Coinfection with Strongyloides and SARS-CoV-2: A Systematic Review.

BACKGROUND: Treatments for COVID-19, including steroids, might exacerbate Strongyloides disease in patients with coinfection. We aimed to systematically review clinical and laboratory features of SARS-CoV-2 and Strongyloides coinfection, investigate possible interventions, assess outcomes, and identify research gaps requiring further attention. METHODS: We searched two electronic databases, LitCOVID and WHO, up to August 2022, including SARS-CoV-2 and Strongyloides coinfection studies. We adapted the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system for standardized case causality assessment to evaluate if using corticosteroids or other immunosuppressive drugs in COVID-19 patients determined acute manifestations of strongyloidiasis. RESULTS: We included 16 studies reporting 25 cases of Strongyloides and SARS-CoV-2 coinfection: 4 with hyperinfection syndrome; 2 with disseminated strongyloidiasis; 3 with cutaneous reactivation of strongyloidiasis; 3 with isolated digestive symptoms; and 2 with solely eosinophilia, without clinical manifestations. Eleven patients were asymptomatic regarding strongyloidiasis. Eosinopenia or normal eosinophil count was reported in 58.3% of patients with Strongyloides reactivation. Steroids were given to 18/21 (85.7%) cases. A total of 4 patients (19.1%) received tocilizumab and/or Anakirna in addition to steroids. Moreover, 2 patients (9.5%) did not receive any COVID-19 treatment. The causal relationship between Strongyloides reactivation and COVID-19 treatments was considered certain (4% of cases), probable (20% of patients), and possible (20% of patients). For 8% of cases, it was considered unlikely that COVID-19 treatment was associated with strongyloidiasis reactivations; the relationship between the Strongyloides infection and administration of COVID-19 treatment was unassessable/unclassifiable in 48% of cases. Of 13 assessable cases, 11 (84.6%) were considered to be causally associated with Strongyloides, ranging from certain to possible. CONCLUSIONS: Further research is needed to assess the frequency and risk of Strongyloides reactivation in SARS-CoV-2 infection. Our limited data using causality assessment supports recommendations that clinicians should screen and treat for Strongyloides infection in patients with coinfection who receive immunosuppressive COVID-19 therapies. In addition, the male gender and older age (over 50 years) may be predisposing factors for Strongyloides reactivation. Standardized guidelines should be developed for reporting future research.

Meta-analysis of diagnostic performance of serological tests for SARS-CoV-2 antibodies up to 25 April 2020 and public health implications.

We reviewed the diagnostic accuracy of SARS-CoV-2 serological tests. Random-effects models yielded a summary sensitivity of 82% for IgM, and 85% for IgG and total antibodies. For specificity, the pooled estimate were 98% for IgM and 99% for IgG and total antibodies. In populations with ≤ 5% of seroconverted individuals, unless the assays have perfect (i.e. 100%) specificity, the positive predictive value would be ≤ 88%. Serological tests should be used for prevalence surveys only in hard-hit areas.

Observational Study on Antibody Response to COVID-19 Vaccines in PAtients with Gastro-Entero-PanCreatic Cancers and NeuroendocrIne NeoplAsms on Systemic TreatmEnts (VACCINATE).

The coronavirus disease-19 (COVID-19) pandemic dramatically impacted oncological patients' care. Since the introduction of vaccines and the demonstration of their benefit on frail patients, COVID-19 vaccinations were indicated to also be beneficial to oncological population. However, data about the impact of anticancer-treatments and the timing between vaccinations and systemic therapy delivery were not available. We aimed to evaluate potential factors influencing the outcome of the COVID-19 vaccination in cancer patients. We prospectively collected data of patients undergoing the COVID-19 vaccination with gastro-entero-pancreatic and neuroendocrine neoplasms, treated at our institute, between 03/2021 and 12/2021. We enrolled 46 patients, 63.1% males; at the time of data collection, 86.9% had received two-doses of Pfizer-BioNTech and the rest had received the Moderna vaccine. All patients obtained a subsequent immune-response. Chemotherapy seems to determinate a significantly lower antibody response after vaccination compared to the other anti-cancer agents (p = 0.004). No significant effect on immune-response was reported for both vaccinations performed ≤7 vs. >7 days from the last systemic treatment (p = 0.77) and lymphocytes count (p = 0.11). The findings suggest that the optimal timing for COVID-19 vaccination and lymphocytes count are not the issue, but rather that the quality of the subset of lymphocytes before the vaccination determine the efficacy level of immune-response in this population.

European Cohorts of patients and schools to Advance Response to Epidemics (EuCARE): a cluster randomised interventional and observational study protocol to investigate the relationship between schools and SARS-CoV-2 infection.

BACKGROUND: Contradictory results were reported on the role of school closure/reopening on the overall SARS-CoV-2 transmission rate, as well as on which kind and level of mitigation measures implemented in schools may be effective in limiting its diffusion. Some recent studies were reassuring, showing that opening did not increase the community spread, although teachers and families are worried about the high class density. On the other hand, distance learning was associated with a negative impact on learning, sociability and psychological health, especially in vulnerable children. As it becomes clear that the SARS-CoV-2 pandemic will last for a long time, there is a high need for studies and solutions to support safe schools opening based on scientific evidence of harms and benefits. The Lolli-Methode (LM) is a strategy for epidemiological surveillance and early intervention aiming at SARS-CoV-2 outbreaks' reduction in schools, relying on polymerase chain reaction analysis of saliva samples. METHODS: In this cluster randomised trial protocol, we aim to determine whether the LM is useful to support schools opening and to reduce clusters and attack rates in schools, compared with the standard of care (SoC) surveillance by public health departments. This multicenter study will enrol 440 classes (around 8800 students, teachers and other personnel) from two countries, cluster randomised to LM or SoC. The samples from the pools will be collected and tested using PCR-based techniques. Test results will be combined with questionnaires filled in by children, parents, schoolteachers, and principals, concerning ongoing mitigation measures, their perceived psychological impact and other health and socio-economic information. An ancillary observational study will be carried out to study the prevalence of SARS-CoV-2 in schools, frequencies and size of clusters and attack rates, to compare the effectiveness of the different preventive measures adopted and to evaluate psychological issues in students and teachers in relation to the pandemic's containment measures. DISCUSSION: By the end of this study, we will have defined and characterised the applicability of the LM for SARS-CoV-2 surveillance, as well as the impact of pandemic preventive measures on children and teachers. Trial registration International Standard Randomised Controlled Trial Number: NCT05396040, 27.05.2022.

Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis.

To assess the evidence on SARS-CoV2 infection and Covid-19 in relation to deficiency and supplementation of vitamin D, we conducted a systematic review up to April 2021. We summarised data from 38 eligible studies, which presented risk estimates for at least one endpoint, including two RCT and 27 cohort-studies: 205565 patients with information on 25OHD status and 2022 taking vitamin D supplementation with a total of 1197 admitted to the ICU or who needed invasive mechanical ventilation or intubation and hospital stay, and more than 910 Covid-19 deaths. Primary outcomes were severity and mortality and the main aim was to evaluate the association with vitamin D supplementation. Random effects models showed that supplementation was associated with a significant lower risk of both Covid-19 severe disease (SRR 0.38, 95% CI 0.20-0.72, 6 studies) and mortality (SRR 0.35, 95% CI 0.17-0.70, 8 studies). There were no statistically significant dose differences between studies: summary estimates with regular doses remain statistically significant, suggesting that higher doses are not necessary. For patients on vitamin D supplementation, a greater reduction in mortality risk emerged in older individuals and at higher latitudes. Regarding the quality of studies, assessed using the New Castle-Ottawa quality scale, the analysis revealed in most cases no statistically significant differences between low, medium or high quality studies. We found significant associations of vitamin D supplementation with Covid-19, encompassing risks of disease worsening and mortality, especially in seasons characterized by 25OHD deficiency and with not severe patients. Dedicated randomized clinical studies are encouraged to confirm these results.

The Impact of Sport Activity Shut down during the COVID-19 Pandemic on Children, Adolescents, and Young Adults: Was It Worthwhile?

We conducted a national retrospective survey of 1764 athletes aged ≤25 years to investigate the benefit-risk balance of sport closure during the COVID-19 pandemic peaks in Italy. Univariate and multivariable analyses were carried out to investigate the association between sport practice during the study period and (1) the risk of SARS-CoV-2 infection in athletes and their families and (2) body mass index (BMI) change, and adherence to World Health Organization (WHO) guidelines for physical activity. The percentage of subjects with a positive SARS-CoV-2 test was similar in those participating and not taking part into sport activities (11% vs. 12%, respectively, p = 0.31). Restricting the analysis to subjects who practiced sports within an organized sport society/center, the risk of SARS-CoV-2 positivity was reduced for athletes who had never stopped their training (odds ratio (OR); 95% confidence intervals (CI): 0.62; 0.41-0.93). On the other side, responders who had stopped sport activity showed a 1% increase in BMI. Adherence to WHO guidelines for physical activity was significantly higher for athletes who had continued sport activities. In conclusion, sport closure and limitations had an important negative impact on the overall health of young athletes, being also not effective in reducing the spread of COVID-19.

SARS-CoV-2 Immunization Orchestrates the Amplification of IFNγ-Producing T Cell and NK Cell Persistence.

A successful vaccination would represent the most efficient means to control the pandemic of Coronavirus Disease-19 (COVID-19) that led to millions of deaths worldwide. Novel mRNA-based vaccines confer protective immunity against SARS-CoV-2, but whether immunity is immediately effective and how long it will remain in recipients are uncertain. We sought to assess the effectiveness of a two-dose regimen since the boosts are often delayed concerning the recommended intervals. Methods: A longitudinal cohort of healthcare workers (HCW, N = 46; 30.4% men; 69.6% women; mean age 36.05 ± 2.2 years) with no SARS-CoV-2 infection as documented by negative polymerase chain reaction was immunophenotyped in PBMC once a week for 4 weeks from the prime immunization (Pfizer mRNA BNT162b2) and had received 2 doses, to study the kinetic response. Results: We identified three risk groups to develop SARS-CoV-2 infection IgG+-based (late responders, R-; early responders, R+; pauci responders, PR). In all receipts, amplification of B cells and NK cells, including IL4-producing B cells and IL4-producing CD8+ T cells, is early stimulated by the vaccine. After the boost, we observed a growing increase of NK cells but a resistance of T cells, IFNγ-producing CD4+T cells, and IFNγ-producing NK cells. Also, hematologic parameters decline until the boost. The positive association of IFNγ-producing NK with IFNγ-producing CD4+T cells by the multiple mixed-effect model, adjusted for confounders (p = 0.036) as well as the correlation matrix (r = 0.6, p < 0.01), suggests a relationship between these two subsets of lymphocytes. Conclusions: These findings introduce several concerns about policy delay in vaccination: based on immunological protection, B cells and the persistent increase of NK cells during 2 doses of the mRNA-based vaccine could provide further immune protection against the virus, while CD8+ T cells increased slightly only in the R+ and PR groups.

SARS-CoV-2 Circulation in the School Setting: A Systematic Review and Meta-Analysis.

The contribution of children to viral spread in schools is still debated. We conducted a systematic review and meta-analysis of studies to investigate SARS-CoV-2 transmission in the school setting. Literature searches on 15 May 2021 yielded a total of 1088 publications, including screening, contact tracing, and seroprevalence studies. MOOSE guidelines were followed, and data were analyzed using random-effects models. From screening studies involving more than 120,000 subjects, we estimated 0.31% (95% confidence interval (CI) 0.05-0.81) SARS-CoV-2 point prevalence in schools. Contact tracing studies, involving a total of 112,622 contacts of children and adults, showed that onward viral transmission was limited (2.54%, 95% CI 0.76-5.31). Young index cases were found to be 74% significantly less likely than adults to favor viral spread (odds ratio (OR) 0.26, 95% CI 0.11-0.63) and less susceptible to infection (OR 0.60; 95% CI 0.25-1.47). Lastly, from seroprevalence studies, with a total of 17,879 subjects involved, we estimated that children were 43% significantly less likely than adults to test positive for antibodies (OR 0.57, 95% CI 0.49-0.68). These findings may not applied to the Omicron phase, we further planned a randomized controlled trial to verify these results.

Predictors of poor seroconversion and adverse events to SARS-CoV-2 mRNA BNT162b2 vaccine in cancer patients on active treatment. Role of the Research Nurse.

BACKGROUND: Vaccines have shown 95% protection from COVID-19 disease in healthy populations. Initial findings in cancer patients suggest a lower seroconversion and greater toxicity possibly related to myelo-immunosuppressive therapies. AIM: We conducted a prospective study to assess factors predicting poor seroconversion and adverse events following immunization (AEFI) to the BNT162b2 vaccine in cancer patients on active treatment. METHODS: Blood samples were collected by the research nurse at first dose (visit 1), second dose (visit 2), after 42 days (visit 3) and after 6 months (visit 4). At visit 1, 3 and 4 participants received: Hospital Anxiety and Depression Scale (HADS) and Distress Thermometer. Patients who ended treatment >6 months on active surveillance served as controls. RESULTS: Between March and July 2021, 320 subjects were recruited and 291 were assessable. The lack of seroconversion at 21 days from the second dose was 1.6% (95% CI, 0.4-8.7) on active surveillance, 13.9% (8.2-21.6) on chemotherapy, 11.4% (5.1-21.3) on hormone therapy, 21.7% (7.5-43.7) on targeted therapy and 4.8% (0.12-23.8) on immunotherapy. Compared to controls, the risk of no IgG response was greater for chemotherapy (P=0.033), targeted therapy (0.005) and hormonotherapy (P=0.051). Lymphocyte count less than 1x109/L, older age and advanced stage also significantly predicted poor seroconversion. Overall, 43 patients (14.8%) complained of AEFI, mostly of mild grade. Risk of AEFI was greater in females (P=0.001) and younger patients (P=0.009). CONCLUSIONS: A third booster dose and long-term serological testing is required in subjects who have not responded to the vaccine. NURSING IMPLICATIONS: nurses must take responsibility for promoting and protecting the health of cancer patients.

Predictors of poor seroconversion and adverse events to SARS-CoV-2 mRNA BNT162b2 vaccine in cancer patients on active treatment.

PURPOSE: Initial findings in patients with cancer suggest a lower seroconversion to SARS-CoV-2 vaccination possibly related to myelo-immunosuppressive therapies. We conducted a prospective study to assess factors predicting poor seroconversion and adverse events following immunisation (AEFI) to the BNT162b2 vaccine in patients on active treatment. PATIENTS AND METHODS: Cancer patients, candidates to two doses of BNT162b2 SARS-CoV-2 vaccination, were enrolled. Patients on active surveillance served as controls. The primary endpoint was poor seroconversion (anti S1/S2 IgG < 25 AU/mL) after 21 days from the second dose. RESULTS: Between March and July 2021, 320 subjects were recruited, and 291 were assessable. The lack of seroconversion at 21 days from the second dose was 1.6% (95% CI, 0.4-8.7) on active surveillance, 13.9% (8.2-21.6) on chemotherapy, 11.4% (5.1-21.3) on hormone therapy, 21.7% (7.5-43.7) on targeted therapy and 4.8% (0.12-23.8) on immune-checkpoint-inhibitors (ICI). Compared to controls, the risk of no IgG response was greater for chemotherapy (p = 0.033), targeted therapy (0.005) and hormonotherapy (p = 0.051). Lymphocyte count < 1 × 109/L (p = 0.04) and older age (p = 0.03) also significantly predicted poor seroconversion. Overall, 43 patients (14.8%) complained of AEFI, mostly of mild grade. Risk of AEFI was greater in females (p = 0.001) and younger patients (p = 0.009). CONCLUSION: Chemotherapy, targeted therapy, hormone therapy, lymphocyte count < 1 × 109/L, and increasing age predict poor seroconversion after two doses of BNT162b2 in up to 20% of patients, indicating the need for a third dose and long-term serological testing in non-responders. AEFI occur much more frequently in women and younger subjects who may benefit from preventive medications. CLINICALTRIALS. GOV IDENTIFIER: NCT04932863.

Lower probability and shorter duration of infections after COVID-19 vaccine correlate with anti-SARS-CoV-2 circulating IgGs.

The correlation between immune responses and protection from SARS-CoV-2 infections and its duration remains unclear. We performed a sanitary surveillance at the European Institute of Oncology (IEO) in Milan over a 17 months period. Pre-vaccination, in 1,493 participants, we scored 266 infections (17.8%) and 8 possible reinfections (3%). Post-vaccination, we identified 30 infections in 2,029 vaccinated individuals (1.5%). We report that the probability of infection post-vaccination is i) significantly lower compared to natural infection, ii) associated with a significantly shorter median duration of infection than that of first infection and reinfection, iii) anticorrelated with circulating antibody levels.

A SARS-CoV-2 Infection High-Uptake Program on Healthcare Workers and Cancer Patients of the National Cancer Institute of Naples, Italy.

BACKGROUND: From the beginning of 2020, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) quickly spread worldwide, becoming the main problem for the healthcare systems. Healthcare workers (HCWs) are at higher risk of infection and can be a dangerous vehicle for the spread of the virus. Furthermore, cancer patients (CPs) are a vulnerable population, with an increased risk of developing severe and lethal forms of Coronavirus Disease 19 (COVID-19). Therefore, at the National Cancer Institute of Naples, where only cancer patients are treated, a surveillance program aimed to prevent the hospital access of SARS-CoV-2 positive subjects (HCWs and CPs) was implemented. The study aims to describe the results of the monitoring activity for the SARS-CoV-2 spread among HCWs and CPs, from March 2020 to March 2021. METHODS: This surveillance program included a periodic sampling through nasopharyngeal molecular swabs for SARS-CoV-2 (Real-Time Polymerase Chain Reaction, RT-PCR). CPs were submitted to the molecular test at least 48 h before hospital admission. Survival analysis and multiple logistic regression models were performed among HCWs and CPs to assess the main SARS-CoV-2 risk factors. RESULTS: The percentages of HCWs tested with RT-PCR for the detection of SARS-CoV-2, according to the first and the second wave, were 79.7% and 91.7%, respectively, while the percentages for the CPs were 24.6% and 39.6%. SARS-CoV-2 was detected in 20 (1.7%) HCWs of the 1204 subjects tested during the first wave, and in 127 (9.2%) of 1385 subjects tested in the second wave (p < 0.001); among CPs, the prevalence of patients tested varied from 100 (4.6%) during the first wave to 168 (4.9%) during the second wave (p = 0.8). The multivariate logistic analysis provided a significant OR for nurses (OR = 2.24, 95% CI 1.23-4.08, p < 0.001) compared to research, administrative staff, and other job titles. CONCLUSIONS: Our findings show that the positivity rate between the two waves in the HCWs increased over time but not in the CPs; therefore, the importance of adopting stringent measures to contain the shock wave of SARS-CoV-2 infection in the hospital setting was essential. Among HCWs, nurses are more exposed to contagion and patients who needed continuity in oncological care for diseases other than COVID-19, such as suspected cancer.

Outcomes of head and neck cancer management from two cancer centres in Southern and Northern Europe during the first wave of COVID-19.

OBJECTIVE: To describe the approach and outcomes from two cancer centres in Southern and Northern Europe during the first wave of coronavirus disease 2019 (COVID-19) of patients with head and neck cancer (HNC). METHODS: Data collection was performed on a retrospective cohort of patients surgically treated for primary HNC between March and May 2020, using data from two tertiary hospitals: the European Institute of Oncology (Milan) and Guy's & St Thomas' NHS Foundation Trust (London). RESULTS: We included 77 patients with HNC. More patients with COVID-19 were taking angiotensin-converting enzyme (ACE) inhibitors and had Clavien-Dindo Classification grade I compared to negative patients, respectively (60% vs 22% [p = 0.058] and 40% vs 8% [p = 0.025]). Multivariate logistic regression analyses confirmed our data (p = 0.05 and 0.03, respectively). Sex and age were statistically significantly different (p = 0.05 and <0.001 respectively), showing more male patients (75% vs 53.66%, respectively) and more elderly patients in Italy than in the United Kingdom (patients aged >63 years: 69.44% vs 29.27%). CONCLUSIONS: This study presents a large cohort of patients with HNC with nasopharyngeal swab during the first peak of the COVID-19 pandemic in Europe. Patients with HNC with COVID-19 appeared more likely to develop postsurgical complications and to be taking ACE inhibitors. The preventive measures adopted guaranteed the continuation of therapeutic surgical intervention.

Continuity of Cancer Care: The Surgical Experience of Two Large Cancer Hubs in London and Milan.

The SARS-CoV-2 (COVID-19) pandemic is having a large effect on the management of cancer patients. This study reports on the approach and outcomes of cancer patients receiving radical surgery with curative intent between March and September 2020 (in comparison to 2019) in the European Institute of Oncology, IRCCS (IEO) in Milan and the South East London Cancer Alliance (SELCA). Both institutions implemented a COVID-19 minimal pathway where patients were required to self-isolate prior to admission and were swabbed for COVID-19 within 72 h of surgery. Positive patients had surgery deferred until a negative swab. At IEO, radical surgeries declined by 6% as compared to the same period in 2019 (n = 1477 vs. 1560, respectively). Readmissions were required for 3% (n = 41), and <1% (n = 9) developed COVID-19, of which only one had severe disease and died. At SELCA, radical surgeries declined by 34% (n = 1553 vs. 2336). Readmissions were required for 11% (n = 36), <1% (n = 7) developed COVID-19, and none died from it. Whilst a decline in number of surgeries was observed in both centres, the implemented COVID-19 minimal pathways have shown to be safe for cancer patients requiring radical treatment, with limited complications and almost no COVID-19 infections.

A cross-sectional and prospective cohort study of the role of schools in the SARS-CoV-2 second wave in Italy.

BACKGROUND: During COVID-19 pandemic, school closure has been mandated in analogy to its effect against influenza, but it is unclear whether schools are early COVID-19 amplifiers. METHODS: We performed a cross-sectional and prospective cohort study in Italy during the second COVID-19 wave (from September 30, 2020 until at least February 28, 2021). We used databases from the Italian Ministry of Education, the Veneto region systems of SARS-CoV-2 cases notification and of schools' secondary cases tracing to compare SARS-CoV-2 incidence in students/school staff and general population and incidence across age groups. Number of tests, secondary infections by type of index case and ratio cases/ tests per school were estimated using an adjusted multivariable generalized linear regression model. Regional reproduction numbers Rt were estimated from Italian Civil Protection daily incidence data with a method of posterior distribution using a Markov Chain Monte Carlo algorithm. FINDINGS: SARS-CoV-2 incidence among students was lower than in the general population. Secondary infections at school were <1%, and clusters of ≥2 secondary cases occurred in 5-7% of the analysed schools. Incidence among teachers was comparable to the population of similar age (P = 0.23). Secondary infections among teachers were rare, occurring more frequently when the index case was a teacher than a student (37% vs. 10%, P = 0.007). Before and around the date of school opening in Veneto, SARS-CoV-2 incidence grew maximally in 20-29- and 45-49-years old individuals, not among students. The lag between school opening dates in Italian regions and the increase in the regional COVID-19 Rt was not uniform. Finally, school closures in two regions where they were implemented before other measures did not affect Rt decrease. INTERPRETATION: This analysis does not support a role for school opening as a driver of the second COVID-19 wave in Italy, a large European country with high SARS-CoV-2 incidence. FUNDING: Fondazione MITE.

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.

Semantic and Geographical Analysis of COVID-19 Trials Reveals a Fragmented Clinical Research Landscape Likely to Impair Informativeness.

Background: The unprecedented impact of the COVID-19 pandemic on modern society has ignited a "gold rush" for effective treatment and diagnostic strategies, with a significant diversion of economic, scientific, and human resources toward dedicated clinical research. We aimed to describe trends in this rapidly changing landscape to inform adequate resource allocation. Methods: We developed an online repository (COVID Trial Monitor) to analyze in real time the growth rate, geographical distribution, and characteristics of COVID-19 related trials. We defined structured semantic ontologies with controlled vocabularies to categorize trial interventions, study endpoints, and study designs. Analyses are publicly available at https://bioinfo.ieo.it/shiny/app/CovidCT. Results: We observe a clear prevalence of monocentric trials with highly heterogeneous endpoints and a significant disconnect between geographic distribution and disease prevalence, implying that most countries would need to recruit unrealistic percentages of their total prevalent cases to fulfill enrolment. Conclusions: This geographically and methodologically incoherent growth casts doubts on the actual feasibility of locally reaching target sample sizes and the probability of most of these trials providing reliable and transferable results. We call for the harmonization of clinical trial design criteria for COVID-19 and the increased use of larger master protocols incorporating elements of adaptive designs. COVID Trial Monitor identifies critical issues in current COVID-19-related clinical research and represents a useful resource with which researchers and policymakers can improve the quality and efficiency of related trials.