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Preprint in English | medRxiv | ID: ppmedrxiv-21256539


There is increasing reporting by patients organization and researchers of long covid (or post-acute sequelae of SARS-CoV-2 - PASC), characterized by symptoms such as fatigue, dyspnea, chest pain, cognitive and sleeping disturbances, arthralgia and decline in quality of life. Immune system dysregulation with a hyperinflammatory state, direct viral toxicity, endothelial damage and microvascular injury have been proposed as pathologenic mechanisms. Recently, cohorts of children with PASC have been reported in Italy, Sweden and Russia. However, immunological studies of children with PASC have never been performed. In this study, we documented significant immunologic differences between children that completely recovered from acute infection and those with PASC, providing the first objective laboratory sign of the existence of PASC in children.

Preprint in English | bioRxiv | ID: ppbiorxiv-405738


BackgroundSARS-CoV-2 genotyping has been instrumental to monitor virus evolution and transmission during the pandemic. The reliability of the information extracted from the genotyping efforts depends on a number of aspects, including the quality of the input material, applied technology and potential laboratory-specific biases. These variables must be monitored to ensure genotype reliability. The current lack of guidelines for SARS-CoV-2 genotyping leads to inclusion of error-containing genome sequences in studies of viral spread and evolution. ResultsWe used clinical samples and synthetic viral genomes to evaluate the impact of experimental factors, including viral load and sequencing depth, on correct sequence determination using an amplicon-based approach. We found that at least 1000 viral genomes are necessary to confidently detect variants in the genome at frequencies of 10% or higher. The broad applicability of our recommendations was validated in >200 clinical samples from six independent laboratories. The genotypes of clinical isolates with viral load above the recommended threshold cluster by sampling location and period. Our analysis also supports the rise in frequency of 20A.EU1 and 20A.EU2, two recently reported European strains whose dissemination was favoured by travelling during the summer 2020. ConclusionsWe present much-needed recommendations for reliable determination of SARS-CoV-2 genome sequence and demonstrate their broad applicability in a large cohort of clinical samples.

Preprint in English | medRxiv | ID: ppmedrxiv-20194316


Recent advancements in bidimensional nanoparticles such as Graphene nanoplatelets (G) and the derivative Graphene oxide (GO) have the potential to meet the need for highly functional personal protective equipment (PPE) that confers increased protection against SARS-CoV-2 infection and the spread COVID-19. The ability of G and GO to interact with and bind microorganisms as well as RNA and DNA provides an opportunity to develop engineered textiles for use in PPE. The face masks widely used in health care and other high-risk settings for COVID transmission provide only a physical barrier that decreases likelihood of infection and do not inactivate the virus. Here, we show pre-incubation of viral particles with free GO inhibits SARS-CoV-2 infection of VERO cells. Highly relevant to PPE materials, when either polyurethane or cotton material was loaded with G or GO and culture medium containing SARS-CoV-2 viral particles either filtered through or incubated with the functionalized materials, the infectivity of the medium was nearly completely inhibited. The findings presented here constitute an important nanomaterials-based strategy to significantly increase face mask and other PPE efficacy in protection against the SARS-CoV-2 virus and COVID-19 that may be applicable to additional anti-SARS-CoV-2 measures including water filtration, air purification, and diagnostics. One Sentence SummaryCotton and polyurethane materials functionalized with bidimensional Graphene nanoplatelets trap SARS-CoV-2 and have the potential to reduce spread of COVID-19.

Preprint in English | medRxiv | ID: ppmedrxiv-20184242


BackgroundTo date, there are no comprehensive data on pediatric COVID-19 from Latin America. This study aims to assess COVID-19 and Multisystem Inflammatory Syndrome (MIS-C) in Latin American children, in order to appropriately plan and allocate resources to face the pandemic on a local and International lever MethodsAmbispective multicentre cohort study from five Latin American countries. Children aged 18 years or younger with microbiologically confirmed SARS-CoV-2 infection were included. Findings409 children were included, with a median age of 53.0 years (IQR 0.6-9.0). Of these, 95 191 (23.2%) were diagnosed with MIS-C. 191 (46.7%) children were admitted to hospital and 52 (12.7%) required admission to a Pediatric Intensive Care Unite (PICU). 92 (22.5%) patients required oxygen support: 8 (2%) were started on continuous positive airway pressure (CPAP) and 29 (7%) on mechanical ventilation. 35 (8.5%) patients required inotropic support. The following factors were associated with PICU admission: pre-existing medical condition (P < 0.0001), immunodeficiency (P = 0.01), lower respiratory tract infection (P< 0.0001), gastrointestinal symptoms (P = 0.006), radiological changes suggestive of pneumonia and acute respiratory distress syndrome (P< 0.0001), low socioeconomic conditions (P 0.009). ConclusionsThis study shows a generally more severe form of COVID-19 and a high number of MIS-C in Latin American children, compared with studies from China, Europe and North America, and support current evidence of a more severe disease in Latin/Hyspanic children or in people of lower socioeconomic level. The findings highlight an urgent need of more data of COVID-19 in South America.

Preprint in English | medRxiv | ID: ppmedrxiv-20169912


Wheather children are easily susceptible to SARS-CoV-2 infection is still a debated question and a currently a hot topic, particularly in view of important decisions on school opening. For this reason, we decide to describe preliminary data showing the prevalence of anti-SARS-CoV-2 IgG in children with known household exposure to SARS-CoV-2. Our report shows that household transmission of SARS-CoV-2 is high in both adults and children, with similar rates of SARS-CoV-2 IgG in all age groups, including the younger children. A total of 44 out of 80 household contacts (55%) of index patients had anti SARS-CoV-2 IgG. In particular, 16 (59,26%) adult partners had IgG antibodies compared with 28 (52,83%) of pediatric contacts (P > 0.05). Among the pediatric population, children [≥] 5 years of age had similar probability of having SARS-CoV-2 IgG (21/39, 53.8%) compared with those < 5 years (7/14, 50%) (P > 0.05). Adult partners and children also had a probability of having SARS-CoV-2 IgG. Interestingly, 35.7% of children and 33.3% of adults with SARS-CoV-2 IgG were previously diagnosed as COVID-19 cases. Since this evidence of high rate of IgG in children exposed to SARS-CoV-2 has public health implication, with this comment we highlight the need of establishing appropriate guidelines for school opening and other social activities related to childhood.

Preprint in English | medRxiv | ID: ppmedrxiv-20094144


ImportanceInterleukin-6 signal blockade has shown preliminary beneficial effects in treating aberrant host inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Objectiveto describe the effect of off-label intravenous use of Sarilumab in patients with severe SARS-CoV-2-related pneumonia. DesignObservational clinical cohort study. SettingFondazione Policlinico Universitario A. Gemelli IRCCS as Italian Covid reference center. ParticipantsPatients with laboratory-confirmed SARS-CoV-2 infection and respiratory distress with PaO2/FiO2 ratio<300 treated with Sarilumab between March 23rd - April 4th, 2020. Date of final follow-up was April 18, 2020. Main outcomes and measuresWe describe the clinical outcomes of 53 patients with SARS-CoV-2 severe pneumonia treated with intravenous Sarilumab in terms of pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards setting and of live discharge rate in ICU treated patients as well as in terms of safety. Each patient received Sarilumab 400 mg administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and was followed for at least 14 days, unless previously discharged or dead. No gluco-corticosteroids were used at baseline. ResultsOf the 53 SARS-CoV-2pos patients receiving Sarilumab, 39 (73.6%) were treated in medical wards (66.7% with a single infusion) while 14 (26.4%) in ICU (92.6% with a second infusion). The median PaO2/FiO2 of patients in the Medical Ward was 146(IQR:120-212) while the median PaO2/FiO2 of patients in ICU was 112(IQR:100-141.5), respectively. Within the medical wards, 7(17.9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89.7% of medical inpatients significantly improved (46.1% after 24 hours, 61.5% after 3 days), 70.6% were discharged from the hospital and 85.7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64.2% were discharged from ICU to the ward and 35.8% were still alive at the last follow-up. Overall mortality rate was 5.7% after Sarilumab administration: 1(2.5%) patient died in the Medical Ward whilst 2(14.2%) patients died in ICU, respectively. Conclusions and relevanceIL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical benefit and good safety. Key pointsO_ST_ABSQuestionC_ST_ABSSARS-CoV-2 infection remains a disease with many unknown aspects for which there are no therapies with proven efficacy. To date, it is recognized that COVID-19 disease may lead to the development of a cytokine storm for which drugs as IL-6R inhibitors may have beneficial effect. FindingsIn this observational clinical study, we reported the efficacy and safety of intravenous Sarilumab use in SARS-CoV-2 severe pneumonia with a global resolution rate of 83.0% (89.7% in medical wards and 64.3% in ICU) and an overall mortality rate of 5.7%. MeaningIL-6R-inhibition is an effective approach for severe SARS-CoV-2 pneumonia and intravenous Sarilumab is a promising treatment approach leading to an important clinical benefit and good safety in the short term.