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Summary: COVID‐19 is associated with high mortality in patients with haematological malignancies (HM) and rate of seroconversion is unknown. The ITA‐HEMA‐COV project (NCT04352556) investigated patterns of seroconversion for SARS‐CoV‐2 IgG in patients with HMs. A total of 237 patients, SARS‐CoV‐2 PCR‐positive with at least one SARS‐CoV‐2 IgG test performed during their care, entered the analysis. Among these, 62 (26·2%) had myeloid, 121 (51·1%) lymphoid and 54 (22·8%) plasma cell neoplasms. Overall, 69% of patients (164 of 237) had detectable IgG SARS‐CoV‐2 serum antibodies. Serologically negative patients (31%, 73 of 237) were evenly distributed across patients with myeloid, lymphoid and plasma cell neoplasms. In the multivariable logistic regression, chemoimmunotherapy [odds ratio (OR), 3·42; 95% confidence interval (CI), 1·04–11·21; P = 0·04] was associated with a lower rate of seroconversion. This effect did not decline after 180 days from treatment withdrawal (OR, 0·35; 95% CI: 0·11–1·13; P = 0·08). This study demonstrates a low rate of seroconversion in HM patients and indicates that treatment‐mediated immune dysfunction is the main driver. As a consequence, we expect a low rate of seroconversion after vaccination and thus we suggest testing the efficacy of seroconversion in HM patients. [ABSTRACT FROM AUTHOR]

Laryngectomized patients showed an unconventional response to SARS‐CoV‐2 viral infection. Here, we describe five different patient cases along with our interpretation of the phenomena and suggestions for their safe management. [ABSTRACT FROM AUTHOR]

Background: Managing SARS‐CoV‐2 infection in frail and immunosuppressed patients still represents an open challenge, but, starting from the phase 3 PROVENT study, prophylaxis with tixagevimab‐cilgavimab has improved the approach in this category of patients, guaranteeing a better outcome and inferior mortality. Real‐life data in a heterogeneous cohort are few. Methods: The aim of this study is to evaluate the benefit of prophylaxis with tixagevimab‐cilgavimab in a cohort of 202 patients affected by different hematological diseases (lymphoproliferative, myeloproliferative, autoimmune, patients recently receiving a bone marrow transplant), active (with ongoing treatment), or in watch‐and‐wait strategy, followed in our center, during a median follow‐up of 249 (45‐325) days. Results: An incidence of 44 breakthrough infections (21.8%) is reported, with no treatment‐related adverse effects. Age ≥70 years, ongoing treatment (above all with monoclonal antibodies), baseline lymphoproliferative disorders, and prior virus exposure are identified as risk factors related to subsequent infection (p < 0.05). Moreover, the incidence is higher in low/nonresponse to prior vaccination (p =.002). Patients treated with tixagevimab‐cilgavimab had a mild course of the infection and a reduction of the duration compared with preprophylaxis infection (11 vs. 15 days, p <.001). The concurrent treatment with anti‐CD20 monoclonal antibodies and B–non‐Hodgkin lymphoma still confers a higher duration of infection despite prophylaxis. No deaths attributable to the infection occurred. Conclusion: Prophylaxis treatment seems to be a valid and safe strategy, although not preventing breakthrough infection, but the severe complications associated with the infection and the possible delays in administering lifesaving therapies from long positivity. The use of tixagevimab‐cilgavimab improved the management of immunocompromised patients with a high risk of severe SARS‐CoV‐2 disease. In a real‐world setting, it confirmed its role not only in preventing the occurrence of breakthrough infection, but also, above all, avoiding the severe complications associated and reducing the total days of positivity. [ABSTRACT FROM AUTHOR]

Summary: Little is known of the course of COVID‐19 and the antibody response to infection or vaccination in patients with hairy‐cell leukaemia (HCL). Among a total of 58 HCL cases we studied in these regards, 37 unvaccinated patients, mostly enjoying a relatively long period free from anti‐leukaemic treatment, developed COVID‐19 between March 2020 and December 2021 with a usually favourable outcome (fatality rate: 5/37, 14%); however, active leukaemia, older age and more comorbidities were associated with a worse course. Postinfection (n = 11 cases) and postvaccination (n = 28) seroconversion consistently developed, except after recent anti‐CD20 or venetoclax therapy, correlating with perivaccine B‐cell count. Vaccination appeared to protect from severe COVID‐19 in 11 patients with breakthrough infection. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 life cycle is strictly dependent on the environmental redox state that influences both virus entry and replication. A reducing environment impairs the binding of the spike protein (S) to the angiotensin-converting enzyme 2 receptor (ACE2), while a highly oxidizing environment is thought to favor S interaction with ACE2. Moreover, SARS-CoV-2 interferes with redox homeostasis in infected cells to promote the oxidative folding of its own proteins. Here we demonstrate that synthetic low molecular weight (LMW) monothiol and dithiol compounds induce a redox switch in the S protein receptor binding domain (RBD) toward a more reduced state. Reactive cysteine residue profiling revealed that all the disulfides present in RBD are targets of the thiol compounds. The reduction of disulfides in RBD decreases the binding to ACE2 in a cell-free system as demonstrated by enzyme-linked immunosorbent and surface plasmon resonance (SPR) assays. Moreover, LMW thiols interfere with protein oxidative folding and the production of newly synthesized polypeptides in HEK293 cells expressing the S1 and RBD domain, respectively. Based on these results, we hypothesize that these thiol compounds impair both the binding of S protein to its cellular receptor during the early stage of viral infection, as well as viral protein folding/maturation and thus the formation of new viral mature particles. Indeed, all the tested molecules, although at different concentrations, efficiently inhibit both SARS-CoV-2 entry and replication in Vero E6 cells. LMW thiols may represent innovative anti-SARS-CoV-2 therapeutics acting directly on viral targets and indirectly by inhibiting cellular functions mandatory for viral replication. [ABSTRACT FROM AUTHOR]

Summary: To optimise management of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection identifying high‐risk patients and maintaining treatment dose intensity is an important issue in patients with aggressive lymphomas. In the present study, we report on the presentation, management, and outcome of an international series of 91 patients with primary central nervous system lymphoma and SARS‐CoV‐2 infection. SARS‐CoV‐2 was diagnosed before/during first‐line treatment in 64 patients, during follow‐up in 21, and during salvage therapy in six. Among the 64 patients infected before/during first‐line chemotherapy, 38 (59%) developed pneumonia and 26 (41%) did not clear the virus. Prolonged exposure to steroids before viral infection and/or treatment with high‐dose cytarabine favoured pneumonia development and virus persistence and were associated with poorer survival; 81% of patients who did not clear virus died early from coronavirus disease 2019 (COVID‐19). Vaccination was associated with lower pneumonia incidence and in‐hospital mortality. Chemotherapy was initiated/resumed in 43 (67%) patients, more commonly among patients who did not develop pneumonia, cleared the virus, or did not receive steroids during infection. Chemotherapy resumption in patients with viral persistence should be indicated cautiously as it was associated with a poorer survival (6‐month, 70% and 87%, p = 0.07). None of the 21 patients infected during follow‐up died from COVID‐19, requiring similar measures as infected subjects in the general population. [ABSTRACT FROM AUTHOR]

VOC Omicron induce "common cold symptoms" and sore throat more often than wild-type and VOC Delta infections (Figures 2 and 3). Presentation of airway and general symptoms in COVID-19 caused by dominant SARS-CoV-2 variants: A follow-up on ARIA consensus GLO:1X5/01nov22:all15416-fig-0001.jpg PHOTO (COLOR): 1 Expected symptom intensity on analogue scale (0: no symptom and 10: strongest symptoms) for wild-type and virus variants of SARS-CoV-2, rated by ARIA specialists. Symptom groups A/B/C/D are explained in the main text and referred to Figure 2 gl Significantly differing symptoms were grouped concerning common cold and sore throat, chemosensory, bronchial and pulmonary, as well as systemic (Figure 2). [Extracted from the article]

Background: SARS‐CoV‐2 caused one of the most devastating pandemics in the recent history of mankind. Due to various countermeasures, including lock‐downs, wearing masks, and increased hygiene, the virus has been controlled in some parts of the world. More recently, the availability of vaccines, based on RNA or adenoviruses, has greatly added to our ability to keep the virus at bay; again, however, in some parts of the world only. While available vaccines are effective, it would be desirable to also have more classical vaccines at hand for the future. Key feature of vaccines for long‐term control of SARS‐CoV‐2 would be inexpensive production at large scale, ability to make multiple booster injections, and long‐term stability at 4℃. Methods: Here, we describe such a vaccine candidate, consisting of the SARS‐CoV‐2 receptor‐binding motif (RBM) grafted genetically onto the surface of the immunologically optimized cucumber mosaic virus, called CuMVTT‐RBM. Results: Using bacterial fermentation and continuous flow centrifugation for purification, the yield of the production process is estimated to be >2.5 million doses per 1000‐litre fermenter run. We demonstrate that the candidate vaccine is highly immunogenic in mice and rabbits and induces more high avidity antibodies compared to convalescent human sera. The induced antibodies are more cross‐reactive to mutant RBDs of variants of concern (VoC). Furthermore, antibody responses are neutralizing and long‐lived. In addition, the vaccine candidate was stable for at least 14 months at 4℃. Conclusion: Thus, the here presented VLP‐based vaccine may be a good candidate for use as conventional vaccine in the long term. [ABSTRACT FROM AUTHOR]

The outbreak of COVID‐19 led to a reduction in the number of organ transplant interventions in most Countries. In April 2020, at the Tor Vergata University in Rome, Italy, two patients on the waiting list for kidney transplantation (KT) declined a deceased donor's kidney offer. Therefore, between April 20 and 25, 2020, we conducted a telephone survey among our 247 KT waitlist patients. Our aim was to explore: (a) the COVID‐19 diffusion among them and (b) their current willingness to be transplanted in case of a kidney offer from a deceased donor. Two hundred and forty‐three patients participated in a phone interview. One patient had died from COVID‐19. Eighty‐five (35%) KT candidates would decline any kidney offer, in most cases until the end of the COVID‐19 pandemic. Upon a multivariate analysis, female gender (OR = 2.25, 95% CI = 1.26‐4.03, P =.006), high cardiovascular risk (OR = 2.33, 95% CI = 1.06‐5.08, P =.034), a waiting list time <3 years (OR = 0.375, 95% CI = 0.15‐0.95, P =.04), and the need to be transferred to another hospital for HD (OR = 2.56, 95% CI = 1.10‐5.9, P =.03) were associated with such refusal. The COVID‐19 pandemic led to a fear of transplantation in a third of the KT candidates. Proactive educational webinars could be a useful tool to remove, or at least lessen, any doubts on the part of KT candidates and to avoid losing the opportunity to quit dialysis. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID‐19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off‐label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings together all the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off‐label drugs and highlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactions in the course of the disease. [ABSTRACT FROM AUTHOR]

Herein, we describe three patients, with no history of SARS-CoV-2 infection, who developed skin reactions after receiving Pfizer-BioNTech (New York, NY, USA) COVID-19 vaccine. The patients in this manuscript have given written informed consent to the publication of their case details Conflict of interest The authors have no financial obligations or conflict of interest to declare. Purpuric lesions on the eyelids developed after BNT162b2 mRNA COVID-19 vaccine: another piece of SARS-CoV-2 skin puzzle?. [Extracted from the article]

The ongoing outbreak of the novel coronavirus (SARS‐CoV‐2) infection is creating serious challenges for health laboratories that seek to identify viral infections as early as possible, optimally at the earliest appearance of symptom. Indeed, there is urgent need to develop and deploy robust diagnostic methodologies not only to use in health laboratory environments but also directly in places where humans circulate and spread the virus such as airports, trains, boats, and any public aggregation places. The success of a reliable and sensitive asymptomatic diagnosis relies on the identification and measurement of informative biomarkers from human host and virus in a rapid, sensitive, and inexpensive manner. The objective of this article is to describe an innovative multidisciplinary approach to develop an efficient, inexpensive, and easy‐to‐use portable instrument (bCUBE® by Hyris Ltd) that can be employed as a surveillance system for the emergency caused by SARS‐CoV‐2. A solution for Coronavirus testing, compliant with CDC guidelines, is scheduled to be released in the next weeks. In addition, we will describe a workflow and path of an integrated multi‐omic approach that will lead to host and pathogen biomarker discovery in order to train the instrument to provide reliable results based on a specific biomarker's fingerprint of SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]