Measurement of antibody levels in patients with COVID-19 over time by immunofluorescence assay: a longitudinal observational study

Background During the coronavirus disease 2019 (COVID-19) pandemic, antibody screening is a critical tool to assess anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity. We examined variation in antibody titers associated with age and sex among patients with confirmed COVID-19. Methods Blood IgG levels were tested in 1081 patients with positive SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR) tests between 1 September and 31 December 2020. Patients who did not experience reinfection were identified. Serum IgG levels were measured by immunofluorescence assay. Antibody positivity and antibody titers were analyzed according to time since infection, sex, and age. Results The mean (standard deviation) age was 41.2 (14.2) years and 41.2% of patients were women. The lowest antibody positivity rate between the first and ninth month post-infection was detected in the sixth month. The lowest antibody titers among patients aged 20 to 80 years occurred in those aged 30 to 39 years. The IgG titer was positively correlated with age in years (r = 0.125) and decades (r = 0.126). Conclusions Six months after infection, anti-SARS-CoV-2 antibody titers increased. Anti-SARS-CoV-2 antibody titers also increased with age. Immunity and pathogenicity should be investigated in addition to antibody positivity rates and antibody titers.

Boosting Humoral Immunity from mRNA COVID-19 Vaccines in Kidney Transplant Recipients

Introduction: The immune response to the primary (two-dose) series of mRNA COVID-19 vaccines in kidney transplant recipients (KTRs) is very weak. We conducted a longitudinal observational study to compare the humoral response to a third, additional primary dose of mRNA vaccines between infection-naïve (IN-KTRs) and previously infected KTRs (PI-KTRs). Methods: We measured the levels of anti-spike (anti-s) IgG antibodies before and 14–21 days after the third dose and, in the secondary analysis, we compared the antibody response to BNT162b2 versus mRNA-1273. The reactogenicity assessment included solicited local and systemic reactions. Results: A total of 112 KTRs were enrolled, including 83 IN-KTR and 29 PI-KTR, among whom seroconversion in anti-s antibodies after the primary two-dose vaccination was achieved in 45.78% and 100% of cases, respectively. After three months, a waning antibodies titer by 67.4% (IN-KTR) and 7.5% (PI-KTR) was observed. After the third dose of the mRNA vaccine, 71.08% (59/83) of IN-KTR and 96.5% (28/29) of PI-KTR samples were seroconverted with a median anti-s titer of 468.0 (195.0–1620.0) BAU/mL and 1629.0 (1205–1815) BAU/mL, respectively. Of those IN-KTR in whom the primary vaccination failed, 46.67% (21/45) of patients achieved seroconversion after the third dose. No serious adverse events after the third dose were reported. In strata analyses, after the third dose, 66% (40/60) of patients vaccinated with BNT162b2 and 82.6% (19/23) of patients vaccinated with mRNA-1273 seroconverted with a median anti-s titer of 384.5 (144–837) BAU/mL and 1620 (671–2040) BAU/mL, respectively. Conclusions: The use of a third dose of mRNA vaccine may be of benefit for KTR, especially for those in whom the primary vaccination failed. Vaccines with a higher dose of mRNA and a longer interval between doses of the primary vaccination, such as mRNA-1273, seem to be the preparations of choice in immunocompromised individuals.

Assessing the health literacy level of students in higher education: evolution throughout the training

Objectives: This work has two objectives: contribute to evaluate the level of health literacy of students in higher education, in the area of health and to contribute to the formulation of strategies to adapt the content of training to the needs of students. Methods: In this longitudinal observational study, a health literacy assessment questionnaire (NVS) was applied to students from 3 Health Schools and 2 different courses (Nursing and Dental Hygiene), at the beginning of the first school year, and at the end of the third year. Results: Less than 5% of the students participating in this study had inadequate health literacy at the entrance to the course. Women had a better level of health literacy than men, although no statistical significance was found (p=0.153). The health literacy gains are different among the courses. Nursing students began with a higher level of health literacy but were overtaken by oral hygiene students at the end of the 3rd year. However, the level of health literacy did not differ statistically throughout the training, although an increase in the level of health literacy was observed. Conclusions: The relationship between health literacy and health is recognized. Higher education institutions need to formulate strategies to adapt the content of training to the needs of students and to the level of health literacy in order to train students for lifelong learning.

Durability of Humoral Immune Responses to SARS-CoV-2 in Citizens of Ariano Irpino (Campania, Italy): A Longitudinal Observational Study With an 11.5-Month Follow-Up

As of November 17, 2021, SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2), the causative agent of COVID-19 (COronaVIrus Disease 19), has infected ~250 million people worldwide, causing around five million deaths. Titers of anti-SARS-CoV-2 neutralizing antibodies were relatively stable for at least 9 months in a population-based study conducted in Wuhan, China, both in symptomatic and in asymptomatic individuals. In the mass screening campaign conducted in the town of Ariano Irpino (Avellino, Italy) in May, 2020, 5.7% (95% CI: 5.3-6-1) of the 13,444 asymptomatic citizens screened were positive for anti-nucleocapsid antibodies against SARS-CoV-2. Among these, 422 citizens were re-tested for anti SARS-CoV-2 antibodies in January, 2021 and/or in April, 2021 and enrolled in this longitudinal observational study. Median (interquartile range) age of the study cohort was 46 years (29–59), with 47 (11.1%) participants of minor age, while 217 (51.4%) participants were females. There was no evidence of re-infection in any of the subjects included. Presence of anti-nuclear antibodies antibodies (Elecysis, Roche) was reported in 95.7 and 93.7% of evaluable participants in January and April, 2021. Multiple logistic regression analysis used to explore associations between age, sex and seroprevalence showed that adults vs. minors had significantly lower odds of having anti-S1 antibodies (Biorad) both in January, 2021 and in April, 2021. Our findings showed that antibodies remained detectable at least 11.5 months after infection in >90% of never symptomatic cases. Further investigation is required to establish duration of immunity against SARS-CoV-2.

Effectiveness of Hypnoanalgesia in Paediatric Dermatological Surgery

Background and objective. Stress in surgical settings has subtle psychological and physiological repercussions in children. The objective is to evaluate whether hypnosedation is effective in reducing the doses of sedation and analgesia required during the periprocedural period in children undergoing dermatological surgery, without negatively affecting pain and satisfaction. Patients and methods: A prospective, longitudinal, observational study where paediatric patients (aged 5–16 years) scheduled for dermatological surgery were analysed according to whether they received hypnosis or distraction during surgery (both common procedures at the centre). As outcome measurements we used sedation doses (propofol) during surgery and the need for analgesia; pain assessment post-surgery and at 24 h using a visual analogue scale (VAS) or revised face pain scale (FPS-r) (both 0–10) depending on age, as well as patient and guardian satisfaction (on a scale of 0–10). Results: Of the 68 patients eligible during the follow-up period, 65 were included. Of these, 33 were treated with hypnosis and 32 with distraction. Children who underwent hypnosis required less total propofol (45.5 ± 11.8 mg vs. 69.3 ± 16.8 mg; p < 0.001) and metamizole in the immediate postoperative period (34.4% vs. 65.6%; p = 0.018). After 24 h, they required less ibuprofen (9.1% vs. 28.1%; p = 0.048) and paracetamol (48.5% vs. 75.0%; p = 0.028). Mean pain according to VAS or FPS-r at 24 h was 3.1 with hypnosis vs. 4.3 with distraction (p < 0.001). Overall satisfaction was higher in the hypnosis group (8.7 ± 0.1 vs. 8.1 ± 0.2; p = 0.009). Conclusions: Hypnoanalgesia in children undergoing dermatological outpatient surgery could not only reduce sedation and analgesia requirements, but also improve child and guardian(s) satisfaction.

Persistence of immune response in health care workers after two doses BNT162b2 in a longitudinal observational study

Background The mRNA-based vaccine BNT162b2 of BioNTech/Pfizer has shown high efficacy against SARS-CoV-2 infection and a severe course of the COVID-19 disease. However, little is known about the long-term durability of the induced immune response resulting from the vaccination. Methods In a longitudinal observational study in employees at a German hospital we compared the humoral and cellular immune response in 184 participants after two doses of the BioNTech/Pfizer vaccine (BNT162b2) with a mid-term follow-up after 9 months. Anti-SARS-CoV-2 binding antibodies were determined using both a quantitative and a semi-quantitative assay. For a qualitative assessment of the humoral immune response, we additionally measured neutralizing antibodies. Cellular immune response was evaluated by measuring Interferon-gamma release after stimulating blood-cells with SARS-CoV-2 specific peptides using a commercial assay. Results In the first analysis, a 100% humoral response rate was described after two doses of BNT162b2 vaccine with a mean antibody ratio of 8.01 ± 1.00. 9 months after the second dose of BNT162b2, serological testing showed a significant decreased mean antibody ratio of 3.84 ± 1.69 (p < 0.001). Neutralizing antibodies were still detectable in 96% of all participants, showing an average binding inhibition value of 68.20% ± 18.87%. Older age, (p < 0.001) and obesity (p = 0.01) had a negative effect on the antibody persistence. SARS-CoV-2 specific cellular immune response was proven in 75% of individuals (mean IFN-gamma release: 579.68 mlU/ml ± 705.56 mlU/ml). Conclusion Our data shows a declining immune response 9 months after the second dose of BNT162b2, supporting the potentially beneficial effect of booster vaccinations, the negative effect of obesity and age stresses the need of booster doses especially in these groups.

Two-year longitudinal observational study of junior doctors as clinical teachers: the Associate Clinical Teaching Fellow Program

Introduction: Most clinical teachers are not trained to teach, though they are critical to determining the quality of clinical learning environment. The General Medical Council, United Kingdom, recognises that being a good teacher is not innate, but that skills and attributes can usually be acquired. Clinical teaching is part of training of junior doctors in the United Kingdom, and from learners’ perspectives, junior doctors are effective clinical teachers, but there are few structured opportunities to learn how to teach during clinical training. The Associate Clinical Teaching Fellow (ACTF) program was developed to provide such structured platform for clinical trainees. The aim of this paper is to evaluate the quality of teaching by the trainees against the current-standard of clinical teaching in the first 2 years of its inception, and to adapt validated feedback questionnaires for practical use. Methods: A prospective longitudinal observational study was done over 2 years in a large 1,215 bed tertiary hospital. Multiple cross-sectional assessments of teachings by ACTFs and consultant teachers were done using two validated questionnaires, the Stanford Faculty Development Program-26 (SFDP-26) and the Clinical Teaching Effectiveness questionnaire (CTEQ), and an in-house global (IHG) feedback form prepared by third- and fifth-year students. Both trainees and consultants were unaware of the timing of the SFDP-26 and CTEQ feedbacks. A graphical representation of all responses was used to create a grading system for practical feedbacks. Results: A total of 507 of 765 (66%) of SFPD-26 and CTEQ and 224 of 286 (78%) of IHG questionnaires were returned for 26 trainees and 31 consultants by 266 medical students. There was a statistically significant higher ratings of trainees in seven of eight domains of SFDP-26, and the median (interquartile ranges [IQR]) overall score was 115 (105–126) and 108 (99–121) for trainees and consultants, respectively (P < 0.0001). Similarly, trainees were rated significantly higher in seven of nine CTEQ domains, and this was reflected in the overall score. The patterns were similar for third- and fifth-year students, and the type of learning exposure did not make a difference. With these students, the overall teaching effectiveness correlated (Spearman Correlation Coefficient [SCC]) the most with enthusiastic and stimulating (SCC 0.711; P < 0.0001), establishes rapport (SCC 0.69; P < 0.0001) and is accessible (SCC 0.67; P < 0.0001) in CTEQ, and with learning climate (SCC 0.62; P < 0.0001), communication of goals (SCC 0.54; P < 0.0001) and evaluation (SCC 0.52; P < 0.0001) in SFDP-26. At the end of their rotations, 30% of both groups of students were neutral or disagreed that consultants were essential to their clinical programs compared to 15% (P = 0.001) and 11% (P < 0.0001) of third- and fifth-year students, respectively, felt about trainees. By applying a new grading system derived from the full database of responses, the trainees would be graded 1 and consultants 7 out of 10 possible grades. Conclusions: Teaching delivered by doctors in training within a formal teaching program is of good quality and well received by medical students. There is a need for an equivalent program for trainee clinical educationalists like the Integrated Academic Training scheme of the National Institute of Health Research (NIHR), UK, for trainee academics. More qualitative studies are needed to analyse some of the findings in this study.