Kinetics of Humoral Immunity against SARS-CoV-2 in Healthcare Workers after the Third Dose of BNT162b2 mRNA Vaccine.

Protection provided by COVID-19 vaccines is compromised due to waning immunity over time. This study aimed to assess the level of antibodies anti-S-RBD of SARS-CoV-2 in a cohort of healthcare workers before and, on average, one and four months after the third dose of the BNT162b2 vaccine. The determination of antibodies was carried out in serum samples using an electrochemiluminescence immunoassay (ECLIA). All 34 participants (10 males, 24 females, 19 participants <50 years old, 15 participants ≥50 years old) showed a significant antibody level increase after the booster dose. Subsequently, a significant decrease in the antibody concentration was observed, with a reduction of about 60% after 150 days from the booster. Six subjects were infected by SARS-CoV-2 after the booster and showed a significantly higher antibody concentration on average four months after the third dose compared to naïve ones. Male and female participants had a similar trend in the antibody decline, while older subjects, compared to the younger ones, had a slightly slower decrease, even if they developed a lower level of antibodies after the third dose. These findings support the importance of the booster dose and underline the need for surveillance programs to better understand the antibody kinetics and optimize vaccination strategies.

Antibody Response in Healthcare Workers before and after the Third Dose of Anti-SARS-CoV-2 Vaccine: A Pilot Study.

The SARS-CoV-2 pandemic led to the development of various vaccines. The BNT162b2 mRNA vaccine was the first approved due to its efficacy in eliciting a humoral immunity response after the second dose. However, a decrease in the antibody concentration was observed over time. Therefore, the administration of a third dose was scheduled, primarily for frail people and workers of essential public activities. The aim of this study was to assess the level of antibodies against the spike (S) RBD of SARS-CoV-2 in healthcare workers before and after the third dose of BNT162b2 vaccine, according to sex, age, and the time interval between vaccine doses and tests. All 37 (12 males, 25 females, 19 < 50 years old, 18 ≥ 50 years old) healthcare workers recruited showed a consistent antibody titer increase after the third dose. Data analysis showed that the antibody concentration before the third dose significantly decreased as the time interval up to the test increased, and a significantly higher level was shown in young than older people. Cluster analysis revealed that young females had a higher antibody level than older females before the third dose (p < 0.05). This study indicated the benefit of the third dose of BNT162b2 vaccine and its effect on leveling up the humoral immune response.

Effects of Influenza Vaccination on the Response to BNT162b2 Messenger RNA COVID-19 Vaccine in Healthcare Workers.

BACKGROUND: Vaccine-induced immunity is at present the main strategy to stop the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent evidences suggested a protective effect of influenza vaccination against coronavirus disease 2019 (COVID-19) severity, while impact on the immune response to BNT162b2 messenger RNA (mRNA) vaccine is under investigation. METHODS: We aimed to evaluate this aspect in a cohort of 297 healthcare workers (108 males, 189 females) after seasonal influenza vaccination compared to no-flu-vaccination. VAX+ (165 individuals; 63 males and 102 females) had tetravalent influenza vaccine, and VAX- (132 individuals; 45 males and 87 females) had no flu vaccination. Anti-spike-receptor binding domain (RBD) level was tested 15 - 70 days after BNT162b2 second inoculum. RESULTS: Increased antibody response was observed in total VAX+ compared to VAX- (2,047.4 vs. 1,494.2 binding antibody unit (BAU)/mL, P = 0.0039), independently from gender and body mass index (BMI). Younger total individuals (< 35 years) showed significant increase of the level of binding antibodies (2,184.8 vs. 1,590.9 BAU/mL, P = 0.0038) compared to ≥ 35 years; young/old difference was lost restricting to VAX+ subgroup. Flu vaccinations appear associated to better antibody response in older individuals (P = 0.027, ≥ 35 years VAX+ vs. VAX-). A decreasing trend during time was observed for both VAX+ and VAX-, except for < 35 years VAX- individuals. Early response was higher in VAX+ compared to VAX-; however a more rapid waning was observed in VAX+ subjects. CONCLUSIONS: Our data showed better antibody response to SARS-CoV-2 vaccine in subjects already vaccinated against seasonal influenza; this may represent one of the mechanisms underlying the cross-protective effects of influenza vaccination against heterologous infections reported in recent epidemiological studies.

sFlt-1 and CA 15.3 are indicators of endothelial damage and pulmonary fibrosis in SARS-CoV-2 infection.

COVID-19 pandemic led to a worldwide increase of hospitalizations for interstitial pneumonia with thrombosis complications, endothelial injury and multiorgan disease. Common CT findings include lung bilateral infiltrates, bilateral ground-glass opacities and/or consolidation whilst no current laboratory parameter consents rapidly evaluation of COVID-19 risk and disease severity. In the present work we investigated the association of sFLT-1 and CA 15.3 with endothelial damage and pulmonary fibrosis. Serum sFlt-1 has been associated with endothelial injury and sepsis severity, CA 15.3 seems an alternative marker for KL-6 for fibrotic lung diseases and pulmonary interstitial damage. We analysed 262 SARS-CoV-2 patients with differing levels of clinical severity; we found an association of serum sFlt-1 (ROC AUC 0.902, decision threshold > 90.3 pg/mL, p < 0.001 Sens. 83.9% and Spec. 86.7%) with presence, extent and severity of the disease. Moreover, CA 15.3 appeared significantly increased in COVID-19 severe lung fibrosis (ICU vs NON-ICU patients 42.6 ± 3.3 vs 25.7 ± 1.5 U/mL, p < 0.0001) and was associated with lung damage severity grade (ROC AUC 0.958, decision threshold > 24.8 U/mL, p < 0.0001, Sens. 88.4% and Spec. 91.8%). In conclusion, serum levels of sFlt-1 and CA 15.3 appeared useful tools for categorizing COVID-19 clinical stage and may represent a valid aid for clinicians to better personalise treatment.

IgM and IgG Profiles Reveal Peculiar Features of Humoral Immunity Response to SARS-CoV-2 Infection.

The emergence of coronavirus disease 2019 (COVID-19) is globally a major healthcare threat. There is little information regarding the mechanisms and roles of the humoral response in SARS-CoV-2 infection. The aim of this study was to analyze the antibody levels (IgM and IgG) by chemiluminescence immunoassay in 54 subjects positive to SARS-CoV-2 swab test in relation to their clinical status (whether asymptomatic, pauci-symptomatic or with mild, sever or critical symptoms), the time from the symptom onset, sex, age, and comorbidities. Overall, the presence of comorbidities and the age of subjects were associated with their clinical status. The IgG concentrations were significantly higher in patients who developed critical and severe symptoms and seemed to be independent from age, sex and comorbidities. IgG titers peaked around day 60, and then began gradually to drop, decreasing by approximately 50% on the 180th day, while the IgM titers progressively decreased as early as the tenth day, but they could be detected even at later time points. Despite the small number of individuals, some peculiar characteristics of the humoral response in COVID-19 emerged. We observed a high inter-individual variability, an ephemeral IgG half-life in several patients, and a persistence of IgM in others.

Breast Adjuvant Radiotherapy Amid the COVID-19 Crisis in a Hub Cancer Center, Lombardy, Italy.

INTRODUCTION: During the COVID-19 pandemic, Lombardy (Northern Italy) Regional Health Council created hubs for cancer care, meant to be SARS-CoV-2-free pathways for cancer patients. The workflow of breast cancer (BC) radiotherapy (RT) in one of the hubs is presented here. METHODS: Candidates to adjuvant RT during the pandemic peak of March-April 2020 were compared to those treated in the same period of 2019, and patient volume, deferral rate, and type of RT were analyzed. Statistics were calculated with χ2 or Fisher exact tests for categorical variables, and the Wilcoxon rank test for continuous variables. RESULTS: In March-April 2020 the BC patient volume increased by 28% compared to the same period in 2019 (scheduled patients: 175 vs. 137) and amid travel restrictions it was kept high (treated patients: 136 vs. 133), mainly due to an influx from across Lombardy. RT schemes basically did not change, being already centered on hypofractionation. The increase of median time (67 vs. 74.5 days in 2019 and 2020, respectively) to the commencement of RT for low-risk patients was clinically negligible yet statistically significant (p = 0.03), and in line with the pertinent recommendations. No significant difference was found in the time interval between treatments and RT for high-risk patients. Concomitant chemoradiotherapy was avoided throughout the pandemic peak. Twenty-one women (13.6%) delayed either computed tomography simulation or RT commencement mainly because of COVID-19-related concerns and mobility restrictions. CONCLUSION: The workload for BC was high during the pandemic peak. Hubs allowed the continuation of oncologic treatments, while mitigating the strain on frontline COVID-19 hospitals.

COVID-19 impact in radiotherapy practice in an oncology hub: a screenshot from Lombardy, Italy.

OBJECTIVE: During 2020, medical clinical activities were dramatically modified by the coronavirus disease 2019 (COVID-19) emergency. We aim to evaluate the impact of COVID-19 on radiotherapy (RT) practice in a hub cancer center. METHODS: Retrospective data collection of patients with suspected COVID-19 infection, identified by pathognomonic symptoms feedback at triage realized at the entrance to RT division. Inclusion criteria were diagnosis of oncologic disease, COVID-19-related symptoms, and signed written informed consent. RESULTS: Between 1 March and 30 June 2020, 1,006 patients accessed our RT division for RT simulation or treatment. Forty-four patients matched inclusion criteria (4.4% of all patients): 29 women and 15 men. Seventeen patients had metastatic disease. Twenty-one patients reported fever, 6 presented dyspnea, 4 complained of ageusia and anosmia, and 3 developed conjunctivitis. Thirty-six patients underwent nasal swab, with 7 positive results. From our cohort, 4 cases of pneumonia were diagnosed with computed tomography scan imaging: 3 were related to COVID-19 infection, while the fourth was evaluated as an RT adverse event. From the entire series, 4 patients died: 3 during hospitalization in intensive care unit of complications of COVID-19 and 1 of other causes neither COVID-19 nor cancer-related. CONCLUSIONS: Cancer hub allows for safe RT practice continuation while minimizing the spread of contagion in this frail patient population. A challenge for the future will be to understand pandemic consequences in cancer natural history and manage its clinical impact.

Head and neck cancer radiotherapy amid COVID-19 pandemic: Report from Milan, Italy.

BACKGROUND: Management of head and neck cancers (HNC) in radiation oncology in the coronavirus disease 2019 (COVID-19) era is challenging. Aim of our work is to report organization strategies at a radiation therapy (RT) department in the first European area experiencing the COVID-19 pandemic. METHODS: We focused on (a) dedicated procedures for HNC, (b) RT scheduling, and (c) health care professionals' protection applied during the COVID-19 breakdown (from March 1, 2020 to April 30, 2020). RESULTS: Applied procedures are reported and discussed. Forty-three patients were treated. Image-guided, intensity modulated RT was performed in all cases. Median overall treatment time was 50 (interquartile range: 47-54.25) days. RT was interrupted/delayed in seven patients (16%) for suspected COVID-19 infection. Two health professionals managing HNC patients were proven as COVID-19 positive. CONCLUSION: Adequate and well-timed organization allowed for the optimization of HNC patients balancing at the best of our possibilities patients' care and personnel's safety.