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1.
Crit Care Med ; 2022 Feb 08.
Article in English | MEDLINE | ID: covidwho-1672322

ABSTRACT

OBJECTIVES: To describe 3-6-month neurologic outcomes of survivors of COVID-19-associated acute respiratory distress syndrome, invasively ventilated in the ICU. DESIGN: A bicentric prospective study during the two first waves of the pandemic (March to May and September to December, 2020). SETTING: Two academic hospital ICUs, Paris, France. PATIENTS: Adult COVID-19-associated acute respiratory distress syndrome survivors, invasively ventilated in the ICU, were eligible for a neurologic consultation between 3 and 6 months post ICU discharge. INTERVENTIONS: Follow-up by face-to-face neurologic consultation. MEASURES AND MAIN RESULTS: The primary endpoint was favorable functional outcome defined by a modified Rankin scale score less than 2, indicating survival with no significant disability. Secondary endpoints included mild cognitive impairment (Montreal Cognitive Assessment score < 26), ICU-acquired weakness (Medical Research Council score < 48), anxiety and depression (Hospital Anxiety and Depression score > 7), and posttraumatic stress disorder (posttraumatic stress disorder checklist for Diagnostic and Statistical Manual of Mental Disorders 5 score > 30). Of 54 eligible survivors, four non-French-speaking patients were excluded, eight patients were lost-to-follow-up, and one died during follow-up. Forty-one patients were included. Time between ICU discharge and neurologic consultation was 3.8 months (3.6-5.9 mo). A favorable functional outcome was observed in 16 patients (39%) and mild cognitive impairment in 17 of 33 patients tested (52%). ICU-acquired weakness, depression or anxiety, and posttraumatic stress disorder were reported in six of 37 cases (16%), eight of 31 cases (26%), and two of 27 cases (7%), respectively. Twenty-nine patients (74%) required rehabilitation (motor, cognitive, or psychologic). ICU and hospital lengths of stay, tracheostomy, and corticosteroids were negatively associated with favorable outcome. By contrast, use of alpha-2 agonists during ICU stay was associated with favorable outcome. CONCLUSIONS: COVID-19-associated acute respiratory distress syndrome requiring intubation led to slight-to-severe functional disability in about 60% of survivors 4 months after ICU discharge. Cognitive impairment, muscle weakness, and psychologic symptoms were frequent. A large multicenter study is warranted to allow identification of modifiable factors for improving long-term outcome.

2.
Curr Opin Infect Dis ; 35(2): 170-175, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1642444

ABSTRACT

PURPOSE OF REVIEW: The first studies on COVID-19 patients with acute respiratory distress syndrome (ARDS) described a high rate of secondary bacterial ventilator-associated pneumonia (VAP). The specificity of VAP diagnoses in these patients are reviewed, including their actual rate. RECENT FINDINGS: Published studies described high rates of bacterial VAP among COVID-19 patients with ARDS, and these VAP episodes are usually severe and of specifically poor prognosis with high mortality. Indeed, Severe acute respiratory syndrome - coronavirus disease 19 (SARS-CoV2) infection elicits alterations that may explain a high risk of VAP. In addition, breaches in the aseptic management of patients might have occurred when the burden of care was heavy. In addition, VAP in these patients is more frequently suspected, and more often investigated with diagnostic tools based on molecular techniques. SUMMARY: VAP is frequented and of particularly poor prognosis in COVID-19 patients with ARDS. It can be explained by SARS-CoV-2 pathophysiology, and also breaches in the aseptic procedures. In addition, tools based on molecular techniques allow an early diagnosis and unmask VAP usually underdiagnosed by traditional culture-based methods. The impact of molecular technique-based diagnostics in improving antibacterial therapy and COVID-19 prognosis remain to be evaluated.


Subject(s)
COVID-19 , Pneumonia, Ventilator-Associated , Humans , Pneumonia, Ventilator-Associated/diagnosis , Pneumonia, Ventilator-Associated/epidemiology , Pneumonia, Ventilator-Associated/microbiology , RNA, Viral , Respiration, Artificial , SARS-CoV-2
3.
Sci Rep ; 12(1): 638, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1621278

ABSTRACT

COVID-19 can cause acute respiratory distress syndrome, leading to death in many individuals. Evidence of a deleterious role of the innate immune system is accumulating, but the precise mechanisms involved remain unclear. In this study, we investigated the links between circulating innate phagocytes and severity in COVID-19 patients. We performed in-depth phenotyping of neutrophil and monocyte subpopulations and measured soluble activation markers in plasma. Additionally, anti-microbial functions (phagocytosis, oxidative burst, and NETosis) were evaluated on fresh cells from patients. Neutrophils and monocytes had a strikingly disturbed phenotype, and elevated concentrations of activation markers (calprotectin, myeloperoxidase, and neutrophil extracellular traps) were measured in plasma. Critical patients had increased CD13low immature neutrophils, LOX-1 + and CCR5 + immunosuppressive neutrophils, and HLA-DRlow downregulated monocytes. Markers of immature and immunosuppressive neutrophils were strongly associated with severity. Moreover, neutrophils and monocytes of critical patients had impaired antimicrobial functions, which correlated with organ dysfunction, severe infections, and mortality. Together, our results strongly argue in favor of a pivotal role of innate immunity in COVID-19 severe infections and pleads for targeted therapeutic options.


Subject(s)
COVID-19/immunology , Immunity, Innate , Immunocompromised Host , Adult , Aged , Female , Humans , Male , Middle Aged , Monocytes/immunology , Neutrophils/immunology , Phagocytes/immunology , Prognosis , Severity of Illness Index , Young Adult
4.
Crit Care ; 25(1): 417, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1555803

ABSTRACT

BACKGROUND: Data in the literature about HSV reactivation in COVID-19 patients are scarce, and the association between HSV-1 reactivation and mortality remains to be determined. Our objectives were to evaluate the impact of Herpes simplex virus (HSV) reactivation in patients with severe SARS-CoV-2 infections primarily on mortality, and secondarily on hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP) and intensive care unit-bloodstream infection (ICU-BSI). METHODS: We conducted an observational study using prospectively collected data and HSV-1 blood and respiratory samples from all critically ill COVID-19 patients in a large reference center who underwent HSV tests. Using multivariable Cox and cause-specific (cs) models, we investigated the association between HSV reactivation and mortality or healthcare-associated infections. RESULTS: Of the 153 COVID-19 patients admitted for ≥ 48 h from Feb-2020 to Feb-2021, 40/153 (26.1%) patients had confirmed HSV-1 reactivation (19/61 (31.1%) with HSV-positive respiratory samples, and 36/146 (24.7%) with HSV-positive blood samples. Day-60 mortality was higher in patients with HSV-1 reactivation (57.5%) versus without (33.6%, p = 0.001). After adjustment for mortality risk factors, HSV-1 reactivation was associated with an increased mortality risk (hazard risk [HR] 2.05; 95% CI 1.16-3.62; p = 0.01). HAP/VAP occurred in 67/153 (43.8%) and ICU-BSI in 42/153 (27.5%) patients. In patients with HSV-1 reactivation, multivariable cause-specific models showed an increased risk of HAP/VAP (csHR 2.38, 95% CI 1.06-5.39, p = 0.037), but not of ICU-BSI. CONCLUSIONS: HSV-1 reactivation in critically ill COVID-19 patients was associated with an increased risk of day-60 mortality and HAP/VAP.


Subject(s)
COVID-19 , Herpesvirus 1, Human , Pneumonia , COVID-19/mortality , COVID-19/virology , Critical Illness , Herpesvirus 1, Human/physiology , Humans , Pneumonia/epidemiology , Pneumonia/virology , Risk Assessment
5.
Am J Physiol Lung Cell Mol Physiol ; 321(5): L847-L858, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1403121

ABSTRACT

Increased blood fibrocytes are associated with a poor prognosis in fibrotic lung diseases. We aimed to determine whether the percentage of circulating fibrocytes could be predictive of severity and prognosis during coronavirus disease 2019 (COVID-19) pneumonia. Blood fibrocytes were quantified by flow cytometry as CD45+/CD15-/CD34+/collagen-1+ cells in patients hospitalized for COVID-19 pneumonia. In a subgroup of patients admitted in an intensive care unit (ICU), fibrocytes were quantified in blood and bronchoalveolar lavage (BAL). Serum amyloid P (SAP), transforming growth factor-ß1 (TGF-ß1), CXCL12, CCL2, and FGF2 concentrations were measured. We included 57 patients in the hospitalized group (median age = 59 yr [23-87]) and 16 individuals as healthy controls. The median percentage of circulating fibrocytes was higher in the patients compared with the controls (3.6% [0.2-9.2] vs. 2.1% [0.9-5.1], P = 0.04). Blood fibrocyte count was lower in the six patients who died compared with the survivors (1.6% [0.2-4.4] vs. 3.7% [0.6-9.2], P = 0.02). Initial fibrocyte count was higher in patients showing a complete lung computed tomography (CT) resolution at 3 mo. Circulating fibrocyte count was decreased in the ICU group (0.8% [0.1-2.0]), whereas BAL fibrocyte count was 6.7% (2.2-15.4). Serum SAP and TGF-ß1 concentrations were increased in hospitalized patients. SAP was also increased in ICU patients. CXCL12 and CCL2 were increased in ICU patients and negatively correlated with circulating fibrocyte count. We conclude that circulating fibrocytes were increased in patients hospitalized for COVID-19 pneumonia, and a lower fibrocyte count was associated with an increased risk of death and a slower resolution of lung CT opacities.


Subject(s)
Antigens, CD/blood , Blood Cells/metabolism , COVID-19/blood , Cytokines/blood , SARS-CoV-2/metabolism , Serum Amyloid A Protein/metabolism , Adult , Aged , Aged, 80 and over , Blood Cell Count , COVID-19/diagnosis , COVID-19/diagnostic imaging , Female , Humans , Male , Middle Aged , Prognosis , Severity of Illness Index , Tomography, X-Ray Computed
6.
Crit Care ; 25(1): 153, 2021 04 21.
Article in English | MEDLINE | ID: covidwho-1197349

ABSTRACT

We reviewed similarities and differences of ventilator associated pneumonia in Sars-Cov2 infection and with other ARDS. The differences in epidemiology and outcome will be detailed. Possible explanations of differences in pathophysiology of VAP in Sarscov2 infections will be cited and discussed.


Subject(s)
COVID-19 , Pneumonia, Ventilator-Associated/epidemiology , Humans
8.
Crit Care ; 24(1): 610, 2020 10 16.
Article in English | MEDLINE | ID: covidwho-874051

ABSTRACT

BACKGROUND: Data on SARS-CoV-2 load in lower respiratory tract (LRT) are scarce. Our objectives were to describe the viral shedding and the viral load in LRT and to determine their association with mortality in critically ill COVID-19 patients. METHODS: We conducted a binational study merging prospectively collected data from two COVID-19 reference centers in France and Switzerland. First, we described the viral shedding duration (i.e., time to negativity) in LRT samples. Second, we analyzed viral load in LRT samples. Third, we assessed the association between viral presence in LRT and mortality using mixed-effect logistic models for clustered data adjusting for the time between symptoms' onset and date of sampling. RESULTS: From March to May 2020, 267 LRT samples were performed in 90 patients from both centers. The median time to negativity was 29 (IQR 23; 34) days. Prolonged viral shedding was not associated with age, gender, cardiac comorbidities, diabetes, immunosuppression, corticosteroids use, or antiviral therapy. The LRT viral load tended to be higher in non-survivors. This difference was statistically significant after adjusting for the time interval between onset of symptoms and date of sampling (OR 3.78, 95% CI 1.13-12.64, p = 0.03). CONCLUSIONS: The viral shedding in LRT lasted almost 30 days in median in critically ill patients, and the viral load in the LRT was associated with the 6-week mortality.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , Respiratory System/virology , Aged , COVID-19 , Coronavirus Infections/mortality , Critical Illness/mortality , Female , France/epidemiology , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Prospective Studies , Respiration, Artificial , SARS-CoV-2 , Switzerland/epidemiology , Viral Load , Virus Shedding
9.
Antimicrob Agents Chemother ; 64(11)2020 10 20.
Article in English | MEDLINE | ID: covidwho-738379

ABSTRACT

Remdesivir has reported efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and in vivo Drug-drug interactions limit therapeutic options in transplant patients. Remdesivir and its metabolite GS-441524 are excreted principally in urine. In intensive care unit (ICU) settings, in which multiple-organ dysfunctions can occur rapidly, hemodialysis may be a viable option for maintaining remdesivir treatment, while improving tolerance, by removing both remdesivir's metabolite (GS-441524) and sulfobutylether ß-cyclodextrin sodium (SEBCD). Additional studies may prove informative, particularly in the evaluations of therapeutic options for coronavirus disease 2019 (COVID-19).


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/administration & dosage , Betacoronavirus/drug effects , Coronavirus Infections/therapy , Furans/urine , Pneumonia, Viral/therapy , Pyrroles/urine , Triazines/urine , beta-Cyclodextrins/urine , Adenosine/analogs & derivatives , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/chemistry , Adenosine Monophosphate/metabolism , Alanine/administration & dosage , Alanine/adverse effects , Alanine/chemistry , Alanine/metabolism , Antiviral Agents/adverse effects , Antiviral Agents/chemistry , Antiviral Agents/metabolism , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/surgery , Coronavirus Infections/virology , Drug Interactions , Furans/adverse effects , Furans/chemistry , Humans , Intensive Care Units , Lung Transplantation , Multiple Organ Failure , Pandemics , Pneumonia, Viral/surgery , Pneumonia, Viral/virology , Pyrroles/adverse effects , Pyrroles/chemistry , Renal Dialysis , SARS-CoV-2 , Transplant Recipients , Triazines/adverse effects , Triazines/chemistry , beta-Cyclodextrins/adverse effects , beta-Cyclodextrins/chemistry
10.
J Clin Immunol ; 40(8): 1082-1092, 2020 11.
Article in English | MEDLINE | ID: covidwho-724903

ABSTRACT

We report a longitudinal analysis of the immune response associated with a fatal case of COVID-19 in Europe. This patient exhibited a rapid evolution towards multiorgan failure. SARS-CoV-2 was detected in multiple nasopharyngeal, blood, and pleural samples, despite antiviral and immunomodulator treatment. Clinical evolution in the blood was marked by an increase (2-3-fold) in differentiated effector T cells expressing exhaustion (PD-1) and senescence (CD57) markers, an expansion of antibody-secreting cells, a 15-fold increase in γδ T cell and proliferating NK-cell populations, and the total disappearance of monocytes, suggesting lung trafficking. In the serum, waves of a pro-inflammatory cytokine storm, Th1 and Th2 activation, and markers of T cell exhaustion, apoptosis, cell cytotoxicity, and endothelial activation were observed until the fatal outcome. This case underscores the need for well-designed studies to investigate complementary approaches to control viral replication, the source of the hyperinflammatory status, and immunomodulation to target the pathophysiological response. The investigation was conducted as part of an overall French clinical cohort assessing patients with COVID-19 and registered in clinicaltrials.gov under the following number: NCT04262921.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/complications , Cytokine Release Syndrome/immunology , Multiple Organ Failure/immunology , Pneumonia, Viral/complications , Respiratory Distress Syndrome/immunology , Aged, 80 and over , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/therapy , Cytokine Release Syndrome/virology , Fatal Outcome , France , Humans , Longitudinal Studies , Lymphocyte Activation , Male , Multiple Organ Failure/blood , Multiple Organ Failure/therapy , Multiple Organ Failure/virology , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , Prospective Studies , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , SARS-CoV-2 , Severity of Illness Index , T-Lymphocytes, Cytotoxic/immunology , Th1 Cells/immunology , Th2 Cells/immunology
11.
J Antimicrob Chemother ; 75(9): 2657-2660, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-705983

ABSTRACT

BACKGROUND: The combination lopinavir/ritonavir is recommended to treat HIV-infected patients at the dose regimen of 400/100 mg q12h, oral route. The usual lopinavir trough plasma concentrations are 3000-8000 ng/mL. A trend towards a 28 day mortality reduction was observed in COVID-19-infected patients treated with lopinavir/ritonavir. OBJECTIVES: To assess the plasma concentrations of lopinavir and ritonavir in patients with severe COVID-19 infection and receiving lopinavir/ritonavir. PATIENTS AND METHODS: Mechanically ventilated patients with COVID-19 infection included in the French COVID-19 cohort and treated with lopinavir/ritonavir were included. Lopinavir/ritonavir combination was administered using the usual adult HIV dose regimen (400/100 mg q12h, oral solution through a nasogastric tube). A half-dose reduction to 400/100 mg q24h was proposed if lopinavir Ctrough was >8000 ng/mL, the upper limit considered as toxic and reported in HIV-infected patients. Lopinavir and ritonavir pharmacokinetic parameters were determined after an intensive pharmacokinetic analysis. Biological markers of inflammation and liver/kidney function were monitored. RESULTS: Plasma concentrations of lopinavir and ritonavir were first assessed in eight patients treated with lopinavir/ritonavir. Median (IQR) lopinavir Ctrough reached 27 908 ng/mL (15 928-32 627). After the dose reduction to 400/100 mg q24h, lopinavir/ritonavir pharmacokinetic parameters were assessed in nine patients. Lopinavir Ctrough decreased to 22 974 ng/mL (21 394-32 735). CONCLUSIONS: In mechanically ventilated patients with severe COVID-19 infections, the oral administration of lopinavir/ritonavir elicited plasma exposure of lopinavir more than 6-fold the upper usual expected range. However, it remains difficult to safely recommend its dose reduction without compromising the benefit of the antiviral strategy, and careful pharmacokinetic and toxicity monitoring are needed.


Subject(s)
Betacoronavirus , Coronavirus Infections/blood , Intensive Care Units/trends , Lopinavir/blood , Pneumonia, Viral/blood , Respiration, Artificial/trends , Ritonavir/blood , Administration, Oral , COVID-19 , Coronavirus Infections/drug therapy , Cytochrome P-450 CYP3A Inhibitors/administration & dosage , Cytochrome P-450 CYP3A Inhibitors/blood , Drug Therapy, Combination , Female , Humans , Lopinavir/administration & dosage , Male , Middle Aged , Pandemics , Pharmaceutical Solutions/administration & dosage , Pharmaceutical Solutions/pharmacokinetics , Pneumonia, Viral/drug therapy , Prospective Studies , Ritonavir/administration & dosage , SARS-CoV-2
12.
Int J Infect Dis ; 98: 290-293, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-701793

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the virus responsible for the coronavirus disease 2019 (COVID-19) outbreak worldwide. Data on treatment are scare and parallels have been made between SARS-CoV-2 and other coronaviruses. Remdesivir is a broad-spectrum antiviral with efficient in vitro activity against SARS-CoV-2. Evidence of clinical improvement in patients with severe COVID-19 treated with remdesivir is controversial. The aim of this study was to describe the clinical outcomes and virological monitoring of the first five COVID-19 patients admitted to the intensive care unit of Bichat-Claude Bernard University Hospital, Paris, France, for severe pneumonia related to SARS-CoV-2 and treated with remdesivir. Quantitative reverse transcription PCR was used to monitor SARS-CoV-2 in blood plasma and the lower and upper respiratory tract. Among the five patients treated, two needed mechanical ventilation and one needed high-flow cannula oxygen. A significant decrease in SARS-CoV-2 viral load in the upper respiratory tract was observed in most cases, but two patients died with active SARS-CoV-2 replication in the lower respiratory tract. Plasma samples were positive for SARS-CoV-2 in only one patient. Remdesivir was interrupted before the initialy planned duration in four patients, two because of alanine aminotransferase elevations (3 to 5 normal range) and two because of renal failure requiring renal replacement. This case series of five COVID-19 patients requiring intensive care unit treatment for respiratory distress and treated with remdesivir, highlights the complexity of remdesivir use in such critically ill patients.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Adult , Aged , Aged, 80 and over , Alanine/adverse effects , Alanine/therapeutic use , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/virology , Female , France , Hospitalization , Humans , Male , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Viral Load/drug effects , Withholding Treatment
13.
Lancet Infect Dis ; 20(6): 697-706, 2020 06.
Article in English | MEDLINE | ID: covidwho-17918

ABSTRACT

BACKGROUND: On Dec 31, 2019, China reported a cluster of cases of pneumonia in people at Wuhan, Hubei Province. The responsible pathogen is a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the relevant features of the first cases in Europe of confirmed infection, named coronavirus disease 2019 (COVID-19), with the first patient diagnosed with the disease on Jan 24, 2020. METHODS: In this case series, we followed five patients admitted to Bichat-Claude Bernard University Hospital (Paris, France) and Pellegrin University Hospital (Bordeaux, France) and diagnosed with COVID-19 by semi-quantitative RT-PCR on nasopharyngeal swabs. We assessed patterns of clinical disease and viral load from different samples (nasopharyngeal and blood, urine, and stool samples), which were obtained once daily for 3 days from hospital admission, and once every 2 or 3 days until patient discharge. All samples were refrigerated and shipped to laboratories in the National Reference Center for Respiratory Viruses (The Institut Pasteur, Paris, and Hospices Civils de Lyon, Lyon, France), where RNA extraction, real-time RT-PCR, and virus isolation and titration procedures were done. FINDINGS: The patients were three men (aged 31 years, 48 years, and 80 years) and two women (aged 30 years and 46 years), all of Chinese origin, who had travelled to France from China around mid-January, 2020. Three different clinical evolutions are described: (1) two paucisymptomatic women diagnosed within a day of exhibiting symptoms, with high nasopharyngeal titres of SARS-CoV-2 within the first 24 h of the illness onset (5·2 and 7·4 log10 copies per 1000 cells, respectively) and viral RNA detection in stools; (2) a two-step disease progression in two young men, with a secondary worsening around 10 days after disease onset despite a decreasing viral load in nasopharyngeal samples; and (3) an 80-year-old man with a rapid evolution towards multiple organ failure and a persistent high viral load in lower and upper respiratory tract with systemic virus dissemination and virus detection in plasma. The 80-year-old patient died on day 14 of illness (Feb 14, 2020); all other patients had recovered and been discharged by Feb 19, 2020. INTERPRETATION: We illustrated three different clinical and biological types of evolution in five patients infected with SARS-CoV-2 with detailed and comprehensive viral sampling strategy. We believe that these findings will contribute to a better understanding of the natural history of the disease and will contribute to advances in the implementation of more efficient infection control strategies. FUNDING: REACTing (Research & Action Emerging Infectious Diseases).


Subject(s)
Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Adult , Aged, 80 and over , Betacoronavirus/isolation & purification , Blood/virology , COVID-19 , China , Coronavirus Infections/virology , Feces/virology , Female , France/epidemiology , Humans , Male , Middle Aged , Nasopharynx/virology , Pandemics , Pneumonia, Viral/virology , RNA, Viral/isolation & purification , SARS-CoV-2 , Travel , Urine/virology , Viral Load
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