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2.
Open Forum Infect Dis ; 7(10): ofaa403, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1059676

ABSTRACT

BACKGROUND: The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unclear. We report the detection of viral RNA from different anatomical districts and the antibody profile in the first 2 COVID-19 cases diagnosed in Italy. METHODS: We tested for SARS-CoV-2 RNA clinical samples, either respiratory and nonrespiratory (ie, saliva, serum, urine, vomit, rectal, ocular, cutaneous, and cervico-vaginal swabs), longitudinally collected from both patients throughout the hospitalization. Serological analysis was carried out on serial serum samples to evaluate IgM, IgA, IgG, and neutralizing antibody levels. RESULTS: SARS-CoV-2 RNA was detected since the early phase of illness, lasting over 2 weeks in both upper and lower respiratory tract samples. Virus isolate was obtained from acute respiratory samples, while no infectious virus was rescued from late respiratory samples with low viral RNA load, collected when serum antibodies had been developed. Several other specimens came back positive, including saliva, vomit, rectal, cutaneous, cervico-vaginal, and ocular swabs. IgM, IgA, and IgG were detected within the first week of diagnosis, with IgG appearing earlier and at higher titers. Neutralizing antibodies developed during the second week, reaching high titers 32 days after diagnosis. CONCLUSIONS: Our longitudinal analysis showed that SARS-CoV-2 RNA can be detected in different body samples, which may be associated with broad tropism and different spectra of clinical manifestations and modes of transmission. Profiling antibody response and neutralizing activity can assist in laboratory diagnosis and surveillance actions.

3.
J Antimicrob Chemother ; 75(10): 2977-2980, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-626863

ABSTRACT

BACKGROUND: Remdesivir is a prodrug of the nucleoside analogue GS-441524 and is under evaluation for treatment of SARS-CoV-2-infected patients. OBJECTIVES: To evaluate the pharmacokinetics of remdesivir and GS-441524 in plasma, bronchoalveolar aspirate (BAS) and CSF in two critically ill COVID-19 patients. METHODS: Remdesivir was administered at 200 mg loading dose on the first day followed by 12 days of 100 mg in two critically ill patients. Blood samples were collected immediately after (C0) and at 1 (C1) and 24 h (C24) after intravenous administration on day 3 until day 9. BAS samples were collected on Days 4, 7 and 9 from both patients while one CSF on Day 7 was obtained in one patient. Remdesivir and GS-441524 concentrations were measured in these samples using a validated UHPLC-MS/MS method. RESULTS: We observed higher concentrations of remdesivir at C0 (6- to 7-fold higher than EC50 from in vitro studies) and a notable decay at C1. GS-441524 plasma concentrations reached a peak at C1 and persisted until the next administration. Higher concentrations of GS-441524 were observed in the patient with mild renal dysfunction. Mean BAS/plasma concentration ratios of GS-441524 were 2.3% and 6.4% in Patient 1 and Patient 2, respectively. The CSF concentration found in Patient 2 was 25.7% with respect to plasma. GS-441524 levels in lung and CNS suggest compartmental differences in drug exposure. CONCLUSIONS: We report the first pharmacokinetic evaluation of remdesivir and GS-441524 in recovered COVID-19 patients. Further study of the pharmacokinetic profile of remdesivir, GS-441524 and the intracellular triphosphate form are required.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Adenosine Triphosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/pharmacokinetics , Betacoronavirus , Coronavirus Infections/metabolism , Critical Illness/therapy , Pneumonia, Viral/metabolism , Adenosine Monophosphate/pharmacokinetics , Adenosine Monophosphate/therapeutic use , Adenosine Triphosphate/pharmacokinetics , Adenosine Triphosphate/therapeutic use , Aged , Alanine/pharmacokinetics , Alanine/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Female , Humans , Male , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Recovery of Function/drug effects , Recovery of Function/physiology , SARS-CoV-2
4.
J Transl Med ; 18(1): 233, 2020 06 10.
Article in English | MEDLINE | ID: covidwho-592324

ABSTRACT

BACKGROUND: Epidemiological, virological and pathogenetic characteristics of SARS-CoV-2 infection are under evaluation. A better understanding of the pathophysiology associated with COVID-19 is crucial to improve treatment modalities and to develop effective prevention strategies. Transcriptomic and proteomic data on the host response against SARS-CoV-2 still have anecdotic character; currently available data from other coronavirus infections are therefore a key source of information. METHODS: We investigated selected molecular aspects of three human coronavirus (HCoV) infections, namely SARS-CoV, MERS-CoV and HCoV-229E, through a network based-approach. A functional analysis of HCoV-host interactome was carried out in order to provide a theoretic host-pathogen interaction model for HCoV infections and in order to translate the results in prediction for SARS-CoV-2 pathogenesis. The 3D model of S-glycoprotein of SARS-CoV-2 was compared to the structure of the corresponding SARS-CoV, HCoV-229E and MERS-CoV S-glycoprotein. SARS-CoV, MERS-CoV, HCoV-229E and the host interactome were inferred through published protein-protein interactions (PPI) as well as gene co-expression, triggered by HCoV S-glycoprotein in host cells. RESULTS: Although the amino acid sequences of the S-glycoprotein were found to be different between the various HCoV, the structures showed high similarity, but the best 3D structural overlap shared by SARS-CoV and SARS-CoV-2, consistent with the shared ACE2 predicted receptor. The host interactome, linked to the S-glycoprotein of SARS-CoV and MERS-CoV, mainly highlighted innate immunity pathway components, such as Toll Like receptors, cytokines and chemokines. CONCLUSIONS: In this paper, we developed a network-based model with the aim to define molecular aspects of pathogenic phenotypes in HCoV infections. The resulting pattern may facilitate the process of structure-guided pharmaceutical and diagnostic research with the prospect to identify potential new biological targets.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/genetics , Coronavirus Infections/virology , Gene Regulatory Networks , Host-Pathogen Interactions , Models, Biological , Pneumonia, Viral/genetics , Pneumonia, Viral/virology , Protein Interaction Mapping , COVID-19 , Humans , Membrane Glycoproteins/metabolism , Pandemics , SARS-CoV-2 , Signal Transduction/genetics , Viral Envelope Proteins
5.
Infect Dis Rep ; 12(1): 8543, 2020 Feb 25.
Article in English | MEDLINE | ID: covidwho-18538

ABSTRACT

On January 9 2020, the World Health Organization (WHO) declared the identification, by Chinese Health authorities, of a novel coronavirus, further classified as SARS-CoV-2 responsible of a disease (COVID-19) ranging from asymptomatic cases to severe respiratory involvement. On March 9 2020, WHO declared COVID-19 a global pandemic. Italy is the second most affected country by COVID-19 infection after China. The "L. Spallanzani" National Institute for the Infectious Diseases, IRCCS, Rome, Italy, has been the first Italian hospital to admit and manage patients affected by COVID-19. Hereby, we show our recommendations for the management of COVID-19 patients, based on very limited clinical evidences; they should be considered as expert opinions, which may be modified according to newly produced literature data.

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