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.

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.

Neutralizing monoclonal antibodies for early treatment of hospital‐acquired SARS‐CoV‐2 infection in hematologic patients

Efficacy of early treatment with anti‐SARS‐CoV‐2 spike protein monoclonal antibodies (mAbs) for nosocomial SARS‐CoV‐2 infection in hematologic patients is unknown. Retrospective, cohort study conducted in four Italian teaching hospitals. We included adult patients with hematologic malignancies and hospital‐acquired SARS‐CoV‐2 infection diagnosed between November 2020 and December 2021. The principal exposure variable was administration of mAbs. The primary endpoint was clinical failure dea composite outcome of mortality and/or invasive and noninvasive ventilation within 90 days from infection onset. We included 52 patients with hospital‐acquired SARS‐CoV‐2 infection. Males were 29 (60%), median age was 62 (interquartile range [IQR] 48–70). Forty‐five (86%) patients were on chemotherapy or had received chemotherapy within 30 days. MAbs were administered in 19/52 (36%) patients. Clinical failure occurred in 22 (42%) patients;21% (4/19) in mAbs group versus 54% (18/33) in non‐mAbs group (p = 0.03). Other predictors of clinical failure were older age (median [IQR] 69 [61–72] versus 58 [46–66], p = 0.001), and higher Charlson comorbidity index (median [IQR], 5 [3.25‐5] versus 3 [2–5], p = 0.002). At multivariable Cox regression model, mAbs were independently associated with a significantly lower rate of clinical failure (HR 0.11, 95% CI 0.01–0.85, p = 0.01), after adjusting for confounders. In conclusion, mAbs are promising for early treatment of hematologic patients with healthcare‐related SARS‐CoV‐2 infection.

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.

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.

Nasopharyngeal Microbiome Signature in COVID-19 Positive Patients: Can We Definitively Get a Role to Fusobacterium periodonticum?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the pandemic Coronavirus Disease 2019 (COVID-19). This virus is highly transmissible among individuals through both droplets and aerosol leading to determine severe pneumonia. Among the various factors that can influence both the onset of disease and the severity of its complications, the microbiome composition has also been investigated. Recent evidence showed the possible relationship between gut, lung, nasopharyngeal, or oral microbiome and COVID-19, but very little is known about it. Therefore, we aimed to verify the relationships between nasopharyngeal microbiome and the development of either COVID-19 or the severity of symptoms. To this purpose, we analyzed, by next generation sequencing, the hypervariable V1-V2-V3 regions of the bacterial 16S rRNA in nasopharyngeal swabs from SARS-CoV-2 infected patients (n=18) and control (CO) individuals (n=12) using Microbiota solution A (Arrow Diagnostics). We found a significant lower abundance of Proteobacteria and Fusobacteria in COVID-19 patients in respect to CO (p=0.003 and p<0.0001, respectively) from the phylum up to the genus (p<0.001). The Fusobacterium periodonticum (FP) resulted as the most significantly reduced species in COVID-19 patients respect to CO. FP is reported as being able to perform the surface sialylation. Noteworthy, some sialic acids residues on the cell surface could work as additional S protein of SARS-CoV-2 receptors. Consequently, SARS-CoV-2 could use sialic acids as receptors to bind to the epithelium of the respiratory tract, promoting its clustering and the disease development. We can therefore speculate that the significant reduction of FP in COVID-19 patients could be directly or indirectly linked to the modulation of sialic acid metabolism. Finally, viral or environmental factors capable of interfering with sialic metabolism could determine a fall in the individual protection from SARS-CoV-2. Further studies are necessary to clarify the precise role of FP in COVID-19.

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.

Serum KL-6 Could Represent a Reliable Indicator of Unfavourable Outcome in Patients with COVID-19 Pneumonia.

KL-6 is a sialoglycoprotein antigen which proved elevated in the serum of patients with different interstitial lung diseases, especially in those with a poorer outcome. Given that interstitial pneumonia is the most common presentation of SARS-CoV2 infection, we evaluated the prognostic role of KL-6 in patients with COVID-19 pneumonia. Patients with COVID-19 pneumonia were prospectively enrolled. Blood samples were collected at the time of enrolment (TOE) and on day 7 (T1). Serum KL-6 concentrations were measured by chemiluminescence enzyme immunoassay using a KL-6 antibody kit (LUMIPULSE G1200, Fujirebio) and the cut-off value was set at >1000 U/mL. Fifteen out of 34 enrolled patients (44.1%) died. Patients with unfavourable outcome showed significantly lower P/F ratio and higher IL-6 values and plasmatic concentrations of KL-6 at TOE compared with those who survived (median KL-6: 1188 U/mL vs. 260 U/mL, p < 0.001). KL-6 > 1000 U/mL resulted independently associated with death (aOR: 11.29, p < 0.05) with a positive predictive value of 83.3%. Our results suggest that KL-6 is a reliable indicator of pulmonary function and unfavourable outcome in patients with COVID-19 pneumonia. A KL-6 value > 1000 U/mL resulted independently associated with death and showed good accuracy in predicting a poorer outcome. KL-6 may thus represent a quick, inexpensive, and sensitive parameter to stratify the risk of severe respiratory failure and death.

Prevalence of SARS-CoV-2 Antibodies in Multiple Sclerosis: The Hidden Part of the Iceberg.

BACKGROUND: We compared the prevalence of SARS-CoV-2 IgG/IgM in multiple sclerosis (MS), low-risk, and high-risk populations and explored possible clinical correlates. METHODS: In this cross-sectional study, we recruited MS patients, low-risk (university staff from non-clinical departments), and high-risk individuals (healthcare staff from COVID-19 wards) from 11 May to 15 June 2020. We used lateral flow immunoassay to detect SARS-CoV-2 IgG and IgM. We used t-test, Fisher's exact test, chi square test, or McNemar's test, as appropriate, to evaluate between-group differences. RESULTS: We recruited 310 MS patients (42.3 ± 12.4 years; females 67.1%), 862 low-risk individuals (42.9 ± 13.3 years; females 47.8%), and 235 high-risk individuals (39.4 ± 10.9 years; females 54.5%). The prevalence of SARS-CoV-2 IgG/IgM in MS patients (n = 9, 2.9%) was significantly lower than in the high-risk population (n = 25, 10.6%) (p < 0.001), and similar to the low-risk population (n = 11, 1.3%) (p = 0.057); these results were also confirmed after random matching by age and sex (1:1:1). No significant differences were found in demographic, clinical, treatment, and laboratory features. Among MS patients positive to SARS-CoV-2 IgG/IgM (n = 9), only two patients retrospectively reported mild and short-lasting COVID-19 symptoms. CONCLUSIONS: MS patients have similar risk of SARS-CoV-2 infection to the general population, and can be asymptomatic from COVID-19, also if using treatments with systemic immunosuppression.

COVID-19 prevention and multiple sclerosis management: The SAFE pathway for the post-peak.

BACKGROUND: We hereby report on our experience from Naples (South Italy), where the peak of coronavirus disease 2019 (COVID-19) has already passed. METHODS: Assuming that COVID-19 will be circulating until vaccination and/or herd immunity is achieved (possibly not earlier than 2021), we have developed a protocol for the long-term management of multiple sclerosis (MS). RESULTS: We have defined a pathway for the access to the MS Centre with logistic, preventative and clinical recommendations, and have also included 14-day self-isolation and COVID-19 testing before some disease modifying treatments. DISCUSSION: Overall, we believe our experience could be helpful for MS management in the upcoming months.