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1.
BMC Infect Dis ; 21(1): 169, 2021 Feb 10.
Article in English | MEDLINE | ID: covidwho-1079219

ABSTRACT

BACKGROUND: Our main objectives were to estimate the incidence of illnesses presumably caused by SARS-CoV-2 infection during the lockdown period and to identify the associated risk factors. METHODS: Participants from 3 adult cohorts in the general population in France were invited to participate in a survey on COVID-19. The main outcome was COVID-19-Like Symptoms (CLS), defined as a sudden onset of cough, fever, dyspnea, ageusia and/or anosmia, that lasted more than 3 days and occurred during the 17 days before the survey. We used delayed-entry Cox models to identify associated factors. RESULTS: Between April 2, 2020 and May 12, 2020, 279,478 participants were invited, 116,903 validated the questionnaire and 106,848 were included in the analysis. Three thousand thirty-five cases of CLS were reported during 62,099 person-months of follow-up. The cumulative incidences of CLS were 6.2% (95% Confidence Interval (95%CI): 5.7%; 6.6%) on day 15 and 8.8% (95%CI 8.3%; 9.2%) on day 45 of lockdown. The risk of CLS was lower in older age groups and higher in French regions with a high prevalence of SARS-CoV-2 infection, in participants living in cities > 100,000 inhabitants (vs rural areas), when at least one child or adolescent was living in the same household, in overweight or obese people, and in people with chronic respiratory diseases, anxiety or depression or chronic diseases other than diabetes, cancer, hypertension or cardiovascular diseases. CONCLUSION: The incidence of CLS in the general population remained high during the first 2 weeks of lockdown, and decreased significantly thereafter. Modifiable and non-modifiable risk factors were identified.


Subject(s)
/epidemiology , Communicable Disease Control , Adolescent , Adult , Aged , Child , Cohort Studies , Comorbidity , Cough , Female , Fever , France/epidemiology , Humans , Incidence , Male , Middle Aged , Prevalence , Risk Factors
3.
Eur J Epidemiol ; 2021 Feb 06.
Article in English | MEDLINE | ID: covidwho-1064548

ABSTRACT

Using serum samples routinely collected in 9144 adults from a French general population-based cohort, we identified 353 participants with a positive anti-SARS-CoV-2 IgG test, among whom 13 were sampled between November 2019 and January 2020 and were confirmed by neutralizing antibodies testing. Investigations in 11 of these participants revealed experience of symptoms possibly related to a SARS-CoV-2 infection or situations at risk of potential SARS-CoV-2 exposure. This suggests early circulation of SARS-CoV-2 in Europe.

4.
Infect Dis Now ; 2021 Jan 18.
Article in English | MEDLINE | ID: covidwho-1033154

ABSTRACT

Objectives: This study aimed at estimating the SARS-CoV-2 infection hospitalization (IHR) and infection fatality ratios (IFR) in France. Patients and methods: A serosurvey was conducted in 9782 subjects from the two French regions with the highest incidence of COVID-19 during the first wave of the pandemic and coupled with surveillance data. Results: IHR and IFR were 2.7% and 0.49% overall. Both were higher in men and increased exponentially with age. The relative risks of hospitalization and death were 2.1 (95% CI: 1.9-2.3) and 3.8 (2.4-4.2) per 10-year increase, meaning that IHR and IFR approximately doubled every 10 and 5 years, respectively. They were dramatically high in the very elderly (80-90 years: IHR: 26%, IFR: 9.2%), and also substantial in younger adults (40-50 years: IHR: 0.98%, IFR: 0.042%). Conclusions: These findings support the need for comprehensive preventive measures to help reduce the spread of the virus, even in young or middle-aged adults.

5.
Viruses ; 12(7)2020 07 07.
Article in English | MEDLINE | ID: covidwho-639283

ABSTRACT

Standard precautions to minimize the risk of SARS-CoV-2 transmission implies that infected cell cultures and clinical specimens may undergo some sort of inactivation to reduce or abolish infectivity. We evaluated three heat inactivation protocols (56 °C-30 min, 60 °C-60 min and 92 °C-15 min) on SARS-CoV-2 using (i) infected cell culture supernatant, (ii) virus-spiked human sera (iii) and nasopharyngeal samples according to the recommendations of the European norm NF EN 14476-A2. Regardless of the protocol and the type of samples, a 4 Log10 TCID50 reduction was observed. However, samples containing viral loads > 6 Log10 TCID50 were still infectious after 56 °C-30 min and 60 °C-60 min, although infectivity was < 10 TCID50. The protocols 56 °C-30 min and 60 °C-60 min had little influence on the RNA copies detection, whereas 92 °C-15 min drastically reduced the limit of detection, which suggests that this protocol should be avoided for inactivation ahead of molecular diagnostics. Lastly, 56 °C-30 min treatment of serum specimens had a negligible influence on the results of IgG detection using a commercial ELISA test, whereas a drastic decrease in neutralizing titers was observed.


Subject(s)
Betacoronavirus , Containment of Biohazards/methods , Coronavirus Infections/virology , Pneumonia, Viral/virology , Serologic Tests/methods , Virus Inactivation , Antibodies, Neutralizing/immunology , Betacoronavirus/immunology , Containment of Biohazards/standards , Coronavirus Infections/diagnosis , Coronavirus Infections/prevention & control , Enzyme-Linked Immunosorbent Assay , Hot Temperature , Humans , Neutralization Tests , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Pneumonia, Viral/prevention & control , Serologic Tests/standards
6.
Sci Rep ; 10(1): 13093, 2020 08 04.
Article in English | MEDLINE | ID: covidwho-697117

ABSTRACT

A novel coronavirus, named SARS-CoV-2, emerged in 2019 in China and rapidly spread worldwide. As no approved therapeutics exists to treat COVID-19, the disease associated to SARS-Cov-2, there is an urgent need to propose molecules that could quickly enter into clinics. Repurposing of approved drugs is a strategy that can bypass the time-consuming stages of drug development. In this study, we screened the PRESTWICK CHEMICAL LIBRARY composed of 1,520 approved drugs in an infected cell-based assay. The robustness of the screen was assessed by the identification of drugs that already demonstrated in vitro antiviral effect against SARS-CoV-2. Thereby, 90 compounds were identified as positive hits from the screen and were grouped according to their chemical composition and their known therapeutic effect. Then EC50 and CC50 were determined for a subset of 15 compounds from a panel of 23 selected drugs covering the different groups. Eleven compounds such as macrolides antibiotics, proton pump inhibitors, antiarrhythmic agents or CNS drugs emerged showing antiviral potency with 2 < EC50 ≤ 20 µM. By providing new information on molecules inhibiting SARS-CoV-2 replication in vitro, this study provides information for the selection of drugs to be further validated in vivo. Disclaimer: This study corresponds to the early stages of antiviral development and the results do not support by themselves the use of the selected drugs to treat SARS-CoV-2 infection.


Subject(s)
Betacoronavirus/physiology , Small Molecule Libraries/chemistry , Animals , Antiviral Agents/chemistry , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Betacoronavirus/isolation & purification , Caco-2 Cells , Cell Survival/drug effects , Chlorocebus aethiops , Coronavirus Infections/pathology , Coronavirus Infections/virology , Drug Approval , Drug Evaluation, Preclinical , Drug Repositioning , Humans , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Small Molecule Libraries/metabolism , Small Molecule Libraries/pharmacology , Vero Cells , Virus Replication/drug effects
7.
Nature ; 585(7826): 584-587, 2020 09.
Article in English | MEDLINE | ID: covidwho-664587

ABSTRACT

Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic and no antiviral drug or vaccine is yet available for the treatment of this disease1-3. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the virus that causes COVID-19-worldwide but there is no definitive evidence that HCQ is effective for treating COVID-194-7. Here we evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in African green monkey kidney cells (Vero E6) but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to a placebo treatment, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor the combination of HCQ and AZTH showed a significant effect on viral load in any of the analysed tissues. When the drug was used as a pre-exposure prophylaxis treatment, HCQ did not confer protection against infection with SARS-CoV-2. Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral drug for the treatment of COVID-19 in humans.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Animals , Azithromycin/pharmacology , Azithromycin/therapeutic use , Chlorocebus aethiops , Coronavirus Infections/pathology , Coronavirus Infections/physiopathology , Cytokines/blood , Disease Models, Animal , Female , Humans , Hydroxychloroquine/pharmacokinetics , Hydroxychloroquine/pharmacology , In Vitro Techniques , Kinetics , Macaca fascicularis , Male , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/physiopathology , Pre-Exposure Prophylaxis , Respiratory Mucosa/cytology , Respiratory Mucosa/drug effects , Respiratory Mucosa/virology , Time Factors , Treatment Failure , Vero Cells , Viral Load/drug effects
8.
Antiviral Res ; 181: 104880, 2020 09.
Article in English | MEDLINE | ID: covidwho-645374

ABSTRACT

We investigated the distribution of antibodies neutralizing SARS-CoV-2 according to age, sex or blood group in French blood donors. In 464 samples collected before the emergence of SARS-CoV-2 (2017 and 2018), our virus neutralization assay had a 100% specificity. It was used to test 998 samples collected from blood donors during the last week of March or the first week of April 2020. As expected at this stage of the outbreak, the prevalence was low (2.7%) and, importantly, criteria for blood donation imply that the vast majority of seropositives had asymptomatic or pauci-symptomatic SARS-CoV-2 infections. Seroprevalence values did not differ significantly among age groups (but were slightly higher in donors <30yo and ≥60yo), and between males and females (2.82% vs 2.69%), unlike what has been observed regarding hospitalizations admission to ICU and death rates in France. By contrast, we observed that the proportion of seropositives was significantly lower in group O donors (1.32% vs 3.86% in other donors, p = 0.014). We conclude that virus infection seems to occur with a similar incidence in men and women among French blood donors, but that blood group O persons are less at risk of being infected and not only of suffering from severe clinical presentations, as previously suggested.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Betacoronavirus/immunology , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Blood Donors , Blood Group Antigens , Coronavirus Infections/epidemiology , Female , France/epidemiology , Hospitalization , Humans , Incidence , Intensive Care Units , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Risk , Sensitivity and Specificity , Seroepidemiologic Studies , Young Adult
9.
Emerg Infect Dis ; 26(9)2020 09.
Article in English | MEDLINE | ID: covidwho-614160

ABSTRACT

We spotted severe acute respiratory syndrome coronavirus 2 on polystyrene plastic, aluminum, and glass for 96 hours with and without bovine serum albumin (3 g/L). We observed a steady infectivity (<1 log10 drop) on plastic, a 3.5 log10 decrease on glass, and a 6 log10 drop on aluminum. The presence of proteins noticeably prolonged infectivity.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/transmission , Disease Transmission, Infectious , Fomites/virology , Pneumonia, Viral/transmission , Aluminum/analysis , Coronavirus Infections/virology , Glass/analysis , Humans , Pandemics , Plastics/analysis , Pneumonia, Viral/virology , Time Factors
10.
Viruses ; 12(6)2020 06 25.
Article in English | MEDLINE | ID: covidwho-613542

ABSTRACT

The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide has highlighted the importance of reliable and rapid diagnostic testing to prevent and control virus circulation. Dozens of monoplex in-house RT-qPCR assays are already available; however, the development of dual-target assays is suited to avoid false-negative results caused by polymorphisms or point mutations, that can compromise the accuracy of diagnostic and screening tests. In this study, two mono-target assays recommended by WHO (E-Sarbeco (enveloppe gene, Charite University, Berlin, Germany) and RdRp-IP4 (RdRp, Institut Pasteur, Paris, France)) were selected and combined in a unique robust test; the resulting duo SARS-CoV-2 RT-qPCR assay was compared to the two parental monoplex tests. The duo SARS-CoV-2 assay performed equally, or better, in terms of sensitivity, specificity, linearity and signal intensity. We demonstrated that combining two single systems into a dual-target assay (with or without an MS2-based internal control) did not impair performances, providing a potent tool adapted for routine molecular diagnosis in clinical microbiology laboratories.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Real-Time Polymerase Chain Reaction/methods , Viral Envelope Proteins/genetics , Viral Nonstructural Proteins/genetics , Betacoronavirus/genetics , Coronavirus Infections/virology , Humans , Pandemics , Pneumonia, Viral/virology , RNA, Viral/analysis , Sensitivity and Specificity , World Health Organization
11.
CPT Pharmacometrics Syst Pharmacol ; 9(9): 509-514, 2020 09.
Article in English | MEDLINE | ID: covidwho-603799

ABSTRACT

We modeled the viral dynamics of 13 untreated patients infected with severe acute respiratory syndrome-coronavirus 2 to infer viral growth parameters and predict the effects of antiviral treatments. In order to reduce peak viral load by more than two logs, drug efficacy needs to be > 90% if treatment is administered after symptom onset; an efficacy of 60% could be sufficient if treatment is initiated before symptom onset. Given their pharmacokinetic/pharmacodynamic properties, current investigated drugs may be in a range of 6-87% efficacy. They may help control virus if administered very early, but may not have a major effect in severely ill patients.

12.
Viruses ; 12(6)2020 06 08.
Article in English | MEDLINE | ID: covidwho-574875

ABSTRACT

Clinical samples collected in coronavirus disease 19 (COVID-19), patients are commonly manipulated in biosafety level 2 laboratories for molecular diagnostic purposes. Here, we tested French norm NF-EN-14476+A2 derived from European standard EN-14885 to assess the risk of manipulating infectious viruses prior to RNA extraction. SARS-CoV-2 cell-culture supernatant and nasopharyngeal samples (virus-spiked samples and clinical samples collected in COVID-19 patients) were used to measure the reduction of infectivity after 10 minute contact with lysis buffer containing various detergents and chaotropic agents. A total of thirteen protocols were evaluated. Two commercially available formulations showed the ability to reduce infectivity by at least 6 log 10, whereas others proved less effective.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/virology , Pneumonia, Viral/virology , Virus Inactivation/drug effects , Animals , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Betacoronavirus/physiology , Cell Culture Techniques/methods , Chlorocebus aethiops , Containment of Biohazards/methods , Containment of Biohazards/standards , Humans , Nasopharynx/virology , Pandemics , RNA, Viral/isolation & purification , Specimen Handling/methods , Vero Cells , Viral Load/methods
14.
Vox Sang ; 115(6): 488-494, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-26729

ABSTRACT

Plasma provided by COVID-19 convalescent patients may provide therapeutic relief as the number of COVID-19 cases escalates steeply worldwide. Prior findings in various viral respiratory diseases including SARS-CoV-related pneumonia suggest that convalescent plasma can reduce mortality, although formal proof of efficacy is still lacking. By reducing viral spread early on, such an approach may possibly downplay subsequent immunopathology. Identifying, collecting, qualifying and preparing plasma from convalescent patients with adequate SARS-CoV-2-neutralizing Ab titres in an acute crisis setting may be challenging, although well within the remit of most blood establishments. Careful clinical evaluation should allow to quickly establish whether such passive immunotherapy, administered at early phases of the disease in patients at high risk of deleterious evolution, may reduce the frequency of patient deterioration, and thereby COVID-19 mortality.


Subject(s)
Blood Specimen Collection/methods , Coronavirus Infections/blood , Pneumonia, Viral/blood , Blood Safety/methods , Blood Safety/standards , Blood Specimen Collection/standards , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Humans , Immunization, Passive/methods , Immunization, Passive/standards , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy
15.
Antiviral Res ; 177: 104762, 2020 05.
Article in English | MEDLINE | ID: covidwho-4426

ABSTRACT

Recent publications have brought attention to the possible benefit of chloroquine, a broadly used antimalarial drug, in the treatment of patients infected by the novel emerged coronavirus (SARS-CoV-2). The scientific community should consider this information in light of previous experiments with chloroquine in the field of antiviral research.


Subject(s)
Antiviral Agents/therapeutic use , Chloroquine/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Antiviral Agents/adverse effects , Antiviral Agents/pharmacology , Antiviral Agents/standards , Betacoronavirus/drug effects , China , Chloroquine/adverse effects , Chloroquine/pharmacology , Chloroquine/standards , Clinical Trials as Topic/standards , Humans , Hydroxychloroquine/adverse effects , Hydroxychloroquine/pharmacology , Hydroxychloroquine/standards , Hydroxychloroquine/therapeutic use , Pandemics
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