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1.
Ann Intern Med ; 2022 Mar 15.
Article in English | MEDLINE | ID: covidwho-1742923

ABSTRACT

BACKGROUND: At the end of 2021, the B.1.1.529 SARS-CoV-2 variant (Omicron) wave superseded the B.1.617.2 variant (Delta) wave. OBJECTIVE: To compare baseline characteristics and in-hospital outcomes of patients with SARS-CoV-2 infection with the Delta variant versus the Omicron variant in the emergency department (ED). DESIGN: Retrospective chart reviews. SETTING: 13 adult EDs in academic hospitals in the Paris area from 29 November 2021 to 10 January 2022. PATIENTS: Patients with a positive reverse transcriptase polymerase chain reaction (RT-PCR) test result for SARS-CoV-2 and variant identification. MEASUREMENTS: Main outcome measures were baseline clinical and biological characteristics at ED presentation, intensive care unit (ICU) admission, mechanical ventilation, and in-hospital mortality. RESULTS: A total of 3728 patients had a positive RT-PCR test result for SARS-CoV-2 during the study period; 1716 patients who had a variant determination (818 Delta and 898 Omicron) were included. Median age was 58 years, and 49% were women. Patients infected with the Omicron variant were younger (54 vs. 62 years; difference, 8.0 years [95% CI, 4.6 to 11.4 years]), had a lower rate of obesity (8.0% vs. 12.5%; difference, 4.5 percentage points [CI, 1.5 to 7.5 percentage points]), were more vaccinated (65% vs. 39% for 1 dose and 22% vs. 11% for 3 doses), had a lower rate of dyspnea (26% vs. 50%; difference, 23.6 percentage points [CI, 19.0 to 28.2 percentage points]), and had a higher rate of discharge home from the ED (59% vs. 37%; difference, 21.9 percentage points [-26.5 to -17.1 percentage points]). Compared with Delta, Omicron infection was independently associated with a lower risk for ICU admission (adjusted difference, 11.4 percentage points [CI, 8.4 to 14.4 percentage points]), mechanical ventilation (adjusted difference, 3.6 percentage points [CI, 1.7 to 5.6 percentage points]), and in-hospital mortality (adjusted difference, 4.2 percentage points [CI, 2.0 to 6.5 percentage points]). LIMITATION: Patients with COVID-19 illness and no SARS-CoV-2 variant determination in the ED were excluded. CONCLUSION: Compared with the Delta variant, infection with the Omicron variant in patients in the ED had different clinical and biological patterns and was associated with better in-hospital outcomes, including higher survival. PRIMARY FUNDING SOURCE: None.

3.
J Antimicrob Chemother ; 76(Suppl 3): iii33-iii49, 2021 09 23.
Article in English | MEDLINE | ID: covidwho-1664107

ABSTRACT

OBJECTIVES: It is unclear whether real-time (rt)-PCR cycle threshold (Ct) values can be utilized to guide clinical and infection-control decisions. This systematic review assesses the association between respiratory pathogen rt-PCR Ct values and clinical presentation or outcomes. METHODS: We searched MEDLINE, EMBASE and Cochrane library databases on 14-17 January 2020 for studies reporting the presence or absence of an association between Ct values and clinical presentation or outcomes, excluding animal studies, reviews, meta-analyses, and non-English language studies. RESULTS: Among 33 studies identified (reporting on between 9 and 4918 participants by pathogen), influenza (n = 11 studies; 4918 participants), human rhinovirus (HRV, n = 11; 2012) and respiratory syncytial virus (RSV, n = 8; 3290) were the most-studied pathogens. Low influenza Ct values were associated with mortality in 1/3 studies, with increased disease severity/duration or ICU admission in 3/9, and with increased hospitalization or length of hospital stay (LOS) in 1/6. Low HRV Ct values were associated with increased disease severity/duration or ICU admission in 3/10 studies, and with increased hospitalization or LOS in 1/3. Low RSV Ct values were associated with increased disease severity/duration or ICU admission in 3/6 studies, and with increased hospitalization or LOS in 4/4. Contradictory associations were also identified for other respiratory pathogens. CONCLUSIONS: Respiratory infection Ct values may inform clinical and infection-control decisions. However, the study heterogeneity observed in this review highlights the need for standardized workflows to utilize Ct values as a proxy of genomic load and confirm their value for respiratory infection management.


Subject(s)
Influenza, Human , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Hospitalization , Humans , Infant , Real-Time Polymerase Chain Reaction , Respiratory Syncytial Virus Infections/diagnosis , Respiratory Syncytial Virus, Human/genetics
4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-316523

ABSTRACT

Background: Worldwide demand for SARS-CoV-2 RT-PCR testing is increasing as more countries are impacted by COVID-19 and as testing remains central to contain the spread of the disease, both in countries where the disease is emerging and in countries that are past the first wave but exposed to re-emergence. Group testing has been proposed as a solution to expand testing capabilities but sensitivity concerns have limited its impact on the management of the pandemic. Digital PCR (RT-dPCR) has been shown to be more sensitive than RT-PCR and could help in this context. Methods: We implemented RT-dPCR based COVID-19 group testing on commercially available system and assay (Naica System from Stilla Technologies) and investigated the sensitivity of the method in real life conditions of a university hospital in Paris, France, in May 2020. We tested the protocol in a direct comparison with reference RT-PCR testing on 448 samples split into groups of 3 sizes for RT-dPCR analysis: 56 groups of 8 samples, 28 groups of 16 samples and 14 groups of 32 samples. Results: Individual RT-PCR testing identified 25 positive samples. Using groups of 8, testing by RT-dPCR identified 23 groups as positive, corresponding to 26 true positive samples including 2 samples not initially detected by individual RT-PCR but confirmed positive by further RT-PCR and RT-dPCR investigation. For groups of 16, 15 groups tested positive, corresponding to 25 true positive samples identified. 100% concordance is found for groups of 32 but with limited data points.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-312819

ABSTRACT

Backround During the COVID-19 pandemic, antibiotics use was very common. However, bacterial co/secondary infections with coronaviruses remain largely unknown, especially outside of intensive care. The aim of this study was to investigate the pulmonary bacterial infections characteristics associated with COVID-19 in hospitalized patients. Methods A retrospective monocentric observational study was conducted in Bichat hospital in France, between February 26 and April 22, 2020. All patients hospitalized in standard wards with COVID-19 (positive nasopharyngeal PCR and/or typical aspect on CT scan) and diagnosed with a pulmonary bacterial infection (positive bacteriological samples) were included. Bacteriological and clinical data were collected from the microbiology laboratories and the patient's medical records. Results Twenty-three bacteriological samples from 22 patients were positive out of 2075 screened samples (1.1%) from 784 patients (2.8%). Bacterial infection occurred with a median of ten days after COVID-19 onset. Diagnosis of pulmonary bacterial infection was suspected on the increase of oxygen requirements (20/22), productive cough or modification of sputum (17/22), or fever (10/22). Positive samples included 13 sputum cultures, one Film Array® on sputum, one bronchoalveolar lavage, six blood cultures and two pneumococcal antigenuria. The most frequent bacteria were Pseudomonas aeruginosa (6/23), Staphylococcus aureus (5/23), Streptococcus pneumoniae (4/23), Enterococcus faecalis (3/23) and Klebsiella aerogenes (3/23). No Legionella antigenuria was positive. Four out of 496 nasopharyngeal PCR (0.8%) were positive for intracellular bacteria (two Bordetella pertussis and two Mycoplasma pneumonia ). Conclusions Pulmonary bacterial secondary infections and co-infections with SARS-CoV-2 are uncommon. Antibiotic use should remain limited in the management of COVID-19.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-307242

ABSTRACT

Abstract: Objectives: Our work assessed the prevalence of co-infections in patients with SARS-CoV-2. Methods: All patients hospitalized in a Parisian hospital during the first wave of COVID-19 were tested by mPCR if they presented ILI symptoms. Results: A total of 806 patients (21%) were positive for SARS-CoV-2, 755 (20%) were positive for other respiratory viruses. Among the SARS-CoV-2 positive patients, 49 (6%) had viral co-infections. They presented similar age, symptoms, except for fever (p=0.013) and headaches (p=0.048), than single SARS-CoV-2 infections. Conclusions: SARS-CoV-2 infected patients presenting viral co-infections had similar clinical characteristics and prognosis than patients solely infected with SARS-CoV-2.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-306787

ABSTRACT

Background: SARS-CoV-2 induces a humoral response with seroconversion occurring within the first weeks after COVID-19 disease. Those antibodies exert a neutralizing activity against SARS-CoV-2, whose evolution overtime after COVID-19 is however unknown.Methods: In this monocentric prospective study, sera of 107 patients hospitalized with COVID-19 were collected at 3 months and 6 months post-infection. We performed quantitative neutralization experiments on top of high-throughput serological assays evaluating anti-Spike (S) and anti-Nucleocapsid (NP) IgG.Findings: Levels of sero-neutralization decreased significantly over study time, as well as IgG rates. After 6 months, 2.8% of the patients had a negative serological status for both anti-S and anti-NP IgG. However, all sera had a persistent and effective neutralizing effect on SARS-CoV-2 neutralizing assays. IgG levels correlated with sero-neutralization and this correlation was stronger for anti-S than for anti-NP antibodies. The level of sero-neutralization quantified at 6 months correlated with markers of initial severity, notably admission in intensive care units and the need for mechanical invasive ventilation.Interpretation: Decrease of IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity in our patients. Those results are encouraging and in favor of sustained humoral response for at least 6 months in patients previously hospitalized for COVID-19, which will have to be considered in global deployment of vaccination strategy.Trial Registration: The French Covid cohort (NCT04262921)Funding Statement: The French COVID cohort is funding by the REACTing (REsearch & ACtion emergING infectious diseases) consortium and by a grant of the French Ministry of Health (PHRC n°20-0424).Outside the submitted work, JSH is supported by AP-HP, INSERM, the French National Research Agency (NADHeart ANR-17-CE17-0015-02, PACIFIC ANR-18-CE14-0032-01, CORRECT_LMNA ANR-19-CE17-0013-02), the ERA-Net-CVD (ANR-16-ECVD-0011-03, Clarify project), Fédération Française de Cardiologie, the Fondation pour la Recherche Médicale, and by a grant from the Leducq Foundation (18CVD05), and is coordinating a French PIA Project (2018-PSPC-07, PACIFIC-preserved, BPIFrance) and a University Research Federation against heart failure (FHU2019, PREVENT_Heart Failure). JG reports personal fees from ViiV Healthcare, Gilead Science, Janssen Cilag, and research grants from Gilead Sciences, MSD and ViiV Healthcare, outside the submitted work.Declaration of Interests: Authors have nothing to disclose. There are no relationships with industry.Ethics Approval Statement: The French Covid cohort (NCT04262921) is a prospective multi-center observational cohort sponsored by Inserm which was authorized by the French Ethics Committee CPP Ile-de-France VI (ID RCB:2020-A00256-33).

8.
Euro Surveill ; 27(6)2022 Feb.
Article in English | MEDLINE | ID: covidwho-1686391

ABSTRACT

BackgroundThe COVID-19 pandemic has led to an unprecedented daily use of RT-PCR tests. These tests are interpreted qualitatively for diagnosis, and the relevance of the test result intensity, i.e. the number of quantification cycles (Cq), is debated because of strong potential biases.AimWe explored the possibility to use Cq values from SARS-CoV-2 screening tests to better understand the spread of an epidemic and to better understand the biology of the infection.MethodsWe used linear regression models to analyse a large database of 793,479 Cq values from tests performed on more than 2 million samples between 21 January and 30 November 2020, i.e. the first two pandemic waves. We performed time series analysis using autoregressive integrated moving average (ARIMA) models to estimate whether Cq data information improves short-term predictions of epidemiological dynamics.ResultsAlthough we found that the Cq values varied depending on the testing laboratory or the assay used, we detected strong significant trends associated with patient age, number of days after symptoms onset or the state of the epidemic (the temporal reproduction number) at the time of the test. Furthermore, knowing the quartiles of the Cq distribution greatly reduced the error in predicting the temporal reproduction number of the COVID-19 epidemic.ConclusionOur results suggest that Cq values of screening tests performed in the general population generate testable hypotheses and help improve short-term predictions for epidemic surveillance.


Subject(s)
COVID-19 , SARS-CoV-2 , France/epidemiology , Humans , Pandemics , Reverse Transcriptase Polymerase Chain Reaction
9.
Médecine et Maladies Infectieuses Formation ; 1(1):34-41, 2022.
Article in French | EuropePMC | ID: covidwho-1678972

ABSTRACT

L’émergence du SARS-CoV-2 a renforcé l'intérêt pour la place des virus respiratoires, dans les pneumonies aiguës communautaires, en mettant en exergue de nombreux points encore mal connus tels que la part des infections asymptomatiques, les interactions entre virus respiratoires et pathogènes non viraux, leurs périodes d'incubation, leur pathogénicité ou encore la durée d'excrétion variable. La présentation clinique et radiologique des pneumonies aiguës communautaires ne permet pas toujours de distinguer l'origine virale de l'origine bactérienne. L'absence de réelle conséquence thérapeutique semble un frein à l'utilisation des PCR multiplex dans la pratique quotidienne. Toutefois, l'amélioration en termes de délai de rendu des résultats et du nombre de pathogènes inclus dans les panels, ainsi que l'accumulation récente de données épidémiologiques et cliniques, devraient aider à rationaliser l'utilisation de ces tests, faciliter l'interprétation de leurs résultats et guider l'utilisation des molécules antivirales en développement.

10.
Sci Rep ; 12(1): 1094, 2022 01 20.
Article in English | MEDLINE | ID: covidwho-1634513

ABSTRACT

France went through three deadly epidemic waves due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing major public health and socioeconomic issues. We proposed to study the course of the pandemic along 2020 from the outlook of two major Parisian hospitals earliest involved in the fight against COVID-19. Genome sequencing and phylogenetic analysis were performed on samples from patients and health care workers (HCWs) from Bichat (BCB) and Pitié-Salpêtrière (PSL) hospitals. A tree-based phylogenetic clustering method and epidemiological data were used to investigate suspected nosocomial transmission clusters. Clades 20A, 20B and 20C were prevalent during the spring wave and, following summer, clades 20A.EU2 and 20E.EU1 emerged and took over. Phylogenetic clustering identified 57 potential transmission clusters. Epidemiological connections between participants were found for 17 of these, with a higher proportion of HCWs. The joint presence of HCWs and patients suggest viral contaminations between these two groups. We provide an enhanced overview of SARS-CoV-2 phylogenetic changes over 2020 in the Paris area, one of the regions with highest incidence in France. Despite the low genetic diversity displayed by the SARS-CoV-2, we showed that phylogenetic analysis, along with comprehensive epidemiological data, helps to identify and investigate healthcare associated clusters.


Subject(s)
COVID-19 , Genome, Viral , Phylogeny , SARS-CoV-2/genetics , Adult , Aged , COVID-19/epidemiology , COVID-19/genetics , COVID-19/transmission , Female , Humans , Male , Middle Aged , Paris/epidemiology , Retrospective Studies
11.
M�decine et Maladies Infectieuses Formation ; 2022.
Article in French | ScienceDirect | ID: covidwho-1634861

ABSTRACT

Résumé L’émergence du SARS-CoV-2 a renforcé l'intérêt pour la place des virus respiratoires, dans les pneumonies aiguës communautaires, en mettant en exergue de nombreux points encore mal connus tels que la part des infections asymptomatiques, les interactions entre virus respiratoires et pathogènes non viraux, leurs périodes d'incubation, leur pathogénicité ou encore la durée d'excrétion variable. La présentation clinique et radiologique des pneumonies aiguës communautaires ne permet pas toujours de distinguer l'origine virale de l'origine bactérienne. L'absence de réelle conséquence thérapeutique semble un frein à l'utilisation des PCR multiplex dans la pratique quotidienne. Toutefois, l'amélioration en termes de délai de rendu des résultats et du nombre de pathogènes inclus dans les panels, ainsi que l'accumulation récente de données épidémiologiques et cliniques, devraient aider à rationaliser l'utilisation de ces tests, faciliter l'interprétation de leurs résultats et guider l'utilisation des molécules antivirales en développement. The emergence of SARS-CoV-2 has reinforced the growing interest in the role of respiratory viruses in community-acquired pneumonia, in highlighting many points that are still poorly understood, such as the proportion of asymptomatic infections, the interactions between respiratory viruses and non-viral pathogens, their incubation periods and pathogenicity, and the variable duration of excretion. The clinical and radiological presentation of acute community-acquired pneumonia does not always make it possible to distinguish viral from bacterial etiology. The lack of therapeutic options in viral infections seems to be a brake on the use of multiplex PCR in daily practice. The improvement of turnaround time and number of pathogens included in the panels, as well as the growing body of epidemiological and clinical data, should help rationalize the use of these tests, facilitate the interpretation of their results and guide the use of antiviral treatments in development.

12.
Front Cell Infect Microbiol ; 11: 792202, 2021.
Article in English | MEDLINE | ID: covidwho-1595214

ABSTRACT

Since its emergence in China at the end of 2019, SARS-CoV-2 has rapidly spread across the world to become a global public health emergency. Since then, the pandemic has evolved with the large worldwide emergence of new variants, such as the Alpha (B.1.1.7 variant), Beta (B.1.351 variant), and Gamma (P.1 variant), and some other under investigation such as the A.27 in France. Many studies are focusing on antibody neutralisation changes according to the spike mutations, but to date, little is known regarding their respective replication capacities. In this work, we demonstrate that the Alpha variant provides an earlier replication in vitro, on Vero E6 and A549 cells, than Beta, Gamma, A.27, and historical lineages. This earlier replication was associated with higher infectious titres in cell-culture supernatants, in line with the higher viral loads observed among Alpha-infected patients. Interestingly, Beta and Gamma variants presented similar kinetic and viral load than the other non-Alpha-tested variants.


Subject(s)
COVID-19 , SARS-CoV-2 , Viral Load , COVID-19/virology , Humans , Kinetics , Pandemics
13.
PLoS One ; 16(12): e0260187, 2021.
Article in English | MEDLINE | ID: covidwho-1571986

ABSTRACT

To date, there is limited information about the presence of SARS-CoV-2 in semen especially in the acute phase of the infection. While available data from cohort studies including a total of 342 patients in the acute or recovery phase of the infection are reassuring, one study mentioned detecting virus in the semen of 6/38 COVID-19 patients. Here we assessed SARS-CoV-2 presence in the semen of COVID-19 positive patients in the acute stage of infection, within 24 hours of the positive nasopharyngeal swabs. Semen, seminal plasma and spermatozoa pellet were screened for SARS-CoV-2 and manual or airborne contamination during semen sampling. Among the 32 COVID-19 volunteers, the median interval from the onset of symptoms to semen collection was 4 days [IQR: 0-8]. Only one presented positive SARS-CoV-2 PCR in semen and seminal plasma fractions, although the spermatozoa pellet was negative. Viral cultures were all negative. We observed slightly higher concentrations of bacterial DNA in the SARS-CoV-2 positive specimen than in all negative samples. The bacteria identified neither confirm nor rule out contamination by oropharyngeal secretions during collection. SARS-CoV-2 was rarely present in semen during the acute phase of the disease. This very rare situation could be connected to oral or manual contamination during semen collection. The possible presence of SARS-CoV-2 in semen calls for nasopharyngeal viral testing and strict hygiene protocols during semen collection before assisted reproductive attempts.


Subject(s)
COVID-19/virology , SARS-CoV-2/isolation & purification , Semen/chemistry , Spermatozoa/chemistry , Adult , Humans , Male , Middle Aged , Nasopharynx/virology , Semen/virology , Specimen Handling , Spermatozoa/virology
15.
Anaesth Crit Care Pain Med ; 41(1): 100998, 2022 02.
Article in English | MEDLINE | ID: covidwho-1561582

Subject(s)
COVID-19 , SARS-CoV-2 , Humans
17.
J Antimicrob Chemother ; 76(Supplement_3): iii20-iii27, 2021 Sep 23.
Article in English | MEDLINE | ID: covidwho-1493833

ABSTRACT

BACKGROUND: Virus-associated respiratory infections are in the spotlight with the emergence of SARS-CoV-2 and the expanding use of multiplex PCR (mPCR). The impact of molecular testing as a point-of-care test (POCT) in the emergency department (ED) is still unclear. OBJECTIVES: To compare the impact of a syndromic test performed in the ED as a POCT and in the central laboratory on length of stay (LOS), antibiotic use and single-room assignment. METHODS: From 19 November 2019 to 9 March 2020, adults with acute respiratory illness seeking care in the ED of a large hospital were enrolled, with mPCR performed with a weekly alternation in the ED as a POCT (week A) or in the central laboratory (week B). RESULTS: 474 patients were analysed: 275 during A weeks and 199 during B weeks. Patient characteristics were similar. The hospital LOS (median 7 days during week A versus 7 days during week B, P = 0.29), the proportion of patients with ED-LOS <1 day (63% versus 60%, P = 0.57) and ED antibiotic prescription (59% versus 58%, P = 0.92) were not significantly different. Patients in the POCT arm were more frequently assigned a single room when having a positive PCR for influenza, respiratory syncytial virus and metapneumovirus [52/70 (74%) versus 19/38 (50%) in the central testing arm, P = 0.012]. CONCLUSIONS: Syndromic testing performed in the ED compared with the central laboratory failed to reduce the LOS or antibiotic consumption in patients with acute respiratory illness, but was associated with an increased single-room assignment among patients in whom a significant respiratory pathogen was detected.


Subject(s)
COVID-19 , Point-of-Care Systems , Adult , Emergency Service, Hospital , Humans , Length of Stay , Point-of-Care Testing , SARS-CoV-2
20.
Clin Infect Dis ; 73(6): e1337-e1344, 2021 09 15.
Article in English | MEDLINE | ID: covidwho-1411827

ABSTRACT

BACKGROUND: Humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs within the first weeks after coronavirus disease 2019 (COVID-19). Those antibodies exert a neutralizing activity against SARS-CoV-2, whose evolution over time after COVID-19 as well as efficiency against novel variants are poorly characterized. METHODS: In this prospective study, sera of 107 patients hospitalized with COVID-19 were collected at 3 and 6 months postinfection. We performed quantitative neutralization experiments on top of high-throughput serological assays evaluating anti-spike (S) and anti-nucleocapsid (NP) immunoglobulin G (IgG). RESULTS: Levels of seroneutralization and IgG rates against the ancestral strain decreased significantly over time. After 6 months, 2.8% of the patients had a negative serological status for both anti-S and anti-NP IgG. However, all sera had a persistent and effective neutralizing effect against SARS-CoV-2. IgG levels correlated with seroneutralization, and this correlation was stronger for anti-S than for anti-NP antibodies. The level of seroneutralization quantified at 6 months correlated with markers of initial severity, notably admission to intensive care units and the need for mechanical invasive ventilation. In addition, sera collected at 6 months were tested against multiple SARS-CoV-2 variants and showed efficient neutralizing effects against the D614G, B.1.1.7, and P.1 variants but significantly weaker activity against the B.1.351 variant. CONCLUSIONS: Decrease in IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7, and P.1 variants for at least 6 months in patients previously hospitalized for COVID-19. A weaker protection was, however, observed for the B.1.351 variant.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Hospitalization , Humans , Prospective Studies , Spike Glycoprotein, Coronavirus
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