Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial

As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63–1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70–1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitalized patients with moderate-to-severe COVID-19.

The Importance of RSV Epidemiological Surveillance: A Multicenter Observational Study of RSV Infection during the COVID-19 Pandemic.

The restrictive measures adopted worldwide against SARS-CoV-2 produced a drastic reduction in respiratory pathogens, including RSV, but a dramatic rebound was thereafter reported. In this multicenter retrospective observational study in 15 Pediatric Emergency Departments, all children <3 years old with RSV infection admitted between 1 September and 31 December 2021 were included and compared to those admitted in the same period of 2020 and 2019. The primary aim was to evaluate RSV epidemiology during and after the COVID-19 pandemic peak. The secondary aims were to evaluate the clinical features of children with RSV infection. Overall, 1015 children were enrolled: 100 in 2019, 3 in 2020 and 912 in 2021. In 2019, the peak was recorded in December, and in 2021, it was recorded in November. Comparing 2019 to 2021, in 2021 the median age was significantly higher and the age group 2-3 years was more affected. Admissions were significantly higher in 2021 than in 2020 and 2019, and the per-year hospitalization rate was lower in 2021 (84% vs. 93% in 2019), while the duration of admissions was similar. No difference was found in severity between 2019-2020-2021. In conclusion, after the COVID-19 pandemic, an increase in RSV cases in 2021 exceeding the median seasonal peak was detected, with the involvement of older children, while no difference was found in severity.

The Essentials about Neonatal Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Coronavirus Disease: A Narrative Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can occur in neonates as the virus can be transmitted both horizontally (from the environment) and vertically (during the pregnancy or at the delivery). Compared to the adult outbreak, neonatal infections do not represent a public health problem. Nonetheless, severe and life-threatening cases may rarely occur and both obstetricians and neonatologists should have a good knowledge of perinatal SARS-CoV-2 infection and related consequences. A high suspicion index must be applied and ruling out neonatal SARS-CoV-2 infection must become a part of the routine clinical workout. Moreover, neonates may be affected by the multisystem inflammatory syndrome, due to a dysregulated host response in the absence of any SARS-CoV-2 infection. We performed a narrative review to summarize here the available literature describing the essentials that should be known by every neonatologist and obstetrician, starting from what has been discovered in 2020 and adding what has been learned in the following years. The paper describes the mechanisms of transmission, clinical features, diagnostic tools, and criteria, as well as possible treatment and prevention strategies. The goal is to provide the practical points to be remembered at the bedside while caring for a pregnant woman or a neonate with suspected or proven coronavirus disease 2019 or multisystem inflammatory syndrome. KEY POINTS: · SARS-CoV-2 neonatal infections occur both vertically (30%) and horizontally (70%).. · Approximately, half of patients do not have clinical manifestations; clinical and laboratory signs are similar to those of adults but usually milder.. · Remdesivir and steroids can be used as a treatment..

Fetal Brain Damage during Maternal COVID-19: Emerging Hypothesis, Mechanism, and Possible Mitigation through Maternal-Targeted Nutritional Supplementation.

The recent outbreak of the novel Coronavirus (SARS-CoV-2 or CoV-2) pandemic in 2019 and the risk of CoV-2 infection during pregnancy led the scientific community to investigate the potential negative effects of Coronavirus infection on pregnancy outcomes and fetal development. In particular, as CoV-2 neurotropism has been demonstrated in adults, recent studies suggested a possible risk of fetal brain damage and fetal brain development impairment, with consequent psychiatric manifestations in offspring of mothers affected by COronaVIrus Disease (COVID) during pregnancy. Through the understanding of CoV-2's pathogenesis and the pathways responsible for cell damage, along with the available data about neurotropic virus attitudes, different strategies have been suggested to lower the risk of neurologic disease in newborns. In this regard, the role of nutrition in mitigating fetal damages related to oxidative stress and the inflammatory environment during viral infection has been investigated, and arginine, n3PUFA, vitamins B1 and B9, choline, and flavonoids were found to be promising in and out of pregnancy. The aim of this review is to provide an overview of the current knowledge on the mechanism of fetal brain damage and the impact of nutrition in reducing inflammation related to worse neurological outcomes in the context of CoV-2 infections during pregnancy.

Factors Associated With Severe Gastrointestinal Diagnoses in Children With SARS-CoV-2 Infection or Multisystem Inflammatory Syndrome.

Importance: Severe gastrointestinal (GI) manifestations have been sporadically reported in children with COVID-19; however, their frequency and clinical outcome are unknown. Objective: To describe the clinical, radiological, and histopathologic characteristics of children with COVID-19 presenting with severe GI manifestations to identify factors associated with a severe outcome. Design, Setting, and Participants: A multicenter retrospective cohort study (February 25, 2020, to January 20, 2021) enrolled inpatient and outpatient children (aged <18 years) with acute SARS-CoV-2 infection, confirmed by positive real-time reverse-transcriptase-polymerase chain reaction on nasopharyngeal swab or fulfilling the US Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children (MIS-C). The study was conducted by pediatricians working in primary care or hospitals in Italy participating in the COVID-19 Registry of the Italian Society of Pediatric Infectious Diseases. Main Outcomes and Measures: The occurrence of severe GI manifestations, defined by a medical and/or radiological diagnosis of acute abdomen, appendicitis (complicated or not by perforation and/or peritonitis), intussusception, pancreatitis, abdominal fluid collection, and diffuse adenomesenteritis requiring surgical consultation, occurring during or within 4 to 6 weeks after infection with SARS-CoV-2 infection. Logistic regression was used to estimate odds ratios (ORs) with 95% CIs of factors potentially associated with severe outcomes. Results: Overall, 685 children (386 boys [56.4%]; median age, 7.3 [IQR, 1.6-12.4] years) were included. Of these children, 628 (91.7%) were diagnosed with acute SARS-CoV-2 infection and 57 (8.3%) with MIS-C. The presence of GI symptoms was associated with a higher chance of hospitalization (OR, 2.64; 95% CI, 1.89-3.69) and intensive care unit admission (OR, 3.90; 95% CI, 1.98-7.68). Overall, 65 children (9.5%) showed severe GI involvement, including disseminated adenomesenteritis (39.6%), appendicitis (33.5%), abdominal fluid collection (21.3%), pancreatitis (6.9%), or intussusception (4.6%). Twenty-seven of these 65 children (41.5%) underwent surgery. Severe GI manifestations were associated with the child's age (5-10 years: OR, 8.33; 95% CI, 2.62-26.5; >10 years: OR, 6.37; 95% CI, 2.12-19.1, compared with preschool-age), abdominal pain (adjusted OR [aOR], 34.5; 95% CI, 10.1-118), lymphopenia (aOR, 8.93; 95% CI, 3.03-26.3), or MIS-C (aOR, 6.28; 95% CI, 1.92-20.5). Diarrhea was associated with a higher chance of adenomesenteritis (aOR, 3.13; 95% CI, 1.08-9.12) or abdominal fluid collection (aOR, 3.22; 95% CI, 1.03-10.0). Conclusions and Relevance: In this multicenter cohort study of Italian children with SARS-CoV-2 infection or MIS-C, 9.5% of the children had severe GI involvement, frequently associated with MIS-C. These findings suggest that prompt identification may improve the management of serious complications.

Pediatric admissions to emergency departments of North-Western Italy during COVID-19 pandemic: A retrospective observational study.

BACKGROUND: COVID-19 pandemic caused huge decrease of pediatric admissions to Emergency Department (ED), arising concerns about possible delays in diagnosis and treatment of severe disorders. METHODS: Impact of COVID-19 on Pediatric Emergency Room (ICOPER) was a retrospective multicentre observational study including 23 Italian EDs.All the children <18 years admitted, between March 9th and May 3rd 2020 stratified by age, priority code, cause of admission and outcome have been included and compared to those admitted in the same period of 2019.Our objectives were to assess the characteristics of pediatric admissions to EDs since COVID-19 outbreak until the end of lockdown, and to describe the features of critical children. FINDINGS: 16,426 children were admitted in 2020, compared to 55,643 in 2019 (-70·48%). Higher reduction was reported in hospitals without Pediatric Intensive Care Unit (PICU) (-73·38%) than in those with PICU (-64·08%) (P<0·0001). Admissions with low priority decreased more than critical ones (-82·77% vs. 44·17% respectively; P<0·0001). Reduction of discharged patients was observed both in hospitals with (-66·50%) and without PICU (-74·65%) (P<0·0001). No difference in the duration of symptoms before admission was reported between 2019 and 2020, with the majority of children accessing within 24 h (55·08% vs. 57·28% respectively; P = 0·2344). INTERPRETATION: Admissions with low priority decreased significantly more than those with high priority; we suppose that the fear of being infected in hospital maybe overcame the concerns of caregivers. Compared to 2019, no significant referral delay by caregivers was reported. Our data suggest the need of adaptation of EDs and primary care services to different needs of children during COVID-9 pandemic.

Phytonutrient and Nutraceutical Action against COVID-19: Current Review of Characteristics and Benefits.

The trend toward using phytonutrients and/or nutraceuticals (P/Ns) with the aim of impacting immune health has increased in recent years. The main reason is that properties of P/Ns are associated with possible immunomodulating effects in the prevention and complementary treatment of viral diseases, including COVID-19 and other respiratory infections. In the present review, we assess the scientific plausibility of specific P/Ns for this purpose of preventative and therapeutic interventions against COVID-19, with an emphasis on safety, validity, and evidence of efficacy against other viruses. Five potential candidates have been identified after reviewing available studies (in silico, in vitro, and in vivo) in which certain flavonoids have demonstrated a potential for use as adjuvant therapeutic agents against viral infections, including COVID-19. As these are often better tolerated than pharmacological treatments, their use could be more widely considered if additional detailed studies can validate the existing evidence.

Management and Nutrition of Neonates during the COVID-19 Pandemic: A Review of the Existing Guidelines and Recommendations.

OBJECTIVE: We aimed at reviewing the currently available guidelines and scientific recommendations regarding the neonatal in-hospital management and feeding in the light of the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: We systematically searched the guideline databases, Medline, Embase, and nationale/international neonatal societies websites as of June 19, 2020, for guidelines on neonatal management and feeding during the COVID-19 pandemic, at the same time assessing the methodological quality using the Appraisal of Guidelines for Research and Evaluation II tool. RESULTS: Eleven guidelines were included. The Chinese and American recommendations suggest separation of the mother and her neonate, whereas in French, Italian, UK, Canadian, and World Health Organization consensus documents the rooming-in is suggested, with Centers for Disease Control and Prevention guidelines suggesting to decide on a case-by-case basis. All the guidelines recommend breastfeeding or feeding with expressed maternal milk; the only exception is the Chinese recommendations, these last suggesting to avoid breastfeeding. CONCLUSION: This review may provide a useful tool for clinicians and organizers, highlighting differences and similarities of the existing guidelines on the management and feeding strategies in the light of the COVID-19 pandemic. KEY POINTS: · This study compares guidelines on management and nutrition of a newborn born to a mother with SARS-CoV-2 infection.. · Existing guidelines on neonatal management and nutrition during the SARS-CoV-2 pandemic show many differences.. · The majority of recommendations are mainly based on experts' opinion and are not evidence-based..

Vertical Transmission of SARS-CoV-2 (COVID-19): Are Hypotheses More than Evidences?

In spite of the increasing, accumulating knowledge on the novel pandemic coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), questions on the coronavirus disease-2019 (COVID-19) infection transmission from mothers to fetuses or neonates during pregnancy and peripartum period remain pending and have not been addressed so far. SARS-CoV-2, a RNA single-stranded virus, has been detected in the amniotic fluid, in the cord blood and in the placentas of the infected women. In the light of these findings, the theoretical risk of intrauterine infection for fetuses, or of peripartum infection occurring during delivery for neonates, has a biological plausibility. The extent of this putative risk might, however, vary during the different stages of pregnancy, owing to several variables (physiological modifications of the placenta, virus receptors' expression, or delivery route). This brief review provides an overview of the current evidence in this area. Further data, based on national and international multicenter registries, are needed not only to clearly assess the extent of the risk for vertical transmission, but also to ultimately establish solid guidelines and consistent recommendations. KEY POINTS: · Questions on the COVID-19 infection transmission from mothers to fetuses or neonates during pregnancy and peripartum period remain pending so far.. · The theoretical risk of intrauterine infection for fetuses, or of neonatal infection during delivery for neonates, has a biological plausibility.. · A caution is recommended in the interpretation of clinical and laboratory data in neonates..

COVID-19 and Neonatal Respiratory Care: Current Evidence and Practical Approach.

The novel coronavirus disease 2019 (COVID-19) pandemic has urged the development and implementation of guidelines and protocols on diagnosis, management, infection control strategies, and discharge planning. However, very little is currently known about neonatal COVID-19 and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections. Thus, many questions arise with regard to respiratory care after birth, necessary protection to health care workers (HCW) in the delivery room and neonatal intensive care unit (NICU), and safety of bag and mask ventilation, noninvasive respiratory support, deep suctioning, endotracheal intubation, and mechanical ventilation. Indeed, these questions have created tremendous confusion amongst neonatal HCW. In this manuscript, we comprehensively reviewed the current evidence regarding COVID-19 perinatal transmission, respiratory outcomes of neonates born to mothers with COVID-19 and infants with documented SARS-CoV-2 infection, and the evidence for using different respiratory support modalities and aerosol-generating procedures in this specific population. The results demonstrated that to date, neonatal COVID-19 infection is uncommon, generally acquired postnatally, and associated with favorable respiratory outcomes. The reason why infants display a milder spectrum of disease remains unclear. Nonetheless, the risk of severe or critical illness in young patients exists. Currently, the recommended respiratory approach for infants with suspected or confirmed infection is not evidence based but should include all routinely used types of support, with the addition of viral filters, proper personal protective equipment, and placement of infants in isolation rooms, ideally with negative pressure. As information is changing rapidly, clinicians should frequently watch out for updates on the subject. KEY POINTS: · Novel coronavirus disease 2019 (COVID-19) pandemic urged development of guidelines.. · Neonatal COVID-19 disease is uncommon.. · Respiratory outcomes in neonates seems favorable.. · Current neonatal respiratory care should continue.. · Clinicians should watch frequently for updates..