Covid-19 and radiotherapy: a systematic review after 2 years of pandemic.

Introduction: Following the Covid-19 pandemic spread, changes in clinical practice were necessary to limit the pandemic diffusion. Also, oncological practice has undergone changes with radiotherapy (RT) treatments playing a key role.Although several experiences have been published, the aim of this review is to summarize the current evidence after 2 years of pandemic to provide useful conclusions for clinicians. Methods: A Pubmed/MEDLINE and Embase systematic review was conducted. The search strategy was "Covid AND Radiotherapy" and only original articles in the English language were considered. Results: A total of 2.733 papers were obtained using the mentioned search strategy. After the complete selection process, a total of 281 papers were considered eligible for the analysis of the results. Discussion: RT has played a key role in Covid-19 pandemic as it has proved more resilient than surgery and chemotherapy. The impact of the accelerated use of hypofractionated RT and telemedicine will make these strategies central also in the post-pandemic period.

Attenuation of SARS-CoV-2 replication and associated inflammation by concomitant targeting of viral and host cap 2'-O-ribose methyltransferases.

The SARS-CoV-2 infection cycle is a multistage process that relies on functional interactions between the host and the pathogen. Here, we repurposed antiviral drugs against both viral and host enzymes to pharmaceutically block methylation of the viral RNA 2'-O-ribose cap needed for viral immune escape. We find that the host cap 2'-O-ribose methyltransferase MTr1 can compensate for loss of viral NSP16 methyltransferase in facilitating virus replication. Concomitant inhibition of MTr1 and NSP16 efficiently suppresses SARS-CoV-2 replication. Using in silico target-based drug screening, we identify a bispecific MTr1/NSP16 inhibitor with anti-SARS-CoV-2 activity in vitro and in vivo but with unfavorable side effects. We further show antiviral activity of inhibitors that target independent stages of the host SAM cycle providing the methyltransferase co-substrate. In particular, the adenosylhomocysteinase (AHCY) inhibitor DZNep is antiviral in in vitro, in ex vivo, and in a mouse infection model and synergizes with existing COVID-19 treatments. Moreover, DZNep exhibits a strong immunomodulatory effect curbing infection-induced hyperinflammation and reduces lung fibrosis markers ex vivo. Thus, multispecific and metabolic MTase inhibitors constitute yet unexplored treatment options against COVID-19.

The Impact of COVID-19 on Universal Newborn Hearing Screening.

OBJECTIVES: To report the direct and indirect impact of coronavirus disease 2019 pandemic on the Universal Newborn Hearing Screening program of our institution (Azienda Ospedaliero Universitaria di Sassari). DESIGN: Monocentric retrospective study whose target population included all the newborns born in or referred to our hospital in 2019 and 2020. RESULTS: There is no statistically significant difference in time to retest or loss to follow-up rate between the 2 years considered (2019 to 2020). Referral rate is not higher for newborns born to severe acute respiratory syndrome coronavirus 2 polymerase chain reaction positive mothers. CONCLUSIONS: In relation to the analyzed variables, coronavirus disease 2019 seems to have a limited impact on our screening program. Severe acute respiratory syndrome coronavirus 2 did not behave as an audiological risk factor in our series.

New fractionations in breast cancer: a dosimetric study of 3D‐CRT versus VMAT

IntroductionAdjuvant radiation therapy (RT) following primary surgery in women affected by early breast cancer (EBC) plays a central role in reducing local recurrences and overall mortality. The FAST‐FORWARD trial recently demonstrated that 1‐week hypofractionated adjuvant RT is not inferior to the standard schedule in terms of local relapse, cosmetic outcomes and toxicity. The aim of this in silico study was to evaluate the dosimetric aspects of a 1‐week RT course, administered through volumetric modulated arc therapy (VMAT), compared with traditional three‐dimensional conformal radiation therapy (3D‐CRT) with tangential fields.MethodsPatients affected by left‐side EBC undergoing adjuvant RT were selected. ESTRO guidelines for the clinical target volume (CTV) delineation and FAST‐FORWARD protocol for CTV to planning target volume (PTV) margin definition were followed. Total prescribed dose was 26 Gy in five fractions. The homogeneity index (HI) and the global conformity index (GCI) were taken into account for planning and dose distribution optimisation purposes. Both 3D‐CRT tangential fields and VMAT plans were generated for each patient.ResultsThe analysis included 21 patients. PTV coverage comparison between 3D‐CRT and VMAT plans showed significant increases for GCI (P < 0.05) in VMAT technique;no statistically significant differences were observed regarding HI. For organs at risks (OAR), statistically significant increases were observed in terms of skin V103% (P < 0.002) and ipsilateral lung V30% (P < 0.05) with 3D‐CRT and of heart V5% (P < 0.05) with VMAT technique.ConclusionsThis in silico study showed that both 3D‐CRT and VMAT are dosimetrically feasible techniques in the framework of 1‐week hypofractionated treatments for left EBC.

"Swab Team" in the SARS-CoV-2 outbreak containment among healthcare workers.

INTRODUCTION: To analyze the virus spread among Sassari Hospital staff in the first Covid-19 wave and the impact of the Swab Team, a multidisciplinary task force entitled of nasopharyngeal swab collection and testing. METHODOLOGY: Nasopharyngeal swabs from HCWs between March 6 and May 28 2020 are evaluated. RESULTS: 4919 SARS-CoV-2 tests were performed on 3521 operators. Nurses and doctors are the categories at highest risk. After the Swab Team institution, the average number of swabs raised from 47/day to 86/day (p = 0.007). Positive samples decreased from 18.6% to 1.7% (p < 0.0001). CONCLUSIONS: The Swab Team is effective in increasing the cases tested and in reducing the reporting time. Procedure standardization reduces the risk for all the subjects involved (no transmission among swab team members, nor during the sample collection).

Hypofractionated Radiotherapy in Head and Neck Cancer Elderly Patients: A Feasibility and Safety Systematic Review for the Clinician.

OBJECTIVE: Radiotherapy (RT) in the head and neck (H&N) site are undoubtedly the most challenging treatments for patients. Older and frail patients are not always able to tolerate it, and there are still no clear guidelines on the type of treatments to be preferred for them. The recommendations for Risk-Adapted H&N Cancer Radiation Therapy during the coronavirus disease 2019 (COVID-19) pandemic provided by the ASTRO-ESTRO consensus statement achieved a strong agreement about hypofractionated RT (HFRT). A systematic literature review was conducted in order to evaluate the feasibility and safety of HFRT for older patients affected by H&N malignancies. MATERIALS AND METHODS: A systematic database search was performed on PubMed and Embase according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Original studies, case series, and case reports describing the use of HFRT (with at least 2.2 Gy fractions) in patients with mean age ≥65 years were included. The analysis was based on the type of study, number of patients, mean age, tumor site, histology, performance status (PS), RT details, concomitant chemotherapy (CT), and described clinical outcomes. All the reported doses have been calculated in equivalent dose in 2 Gy fractions (EQD2) and biologically effective dose (BED) using α/ß = 10 Gy or α/ß = 12 Gy. RESULTS: We selected 17 papers that met the inclusion criteria and divided them in 4 categories: 6 articles analyze HFRT performed twice daily in repeated cycles, 3 once a day in repeated cycles, 4 in alternative days, and the last 4 in consecutive days. CONCLUSION: HFRT seems to be a good treatment with an acceptable prolonged disease control. In older patients fit for radical treatments, a 55 Gy in 20 fractions regimen can be proposed as a valid alternative to the standard fractionated RT, but there are a multitude of hypofractionated regimens, ranging from single fraction, quad shot, and 1-, 2-, 3-, 4-, and 5-week schedules that all may be appropriate. The correct regimen for a patient depends on many factors, and it represents the result of a more specific and complex decision.

Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV.

The emergence and global spread of SARS-CoV-2 has resulted in the urgent need for an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several individual omics studies have extended our knowledge of COVID-19 pathophysiology1-10. Integration of such datasets to obtain a holistic view of virus-host interactions and to define the pathogenic properties of SARS-CoV-2 is limited by the heterogeneity of the experimental systems. Here we report a concurrent multi-omics study of SARS-CoV-2 and SARS-CoV. Using state-of-the-art proteomics, we profiled the interactomes of both viruses, as well as their influence on the transcriptome, proteome, ubiquitinome and phosphoproteome of a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed crosstalk between the perturbations taking place upon infection with SARS-CoV-2 and SARS-CoV at different levels and enabled identification of distinct and common molecular mechanisms of these closely related coronaviruses. The TGF-ß pathway, known for its involvement in tissue fibrosis, was specifically dysregulated by SARS-CoV-2 ORF8 and autophagy was specifically dysregulated by SARS-CoV-2 ORF3. The extensive dataset (available at https://covinet.innatelab.org ) highlights many hotspots that could be targeted by existing drugs and may be used to guide rational design of virus- and host-directed therapies, which we exemplify by identifying inhibitors of kinases and matrix metalloproteases with potent antiviral effects against SARS-CoV-2.

Audiovestibular symptoms and sequelae in COVID-19 patients.

BACKGROUND: since the beginning of COVID-19 outbreak a growing number of symptoms and deficits associated with the new pathology have emerged, among them cochlear damage in otherwise asymptomatic COVID-19 patients has been described. OBJECTIVE: to investigate general and audiovestibular symptoms and sequelae in healed patients, and to seek for any sign of residual or permanent hearing or vestibular loss. METHODS: we reviewed the data coming from 48 Covid-19 patients whose nasopharyngeal swabs have turned negative, all employed at our facility, that opted in for a free screening of audiovestibular symptoms offered by our hospital after the aforementioned report was published. The screening included a tonal pure tone audiometry, a vHIT and SHIMP test, as well as a survey including known symptoms and audiovestibular symptoms. RESULTS: general symptoms as reported by our patients largely reflect what reported by others in the literature. 4 (8.3%) patients reported hearing loss, 2 (4.2%) tinnitus, 4 dizziness (8.3%), 1 spinning vertigo (2%), 1 dynamic imbalance (2%), 3 static imbalance (6.3%). Most audiovestibular symptoms have regressed. Thresholds at pure tone audiometry and vHIT gain were within normality range in all post-Covid-19 patients. CONCLUSIONS: even if some patients suffer from audiovestibular symptoms, these are mostly transitory and there is no clear evidence of clinically relevant persistent cochlear or vestibular damage after recovery.

Nasopharyngeal swab collection in the suspicion of Covid-19.

RT-PCR detection of SARS-CoV-2 mRNA on nasopharyngeal swab is the standard for diagnosing active Covid-19 disease in asymptomatic subjects and in symptomatic patients without the typical radiological findings. Nasopharyngeal swabbing appears a trivial procedure, still an inappropriate nasopharyngeal sampling, performed by untrained operators, can be a relevant cause of false negative findings with a clear negative impact on the effort to control the epidemic and, when PPE is not properly used, this can expose healthcare workers and patients to risks of contagion.

Inappropriate Nasopharyngeal Sampling for SARS-CoV-2 Detection Is a Relevant Cause of False-Negative Reports.

Reverse transcriptase polymerase chain reaction (RT-PCR) detection of SARS-CoV-2 mRNA on nasopharyngeal swab is the standard for diagnosing active COVID-19 disease in asymptomatic cases and in symptomatic patients without the typical radiologic findings. For the present COVID-19 outbreak in Italy, we describe 4 symptomatic patients with negative RT-PCR results at the first nasopharyngeal swab, which became positive when collected a few hours later by an otolaryngologist. All the patients showed nasal obstruction. The present report suggests that inadequate nasopharyngeal sampling performed by untrained operators in the presence of nasal obstruction can be a relevant case of false-negative findings at RT-PCR, with a clear negative impact on the efforts to contain the current outbreak.