of waning immunity. Serum antibodies represent the most measurable outcome of vaccine-induced B cell memory. When antibodies decline, memory B cells are expected to persist and perform their function, preventing clinical disease. We investigated whether BNT162b2 mRNA vaccine induces durable and functional B cell memory in vivo against SARS-CoV-2 3, 6, and 9 months after the second dose in a cohort of health care workers (HCWs). While we observed physiological decline of SARS-CoV-2-specific antibodies, memory B cells persist and increase until 9 months after immunization. HCWs with breakthrough infections had no signs of waning immunity. In 3-4 days, memory B cells responded to SARS-CoV-2 infection by producing high levels of specific antibodies in the serum and anti-Spike IgA in the saliva. Antibodies to the viral nucleoprotein were produced with the slow kinetics typical of the response to a novel antigen.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Vaccination , Vaccines, Synthetic
3.
PLoS One ; 16(12): e0260947, 2021.
Article in English | MEDLINE | ID: covidwho-1556896

ABSTRACT

BACKGROUND: On 9th January 2020, China CDC reported a novel coronavirus (later named SARS-CoV-2) as the causative agent of the coronavirus disease 2019 (COVID-19). Identifying the first appearance of virus is of epidemiological importance to tracking and mapping the spread of SARS-CoV-2 in a country. We therefore conducted a retrospective observational study to detect SARS-CoV-2 in oropharyngeal samples collected from hospitalized patients with a Severe Acute Respiratory Infection (SARI) enrolled in the DRIVE (Development of Robust and Innovative Vaccine Effectiveness) study in five Italian hospitals (CIRI-IT BIVE hospitals network) (1st November 2019 - 29th February 2020). OBJECTIVES: To acquire new information on the real trend in SARS-CoV-2 infection during pandemic phase I and to determine the possible early appearance of the virus in Italy. MATERIALS AND METHODS: Samples were tested for influenza [RT-PCR assay (A/H1N1, A/H3N2, B/Yam, B/Vic)] in accordance with the DRIVE study protocol. Subsequently, swabs underwent molecular testing for SARS-COV-2. [one-step real-time multiplex retro-transcription (RT) PCR]. RESULTS: In the 1683 samples collected, no evidence of SARS-CoV-2 was found. Moreover, 28.3% (477/1683) of swabs were positive for influenza viruses, the majority being type A (358 vs 119 type B). A/H3N2 was predominant among influenza A viruses (55%); among influenza B viruses, B/Victoria was prevalent. The highest influenza incidence rate was reported in patients aged 0-17 years (40.3%) followed by those aged 18-64 years (24.4%) and ≥65 years (14.8%). CONCLUSIONS: In Italy, some studies have shown the early circulation of SARS-CoV-2 in northern regions, those most severely affected during phase I of the pandemic. In central and southern regions, by contrast no early circulation of the virus was registered. These results are in line with ours. These findings highlight the need to continue to carry out retrospective studies, in order to understand the epidemiology of the novel coronavirus, to better identify the clinical characteristics of COVID-19 in comparison with other acute respiratory illnesses (ARI), and to evaluate the real burden of COVID-19 on the healthcare system.


Subject(s)
Influenza, Human/epidemiology , Severe Acute Respiratory Syndrome/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/virology , Female , Hospitals , Humans , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza A Virus, H3N2 Subtype/genetics , Influenza A Virus, H3N2 Subtype/isolation & purification , Influenza B virus/genetics , Influenza B virus/isolation & purification , Influenza, Human/pathology , Influenza, Human/virology , Italy/epidemiology , Male , Middle Aged , RNA, Viral/genetics , RNA, Viral/metabolism , Retrospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Severe Acute Respiratory Syndrome/pathology , Severe Acute Respiratory Syndrome/virology , Young Adult
4.
SSRN; 2021.
Preprint in English | SSRN | ID: ppcovidwho-292059

ABSTRACT

Background: Breakthrough infections in fully vaccinated HCWs are considered a marker of waning immunity. Serum antibodies represent the most visible and measurable outcome of vaccine-induced B-cell memory. When antibodies decline, memory B cells are expected to persist and perform their function, thus preventing clinical disease. We investigated whether BNT162b2 mRNA vaccine induces durable and in vivo functional B-cell memory against SARS-CoV-2 3, 6 and 9 months after the second dose. Methods: We assessed the duration of SARS-CoV-2 vaccine-induced immunity by measuring specific antibodies and memory B cells 3, 6 and 9 months after vaccination. In fully vaccinated HCWs with breakthrough SARS-CoV-2 infections, we evaluated the humoral and mucosal response of vaccine-induced memory B cells. Findings: Whereas specific serum antibodies decline, anti-Spike memory B cells continue to increase until 9 months after the last vaccine dose. HCWs with breakthrough infections had no signs of waning immunity on the day of the first positive swab. In 3-4 days, memory B cells responded to SARS-CoV-2 infection by producing high levels of specific antibodies in the serum. In the saliva, anti-Spike IgA also rapidly increased in response to the infection. Antibodies to the viral nucleoprotein were produced with the slow kinetics typical of the response to a novel antigen. Interpretation: SARS-CoV-2 specific antibodies physiologically decline months after vaccination. By contrast, memory B cells persist and increase over time. Parenteral administered vaccines do not generate mucosal immunity and serum antibodies reach mucosal sites in small amounts by transudation. In HCWs with SARS-CoV-2 breakthrough infections, memory B cells react by rapidly differentiating into antibody-producing cells and generating IgA for protection of mucosal sites.

5.
Front Immunol ; 12: 727850, 2021.
Article in English | MEDLINE | ID: covidwho-1477821

ABSTRACT

Mass SARS-Cov-2 vaccination campaign represents the only strategy to defeat the global pandemic we are facing. Immunocompromised patients represent a vulnerable population at high risk of developing severe COVID-19 and thus should be prioritized in the vaccination programs and in the study of the vaccine efficacy. Nevertheless, most data on efficacy and safety of the available vaccines derive from trials conducted on healthy individuals; hence, studies on immunogenicity of SARS-CoV2 vaccines in such populations are deeply needed. Here, we perform an observational longitudinal study analyzing the humoral and cellular response following the BNT162b2 mRNA COVID-19 vaccine in a cohort of patients affected by inborn errors of immunity (IEI) compared to healthy controls (HC). We show that both IEI and HC groups experienced a significant increase in anti-SARS-CoV-2 Abs 1 week after the second scheduled dose as well as an overall statistically significant expansion of the Ag-specific CD4+CD40L+ T cells in both HC and IEI. Five IEI patients did not develop any specific CD4+CD40L+ T cellular response, with one of these patients unable to also mount any humoral response. These data raise immunologic concerns about using Ab response as a sole metric of protective immunity following vaccination for SARS-CoV-2. Taken together, these findings suggest that evaluation of vaccine-induced immunity in this subpopulation should also include quantification of Ag-specific T cells.


Subject(s)
Antibodies, Viral/blood , CD4-Positive T-Lymphocytes/immunology , COVID-19 Vaccines/immunology , Immunogenicity, Vaccine/immunology , Primary Immunodeficiency Diseases/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , CD4 Lymphocyte Count , COVID-19/prevention & control , Female , Humans , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Immunocompromised Host/immunology , Longitudinal Studies , Male , Middle Aged , Vaccination , Young Adult
6.
Cells ; 10(10)2021 09 26.
Article in English | MEDLINE | ID: covidwho-1438527

ABSTRACT

Specific memory B cells and antibodies are a reliable read-out of vaccine efficacy. We analysed these biomarkers after one and two doses of BNT162b2 vaccine. The second dose significantly increases the level of highly specific memory B cells and antibodies. Two months after the second dose, specific antibody levels decline, but highly specific memory B cells continue to increase, thus predicting a sustained protection from COVID-19. We show that although mucosal IgA is not induced by the vaccination, memory B cells migrate in response to inflammation and secrete IgA at mucosal sites. We show that the first vaccine dose may lead to an insufficient number of highly specific memory B cells and low concentration of serum antibodies, thus leaving vaccinees without the immune robustness needed to ensure viral elimination and herd immunity. We also clarify that the reduction of serum antibodies does not diminish the force and duration of the immune protection induced by vaccination. The vaccine does not induce sterilizing immunity. Infection after vaccination may be caused by the lack of local preventive immunity because of the absence of mucosal IgA.


Subject(s)
Antibodies, Viral/immunology , B-Lymphocytes/cytology , COVID-19 Vaccines/therapeutic use , COVID-19/immunology , COVID-19/prevention & control , Immunoglobulin A/immunology , Immunologic Memory , Adult , Antibodies, Neutralizing/blood , Antigens, Viral/immunology , B-Lymphocytes/immunology , Cryopreservation , Female , Health Personnel , Healthy Volunteers , Hospitals, Pediatric , Humans , Immunoglobulin G , Immunoglobulin M/immunology , Lactation , Male , Middle Aged , Mucous Membrane/immunology , Patient Safety , SARS-CoV-2 , Vaccination
8.
Front Pediatr ; 9: 620598, 2021.
Article in English | MEDLINE | ID: covidwho-1247886

ABSTRACT

Background: In December 2019, a novel coronavirus named SARS-CoV-2 started circulating in China and this led to a major epidemic in Northern Italy between February and May 2020. Young children (aged <5 years) seem to be less affected by this coronavirus disease (COVID-19) compared to adults, although there is very little information on the circulation of this new virus among children in Italy. We retrospectively tested nasopharyngeal swabs for SARS-CoV-2 in samples collected in young children between November, 2019 and March, 2020 in the context of the RSV ComNet study. Methods: Two networks of primary care pediatricians in Lazio (Central Italy) and Puglia (Southern Italy) collected nasopharyngeal swabs from children, aged <5 years, presenting with symptoms for an acute respiratory infection (ARI). The RSV ComNet study is a multicenter study implemented to estimate the burden of RSV in young children (aged <5 years) in the community. Swabs were sent to a central reference laboratory and tested for 14 respiratory viruses through RT-PCR. All collected samples were retrospectively tested for SARS-CoV-2 using RT-PCR (Istituto Superiore di Sanità protocol). Results: A total of 293 children with ARI were identified in the two participating networks. The highest number of cases were recruited in weeks 51/2019 and 3/2020. The majority of patients (57%) came from the Lazio region. All of the 293 samples tested negative for SARS-Cov2. Rhinovirus was the most frequently detected virus (44%), followed by RSV (41%) and influenza viruses (14%). Conclusions: Our study shows that in Lazio (a region of intermediate SARS-COV-2 incidence) and Puglia (a region of low incidence), the SARS-Cov2 virus did not circulate in a sample of ARI pediatric cases consulting primary care pediatricians between November 2019 and March 2020.

11.
Int J Environ Res Public Health ; 18(7)2021 04 04.
Article in English | MEDLINE | ID: covidwho-1167587

ABSTRACT

Italy was the first country in Europe to face the coronavirus pandemic. The aim of the study was to analyze healthcare workers' (HCWs) level of information, practice, and risk perception towards COVID-19. We set up a cross-sectional study through SurveyMonkey® and distributed the link through Facebook and Whatsapp closed groups. The research instrument was a 31 items questionnaire distributed using Facebook and Whatsapp. It was conducted in Italy from February to May 2020. The study participants were general practitioners, pediatricians and other health professionals. A total of 958 participants were included: 320 (33.4%) general practitioners, 248 (25.9%) pediatricians and 390 (40.7%) other health professionals. The highest response rate was from Northern Italy (48.1%), followed by Central Italy (29.9%) and Southern Italy (22.0%). Less than a half (46%) of respondents felt they had a good level of information of COVID-19 case definition and of national prevention guidelines. Respondents reported to have changed their clinical practice; particularly, they increased the use of masks (87.1%, p < 0.001), disinfection and sanitization of doctors' offices (75.8%, p < 0.001), the use of protective glasses (71.2%, p < 0.001), alcoholic hand solution (71.2%, p < 0.001), and hand washing (31.8%, p = 0.028). HCWs are at high risk of infection; less than a half of them felt adequately prepared to face COVID-19 pandemic, so they need extensive information and awareness of the disease to take adequate precautionary measures, and they are crucial to disseminate good practices.


Subject(s)
COVID-19 , Pandemics , Cross-Sectional Studies , Europe , Health Knowledge, Attitudes, Practice , Health Personnel , Humans , Italy/epidemiology , Perception , SARS-CoV-2 , Surveys and Questionnaires
12.
Ital J Pediatr ; 47(1): 21, 2021 Jan 29.
Article in English | MEDLINE | ID: covidwho-1054830

ABSTRACT

BACKGROUND: Italy was the first country in Europe affected by COVID-19: the emergency started on February 20, 2020, culminating with national lockdown on March 11, which terminated on May 4, 2020. We describe how the pandemic affected Emergency Department (ED) accesses in a tertiary children's hospital, composed by two different pediatric centers, one located in Rome's city center and the second, Palidoro (regional COVID-19 center), in its surrounding metropolitan area, both in the Lazio region, analyzing the profile of admitted patients during the pandemic period in terms of their general characteristics (at presentation in the ED's) and urgent hospitalizations compared to prepandemic period. METHODS: The study compare the period between the 21st of February and the 30th of April 2020, covering the three phases of the national responses (this period will be referred to as the pandemic period) with the same period of 2019 (prepandemic period). The study analyzes the number of ED visits and urgent hospitalizations and their distribution according to selected characteristics. RESULTS: The reduction of ED visits was 56 and 62%, respectively in Rome and Palidoro centers. The higher relative decline was encountered for Diseases of Respiratory System, and for Diseases of the Nervous System and Sense Organs. A doubling of the relative frequency of hospitalizations was observed, going from 14.2 to 24.4% in Rome and from 6.4 to 10.3% in Palidoro. In terms of absolute daily numbers the decrease of urgent hospitalizations was less sharp than ED visits. For pathologies such as peritonitis, tumors or other possible life-treathening conditions we did not observe a significative increase due to delayed access. CONCLUSIONS: In the pandemic period there was a general reduction in the number of children referred to ED, such reduction was greater in low-acuity levels. The reduction for respiratory tract infections and other communicable diseases during school closure and the national lockdown must make us reflect on the possible impact that these conditions may have on the health system, in particular the ED, at the reopening of schools. The major problem remains the fear for possible diagnostic delays in life-threatening or crippling diseases; our study doesn't demonstrate an increase in number or significant delay in some serious conditions such as tumors, peritonitis, diabetic ketoacidosis, ileo-colic intussusception and testis/ovary torsion. A continuous, deep re-organizational process step by step of the ED is nececessary in the present and upcoming pandemic situation.


Subject(s)
COVID-19/epidemiology , Emergency Service, Hospital/statistics & numerical data , Health Services Accessibility , Hospitalization/statistics & numerical data , Hospitals, Pediatric/statistics & numerical data , Referral and Consultation/statistics & numerical data , Child , Female , Humans , Italy/epidemiology , Male , Pandemics , SARS-CoV-2
15.
Pediatr Infect Dis J ; 39(9): e221-e225, 2020 09.
Article in English | MEDLINE | ID: covidwho-636869

ABSTRACT

BACKGROUND: In Italy, the response to coronavirus disease 2019 (COVID-19) pandemic upgraded from social distancing on February 23, 2020, to national lockdown on March 11, 2020. We described how the pandemic affected a tertiary care children hospital with a dedicated COVID-19 regional center. METHODS: We analyzed the characteristics of emergency department (ED) visits, urgent hospitalizations and severe acute respiratory syndrome (SARS)-COV-2 reverse transcription-polymerase chain reaction testing, and COVID-19 patients across 3 response phases: before the first Italian case, before national lockdown and during lockdown. RESULTS: ED visits decreased from a daily mean of 239.1 before the first COVID-19 Italian case, to 79.6 during lockdown; urgent hospitalizations decreased from 30.6 to 21.2. As of April 20, 2020, 1970 persons were tested for SARS-CoV-2 reverse transcription-polymerase chain reaction and 2.6% were positive. Positive rates were 1.2% in the ED, 21.1% in the COVID center and 0.5% in other wards. The median age of COVID-19 patients (N = 33) was 6.7 years, 27% had coexisting conditions and 79% were related to family clusters. CONCLUSIONS: The pandemic strongly impacted on the use of hospital services, with a 67% reduction in ED visits and a 31% reduction in urgent hospitalizations. Separating the flows of suspected patients from all other patients, and centralization of suspected and confirmed cases in the COVID center enabled to control the risk of nosocomial SARS-CoV-2 transmission. Delay in hospital use for urgent care must be avoided, and clear communication on infection prevention and control must be provided to families. Further studies are needed to assess how the reduction in hospital use affected children healthcare needs during the pandemic.


Subject(s)
Civil Defense , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Adolescent , Ambulatory Care , Betacoronavirus/isolation & purification , COVID-19 , Child , Child, Preschool , Coronavirus Infections/therapy , Coronavirus Infections/virology , Emergency Service, Hospital/organization & administration , Emergency Service, Hospital/statistics & numerical data , Female , Hospitalization/statistics & numerical data , Hospitals, Pediatric/organization & administration , Hospitals, Pediatric/statistics & numerical data , Humans , Infant , Italy/epidemiology , Male , Pandemics , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , SARS-CoV-2 , Tertiary Care Centers/organization & administration , Tertiary Care Centers/statistics & numerical data
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