A longitudinal analysis of humoral, T cellular response and influencing factors in a cohort of healthcare workers: Implications for personalized SARS-CoV-2 vaccination strategies.

Introduction: SARS-CoV-2 mRNA vaccinations elicit both virus-specific humoral and T-cell responses, but a complex interplay of different influencing factors, such as natural immunity, gender, and age, guarantees host protection. The present study aims to assess the immune dynamics of humoral, T-cell response, and influencing factors to stratify individual immunization status up to 10 months after Comirnaty-vaccine administration. Methods: To this aim, we longitudinally evaluated the magnitude and kinetics of both humoral and T-cell responses by serological tests and enzyme-linked immunospot assay at 5 time points. Furthermore, we compared the course over time of the two branches of adaptive immunity to establish an eventual correlation between adaptive responses. Lastly, we evaluated putative influencing factors collected by an anonymized survey administered to all participants through multiparametric analysis. Among 984 healthcare workers evaluated for humoral immunity, 107 individuals were further analyzed to describe SARS-CoV-2-specific T-cell responses. Participants were divided into 4 age groups: <40 and ≥40 years for men, <48 and ≥48 years for women. Furthermore, results were segregated according to SARS-CoV-2-specific serostatus at baseline. Results: The disaggregated evaluation of humoral responses highlighted antibody levels decreased in older subjects. The humoral responses were higher in females than in males (p=0.002) and previously virus-exposed subjects compared to naïve subjects (p<0.001). The vaccination induced a robust SARS-CoV-2 specific T-cell response at early time points in seronegative subjects compared to baseline levels (p<0.0001). However, a contraction was observed 6 months after vaccination in this group (p<0.01). On the other hand, the pre-existing specific T-cell response detected in natural seropositive individuals was longer-lasting than the response of the seronegative subjects, decreasing only 10 months after vaccination. Our data suggest that T-cell reactiveness is poorly impacted by sex and age. Of note, SARS-CoV-2-specific T-cell response was not correlated to the humoral response at any time point. Discussion: These findings suggest prospects for rescheduling vaccination strategies by considering individual immunization status, personal characteristics, and the appropriate laboratory tests to portray immunity against SARS-CoV-2 accurately. Deepening our knowledge about T and B cell dynamics might optimize the decision-making process in vaccination campaigns, tailoring it to each specific immune response.

Six months SARS-CoV-2 serology in a cohort of mRNA vaccinated subjects over 90 years old.

Ageing is associated with a progressive decline and remodelling of the immune system. Also, the efficacy of COVID-19 vaccines has been observed to depend on subjects' age. The post-vaccination data about patients aged > 90 years old is scarcely represented in the literature. The antibody titre profiles of elderly vaccinated subjects (age > 90 years old) were evaluated and compared with profiles obtained in a younger population (age 23-69 years old). To the best of our knowledge, this is the first report providing post-vaccination serological data in subjects aged 90 + years old. This study suggests that distinct SARS-CoV-2 viral-specific antibody response profiles vary based on anti-N serostatus, age, and sex in the very elderly adults. The data obtained could impact the organisation of the vaccination campaign (i.e., prioritisation strategies, administration of additional doses) and the factors that facilitate intentions to receive the vaccination among elderly adults (i.e., vaccine effectiveness).

Italian Translation, Adaptation, and Validation of the Novel Satisfaction Measure Assessment after Primary Total Joint Arthroplasty: The Goodman Score Questionnaire.

Patient satisfaction after total joint arthroplasties (TJA) represents a key element for the evaluation of surgery success in relation to subjects' needs and expectations. The assessment tools are applied inconsistently throughout the literature, and thus, it is difficult to compare results among different studies. Goodman et al. proposed a standardized questionnaire with strong psychometric properties for the assessment of satisfaction. The present study aims to translate, adapt, and validate the Goodman questionnaire for the Italian population. After translation and back translation, the questionnaire was administrated to 50 patients. Internal consistency, test-retest reliability, floor and ceiling effects, and construct validity were evaluated (correlation with KOOS/HOOS, SF-12 PCS/MCS, EQ-5D). Responsiveness was evaluated with respect to SF-12 PCS improvements. The Italian version of the Goodman score questionnaire demonstrated psychometric properties similar to those of the original version. The translated questionnaire showed good internal consistency (Cronbach's alpha = 0.836) and test-retest reliability (ICC: 0.507). Moderate/strong correlations were observed between the Italian version of the Goodman score and other scores. The score significantly discriminated patients who improved from those who did not improve in SF-12 PCS after treatment. This study provides an adapted and validated Italian version of the Goodman score questionnaire, with psychometric properties similar to those of its original counterpart.

Exploratory assessment of serological tests to determine antibody titer against SARS-CoV-2: Appropriateness and limits.

BACKGROUND: Serological tests can be used to detect antibodies in the serum of subject's after SARS-CoV-2 infection and vaccination. Currently, variability in antibody titers and the availability of a multiplicity of serological tests have made it necessary to highlight their appropriateness and limitations in various diagnostic settings. METHODS: This study is part of Covidiagnostix, a multicenter project aimed at the assessment of the health technology used in SARS-CoV-2 serological tests. Based on data gained from the analysis of over 5000 subjects, a selected number of serum samples, representative of different diagnostic settings, were analyzed first by qualitative immunoassays (IgA, M, and G MILLIPLEX® SARS-CoV-2 tests based on Luminex® ) to define the immunoglobulins serum composition and subsequently by four serological diagnostic tests (Elecsys Anti-SARS-CoV-2 and Elecsys Anti-SARS-CoV-2 S by Roche, SARS-CoV-2 IgG by Siemens Healthcare, and CHORUS SARS-CoV-2 "NEUTRALIZING" Ab by DIESSE). The first WHO International Standard for SARS-CoV-2 was also analyzed using the same methods. RESULTS: This study evaluated the antibody content and titer of the WHO Standard and serum of subjects with/without previous infection and before/after vaccination for SARS-CoV-2. CONCLUSION: The definition of antibodies in the WHO standard and the analysis of serum samples allowed for the identification of the appropriateness of serological tests in each diagnostic setting, increasing the effectiveness of the resulting laboratory data. Furthermore, we found that it would be optimal to produce new international standards against the S1 domain and RBD of the SARS-CoV-2 spike protein for a more effective serological monitoring of vaccination.

Quantitative serological evaluation as a valuable tool in the COVID-19 vaccination campaign.

OBJECTIVES: After exceptional research efforts, several vaccines were developed against SARS-CoV-2 which sustains the pandemic COVID-19. The Comirnaty vaccine showed high efficacy in clinical trials and was the first to be approved for its distribution to the general population. We evaluated the immune response induced by the first vaccine dose in different sex/age groups and subjects with or without naturally present anti-SARS-CoV-2 antibodies. METHODS: As part of an Italian multicenter project (Covidiagnostix), serum samples from 4,290 health-professionals were serologically tested the day of the first vaccination dose, and 21 days later, using two different instrumentations (Siemens-Healthineers and Roche). RESULTS: In total, 97% of samples showed the presence of specific antibodies 21 days after the vaccination dose; the percentage of non-responders increased with age in both genders. Remarkably, naturally seropositive individuals showed antibody persistence up to 11 months and an exceptionally higher vaccination response compared to subjects never infected by SARS-CoV-2. CONCLUSIONS: This study highlighted the importance of the serological test i) to identify naturally SARS-CoV-2 seropositive individuals and ii) to evaluate the antibody level elicited by the first vaccination dose. Both tests, highlighted differences in the immune response, when subjects were stratified by sex and age, and between naturally seropositive and seronegative subjects. The data obtained show how serological tests could play a crucial role in the triage of the population subjected to the vaccination campaign for COVID-19. The definition of suitable instrumentation-specific thresholds is needed to correctly follow eventually acquired post-vaccination immunity in the general population.

Knee Pathology before and after SARS-CoV-2 Pandemic: An Analysis of 1139 Patients.

BACKGROUND: The SARS-CoV-2 pandemic drastically changed daily life activities and medical practice, leading to a reorganization of healthcare activities. People spent two months in home-isolation, changing their daily habits and undertaking a more sedentary lifestyle. Change in lifestyle is related to important consequences in knee pathologies. The aim of this study was to evaluate the outpatient activity for knee pathologies before and after lockdown in terms of incidence, severity, diagnosis, and treatment. METHODS: Medical records of patients with knee pathology in outpatient follow-up at IRCCS Istituto Ortopedico Galeazzi in Milan (Italy) were analyzed in the time frame 4 May-4 September 2020 and compared with patients examined between 4 May and 4 September 2019. RESULTS: A significant increase of knee diagnoses associated to patellofemoral disorders in 2020 was found (p = 0.004). In addition, physiotherapy was significantly more prescribed in 2020 than in 2019 (p = 0.012). CONCLUSIONS: The SARS-CoV-2 pandemic lockdown did not drastically change knee pathology, but it may have had an impact on it, highlighting a summary worsening of patellofemoral disorders associated with other knee diagnoses. Further studies are required to validate this result.

Remote Management of Patients after Total Joint Arthroplasty via a Web-Based Registry during the COVID-19 Pandemic.

BACKGROUND: In 2020, due to the outbreak of the COVID-19 (Coronavirus Disease 2019) pandemic, patients who underwent total joint arthroplasty were not able to undergo the proper postoperative surgical and rehabilitative care. This study aims to evaluate the potential of a web-cloud-based database on patients' follow-up in extraordinary situations, when a traditional in-person follow-up cannot be warranted. METHODS: Patients who underwent joint arthroplasty at our Institute between 21 February and 16 March 2020 were included in the study group and were matched to a similar population undergoing joint arthroplasty in February/March 2019. All patients routinely complete questionnaires before and after treatment, including patient-reported outcome measures such as the Visual Analogues Scale (VAS), Knee/Hip Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS/HOOS-PS) and Short-Form Health Survey (SF-12) for the monitoring of clinical improvements. RESULTS: 56 (study group) and 144 (control group) patients were included in the study. Both groups demonstrated significant improvements at 3 months. HOOS-PS improvement was significantly reduced in the 2020 group compared to 2019 (21.7 vs. 33.9, p < 0.001). This reduction was related to intense physical activities. Similarly, the functional score improvement related to these activities was reduced for patients undergoing knee replacement (8 vs. 10, p < 0.05). CONCLUSIONS: The web-based Institute Registry emerged as a meaningful and sensitive tool during an extraordinary situation such as the COVID-19 pandemic to monitor patients' progression after total joint arthroplasties. Thanks to this tool, it was possible to observe that the prevention of usual postoperative care due to pandemic-related restrictions did not alter the benefits observed after joint replacement surgeries, even if this condition reduced the postoperative improvements in the most burdensome physical activities. A broader use of this kind of tool would improve and potentially reduce the burden and costs of postoperative patients' monitoring in standard and extraordinary conditions. In addition, the systematic remote collection of data would allow for the identification of relevant differences in clinical outcomes in specific conditions or following the modification of treatment and rehabilitation protocols.

Coronavirus Disease 2019 Phenotypes, Lung Ultrasound, Chest Computed Tomography and Clinical Features in Critically Ill Mechanically Ventilated Patients.

Chest computed tomography (CT) may provide insights into the pathophysiology of coronavirus disease 2019 (COVID-19), although it is not suitable for a timely bedside dynamic assessment of patients admitted to intensive care unit (ICU); therefore, lung ultrasound (LUS) has been proposed as a complementary diagnostic tool. The aims of this study were to investigate different lungs phenotypes in patients with COVID-19 and to assess the differences in CT and LUS scores between ICU survivors and non-survivors. We also explored the association between CT and LUS, and oxygenation (arterial partial pressure of oxygen [PaO2]/fraction of inspired oxygen [FiO2]) and clinical parameters. The study included 39 patients with COVID-19. CT scans revealed types 1, 2 and 3 phenotypes in 62%, 28% and 10% of patients, respectively. Among survivors, pattern 1 was prevalent (p < 0.005). Chest CT and LUS scores differed between survivors and non-survivors both at ICU admission and 10 days after and were associated with ICU mortality. Chest CT score was positively correlated with LUS findings at ICU admission (r = 0.953, p < 0.0001) and was inversely correlated with PaO2/FiO2 (r = -0.375, p = 0.019) and C-reactive protein (r = 0.329, p = 0.041). LUS score was inversely correlated with PaO2/FiO2 (r = -0.345, p = 0.031). COVID-19 presents distinct phenotypes with differences between survivors and non-survivors. LUS is a valuable monitoring tool in an ICU setting because it may correlate with CT findings and mortality, although it cannot predict oxygenation changes.

Harmonization of six quantitative SARS-CoV-2 serological assays using sera of vaccinated subjects.

BACKGROUND AND AIMS: Vaccines, to limit SARS-CoV-2 infection, were produced and reliable assays are needed for their evaluation. The WHO produced an International-Standard (WHO-IS) to facilitate the standardization/comparison of serological methods. The WHO-IS, produced in limited amount, was never tested for reproducibility. This study aims at developing a reproducible and accessible working standard (WS) to complement the WHO-IS. MATERIALS AND METHODS: Sera from vaccinated individuals were used to produce the WSs. The WHO-IS, the WSs and single serum samples (n = 48) were tested on 6 quantitative serological devices. Neutralization assays were performed for the 48 samples and compared with their antibody titers. RESULTS: The WS carry an antibody titer 20-fold higher than the WHO-IS. It was reproducible, showed both good linearity and insignificant intra- and inter-laboratory variability. However, the WSs behave differently from the WHO-IS. Analysis of the 48 samples showed that single correlation factors are not sufficient to harmonize results from different assays. Yet, all the devices predict neutralization activity based on the antibody titer. CONCLUSIONS: A reproducible and highly concentrated WS, specific for IgG against SARS-CoV-2 Spike-glycoprotein was produced. Such characteristics make it particularly suited for the harmonization of commercially available assays and the consequent evaluation of post-vaccinated individuals.

Effect of the COVID-19 Outbreak on Pediatric Patients' Admissions to the Emergency Department in an Italian Orthopedic Trauma Hub.

BACKGROUND: The rapid diffusion of Coronavirus disease (COVID-19) in Northern Italy led the Italian government to dictate a national lockdown from 12 March 2020 to 5 May 2020. The aim of this observational cohort study is to analyze the differences in the number of pediatric patients' admission to the Emergency Room (ER) and in the type and causes of injury. METHODS: The pediatric population during the pandemic was compared to a similar group of patients admitted to the ER in 2019. Sex, age, triage color-code at admission, cause of trauma and presence of symptoms related to COVID-19 infection, discharge diagnosis and discharge modes were investigated. RESULTS: The lockdown period led to a reduction of 87.0% in ER admissions with a particular decrease in patients older than 12 years old. Moreover, a trend towards more severe codes and an increase in home-related injuries were observed during the pandemic, whereas the diagnosis of fracture was less frequent in the pre-pandemic group (p < 0.0001). CONCLUSIONS: A significant decrease in the ER attendances was reported during the lockdown. A shift in the cause and type of injury was observed; only the most serious traumas sought medical care with a higher percentage of severe triage codes and fractures.

The Gender Impact Assessment among Healthcare Workers in the SARS-CoV-2 Vaccination-An Analysis of Serological Response and Side Effects.

Healthcare professionals are considered to be at high risk of exposure and spread of SARS-CoV-2, and have therefore been considered a priority group in COVID-19 vaccination campaign strategies. However, it must be assumed that the immune response is influenced by numerous factors, including sex and gender. The analysis of these factors is an impact element for stratifying the population and targeting the vaccination strategy. Therefore, a large cohort of healthcare workers participating in the Italian vaccination campaign against SARS-CoV-2 has been studied to establish the impact of sex and gender on vaccination coverage using the Gender Impact Assessment approach. This study shows a significant difference in the antibody titers among different age and sex groups, with a clear decreasing trend in antibody titers in the older age groups. Overall, the serological values were significantly higher in females; the reported side effects are more frequent in females than in males. Therefore, disaggregated data point out how the evaluation of gender factors could be essential in COVID-19 vaccination strategies. On this biomedical and social basis, suggestions are provided to improve the SARS-CoV-2 vaccination campaign in healthcare professionals. Still, they could be adapted to other categories and contexts.

Management of Osteoarthritis During the COVID-19 Pandemic.

The pandemic spread of the new coronavirus disease 2019 (COVID-19) infection in China first, and all over the world at present, has become a global health emergency due to the rapidly increasing number of affected patients. Currently, a clear relationship between COVID-19 infection incidence and/or complications due to chronic or occasional treatments for other pathologies is still not clear, albeit the COVID-19 pandemic may condition the treatment strategy of complex disorders, such as osteoarthritis (OA). Importantly, OA is the most common age-related joint disease, affecting more than 80% of people older than the age of 55, an age burden also shared with the highest severity in COVID-19 patients. OA patients often show a large array of concomitant pathologies, such as diabetes, inflammation, and cardiovascular diseases that are again shared with COVID-19 patients and may therefore increase complications. Moreover, different OA treatments, such as NSAIDs, paracetamol, corticosteroids, opioids, or other molecules have a wide array of iatrogenic effects, potentially increasing COVID-19 secondary infection incidence or complications. In this review we critically analyze the evidence on either negative or positive effects of drugs commonly used to manage OA in this particular scenario. This would provide orthopedic surgeons in particular, and physicians, pharmacologists, and clinicians in general, a comprehensive description about the safety of the current pharmacological approaches and a decision-making tool to treat their OA patients as the coronavirus pandemic continues.