ABSTRACT
BACKGROUND: Post-artesunate delayed haemolysis (PADH) is common after severe malaria episodes. PADH is related to the "pitting" phenomenon and the synchronous delayed clearance of once-infected erythrocytes, initially spared during treatment. However, direct antiglobulin test (DAT) positivity has been reported in several PADH cases, suggesting a contribution of immune-mediated erythrocyte clearance. The aim of the present study was to compare clinical features of cases presenting a positive or negative DAT. METHODS: Articles reporting clinical data of patients diagnosed with PADH, for whom DAT had been performed, were collected from PubMed database. Data retrieved from single patients were extracted and univariate analysis was performed in order to identify features potentially related to DAT results and steroids use. RESULTS: Twenty-two studies reporting 39 PADH cases were included: median baseline parasitaemia was 20.8% (IQR: 11.2-30) and DAT was positive in 17 cases (45.5%). Compared to DAT-negative individuals, DAT-positive patients were older (49.5 vs 31; p = 0.01), had a higher baseline parasitaemia (27% vs 17%; p = 0.03) and were more commonly treated with systemic steroids (11 vs 3 patients, p = 0.002). Depth and kinetics of delayed anaemia were not associated with DAT positivity. CONCLUSIONS: In this case series, almost half of the patients affected by PADH had a positive DAT. An obvious difference between the clinical courses of patients presenting with a positive or negative DAT was lacking. This observation suggests that DAT result may not be indicative of a pathogenic role of anti-erythrocytes antibodies in patients affected by PADH, but it may be rather a marker of immune activation.
Subject(s)
Antimalarials/administration & dosage , Artesunate/administration & dosage , Coombs Test/statistics & numerical data , Hemolysis/drug effects , Malaria, Falciparum/drug therapy , Malaria, Vivax/drug therapy , Adult , Female , Humans , Male , Middle Aged , Parasitemia/drug therapy , Young AdultABSTRACT
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-2ABSTRACT
A novel coronavirus (SARS-CoV-2) has been identified as the causative pathogen of an ongoing outbreak of respiratory disease, now named COVID-19. Most cases and sustained transmission occurred in China, but travel-associated cases have been reported in other countries, including Europe and Italy. Since the symptoms are similar to other respiratory infections, differential diagnosis in travellers arriving from countries with wide-spread COVID-19 must include other more common infections such as influenza and other respiratory tract diseases.
Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Molecular Diagnostic Techniques , Pneumonia, Viral/diagnosis , Algorithms , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/epidemiology , Diagnosis, Differential , Disease Outbreaks , Humans , Influenza, Human/diagnosis , Italy/epidemiology , Mass Screening , Molecular Diagnostic Techniques/methods , Molecular Diagnostic Techniques/standards , Pneumonia, Viral/epidemiology , Population Surveillance , Respiratory Tract Infections/diagnosis , SARS-CoV-2 , TravelABSTRACT
Data concerning the transmission of the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) in paucisymptomatic patients are lacking. We report an Italian paucisymptomatic case of coronavirus disease 2019 with multiple biological samples positive for SARS-CoV-2. This case was detected using the World Health Organization protocol on cases and contact investigation. Current discharge criteria and the impact of extra-pulmonary SARS-CoV-2 samples are discussed.
Subject(s)
Asymptomatic Infections , Coronavirus Infections/diagnosis , Coronavirus/isolation & purification , Feces/virology , Lung/diagnostic imaging , Nasopharynx/virology , Pneumonia, Viral/diagnosis , Travel , Virus Shedding , Antibodies, Viral/immunology , Betacoronavirus , COVID-19 , COVID-19 Testing , China , Clinical Laboratory Techniques , Contact Tracing , Coronavirus/genetics , Coronavirus Infections/transmission , Coronavirus Infections/virology , Humans , Italy , Lung/pathology , Male , Pandemics , Pneumonia, Viral/therapy , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Quarantine , Radiography, Thoracic , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Tomography, X-Ray Computed , World Health Organization , Young AdultABSTRACT
In Italy, malaria continues to be one of the most common imported parasitoses; therefore, continuous surveillance of epidemiological data and clinical management is needed. In 2016, the National Institute for Infectious Diseases 'Lazzaro Spallanzani' in Rome promoted a retrospective questionnaire-based survey to assess the clinical management of imported malaria cases in Italy in 2015. The questionnaire was sent to 104 Tropical and/or Infectious Diseases Units in the country, and 37 of them filled out and returned the questionnaires. A total of 399 malaria cases were reported in 2015, mostly caused by Plasmodium falciparum and imported from Africa. Malaria chemoprophylaxis was correctly used by a minority of patients. Most patients presented with uncomplicated malaria and were treated orally. In severe cases, intravenous artesunate or quinine alone or in combination were administered, although one third of these severe cases received oral treatment. This retrospective survey reveals a lack of homogeneity in management of malaria-imported cases in Italy. Improvement of malaria chemoprophylaxis, standardization of clinical management of malaria cases and harmonization of oral and intravenous drug availability are needed throughout the country.
Subject(s)
Antimalarials , Malaria , Travel , Antimalarials/therapeutic use , Cross-Sectional Studies , Humans , Italy , Malaria/drug therapy , Malaria/prevention & control , Plasmodium , Retrospective Studies , Surveys and QuestionnairesABSTRACT
BACKGROUND: Although Plasmodium ovale is considered the cause of only mild malaria, a case of severe malaria due to P. ovale with acute respiratory distress syndrome is reported. CASE PRESENTATION: A 37-year old Caucasian man returning home from Angola was admitted for ovale malaria to the National Institute for Infectious Diseases Lazzaro Spallanzani in Rome, Italy. Two days after initiation of oral chloroquine treatment, an acute respiratory distress syndrome was diagnosed through chest X-ray and chest CT scan with intravenous contrast. Intravenous artesunate and oral doxycycline were started and he made a full recovery. CONCLUSION: Ovale malaria is usually considered a tropical infectious disease associated with low morbidity and mortality. However, severe disease and death have occasionally been reported. In this case clinical failure of oral chloroquine treatment with clinical progression towards acute respiratory distress syndrome is described.
Subject(s)
Malaria , Plasmodium ovale , Respiratory Distress Syndrome , Adult , Antimalarials/adverse effects , Antimalarials/therapeutic use , Chloroquine/adverse effects , Chloroquine/therapeutic use , Humans , Malaria/complications , Malaria/diagnosis , Malaria/drug therapy , Malaria/parasitology , Male , Radiography, Thoracic , Respiratory Distress Syndrome/diagnostic imaging , Respiratory Distress Syndrome/etiology , Treatment FailureABSTRACT
This study reports the presence of dengue virus RNA in longitudinally collected semen samples of a previously healthy Caucasian man, returning to Italy from Thailand with primary dengue fever, up to 37 days post-symptom onset, when viraemia and viruria were undetectable. This finding, coupled with the evidence of dengue virus negative-strand RNA, an indirect marker of ongoing viral replication, in the cellular fraction of semen, indicates a need to further investigate possible sexual transmission.
Subject(s)
Dengue Virus/isolation & purification , Dengue/diagnosis , RNA, Viral/genetics , Semen/virology , Travel , Dengue Virus/genetics , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Italy , Male , Real-Time Polymerase Chain Reaction , ThailandABSTRACT
We describe the dynamics of dengue virus (DENV) infection in a woman in her mid-30s who developed fever after returning from Sri Lanka to Italy in April 2017. Laboratory testing demonstrated detectable DENV-RNA in plasma, urine, saliva, vaginal secretion. Persistent shedding of DENV-RNA was demonstrated in vaginal secretion, and DENV-RNA was detectable in the pelleted fraction up to 18 days from symptom onset. These findings give new insights into DENV vaginal shedding and vertical transmission.
Subject(s)
Dengue Virus/genetics , Dengue/diagnosis , Fever/etiology , Travel , Virus Shedding , Dengue Virus/isolation & purification , Female , Fever/virology , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Italy , Real-Time Polymerase Chain Reaction , Sri LankaABSTRACT
Aim of this study was to investigate a pseudo-outbreak of Mycobacterium gordonae analyzing isolates detected from clinical and environmental samples. Mycobacterium gordonae was detected in 7 out of 497 broncho-alveolar lavage (BAL) samples after bronchoscopy procedure in patients admitted to a teaching hospital between January and April 2013. During this pseudo-outbreak clinical, epidemiological, environmental and molecular investigations were performed. None of the patients met the criteria for non-tuberculous mycobacterial (NTM) lung disease and were treated for M. gordonae lung disease. Environmental investigation revealed M. gordonae in 3 samples: in tap water and in the water supply channel of the washer disinfector. All the isolates were subjected to genotyping by pulsed-field gel electrophoresis (PFGE). The PFGE revealed that only patients' isolates presented the same band pattern but no correlation with the environmental strain was detected. Surveillance of the outbreak and the strict adherence to the reprocessing procedure and its supplies resulted afterwards in no detection of M. gordonae in clinical respiratory samples. Clinical surveillance of patients was crucial to establish the start of NTM treatment. Regular screening of tap water and endoscopic equipment should be adopted to compare the clinical strains with the environmental ones when an outbreak occurs.
Subject(s)
Decontamination/standards , Disease Outbreaks , Mycobacterium Infections, Nontuberculous/epidemiology , Nontuberculous Mycobacteria/isolation & purification , Water Microbiology , Bronchoalveolar Lavage Fluid/microbiology , Electrophoresis, Gel, Pulsed-Field , Environmental Monitoring , Equipment Contamination , Genotype , Hospitals, Teaching , Humans , Mycobacterium Infections, Nontuberculous/microbiology , Nontuberculous Mycobacteria/classification , Nontuberculous Mycobacteria/genetics , Sterilization/standards , Water Supply/standardsABSTRACT
Microbiological diagnosis is crucial for the appropriate management of implant-associated orthopedic infections (IAOIs). Sonication of biomaterials for microbiological diagnosis has not yet been introduced in routine clinical practice. Aim of this study was to describe the advantages and feasibility of this procedure in the clinical setting. We prospectively studied 56 consecutive patients undergoing revision because of IAOI and compared the sensitivity of sonication of explanted orthopedic implants with standard cultures. Patients were divided into two groups: those with foreign body infection (FBI, 15 patients) and those with prosthetic joint infection (PJI, 41 patients). Clinical, radiological and microbiological features were recorded. In the PJI group the sensitivity of sonication in detecting bacterial growth was higher than conventional culture (77% vs 34.1% respectively, p<0.002), while no difference was observed in the FBI group (85.7% vs 86% respectively, p>0.05). Coagulase-negative Staphylococci accounted for 90% of the bacteria detected by sonication. Moreover, we found that in the PJI group the sensitivity of sonication was not affected by the timing of antibiotic interruption before surgery. Sonication remains an important tool to improve microbiological diagnosis in PJIs, especially in patients who received previous antimicrobial treatment.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Bacteria/isolation & purification , Joint Prosthesis/microbiology , Prosthesis-Related Infections/prevention & control , Sonication/methods , Adult , Aged , Bacteria/drug effects , Bacteria/genetics , Bacteria/growth & development , Cohort Studies , Female , Humans , Male , Middle Aged , Prosthesis-Related Infections/microbiologyABSTRACT
Chagas disease (CD) is a parasitic infection endemic in Latin America and also affects patients in Western countries due to migration flows. This has a significant impact on health services worldwide due to its high morbidity and mortality burden. This paper aims to share our experience at the National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, in Rome, Italy, where to date, a total of 47 patients-mainly Bolivian women-diagnosed with CD have received treatment with benznidazole, with all but one presenting with chronic disease. Most of the patients were recruited through the first extensive screening program held in 2014 at our Institute. About a quarter of our patients showed adverse effects to benznidazole, including a case of severe drug-induced liver injury, but 83% completed a full course of treatment. In addition to the description of our cohort, the paper reports a brief overview of the disease compiled through a review of the existing literature on CD in non-endemic countries. The growing prevalence of CD in Western countries highlights the importance of screening at-risk populations and urges public concern and medical awareness about this neglected tropical disease. There are still many unanswered questions that need to be addressed to develop a personalized approach in treating patients.
ABSTRACT
In the recent 2022 monkeypox (Mpox) global outbreak, cases have been mostly documented among men who have sex with men. Proctitis was reported in almost 14% of cases. In this study, four Mpox-confirmed cases requiring hospitalizations for severe proctitis were characterized by clinical, virological, microbiological, endoscopic, and histological aspects. The study showed the presence of lymphofollicular lesions associated with Mpox virus rectal infection for the first time.
Subject(s)
Mpox (monkeypox) , Proctitis , Sexual and Gender Minorities , Male , Humans , Monkeypox virus , Homosexuality, Male , Proctitis/drug therapyABSTRACT
Monoclonal antibodies are laboratory-made proteins that mimic the immune system's ability to fight off harmful microorganisms, including viruses such as Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2). The US Food and Drug Administration (FDA) and the European Medical Agency (EMA) have already authorized monoclonal antibodies of anti-SARS-CoV-2 to treat mild to moderate CoronaVIrus Disease-2019 (COVID-19) in patients at risk of developing severe disease. More recently, monoclonal antibodies anti-SARS-CoV-2 have been authorized for primary and secondary prophylaxis in patients at high risk of severe disease for background comorbidity. Primary or pre-exposure prophylaxis prevents COVID-19 in unexposed people, whereas secondary or postexposure prophylaxis prevent COVID-19 in recently exposed people to individuals with laboratory-confirmed SARS-CoV-2. This review focuses briefly on therapeutic indications of currently available monoclonal antibodies for COVID-19 pre- and postexposure prophylaxis and on the efficacy of convalescent plasma.
ABSTRACT
The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates strategies to identify prophylactic and therapeutic drug candidates to enter rapid clinical development. This is particularly true, given the uncertainty about the endurance of the immune memory induced by both previous infections or vaccines, and given the fact that the eradication of SARS-CoV-2 might be challenging to reach, given the attack rate of the virus, which would require unusually high protection by a vaccine. Here, we show how raloxifene, a selective estrogen receptor modulator with anti-inflammatory and antiviral properties, emerges as an attractive candidate entering clinical trials to test its efficacy in early-stage treatment COVID-19 patients.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19 Drug Treatment , Drug Repositioning , Estrogen Receptor Modulators/therapeutic use , Raloxifene Hydrochloride/therapeutic use , Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents/therapeutic use , Estradiol/therapeutic use , Estrogens/metabolism , Female , Humans , Male , SARS-CoV-2/drug effects , Sex FactorsABSTRACT
Aero-medical evacuation has been considered as a feasible and safe treatment option during COVID pandemic, particularly when the needs of affected patients exceed what local clinics and hospitals are supposed to provide. In this article, we analyzed the clinical course of 17 patients medically evacuated to the "L. Spallanzani" Institute in Rome, Italy from foreign countries, mainly Africa and Eastern Europe, who had COVID-19 pneumonia with, or without, coinfections such as malaria, HIV, tuberculosis and microbiologically confirmed sepsis syndrome. The aero-medical evacuation of patients with infectious diseases has become one of the greatest medical achievements we have reached during this pandemic; in fact, only two patients with life threatening coinfections have died. Although logistically difficult and cost consuming, medical evacuation should be considered as a treatment option more than a single extraordinary measure, especially among complex cases that require specific technical and human resources.
ABSTRACT
Background: Current available therapeutic options for Coronavirus Disease-2019 (COVID-19) are primarily focused on treating hospitalized patients, and there is a lack of oral therapeutic options to treat mild to moderate outpatient COVID-19 and prevent clinical progression. Raloxifene was found as a promising molecule to treat COVID-19 due to its activity to modulate the replication of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and act as an immunomodulator to decrease proinflammatory cytokines. Methods: This was a phase 2 multicenter, randomized, placebo-controlled trial to evaluate the efficacy and safety of raloxifene in adult patients with mild to moderate COVID-19 between October 2020 to June 2021 in five centers located in Italy. This was a planned 2/3 adaptive study, but due to operational difficulties, the study was discontinued during the phase 2 study segment. Participants were randomized 1:1:1 to receive oral placebo, raloxifene 60 mg, or raloxifene 120 mg by self-administration for a maximum of two weeks. The primary outcomes were the proportion of patients with undetectable SARS-CoV-2 via nasopharyngeal swabs at day 7 and the proportion of patients who did not require supplemental oxygen therapy or mechanical ventilation on day 14. Safety was assessed. The trial is registered (EudraCT 2021-002,476-39, and ClinicalTrials.gov: NCT05172050). Findings: A total of 68 participants were enrolled and randomized to placebo (n = 21), raloxifene 60 mg (n = 24), and raloxifene 120 mg (n = 23). The proportion of participants with undetectable SARS-CoV-2 after seven days of treatment with raloxifene 60 mg [36.8%, 7/19 vs. 0.0%, 0/14] and 120 mg [22.2%, 4/18 vs. 0.0%, 0/14] was better compared to placebo, [risk difference (RD) = 0·37 (95% C.I.:0·09-0·59)] and [RD = 0·22 (95% C.I.: -0·03-0·45)], respectively. There was no evidence of effect for requirement of supplemental oxygen and/or mechanical ventilation with effects for raloxifene 60 mg and raloxifene 120 mg over placebo, [RD = 0·09 (95% C.I.: -0·22-0·37)], and [RD = 0·03 (95% C.I.: -0·28-0·33)], respectively. Raloxifene was well tolerated at both doses, and there was no evidence of any difference in the occurrence of serious adverse events. Interpretation: Raloxifene showed evidence of effect in the primary virologic endpoint in the treatment of early mild to moderate COVID-19 patients shortening the time of viral shedding. The safety profile was consistent with that reported for other indications. Raloxifene may represent a promising pharmacological option to prevent or mitigate COVID-19 disease progression. Funding: The study was funded by Dompé Farmaceutici SpA and supported by the funds from the European Commission - Health and Consumers Directorate General, for the Action under the Emergency Support Instrument- Grant to support clinical testing of repurposed medicines to treat SARS-COV-2 patients (PPPA-ESI-CTRM-2020-SI2.837140), and by the COVID-2020-12,371,675 Ricerca finalizzata and line 1 Ricerca Corrente COVID both funded by Italian Ministry of Health.
ABSTRACT
The new coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic, which so far has caused over 6 million deaths in 2 years, despite new vaccines and antiviral medications. Drug repurposing, an approach for the potential application of existing pharmaceutical products to new therapeutic indications, could be an effective strategy to obtain quick answers to medical emergencies. Following a virtual screening campaign on the most relevant viral proteins, we identified the drug raloxifene, a known Selective Estrogen Receptor Modulator (SERM), as a new potential agent to treat mild-to-moderate COVID-19 patients. In this paper we report a comprehensive pharmacological characterization of raloxifene in relevant in vitro models of COVID-19, specifically in Vero E6 and Calu-3 cell lines infected with SARS-CoV-2. A large panel of the most common SARS-CoV-2 variants isolated in Europe, United Kingdom, Brazil, South Africa and India was tested to demonstrate the drug's ability in contrasting the viral cytopathic effect (CPE). Literature data support a beneficial effect by raloxifene against the viral infection due to its ability to interact with viral proteins and activate protective estrogen receptor-mediated mechanisms in the host cells. Mechanistic studies here reported confirm the significant affinity of raloxifene for the Spike protein, as predicted by in silico studies, and show that the drug treatment does not directly affect Spike/ACE2 interaction or viral internalization in infected cell lines. Interestingly, raloxifene can counteract Spike-mediated ADAM17 activation in human pulmonary cells, thus providing new insights on its mechanism of action. A clinical study in mild to moderate COVID-19 patients (NCT05172050) has been recently completed. Our contribution to evaluate raloxifene results on SARS-CoV-2 variants, and the interpretation of the mechanisms of action will be key elements to better understand the trial results, and to design new clinical studies aiming to evaluate the potential development of raloxifene in this indication.
Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Humans , Pandemics , Raloxifene Hydrochloride/pharmacology , Raloxifene Hydrochloride/therapeutic use , Spike Glycoprotein, Coronavirus/metabolismABSTRACT
Safe and effective vaccines against coronavirus disease 2019 (COVID-19) are essential for ending the ongoing pandemic. Although impressive progress has been made with several COVID-19 vaccines already approved, it is clear that those developed so far cannot meet the global vaccine demand alone. We describe a COVID-19 vaccine based on a replication-defective gorilla adenovirus expressing the stabilized prefusion severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein named GRAd-COV2. We assessed the safety and immunogenicity of a single-dose regimen of this vaccine in healthy younger and older adults to select the appropriate dose for each age group. For this purpose, a phase 1, dose-escalation, open-labeled trial was conducted including 90 healthy participants (45 aged 18 to 55 years old and 45 aged 65 to 85 years old) who received a single intramuscular administration of GRAd-COV2 at three escalating doses. Local and systemic adverse reactions were mostly mild or moderate and of short duration, and no serious adverse events were reported. Four weeks after vaccination, seroconversion to spike protein and receptor binding domain was achieved in 43 of 44 young volunteers and in 45 of 45 older participants. Consistently, neutralizing antibodies were detected in 42 of 44 younger-age and 45 of 45 older-age volunteers. In addition, GRAd-COV2 induced a robust and T helper 1 cell (TH1)skewed T cell response against the spike protein in 89 of 90 participants from both age groups. Overall, the safety and immunogenicity data from the phase 1 trial support the further development of this vaccine.
Subject(s)
Adenovirus Vaccines , COVID-19 , Adenoviridae , Aged , Animals , COVID-19 Vaccines , Gorilla gorilla , Humans , SARS-CoV-2ABSTRACT
Most patients infected with SARS-CoV-2 (COVID-19) experience mild, non-specific symptoms, but many develop severe symptoms associated with an excessive inflammatory response. Elevated plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) provide early warning of progression to severe respiratory failure (SRF) or death, but access to suPAR testing may be limited. The Severe COvid Prediction Estimate (SCOPE) score, derived from circulating concentrations of C-reactive protein, D- dimers, interleukin-6, and ferritin among patients not receiving non-invasive or invasive mechanical ventilation during the SAVE-MORE study, offers predictive accuracy for progression to SRF or death within 14 days comparable to that of a suPAR concentration of ≥6 ng/mL (area under receiver operator characteristic curve 0.81 for both). The SCOPE score is validated in two similar independent cohorts. A SCOPE score of 6 or more is an alternative to suPAR for predicting progression to SRF or death within 14 days of hospital admission for pneumonia, and it can be used to guide treatment decisions.