The MBL2 genotype relates to COVID-19 severity and may help to select the optimal therapy.

OBJECTIVES: Sars-CoV-2 acute infection is clinically heterogeneous, ranging from asymptomatic cases to patients with a severe, systemic clinical course. Among the involved factors age and preexisting morbidities play a major role; genetic host susceptibility contributes to modulating the clinical expression and outcome of the disease. Mannose-binding lectin is an acute-phase protein that activates the lectin-complement pathway, promotes opsonophagocytosis and modulates inflammation, and is involved in several bacterial and viral infections in humans. Understanding its role in Sars-CoV-2 infection could help select a better therapy. METHODS: We studied MBL2 haplotypes in 419 patients with acute COVID-19 in comparison to the general population and related the haplotypes to clinical and laboratory markers of severity. RESULTS: We recorded an enhanced frequency of MBL2 null alleles in patients with severe acute COVID-19. The homozygous null genotypes were significantly more frequent in patients with advanced WHO score 4-7 (OR of about 4) and related to more severe inflammation, neutrophilia, and lymphopenia. CONCLUSIONS: Subjects with a defective MBL2 genotype (i.e., 0/0) are predisposed to a more severe acute Sars-CoV-2 infection; they may benefit from early replacement therapy with recombinant MBL. Furthermore, a subset of subjects with the A/A MBL genotype develop a relevant increase of serum MBL during the early phases of the disease and develop a more severe pulmonary disease; in these patients, the targeting of the complement may help. Therefore, COVID-19 patients should be tested at hospitalization with serum MBL analysis and MBL2 genotype, to define the optimal therapy.

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.

COVID-19: Where We Are and Where We Are Going.

The impact of COVID-19 on global health has been colossal [...].

Nasal Microbiome in COVID-19: A Potential Role of Corynebacterium in Anosmia.

The evolution and the development of the symptoms of Coronavirus disease 19 (COVID-19) are due to different factors, where the microbiome plays a relevant role. The possible relationships between the gut, lung, nasopharyngeal, and oral microbiome with COVID-19 have been investigated. We analyzed the nasal microbiome of both positive and negative SARS-CoV-2 individuals, showing differences in terms of bacterial composition in this niche of respiratory tract. The microbiota solution A (Arrow Diagnostics) was used to cover the hypervariable V1-V3 regions of the bacterial 16S rRNA gene. MicrobAT Suite and MicrobiomeAnalyst program were used to identify the operational taxonomic units (OTUs) and to perform the statistical analysis, respectively. The main taxa identified in nasal microbiome of COVID-19 patients and in Healthy Control subjects belonged to three distinct phyla: Proteobacteria (HC = 14%, Cov19 = 35.8%), Firmicutes (HC = 28.8%, Cov19 = 30.6%), and Actinobacteria (HC = 56.7%, Cov19 = 14.4%) with a relative abundance > 1% in all groups. A significant reduction of Actinobacteria in Cov19 group compared to controls (P < 0.001, FDR = 0.01) was found. The significant reduction of Actinobacteria was identified in all taxonomic levels down to the genus (P < 0.01) using the ANOVA test. Indeed, a significantly reduced relative abundance of Corynebacterium was found in the patients compared to healthy controls (P = 0.001). Reduced abundance of Corynebacterium has been widely associated with anosmia, a common symptom of COVID-19 as suffered from our patients. Contrastingly, the Corynebacterium genus was highly represented in the nasal mucosa of healthy subjects. Further investigations on larger cohorts are necessary to establish functional relationships between nasal microbiota content and clinical features of COVID-19.

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.

Remdesivir Alone or in Combination with Monoclonal Antibodies as an Early Treatment to Prevent Severe COVID-19 in Patients with Mild/Moderate Disease at High Risk of Progression: A Single Centre, Real-Life Study.

Early treatment with antivirals against SARS-CoV-2 infection can prevent the onset of severe COVID-19 in fragile and immunocompromised patients. In this real-life, prospective, observational study, we evaluated efficacy and safety of a 3-day early treatment with remdesivir in adult and fragile patients with a diagnosis of SARS-CoV-2 infection who referred to the COVID-19 early treatment service of Infectious Diseases Unit of University of Naples Federico from 10 January 2022 to 31 March 2022. The included patients could be treated with either remdesivir alone or with remdesivir plus a monoclonal antibody with activity against SARS-CoV-2. Among the 62 included patients, we showed low rates of hospitalization (8%), increase in oxygen supplementation (3.2%), ICU admission (1.6%) and death (1.6%). The rate of disease progression was 8% and it was similar in patients treated with remdesivir alone or in combination with monoclonal antibodies (6.7% and 9.4%, respectively; p = 0.531). The rate of adverse drug reaction was low and similar in the two groups (13.3% in patients treated with remdesivir, 15.6% in patients treated with the combination; p = 0.543). Most common adverse events were headache and fever. In conclusion, in our cohort of patients at a high risk of worse COVID-19 outcomes, an early course of remdesivir showed low rates of disease progression and adverse drug reactions.

Diabetes and SARS-CoV-2 Infection: The Potential Role of Antidiabetic Therapy in the Evolution of COVID-19.

Diabetes mellitus represents one of the most frequent comorbidities among patients with COVID-19, constituting a risk factor for a more severe prognosis than that of non-diabetic patients. However, the pathophysiological mechanism underlying this unfavorable outcome is still not completely clear. The goal of our study was to evaluate the potential role of antidiabetic therapy in the evolution of 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.

Pre-existing chronic kidney disease (CDK) was not associated with a severe clinical outcome of hospitalized COVID-19: results of a case-control study in Southern Italy.

The presence of co-morbidities is associated with a poor outcome in patients with COVID-19. The aim of the present study was to investigate the outcomes of patients with SARS-CoV-2 infection and chronic kidney disease (CKD) in order to assess its impact on mortality and severity of disease. We performed a multicenter, observational, 1:2 matched case-control study involving seventeen COVID-19 Units in southern Italy. All the adults hospitalized for SARS-CoV-2 infection and with pre-existing CKD were included (Cases). For each Case, two patients without CKD pair matched for gender, age (+5 years), and number of co-morbidities (excluding CKD) were enrolled (Controls). Of the 2,005 patients with SARS-CoV-2 infection followed during the study period, 146 patients with CKD and 292 patients without were enrolled in the case and control groups, respectively. Between the Case and Control groups, there were no statistically significant differences in the prevalence of moderate (17.1% vs 17.8%, p=0.27) or severe (18.8% and 13.7%, p=0.27) clinical presentation of COVID-19 or deaths (20.9% vs 28.1%, p=0.27). In the Case group, the patients dead during hospitalization were statistically higher in the 89 patients with CKD stage 4-5 compared to 45 patients with stages 1-3 CKD (30.3% vs 13.3%, p=0.03). Our data suggests that only CKD stage 4-5 on admission was associated with an increased risk of in-hospital death.

Circulating tissue inhibitor of metalloproteinases 1 (TIMP-1) at COVID-19 onset predicts severity status.

Background: Systemic biomarkers for severity of SARS-CoV-2 infection are of great interest. In this study, we evaluated a set of collagen metabolites and extracellular matrix remodeling biomarkers including procollagen type III amino terminal propeptide (PIIINP), tissue inhibitor of metalloproteinases 1 (TIMP-1) and hyaluronic acid (HA) as prognostic indicators in COVID-19 patients. Methods: Ninety COVID-19 patients with the absence of chronic liver diseases were enrolled. Serum PIIINP, TIMP-1, and HA were measured and correlated with inflammatory indices and clinical variables. Patients were stratified for disease severity according to WHO criteria in two groups, based on the requirement of oxygen support. Results: Serum TIMP-1, but not PIIINP and HA was significantly higher in patients with WHO score ≥5 compared to patients with WHO score <5 [PIIINP: 7.2 (5.4-9.5) vs. 7.1 (4.5-9.9), p = 0.782; TIMP-1: 298.1 (20.5-460) vs. 222.2 (28.5-452.8), p = 0.01; HA: 117.1 (55.4-193.7) vs. 75.1 (36.9-141.8), p = 0.258]. TIMP-1 showed moderate correlation with CRP (r = 0.312, p = 0.003) and with LDH (r = 0.263, p = 0.009). CRP and serum LDH levels were significantly higher in COVID-19 patients with WHO score ≥5 compared to the group of patients with WHO score < 5 [15.8 (9-44.5) vs. 9.3 (3.4-33.8), p = 0.039 and 373 (282-465) vs. 289 (218-383), p = 0.013, respectively]. Conclusion: In patients with COVID-19, circulating TIMP-1 was associated with disease severity and with systemic inflammatory index, suggesting that TIMP-1 could represent a promising non-invasive prognostic biomarker in COVID-19 patients. Interestingly, our results prompted that serum TIMP-1 level may potentially be used to select the patients for therapeutic approaches targeting matrix metalloproteases pathway.

Lactate dehydrogenase and PaO2/FiO2 ratio at admission helps to predict CT score in patients with COVID-19: An observational study.

INTRODUCTION: Since the beginning of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic an important tool for patients with Coronavirus Disease 2019 (COVID-19) has been the computed tomography (CT) scan, but not always available in some settings The aim was to find a cut-off that can predict worsening in patients with COVID-19 assessed with a computed tomography (CT) scan and to find laboratory, clinical or demographic parameters that may correlate with a higher CT score. METHODS: We performed a multi-center, observational, retrospective study involving seventeen COVID-19 Units in southern Italy, including all 321 adult patients hospitalized with a diagnosis of COVID-19 who underwent at admission a CT evaluated using Pan score. RESULTS: Considering the clinical outcome and Pan score, the best cut-off point to discriminate a severe outcome was 12.5. High lactate dehydrogenase (LDH) serum value and low PaO2/FiO2 ratio (P/F) resulted independently associated with a high CT score. The Area Under Curve (AUC) analysis showed that the best cut-off point for LDH was 367.5 U/L and for P/F 164.5. Moreover, the patients with LDH> 367.5 U/L and P/F < 164.5 showed more frequently a severe CT score than those with LDH< 367.5 U/L and P/F> 164.5, 83.4%, vs 20%, respectively. CONCLUSIONS: A direct correlation was observed between CT score value and outcome of COVID-19, such as CT score and high LDH levels and low P/F ratio at admission. Clinical or laboratory tools that predict the outcome at admission to hospital are useful to avoiding the overload of hospital facilities.

Serum galectin-3 and aldosterone: potential biomarkers of cardiac complications in patients with COVID-19.

BACKGROUND: Despite severe acute respiratory syndrome (SARS)-Coronavirus (CoV-2) primarily targeting the lungs, the heart represents another critical virus target. Thus, the identification of SARS-CoV-2 disease of 2019 (COVID-19)-associated biomarkers would be beneficial to stratify prognosis and the risk of developing cardiac complications. Aldosterone and galectin-3 promote fibrosis and inflammation and are considered a prognostic biomarker of lung and adverse cardiac remodeling. Here, we tested whether galectin-3 and aldosterone levels can predict adverse cardiac outcomes in COVID-19 patients. METHODS: To this aim, we assessed galectin-3 and aldosterone serum levels in 51 patients diagnosed with COVID-19, using a population of 19 healthy subjects as controls. In in-vitro studies, we employed 3T3 fibroblasts to assess the potential roles of aldosterone and galectin-3 in fibroblast activation. RESULTS: Serum galectin-3 levels were more elevated in COVID-19 patients than healthy controls and correlated with COVID-19 severity classification and cardiac troponin-I (cTnI) serum levels. Furthermore, we observed an augmented secretion of aldosterone in COVID-19 patients. This adrenal hormone is a direct stimulator of galectin-3 secretion; therefore, we surmised that this axis could perpetrate fibrosis and adverse remodeling in these subjects. Thus, we stimulated fibroblasts with 10% of serum from COVID-19 patients. This challenge markedly rose the expression of smooth muscle alpha (α)-2 actin (ACTA2), a myofibroblast marker. CONCLUSIONS: Our study suggests that COVID-19 can affect cardiac structure and function by triggering aldosterone and galectin-3 release that may serve as prognostic and therapeutic biomarkers while monitoring the course of cardiac complications in patients suffering from 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.

Clinical Characterization of the Three Waves of COVID-19 Occurring in Southern Italy: Results of a Multicenter Cohort Study.

AIMS: To characterize patients hospitalized for COVID-19 in the three waves in Southern Italy. METHODS: We conducted a multicenter observational cohort study involving seventeen COVID-19 Units in Campania, southern Italy: All adult (≥18 years) patients, hospitalized with a diagnosis of SARS-CoV-2 infection from 28 February 2020 to 31 May 2021, were enrolled. RESULTS: Two thousand and fifteen COVID-19 hospitalized patients were enrolled; 392 (19%) in the first wave, 917 (45%) in the second and 706 (35%) in the third wave. Patients showed a less severe clinical outcome in the first wave than in the second and third waves (73%, 65% and 72%, respectively; p = 0.003), but hospitalization expressed in days was longer in the first wave [Median (Q1-Q3): 17 (13-25) v.s. 14 (9-21) and 14 (9-19), respectively, p = 0.001)] and also mortality during hospitalization was higher in the first wave than in the second and third waves: 16.6% v.s. 11.3% and 6.5%, respectively (p = 0.0001). Multivariate analysis showed that older age [OR: 1.069, CI (1046-1092); p = 0.001], a worse Charlson comorbidity index [OR: 1042, CI (1233-1594; p = 0.0001] and enrolment during the first-wave [OR: 1.917, CI (1.054-3.485; p = 0.033] were predictors of mortality in hospitalized patients. CONCLUSIONS: Improved organization of the healthcare facilities and the increase in knowledge of clinical and therapeutic management have contributed to a trend in the reduction in mortality during the three waves of COVID-19.

Monoclonal Antibodies against SARS-CoV-2 Infection: Results from a Real-Life Study before the Omicron Surge.

Despite the lightning-fast advances in the management of SARS-CoV after 2 years of pandemic, COVID-19 continues to pose a challenge for fragile patients, who could benefit from early administration of monoclonal antibodies (mAbs) to reduce the risk of severe disease progression. We conducted a prospective study to evaluate the effectiveness of mAbs against SARS-CoV-2 among patients at risk for severe disease progression, namely elderly and those with comorbidities, before the omicron variant surge. Patients were treated with either casirivimab/imdevimab, sotrovimab, or bamlanivimab/etesevimab. The rates and risk factors for clinical worsening, hospitalization, ICU admission and death (unfavorable outcomes) were evaluated. A stratified analysis according to the presence of SARS-CoV-2 IgG was also performed. Among 185 included patients, we showed low rates of unfavorable outcomes (9.2%), which were more frequent in patients with chronic kidney disease (aOR: 10.44, 95% CI: 1.73-63.03; p < 0.05) and basal D-dimer serum concentrations > 600 ng/mL (aOR 21.74, 95% CI: 1.18-397.70; p < 0.05). Patients with negative SARS-CoV-2 serology at baseline showed higher C-reactive protein values compared with patients with positive serology (p < 0.05) and a trend toward a higher admission rate to SICU and ICU compared with patients with positive serology. Our results thus showed, in a real-life setting, the efficacy of mAbs against SARS-CoV-2 before an Omicron surge when the available mabs become not effective.