Outpatient Use of Monoclonal Antibodies Casirivimab and Imdevimab in Pregnancy for Mild-to-Moderate Coronavirus Disease 2019.

OBJECTIVE: The aim of this study was to report the use casirivimab/imdevimab therapy in pregnant women with moderate coronavirus disease 2019 (COVID-19). STUDY DESIGN: We report 12 cases of unvaccinated pregnant patients with mild-to-moderate COVID-19 treated with casirivimab/imdevimab. RESULTS: Twelve unvaccinated pregnant patients with mild-to-moderate COVID-19 received casirivimab/imdevimab at the dose of 1200/1200 mg by intravenous infusion over 60 minutes. All women were managed outpatient. None experienced severe adverse drug reaction and none progressed to severe disease. CONCLUSION: Casirivimab/imdevimab should be considered for outpatient treatment of unvaccinated pregnant women with mild-to-moderate COVID-19 to decrease the risk of severe disease. KEY POINTS: · Casirivimab/imdevimab is not well studied in pregnant women.. · Casirivimab/imdevimab in pregnant women with mild-to-moderate COVID-19 decreases the risk of severe disease.. · Casirivimab/imdevimab in pregnant women with mild-to-moderate COVID-19 is well tolerated..

Digital Health Service for Identification of Frailty Risk Factors in Community-Dwelling Older Adults: The SUNFRAIL+ Study Protocol.

This article reports the study protocol of a nationwide multicentric study in seven Italian regions aimed at assessing the effectiveness of a digitally supported approach for the early screening of frailty risk factors in community-dwelling older adults. SUNFRAIL+ is a prospective observational cohort study aimed at carrying out a multidimensional assessment of community-dwelling older adults through an IT platform, which allows to connect the items of the SUNFRAIL frailty assessment tool with a cascading multidimensional in-depth assessment of the bio-psycho-social domains of frailty. Seven centers in seven Italian regions will administer the SUNFRAIL questionnaire to 100 older adults. According to the answers provided by older adults, they will be subjected to one or more validated in-depth scale tests in order to perform further diagnostic or dimensional evaluations. The study aims to contribute to the implementation and validation of a multiprofessional and multistakeholder service model for the screening of frailty in community-dwelling older adult population.

Casirivimab/imdevimab + remdesivir in hospitalized patients with severe Covid-19: A single centre experience.

Since 2020, COVID-19 pandemic has spread worldwide causing a huge number of cases and casualties. Among direct anti SARS-CoV-2 agents available for the treatment of COVID-19, only remdesivir and casirivimab/imdevimab have been approved for severe disease. As they act at different levels in blocking viral replication, it is theoretically possible to combine them. In this case series we describe tolerability, safety and effectiveness in a small group of 14 patients of the combination of casirivimab/imdevimab monoclonal antibodies with the polymerase inhibitor remdesivir for the treatment of severe COVID-19. We conducted a retrospective study among consecutive patients admitted to the Infectious Disease ward of the University of Naples (Italy) Hospital for COVID-19 that received the combination of casirivimab/imdevimab and remdesivir for the treatment of severe COVID-19 from the August 1, 2021 to the November 30, 2021. During the study period, 78 patients were admitted for severe COVID-19. Fourteen patients (18%) received the combination casirivimab/imdevimab and remdesivir. They were five males and nine females with a median age of 54 years. Eight patients had significant comorbidities; three patients were in the immediate post-partum period. No adverse drug reaction was observed. All patients except one improved clinical condition and respiratory parameters within seven days following the therapy. All patients were discharged in good conditions.

Casirivimab and Imdevimab for Pregnant Women Hospitalized for Severe Coronavirus Disease 2019 (COVID-19).

OBJECTIVE: To evaluate safety and efficacy of casirivimab/imdevimab therapy in pregnant women with severe COVID-19 requiring oxygen therapy. METHODS: This was a prospective case series study aimed to evaluate safety and efficacy of casirivimab/imdevimab therapy in unvaccinated pregnant women with severe COVID-19. Inclusion criteria were: SARS CoV-2 infection documented with PCR, pregnancy, severe COVID-19 requiring oxygen therapy, duration of symptoms of 10 days or less, able to provide informed consent. Vaccinated women, and those with mild-to-moderate disease were excluded from the study. Included patients received casirivimab and imdevimab as single intravenous dose of 4000/4000 mg. Women were also treated with low molecular weight heparin, steroids and antibiotics, if necessary. The primary outcome was maternal death. Secondary outcomes were: rate of adverse events during infusion or within 72 hours, and rate of abortion. RESULTS: Thirteen hospitalized unvaccinated pregnant women with severe COVID-19 requiring oxygen and treated with casirivimab/imdevimab were included in the study. We observed no maternal death, and no patients required intubation or admission to intensive care unit. No abortion or fetal loss were recorded. Nine pregnancies were still ongoing, and there were three cesarean deliveries and one vaginal delivery. Two were preterm deliveries (at 31 and 34 weeks), and two were term deliveries. CONCLUSION: Casirivimab/imdevimab therapy may be considered as therapy in unvaccinated pregnant women with severe COVID-19.

Invasive Fungal Infections in Hospitalized Patients with COVID-19: A Non-Intensive Care Single-Centre Experience during the First Pandemic Waves.

Invasive fungal infections (IFIs) represent a severe complication of COVID-19, yet they are under-estimated. We conducted a retrospective analysis including all the COVID-19 patients admitted to the Infectious Diseases Unit of the Federico II University Hospital of Naples until the 1 July 2021. Among 409 patients, we reported seven cases of IFIs by Candida spp., seven of Pneumocystis jirovecii pneumonia, three of invasive pulmonary aspergillosis, and one of Trichosporon asahii. None of the cases presented underlying predisposing conditions, excluding one oncohematological patient treated with rituximab. Ten cases showed lymphopenia with high rates of CD4+ < 200/µL. All cases received high-dose steroid therapy (mean duration 33 days, mean cumulative dosage 1015 mg of prednisone equivalent), and seven cases had severe COVID-19 disease (OSCI ≥ 5) prior to IFI diagnosis. The cases showed a higher overall duration of hospitalization (63 vs 24 days) and higher mortality rate (23% vs. 7%) compared with the COVID-19 patients who did not developed IFIs. Cases showed a higher prevalence of high-dose steroid therapy and lymphopenia with CD4+ < 200/µL, primarily due to SARS-CoV-2 infection and not related to underlying comorbidities. IFIs strongly impact the overall length of hospitalization and mortality. Therefore, clinicians should maintain a high degree of suspicion of IFIs, especially in severe COVID-19 patients.

COVID-19 chest CT and laboratory features of B.1.617.2 (Delta variant) vs B.1.1.7 (Alpha variant) surge: a single center case-control study.

Purpose: To assess clinical, laboratory and radiological differences between Delta and Alpha SARS-CoV-2 variants. Materials and Methods: Twenty SARS-CoV-2 patients admitted from 30th of August to 30th of October 2021 (period with estimated highest prevalence of Delta variant circulation in Italy) were enrolled. Patients were matched in a 1:1 ratio with same gender and same age +/- 2 years controls admitted from 1st of September 2020 to 30th of January 2021 (predominant circulation of Alpha variant). Chest computed tomography (CT) were retrospectively evaluated. Main clinical parameters, radiological and laboratory findings were compared between two groups. Results: Patients with probable Delta variant had significantly higher CT severity scores, lower PaO2/FiO2 ratio and higher C-reactive protein and lactate dehydrogenase levels at admission. On multivariate analysis, probable Delta variant infection was associated with higher CT severity score. Ground glass opacities and crazy paving patterns were more frequently noticed than consolidation, with the latter being more frequent in Delta cohort, even though not significantly. According to prevalent imaging pattern, the consolidation one was significantly associated with pregnancy (p=0.008). Conclusions: Patients admitted during predominance of Delta variant circulation had a more severe lung involvement compared to patients in infected when Alpha variant was predominant. Despite imaging pattern seems to be not influenced by viral variant and other clinical variables, the consolidative pattern was observed more frequently in pregnancy.

A Simple Non-Invasive Score Based on Baseline Parameters Can Predict Outcome in Patients with COVID-19.

We evaluated the role of CRP and other laboratory parameters in predicting the worsening of clinical conditions during hospitalization, ICU admission, and fatal outcome among patients with COVID-19. Consecutive adult inpatients with SARS-CoV-2 infection and respiratory symptoms treated in three different COVID centres were enrolled, and they were tested for laboratory parameters within 48 h from admission. Three-hundred ninety patients were enrolled. Age, baseline CRP, and LDH were associated with a P/F ratio < 200 during hospitalization. Male gender and CRP > 60 mg/L were shown to be independently associated with ICU admission. Lymphocytes < 1000 cell/µL were associated with the worst P/F ratio. CRP > 60 mg/L predicted exitus. We subsequently devised an 11-points numeric ordinary scoring system based on age, sex, CRP, and LDH at admission (ASCL score). Patients with an ASCL score of 0 or 2 were shown to be protected against a P/F ratio < 200, while patients with an ASCL score of 6 to 8 were shown to be at risk for P/F ratio < 200. Patients with an ASCL score ≥ 7 had a significantly increased probability of death during hospitalization. In conclusion, patients with elevated CRP and LDH and an ASCL score > 6 at admission should be prioritized for careful respiratory function monitoring and early treatment to prevent a progression of the disease.

COVID-19 Post-Exposure Evaluation (COPE) Study: Assessing the Role of Socio-Economic Factors in Household SARS-CoV-2 Transmission within Campania Region (Southern Italy).

Campania is the sixth poorest region of Italy, and it is the region with the highest income inequality. The secondary attack rates of SARS-CoV-2 among households are found to be substantially heterogeneous among published studies and are influenced by socio-economic factors. We conducted a retrospective study to describe the role of socio-economic factors in the household transmission of SARS-CoV-2 among patients living in Campania Region and referring to "Federico II" Hospital. We interviewed 413 subjects followed-up for COVID-19 between the 8 March 2020 and the 24 May 2021 with the aim to collect demographic, clinical, economic, and social data regarding their household and the index cases. The variables associated with SARS-CoV-2 attack rate higher than 50% among households were higher age (p = 0.023) and higher Charlson Comorbidity Index of the index case (p = 0.023) and, for household characteristics, higher number of families per house (p = 0.02), location of the houses in Naples' suburbs (Chi2 = 5.3, p = 0.02) and in Caserta City area (Chi2 = 4, p = 0.04), and renting the house compared to owning it (Chi2 = 5.83, p = 0.01). This study confirms the finding described by other authors that household transmission of SARS-CoV-2 is correlated with the income inequality of the analyzed geographical area as well as with the indicators of health and economic wealth of the families, and this correlation also applies to the Campania Region.

Monoclonal antibodies for mild-to-moderate COVID-19 in multiple sclerosis: A case series.

We reported on five people with MS, using immunodepleting disease modifying treatments (anti-CD20 monoclonal antibodies and sphingosine-one-phosphate modulators) and with reduced COVID-19 vaccine response, who had mild-to-moderate symptomatic COVID-19, and were treated with anti-SARS-CoV-2 monoclonal antibodies. In particular, we showed the possibility to use monoclonal antibodies to speed-up recovery from COVID-19 in MS, in the absence of any COVID-19 residuals or MS changes (e.g., relapses or disability).

Pneumocystis jirovecii Pneumonia in Non-HIV Patients Recovering from COVID-19: A Single-Center Experience.

OBJECTIVE: to describe a single-center experience of Pneumocystis jirovecii pneumonia (PJP) in non-HIV patients recovering from COVID-19. METHODS: We report the cases of five non-HIV patients with COVID-19 who also developed PJP at a University Hospital. RESULTS: With the exception of one subject, who experienced an atypical and prolonged course of COVID-19, all the patients developed PJP after the clinical resolution of COVID-19 pneumonia. All but one patient had no pre-existing immunosuppressive conditions or other risk factors for PJP development at COVID-19 diagnosis. Nonetheless, following the course of COVID-19 infection, all the patients fulfilled at least one host factor for PJP; indeed, all the patients had received at least 2 weeks of high-dose steroids and three out of five had a CD4+ cell count <200/mm3. CONCLUSIONS: The use of corticosteroids for COVID-19 respiratory impairment seems to be the most common risk factor for PJP, together with viral-induced and iatrogenic lymphopenia. The worsening in respiratory function and the characteristic radiological picture during or after COVID-19 pneumonia should raise the suspicion of PJP, even in immunocompetent patients. PJP primary chemoprophylaxis can be considered in selected high-risk COVID-19 patients, but further studies are needed.

Case Report: Discovery a Novel SARS-CoV-2 Variant in a Six-Months Long-Term Swab Positive Female Suffering From Non-Hodgkin Lymphoma.

BACKGROUND: We report the case of a woman with non-Hodgkin lymphoma who remained positive on the molecular assay for SARS-CoV-2 for six months: she has never experienced a severe form of COVID-19 although in absence of seroconversion. METHODS: The whole SARS-CoV-2 genome analysis was performed by the CleanPlex SARS-CoV-2 Research and Surveillance NGS Panel (PARAGON GENOMICS, Hayward, USA). RESULTS: We found twenty-two mutations in SARS-CoV-2 genome and a novel deleterious ORF3a frameshift c.766_769del corresponding to a unique and novel lineage. The region affected by this frameshift variant is reported as being important in determining SARS-CoV-2 immunogenicity. Patient's immunophenotype showed the absence of B lymphocytes and significantly reduced T-cell count. Only after the treatment with hyperimmune plasma she finally became negative on the swab. CONCLUSIONS: Our findings could be helpful in the management of patients with immunodeficiency, particularly when novel variants, potentially altering the virus immune response, are present.

Pneumocystis jirovecii pneumonia in an immunocompetent patient recovered from COVID-19.

BACKGROUND: Several cases of invasive fungal diseases in patients with COVID-19 have been reported, mostly due to Aspergillus spp., with anecdotic reports of Pneumocystis jirovecii pneumonia (PJP) as co-infections in immunocompromised patients. We describe the first case of PJP in an immunocompetent patient who recovered from COVID-19 pneumonia. CASE DESCRIPTION: Our patient was hospitalized for 18 d for respiratory failure due to Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pneumonia and successfully treated with continuous positive airway pressure (CPAP) respiratory support, enoxaparin, ceftaroline and intravenous 6 mg of dexamethasone for 10 d, then with oral prednisone tapering. Despite his improved radiological and clinical conditions at discharge, he was admitted again after 18 d for worsening of respiratory conditions. Upon the second admission, a high-resolution CT-scan of the chest showed the development of new ground-glass opacities and P. jirovecii was detected on bronchoalveolar lavage fluid. A therapy with trimethoprim-sulphamethoxazole 20 mg/kg and methylprednisolone 40 mg i.v. bis in die (BID) was started, with improvement of clinical, biochemical and radiological conditions. CONCLUSIONS: COVID-19 patients may have multiple risk factors for development of PJP, in particular lymphopaenia and use of steroids. PJP must be ruled out with direct microbiological methods in patients presenting with radiologic and clinical features of possible or probable PJP, even in immunocompetent hosts.

Chest CT in COVID-19 patients: Structured vs conventional reporting.

PURPOSE: To assess clinician satisfaction with structured (SR) and conventional (CR) radiological reports for chest CT exams in coronavirus disease 2019 (COVID-19) patients, objectively comparing both reporting strategies. METHOD: We retrospectively included 68 CTs (61 patients) with COVID-19. CRs were collected from the digital database while corresponding SRs were written by an expert radiologist, including a sign checklist, severity score index and final impressions. New CRs were prepared for a random subset (n = 10) of cases, to allow comparisons in reporting time and word count. CRs were analyzed to record severity score and final impressions inclusion. A random subset of 40 paired CRs and SRs was evaluated by two clinicians to assess, using a Likert scale, readability, comprehensiveness, comprehensibility, conciseness, clinical impact, and overall quality. RESULTS: Overall, 19/68 (28 %) and 9/68 (13 %) of CRs included final impressions and severity score, respectively. SR writing required significantly (p < 0.001) less time (mean = 308 s; SD ± 60 s) compared to CRs (mean = 458 s; SD ± 72 s). On the other hand, word count was not significantly different (p = 0.059, median = 100 and 106, range = 106-139 and 88-131 for SRs and CRs, respectively). Both clinicians expressed significantly (all p < 0.01) higher scores for SRs compared to CRs in all categories. CONCLUSIONS: Our study supports the use of chest CT SRs in COVID-19 patients to improve referring physician satisfaction, optimizing reporting time and provide a greater amount and quality of information within the report.