NILMATREVIR-RITONAVIR TREATMENT IN CHILDREN WITH SARS-CoV-2 INFECTION

Background: Children seem to experience a less severe form of COVID-19 disease than adults, nevertheless, cases of severe infection have been described in a small proportion of patients, requiring hospitalization in 5-10% of cases. Among COVID-19 deaths 0,4% occurred in children and adolescents under 20 years of age. Most hospitalized children with acute COVID-19 had underlying conditions. Moreover, some children with previous COVID-19 infection, may later develop Multisystem Inflammatory Syndrome in Children (MIS-C), a rare but serious condition associated with COVID-19. These data suggest that a specific therapy is necessary in high-risk pediatric population, in order to prevent severe COVID-19, especially in children with underlying conditions. Antiviral paediatric data are currently very few Methods: We conducted a retrospective study on patients < 18 years of age who received Paxlovid (nirmatrelvir-ritonavir) for the treatment of mild-tomoderate COVID-19 at Bambino Gesu Children's Hospital from April 2022 to September 2022. Patients at high risk of progression to severe COVID-19 who had no need of supplemental oxygen received Paxlovid according to AIFA's indications for adults with the Informed Consent of relatives Results: 40 patients aged 1-18 years with confirmed SARS-CoV-2 infection were treated with Paxlovid (Tab 1)The average symptom duration was 4.2 days. No patient developed severe COVID-19 r All patients were treated within 5 days of symptom onset, Four patients received a longer course treatment (10 days) due to the persistence of symptoms combined with the presence of severe comorbidities .The mean time of viral shedding was 12.7 days, with a patient being persistently positive for 56 days. After Paxlovid initiation, only 5 patients (12.5%) experienced adverse reactions: Conclusion(s): Treatment with Paxlovid has proven to be safe. Further pharmacokinetic studies are required species for children < 5 years old.

Very Early Onset of Systemic Lupus Erythematosus

Introduction: Childhood-onset systemic lupus erythematosus(cSLE) is rare, especially before five years of age. Symptoms are commonly overlooked, despite the severity of certain clinical manifestations. Material(s) and Method(s):A three-year-old Guianese girl, born to unrelated parents, presented with macrohematuria. No family history of renal nor rheumatological diseases. She had presented scarlet fever two months earlier and upper respiratory tract infections. Result(s): Clinical examination was unremarkable. Laboratory tests showed nephrotic syndrome, brown macrohematuria, normal GFR and ultrasound . Initial suspicion of post -streptococcal glomerulonephritis(PSGN) was sustained by the hypocomplementemia. However, atypical presentation emerged with non-hemolytic anemia, posi t ive direct Coombs test, thrombocytopeni a , hypergammaglobulinemia and high ESR:CRP ratio. Active EBV replication and IgG anti-SARS-Cov2 were found. Subsequently a malar rash, palatal petechiae and oedema appeared with rapid worsening of anemia and thrombocytopenia. Differential diagnosis focused on hematological malignancies, viral infections or autoimmune diseases. Bone-marrow aspiration and immunophenotyping excluded malignancies or EBVinduced cytopenia;immune-deficiency and SARS-Cov2 associated multisystemic-inflammatory-syndrome were ruled-out. Autoimmune screen revealed high ANA, anti-dsDNA, ENA and p-ANCA titer with anti-C1q, anti-platelet and anti-beta2GP1 antibodies associated with LAC positivity, but no anti-FB antibodies.Thus, cSLE was highly plausible, kidney biopsy was mandatory but postponed due to the hemorrhage risk. Thereafter, normalisation of CBC with three methylprednisolone boluses and oral prednisone, mycophenolate and hydroxychloroquine, enabled it.Histologically, class V lupus nephritis with NIH-score of 0/24 for activity and 0/12 for chronicity was observed. Considering the very earlyonset and suspected monogenic cSLE, genetic study is ongoing. Conclusion(s): PSGN is the leading cause of acute nephritis in children.Kidney biopsy is not required in typical cases with acute nephritic syndrome and C3 hypocomplementemia. However, red-flags such as hypocomplementemia persistence, rapidly progressive glomerulonephritis or extra-renal manifestations, indicate a kidney biopsy to identify conditions associated with a negative renal outcome and requiring prompt appropriate treatment like C3-glomerulopathy, membranoproliferative glomerulonephritis or cSLE.

Balance between parsimony and abundance in diagnosis at the time of COVID-19 (Ockham “against” Hickam)

Background and Aim: The persistence of the SARS-CoV-2 pandemic requires Internal Medicine units to manage the complexity of patients with acute CoViD-19 disease, overlapping in most cases with relevant comorbidities. Methods: In two months we cared for 211 patients affected from CoViD-19 pneumonia in our 44-beds Internal Medicine unit;among these patients, 9% had no chronic comorbidities (CC), 12% had 1 CC, 27% had 2 CCs, 30% had 3 CCs, 22% had 4 or more CCs. Results: The most frequent symptoms that led to hospitalization were fever (79%) dyspnoea (51%), cough (44%);the most frequent admitting diagnosis was “respiratory failure in CoViD-19 pneumonia” (PaO2 <60 mmHg and typical pulmonary CT-scan): “pluralitas non est ponenda sine necessitate” - William of Ockham. Chronic comorbidities have often been decisive in influencing the clinical outcome and the lenght of hospitalization. The most common diseases were, as expected, heart failure, diabetes, hypertension, neoplasms, anemia, dementia, septic complications: “a patient can have as many diagnosis as he darn well pleased”- J. Hickam. The patient treatment included management of respiratory failure (O2 supplementation or non-invasive ventilation), treatment of concomitant diseases and antiviral and antibiotic therapy, if indicated. Conclusions: Our data support, even in time of Covid-19, the continuing need for integration between the principle of parsimony (Ockham's razor) and abundance (Hickam's dictum) for the purpose of a correct diagnosis and therapy.

Adult interstitial pneumonia due to respiratory syncytial virus: look and you shall find

Introduction: Once considered a pediatric concern, respiratory syncytial virus (RSV) infection is gaining importance as a cause of significant hospitalisation, need for ICU care and mortality in adults of all ages with chronic comorbidities. Description of the case: A 66-years old woman with an history of smoking, diabetes, obesity, hypertension, chronic renal failure and COPD was admitted to our hospital because of sudden onset of respiratory failure preceded by fever and dry cough since 1 week. At the admission we obtain two negative nasopharyngeal swab test for SARS-CoV-2 RT-PCR assays and, subsequently a positive test for RSV on Respiratory Multiplex PCR assay. A bilateral interstitial pneumonia was detected by a pulmonary CT-scan;blood tests showed WBC 14.400/mm3 Hb 10,5 g/dL PLT 121.000/mm3, CRP 16,3 mg/dL, creatinine 2,81 mg/dL. The patient was treated with intravenous broad-spectrum antibiotic therapy, supplemental 02 with face mask, corticosteroids and loop diuretics, with progressive improvement of clinical status, blood tests and arterial ABG values. A successive control with CT-scan showed a reduction of pneumonia extension and the patient started a respiratory rehabilitation. Conclusions: The COVID-19 pandemic has pointed-out the need for greater diagnostic accuracy of acute respiratory diseases. RSV infection is an often underdiagnosed cause of hospitalisation and mortality even in non-immunocompromised adults affected from chronic comorbidities.

Role and Experience of a Subintensive Care Unit in Caring for Patients with COVID-19 in Italy: The CO-RESP Study

Objective: This retrospective and prospective cohort study was designed to describe the characteristics, treatments, and outcomes of patients with SARS-CoV-2 infection (COVID-19) admitted to subintensive care units (SICU) and to identify the variables associated with outcomes. SICUs have been extremely stressed during the pandemic, but most data regarding critically ill COVID-19 patients come from intensive care units (ICUs). Studies about COVID-19 patients in SICUs are lacking. Setting and participants: The study included 88 COVID-19 patients admitted to our SICU in Cuneo, Italy, between March and May 2020. Measurements: Clinical and ventilatory data were collected, and patients were divided by outcome. Multivariable logistic regression analysis examined the variables associated with negative outcomes (transfer to the ICU, palliation, or death in a SICU). Results: A total of 60 patients (68%) had a positive outcome, and 28 patients (32%) had a negative outcome;69 patients (78%) underwent continuous positive airway pressure (CPAP). Pronation (n=37 [42%]) had been more frequently adopted in patients who had a positive outcome vs a negative outcome (n=30 [50%] vs n=7 [25%];P=.048), and the median (interquartile range) Pao2/Fio2 ratio after 6 hours of prone positioning was lower in patients who had a negative outcome vs a positive outcome (144 [140-168] vs 249 [195-268], P=.006). Independent predictors of a negative outcome were diabetes (odds ratio [OR], 8.22;95% CI, 1.50-44.70;P=.015), higher D-dimer (OR, 1.28;95% CI, 1.04-1.57;P=.019), higher lactate dehydrogenase level (OR, 1.003;95% CI, 1.000-1.006;P=.039), and lower lymphocytes count (OR, 0.996;95% CI, 0.993-0.999;P=.004). Conclusion: SICUs have a fundamental role in the treatment of critically ill patients with COVID-19, who require long-term CPAP and pronation cycles. Diabetes, lymphopenia, and high D-dimer and LDH levels are associated with negative outcomes.

Dental Education Challenges during the COVID-19 Pandemic Period in Italy: Undergraduate Student Feedback, Future Perspectives, and the Needs of Teaching Strategies for Professional Development

The COVID-19 pandemic literally stopped most human movement and activities as it initially spread, which included dental practices and dental education. This defined the need for significative changes in teaching and learning with the use of "e-learning" methods, also for traineeships. This study was designed to determine the undergraduate student perception of these new methods as part of their education. This involved 353 students attending the Dental School of the G. D'Annunzio University of Chieti-Pescara, from the first to the sixth years. A questionnaire in Italian and was set-up using "Google Forms" and sent by email to the students. The questionnaire was divided into three parts: the first part included questions for general information, including age, sex and year of course;the second part had multiple choice questions related to their evaluation of the e-learning teaching, using a scale of opinion in the replies to each question (e.g., "scarce", "fair", "satisfying", "very good" and "excellent");and the third part included two open questions to indicate the strengths and limitations of these new teaching and learning approaches. The categorical variables in the first and second parts of the questionnaire were evaluated using Chi squared tests, setting significance at p < 0.05, while the comments were evaluated qualitatively. The student feedback showed significant appreciation (p < 0.05) of the new methods and the efforts that the lecturers put in to provide lectures of as high a quality as possible. However, a lack of practical training was significantly perceived as an important problem in the structure of their new curriculum (p < 0.05). COVID-19 has been an epic tragedy that has hit the human population not only in terms of health and healthcare, but also quality of life. This includes the quality of dental education within universities. However, the pandemic can be seen to also represent motivation to invest in the necessary technological innovation to deliver the best possible education to our future dentists.

A simple tool to help ruling-out Covid-19 in the emergency department: derivation and validation of the LDH-CRP-Lymphocyte (LCL) score

After the outbreak of the Covid-19 pandemic, cases of SARS-CoV-2 infections may gradually decrease in the next months. Given the reduced prevalence of the disease, Emergency Departments (ED) are starting to receive more and more non-Covid-19 patients. Thus, a way to quickly discriminate ED patients with potential Covid-19 infection from non-Covid-19 patients is needed in order to keep potentially contagious patients isolated while awaiting second-level testing. In this paper, we present the derivation and validation of a simple, practical, and cheap score that could be helpful to rule out Covid-19 among ED patients with suspicious symptoms (fever and/or dyspnoea). The LCL score was derived from a cohort of 335 patients coming to the ED of our hospital from March 16th to April 1st, 2020. It was then retrospectively validated in a similar cohort of 173 patients admitted to our ED during April. The score is based on blood values of lactate dehydrogenase, C-reactive protein, and lymphocyte count. The LCL score performed well both in the derivation and in the validation cohort, with an AUC respectively of 0.81 (95% CI: 0.77 - 0.86) and of 0.71 (95% CI: 0.63 - 0.78), given the difference in Covid-19 prevalence between the two cohorts (57% vs 41% respectively). An LCL score equal to 0 had a negative predictive value of 0.92 in the derivation cohort and of 0.81 in the validation cohort, with a negative likelihood ratio respectively of 0.08 and 0.36 for Covid-19 exclusion. This score could, therefore, constitute a useful tool to help physicians manage patients in the ED.