Chronic graft vs. host disease and hypogammaglobulinemia predict a lower immunological response to the BNT162b2 mRNA COVID-19 vaccine after allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: Due to the high mortality rate of COVID-19, the assessment of BNT162b2 SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech) efficacy in allogeneic hematopoietic stem cell transplant (HSCT) recipients is mandatory. PATIENTS AND METHODS: We conducted a single-center pilot study with the main objective of evaluating the immunogenicity of the BNT162b2 mRNA vaccine in 31 hematological patients who underwent hematopoietic stem cell transplantation within the previous 12 months and/or were affected by chronic graft-vs.-host-disease (cGVHD), by the assessment of antibody levels at 30-45 days after the second dose of vaccine. RESULTS: After the second dose of vaccine, 23 out of 31 patients (74%) showed a positive immune response. The presence of severe cGVHD or Ig deficiency identified 7 out of 8 (85%) of non-responders. The median absolute cluster of differentiation 19 (CD19) count was significantly lower in non-responders vs. responders (109/µl vs. 351/µl). Underlying pathology, comorbidities, type of donor, time intervals from transplant and cluster of differentiation 3/cluster of differentiation 4/cluster of differentiation 8 (CD3/CD4/CD8) subsets were not significantly associated with an effective immune response to vaccination. CONCLUSIONS: Despite the limited sample of patients enrolled, our findings suggest that hypogammaglobulinemia and cGVHD could be associated with poor humoral response to the BNT162b2.

VARIABLES ASSOCIATED with HOSPITALIZATION DUE to COVID-19 in PEOPLE LIVING with HIV

Background: Argentina has been one of the most affected countries by the COVID-19 pandemic, however, there are limited data regarding evolution of people living with HIV (PLWH) infected with SARS-CoV-2. This study evaluates characteristics associated with hospital admission due to COVID-19 among PLWH in Argentina. Methods: Adult PLWH with confirmed SARS-CoV-2 infection were enrolled in a prospective observational multicentric cohort study to evaluate hospitalization due to COVID-19. Participating centers included nationwide HIV clinics and general hospitals from Argentina. A multivariable logistic regression model was performed to identify variables associated with hospitalization due to COVID-19. Results: Of 844 PLWH enrolled, 21.8% required hospital admission due to COVID-19. Characteristics of PLWH with and without hospitalization are shown in table 1. On a multivariable logistic regression model, age>=60 and presence of other comorbidities were associated with admission (OR: 1.82;95%CI:1.07-3.11;p<0.028;OR: 1.73;95%CI: 1.22-2.46 p<0.002;respectively). Female sex and CD4+ count >=500 cells/ml (OR: 0.60;95%CI:0.41-0.87;p=0.008;and OR:0.30;95% CI:0.14-0.66;p=0.003;respectively) were inversely associated with admission. ART and detectable viral load had no impact on hospitalization. Conclusion: We provide the first analysis regarding variables associated with hospitalization among PLWH in Argentina. Hospitalization in this population was associated with traditional risk factors (age, comorbidities) without influence of ART and viral load. According to our study, female sex and high CD4+ T-cell count provide a significant reduction in the risk of admission to hospital.

Should be a Third Dose of BNT162b2 mRNA COVID-19-Vaccine Administered in Patients with Myelofibrosis Under Ruxolitinib?

[Formula presented] Introduction. Patients with Myelofibrosis (MF) are considered fragile and thus eligible in Italy for COVID-19 BNT162b2 mRNA vaccination. According to the International Prognostic Scoring System (IPSS), patients with intermediate and high MF, may receive clinical benefits from ruxolitinib, the first approved JAK1/JAK2 inhibitor. Given the potent anti-inflammatory properties of ruxolitinib against immunocompetent cells, we previously reported a lower but non-statistically absolute IgG anti-Spike humoral response in vaccinated MF patients treated with ruxolitinib. In the present report we extended the cohort of MF patients. Methods. All MF patients received 2 injections of 30 ug per dose of BNT162b2 mRNA COVID-19 vaccine 3 weeks apart, according to the standard protocol. After injection, mild pain at the injection site was frequently reported. No serious adverse events were registered. The serum level of IgG anti-Spike glycoprotein was tested after a median time of 45 days (range 40-60) from the second vaccine dose, using the approved anti-SARS-CoV-2 IgG CLIA (LIAISON® SARS-CoV-2 TrimericS IgG assay, Diasorin, Saluggia, Italy). An Arbitrary Units per milliliter (AU/mL) ratio of <12.0 was considered to be negative, 12.0-15.0 AU/mL to be borderline and >15 AU/mL to be positive. A conversion of AU/mL to binding antibody units (BAU/mL) as recommended by the World Health Organization (WHO) guidelines was achieved considering the following equation: BAU/mL = 2.6*AU/mL. Results. Overall, 30 MF patients (median age 65 years, range 48-83) were vaccinated. A diagnosis of primary MF was reported in 21 cases (70%), post essential thrombocythemia-MF in 6 (20%) patients and post polycythemia vera-MF in 3 (10%) patients;23 out of 30 patients (76.6%) were positive for the JAK2V617F, 5 (16.6%) for CALR mutation, 1 (3.3%) for MPL mutation and 1 patient (3.3%) resulted triple negative. Splenomegaly was observed in 14 patients (46%) and 19 (63.3%) reported comorbidities. Nineteen patients (63.3%) were classified as DIPSS low or intermediate-1 risk, and 11 (36.6%) as intermediate-2 or high risk. Fifteen patients (50%) were receiving ruxolitinib, at a median total dose of 20 mg/die (range 20-40 mg) and the remaining 15 patients other treatments (8 patients hydroxyurea and 7 only supportive therapy). None of the patients reported COVID-19 infection neither previous nor subsequently to vaccination. Overall, a positive immune response against COVID-19 was observed in 8 out of 15 patients (53.3%) in the ruxolitinib group, in comparison with 13 out 15 patients (86.6%) in the other treatment group (p=0,046). The absolute IgG anti-Spike value was lower in the ruxolitinib group (median 35.2±49.81) in comparison with the other group (median 226.1±163.9;p=<0.001), Figure 1. In univariate analysis, only ruxolitinib treatment was found associated with a lower humoral immune response to the vaccine. Conclusions. MF patients under ruxolitinib achieved a lower humoral immune response in comparison with MF patients who underwent other treatments. No COVID-19 infection was observed in both groups after vaccination, after a median follow up of 3 months since the second dose. Whether patients with a potential insufficient humoral response to vaccine will benefit from a third dose of BNT162b2 mRNA COVID-19 vaccine is a matter of further investigation. Our preliminary data need to be confirmed in larger cohort of MF patients. [Formula presented] Disclosures: Murru: Abbvie: Consultancy, Honoraria, Other: travel and accommodation;Janssen: Consultancy, Honoraria.

Impact of the COVID 19 pandemic on the outpatient management of patients with heart failure: From scheduled outpatient clinics to telemedicine

With the advent of the COVID19 pandemic, all patients in our heart failure clinic (HFC) were assessed by telephone instead of the scheduled visit, thus showing the need for an additional remote monitoring system. Telecardiology (TC) is already a well-established practice in our clinic in patients with devices. From a joint collaboration project of APSS, FBK and Trentino salute 4.0, an APP was developed, available on the Play Store: TreC Cardiologia. The project started with Beta Test on 29 June 2020. The APP was initially given to patients already followed by the TC clinic and subsequently to those followed by the HFC or discharged with a diagnosis of heart failure (HF) . The APP allows you to: 1) monitor the progress of some customizable clinical parameters;2) interface with our clinic via chat to send text messages to communicate any symptoms and send photographic material;3) perform scheduled or on-demand video calls;4) view the therapy;5) set reminders for the patient on certain actions to be performed, fill forms about his health conditions;6) in the future, patients will be able to access educational material on their pathology. The project also includes a dedicated nurse who takes care of the management of the patient with APP from administration onwards, favoring his empowerment, reporting elements of destabilization to the referring doctor with subsequent decisions (video call, in-office visit, hospitalization). As of 31/12/2020 the APP was given to 66 patients. Since March 2020, HFC patients are still followed up with a phone call and/or an in-office visit, according to clinical trend. The use of the APP and the collection of data relating to efficacy and criticality have begun.The use of additional instrumentation to be provided to the patient is being evaluated. The literature that emerged from the COVID19 pandemic has confirmed the role of telemedicine in optimizing management at home in patients with HF. The new readily available technologies (e.g. smartphone with the possibility of video call) also allow you to maintain eye contact with the patient, taking on both clinical and psychological value, highlighting destabilization in time and also being reassuring about the pandemic. The epidemiology of HF and the ongoing pandemic suggest that technology will have to increasingly support the management of these patients.

Recurrence of COVID-19 related symptoms and viral detection in a patient discharged after complete recovery and test negativization

Since the novel coronavirus disease 2019 (COVID-19) has been declared a pandemic, the possibility of recurrence of the disease after recovery has become a debated issue. We report a case of an 84-years-old male patient who was admitted to our hospital for dyspnea and fever. Lab and clinical workout showed that he had COVID-19. After a full recovery of symptoms and a double negative nasopharyngeal swab of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) by realtime polymerase chain reaction assay, he was discharged from the hospital. One month later, he developed dyspnea and fever again with lung involvement. Surprisingly, the nasopharyngeal swab of SARS-CoV-2 was positive. Since he denied contacts with confirmed or suspected cases of COVID-19, he probably experienced a reactivation of a persistent infection. The failed eradication of the virus could depend on both virus' escape mechanisms and dysfunctional immune response. Further studies are needed to confirm the hypothesis of viral reactivation and identify signs of an incomplete clearance.

Early scientific response to COVID-19 epidemic: a scientometric perspective

Background The recent COVID-19 epidemic is showing how the response of the scientific literature is fundamental in the first days following the onset of a new epidemic. Quantifying which studies have a greatest impact can help researchers and policymakers in controlling the epidemic. The aim of this study is to describe the early scientific production in response to the COVID-19 epidemic through a scientometric analysis. Methods The study consisted of: 1) review of the scientific literature produced in the 30 days since the first paper related to COVID-19 has been published on Pubmed;2) Identification of papers' Digital Object Identifiers (DOI) and analysis of related metrics with the construction of a 'Computed Impact Score' (CIS) that represents a unifying score over heterogeneous bibliometric indicators. The CIS takes into account all the bibliometric indicators both traditional (i.e. counting of citations) and alternative (i.e. altmetrics). In this study we use the altmetrics provided by Plum Analytics (PlumX). All bibliometric indicators for the selected papers have been collected by using their corresponding DOIs as the key for querying Scopus API, which integrates PlumX. On top of those indicators we compute the CIS. The papers with higher CIS are discussed and presented. Results 239 papers have been included in the study. A threshold for CIS of t = 1.04 (i.e.95% quantile) allowed us to record 8 papers as potentially impactful. The 8 papers are: 6 case reports, 1 methodological study, 1 editorial. First authors come from China (n = 6), USA (n = 1) and Germany (n = 1). The main topics are: case/s description (n = 5), outbreak investigation (n = 2) and 1 genomic study. Conclusions The early response of the scientific literature during an epidemic does not follow a pre-established pattern. Tracing the traditional and non-traditional metrics measures of papers can help to understand and evaluate the impact of literature on the scientific community and general population. Key messages The dynamic of the scientific community represents an important aspect of the early response to the onset of a new epidemic, which must be studied also to increase systems’ preparedness. In a connected digital world, tracing metrics measures of scientific papers can identify those with the greatest impact and help professionals to correctly inform the population.

Breast surgeons updating on the thresholds of COVID-19 era: results of a multicenter collaborative study evaluating the role of online videos and multimedia sources on breast surgeons education and training.

OBJECTIVE: Current trends show a rise of attention given to breast cancer patients' quality of life and the surgical reconstructive result. Along with this trend, surgical training quality and efficacy are gaining importance and innovative training methods such as online videos shared on social media portals, are becoming main updating tools. In hazardous times like COVID-19 pandemic nowadays, online communication becomes of vital importance and adaptation and innovation are fundamental to keep research and education alive. The authors aimed to investigate the role of video and multimedia sources on the daily activity and surgical training of a representative group of surgeons specifically dedicated to oncologic, oncoplastic and reconstructive breast surgeries. MATERIALS AND METHODS: A survey was produced and administered to 20 major Italian Breast Centers. Collected data were analyzed with Fisher's Exact Test. RESULTS: From October 2019 to March 2020, a total of 320 surveys were collected. Among the responders, there were 188 trainees (intern medical doctors and residents) and 110 faculty, 72% of them belonged to a plastic surgery environment, while 28% to general surgery environment. Almost all respondents have ever watched videos concerning breast surgery. CONCLUSIONS: The results of the study show how breast surgeons rely on videos and web platforms, mostly YouTube, when searching for training info about surgical procedures. Social media offer great opportunities for sharing knowledge and diffusion of new ideas but greater attention to their reliability is mandatory.

Rationale and evidence on the use of tocilizumab in COVID-19: a systematic review.

BACKGROUND: Tocilizumab is an IL-6 receptor-blocking agent proposed for the treatment of severe COVID-19. The aim of this systematic review was to describe the rationale for the use of tocilizumab for the treatment of COVID-19 and to summarize the available evidence regarding its efficacy and safety. METHODS: MEDLINE, PubMed, EMBASE, pre-print repositories (bioRxiv and medRxiv) and two trial Registries were searched for studies on the use of tocilizumab in COVID-19 or SARS-CoV-2 infection, viral pneumonia, and/or sepsis until 20th June 2020. RESULTS: We identified 3 indirect pre-clinical studies and 28 clinical studies including 5776 patients with COVID-19 (13 with a comparison group, 15 single-arm). To date, no randomized trials have been published. We retrieved no studies at low risk of bias. Forty-five ongoing studies were retrieved from trial registries. CONCLUSIONS: There is insufficient evidence regarding the clinical efficacy and safety of tocilizumab in patients with COVID-19. Its use should be considered experimental, requiring ethical approval and clinical trial oversight.

Hospital surge capacity in a tertiary emergency referral centre during the COVID-19 outbreak in Italy.

The first person-to-person transmission of the 2019 novel coronavirus in Italy on 21 February 2020 led to an infection chain that represents one of the largest known COVID-19 outbreaks outside Asia. In northern Italy in particular, we rapidly experienced a critical care crisis due to a shortage of intensive care beds, as we expected according to data reported in China. Based on our experience of managing this surge, we produced this review to support other healthcare services in preparedness and training of hospitals during the current coronavirus outbreak. We had a dedicated task force that identified a response plan, which included: (1) establishment of dedicated, cohorted intensive care units for COVID-19-positive patients; (2) design of appropriate procedures for pre-triage, diagnosis and isolation of suspected and confirmed cases; and (3) training of all staff to work in the dedicated intensive care unit, in personal protective equipment usage and patient management. Hospital multidisciplinary and departmental collaboration was needed to work on all principles of surge capacity, including: space definition; supplies provision; staff recruitment; and ad hoc training. Dedicated protocols were applied where full isolation of spaces, staff and patients was implemented. Opening the unit and the whole hospital emergency process required the multidisciplinary, multi-level involvement of healthcare providers and hospital managers all working towards a common goal: patient care and hospital safety. Hospitals should be prepared to face severe disruptions to their routine and it is very likely that protocols and procedures might require re-discussion and updating on a daily basis.