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1.
Viruses ; 13(12)2021 12 16.
Article in English | MEDLINE | ID: covidwho-1580428

ABSTRACT

BACKGROUND: We aimed to compare the clinical severity in patients who were coinfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and rhinovirus or monoinfected with a single one of these viruses. METHODS: The study period ranged from 1 March 2020 to 28 February 2021 (one year). SARS-CoV-2 and other respiratory viruses were identified by real-time reverse-transcription-PCR as part of the routine work at Marseille University hospitals. Bacterial and fungal infections were detected by standard methods. Clinical data were retrospectively collected from medical files. This study was approved by the ethical committee of our institute. RESULTS: A total of 6034/15,157 (40%) tested patients were positive for at least one respiratory virus. Ninety-three (4.3%) SARS-CoV-2-infected patients were coinfected with another respiratory virus, with rhinovirus being the most frequent (62/93, 67%). Patients coinfected with SARS-CoV-2 and rhinovirus were significantly more likely to report a cough than those with SARS-CoV-2 monoinfection (62% vs. 31%; p = 0.0008). In addition, they were also significantly more likely to report dyspnea than patients with rhinovirus monoinfection (45% vs. 36%; p = 0.02). They were also more likely to be transferred to an intensive care unit and to die than patients with rhinovirus monoinfection (16% vs. 5% and 7% vs. 2%, respectively) but these differences were not statistically significant. CONCLUSIONS: A close surveillance and investigation of the co-incidence and interactions of SARS-CoV-2 and other respiratory viruses is needed. The possible higher risk of increased clinical severity in SARS-CoV-2-positive patients coinfected with rhinovirus warrants further large scale studies.


Subject(s)
COVID-19/epidemiology , Coinfection/epidemiology , Coinfection/virology , Picornaviridae Infections/epidemiology , Adolescent , Adult , Aged , COVID-19/diagnosis , Child , Coinfection/diagnosis , Female , Humans , Incidence , Male , Middle Aged , Picornaviridae Infections/diagnosis , Picornaviridae Infections/virology , Real-Time Polymerase Chain Reaction , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Retrospective Studies , Rhinovirus , SARS-CoV-2 , Severity of Illness Index , Young Adult
2.
5.
Rev Cardiovasc Med ; 22(3): 1063-1072, 2021 09 24.
Article in English | MEDLINE | ID: covidwho-1439023

ABSTRACT

We evaluated the age-specific mortality of unselected adult outpatients infected with SARS-CoV-2 treated early in a dedicated COVID-19 day hospital and we assessed whether the use of hydroxychloroquine (HCQ) + azithromycin (AZ) was associated with improved survival in this cohort. A retrospective monocentric cohort study was conducted in the day hospital of our center from March to December 2020 in adults with PCR-proven infection who were treated as outpatients with a standardized protocol. The primary endpoint was 6-week mortality, and secondary endpoints were transfer to the intensive care unit and hospitalization rate. Among 10,429 patients (median age, 45 [IQR 32-57] years; 5597 [53.7%] women), 16 died (0.15%). The infection fatality rate was 0.06% among the 8315 patients treated with HCQ+AZ. No deaths occurred among the 8414 patients younger than 60 years. Older age and male sex were associated with a higher risk of death, ICU transfer, and hospitalization. Treatment with HCQ+AZ (0.17 [0.06-0.48]) was associated with a lower risk of death, independently of age, sex and epidemic period. Meta-analysis evidenced consistency with 4 previous outpatient studies (32,124 patients-Odds ratio 0.31 [0.20-0.47], I2 = 0%). Early ambulatory treatment of COVID-19 with HCQ+AZ as a standard of care is associated with very low mortality, and HCQ+AZ improve COVID-19 survival compared to other regimens.


Subject(s)
Ambulatory Care , Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Early Medical Intervention , Hydroxychloroquine/therapeutic use , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Antiviral Agents/adverse effects , Azithromycin/adverse effects , COVID-19/diagnosis , COVID-19/mortality , Drug Therapy, Combination , Female , France , Hospitalization , Humans , Hydroxychloroquine/adverse effects , Male , Middle Aged , Outpatients , Retrospective Studies , Risk Assessment , Risk Factors , Sex Factors , Time Factors , Treatment Outcome , Young Adult
6.
Infect Genet Evol ; 95: 105092, 2021 11.
Article in English | MEDLINE | ID: covidwho-1433676

ABSTRACT

OBJECTIVES: To compare the demographics, clinical characteristics and severity of patients infected with nine different SARS-CoV-2 variants, during three phases of the COVID-19 epidemic in Marseille. METHODS: A single centre retrospective cohort study was conducted in 1760 patients infected with SARS-CoV-2 of Nextstrain clades 20A, 20B, and 20C (first phase, February-May 2020), Pangolin lineages B.1.177 (we named Marseille-2) and B.1.160 (Marseille-4) variants (second phase, June-December 2020), and B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma) and A.27 (Marseille-501) variants (third phase, January 2021-today). Outcomes were the occurrence of clinical failures, including hospitalisation, transfer to the intensive-care unit, and death. RESULTS: During each phase, no major differences were observed with regards to age and gender distribution, the prevalence of chronic diseases, and clinical symptoms between variants circulating in a given phase. The B.1.177 and B.1.160 variants were associated with more severe outcomes. Infections occurring during the second phase were associated with a higher rate of death as compared to infections during the first and third phases. Patients in the second phase were more likely to be hospitalised than those in the third phase. Patients infected during the third phase were more frequently obese than others. CONCLUSION: A large cohort study is recommended to evaluate the transmissibility and to better characterise the clinical severity of emerging variants.


Subject(s)
COVID-19/pathology , Diabetes Mellitus/pathology , Genome, Viral , Hypertension/pathology , Obesity/pathology , SARS-CoV-2/pathogenicity , Adult , Aged , COVID-19/epidemiology , COVID-19/mortality , COVID-19/virology , Comorbidity , Diabetes Mellitus/epidemiology , Diabetes Mellitus/mortality , Diabetes Mellitus/virology , Female , France/epidemiology , Genotype , Heart Diseases/epidemiology , Heart Diseases/mortality , Heart Diseases/pathology , Heart Diseases/virology , Hospitalization/statistics & numerical data , Hospitals , Humans , Hypertension/epidemiology , Hypertension/mortality , Hypertension/virology , Intensive Care Units , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/mortality , Neoplasms/pathology , Neoplasms/virology , Obesity/epidemiology , Obesity/mortality , Obesity/virology , Phylogeny , Retrospective Studies , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Sequence Analysis, RNA , Severity of Illness Index , Survival Analysis
7.
J Clin Med ; 10(13)2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1403797

ABSTRACT

(1) Background: We collected COVID-19 mortality data and the age distribution of the deceased in France and other European countries, as well as specifically in the cities of Paris and Marseille, and compared them. (2) Methods: Data on mortality related to COVID-19 and the associated age distribution were collected from government institutions in various European countries. In France, data were obtained from INSEE and Santé Publique France. All-cause mortality was also examined in order to study potential excess mortality using EuroMOMO. The Marseille data came from the epidemiological surveillance system. (3) Results: France is one of the European countries most impacted by COVID-19. Its proportion of deaths in people under 60 years of age is higher (6.5%) than that of Italy (4.6%) or Spain (4.7%). Excess mortality (5% more deaths) was also observed. Ile-de-France and the Grand-Est are the two French regions with the highest mortality. The proportion of deaths in the under-60 age group was considerable in Ile-de-France (9.9% vs. 4.5% in the Southern region). There are significantly higher numbers of patients hospitalized, in intensive care and deceased in Paris than in Marseille. (4) Conclusions: No patient management, i.e., from screening to diagnosis, including biological assessment and clinical examination, likely explains the high mortality associated with COVID-19.

9.
Travel Med Infect Dis ; 43: 102122, 2021.
Article in English | MEDLINE | ID: covidwho-1392589
11.
Journal of Clinical Virology Plus ; : 100036, 2021.
Article in English | ScienceDirect | ID: covidwho-1347691

ABSTRACT

We conducted this meta-analysis to determine the proportion of co-infection with influenza viruses in SARS-CoV-2 positive patients and to investigate the severity of COVID-19 in these patients. We included studies with SARS-CoV-2 infection confirmed by qRT-PCR and influenza virus infection (A and/or B) by nucleic acid tests. The proportion of co-infection was compared between children and adults, and between critically ill or deceased patients compared to overall patients. Fifty-four articles were included. The overall proportion of co-infection was 0.7%, 95%CI = [0.4 – 1.3]. Most influenza co-infections were due to the influenza A virus (74.4%). The proportion of co-infection with influenza viruses among children (3.2%, 95% CI = [0.9 – 10.9]) was significantly higher than that in adult patients (0.3%, 95% CI = [0.1 – 1.2]), p-value <0.01. The proportion of co-infection with influenza viruses among critically ill patients tended to be higher than that in overall patients (2.2%, 95% CI = [0.3 – 22.4] versus 0.6%, 95% CI = [0.3 – 1.2], respectively, p-value = 0.22). Screening for pathogens in co-infection, particularly influenza viruses in patients infected with SARS-CoV-2, is necessary. This warrants close surveillance and investigation of the co-incidences and interactions of SARS-CoV-2 and other respiratory viruses, which is facilitated by the expansion of syndromic diagnosis approaches through the use of multiplex PCR assays.

13.
J Clin Med ; 10(15)2021 Jul 24.
Article in English | MEDLINE | ID: covidwho-1325716

ABSTRACT

Since summer 2020, SARS-CoV-2 strains at the origin of the COVID-19 pandemic have suddenly been replaced by new SARS-CoV-2 variants, some of which are highly transmissible and spread at a high rate. These variants include the Marseille-4 lineage (Nextclade 20A.EU2) in Europe, the 20I/501Y.V1 variant first detected in the UK, the 20H/501Y.V2 variant first detected in South Africa, and the 20J/501Y.V3 variant first detected in Brazil. These variants are characterized by multiple mutations in the viral spike protein that is targeted by neutralizing antibodies elicited in response to infection or vaccine immunization. The usual coronavirus mutation rate through genetic drift alone cannot account for such rapid changes. Recent reports of the occurrence of such mutations in immunocompromised patients who received remdesivir and/or convalescent plasma or monoclonal antibodies to treat prolonged SARS-CoV-2 infections led us to hypothesize that experimental therapies that fail to cure the patients from COVID-19 could favor the emergence of immune escape SARS-CoV-2 variants. We review here the data that support this hypothesis and urge physicians and clinical trial promoters to systematically monitor viral mutations by whole-genome sequencing for patients who are administered these treatments.

14.
J Clin Med ; 10(12)2021 Jun 15.
Article in English | MEDLINE | ID: covidwho-1270066

ABSTRACT

BACKGROUND: We conducted this review to summarize the relation between viral mutation and infectivity of SARS-CoV-2 and also the severity of COVID-19 in vivo and in vitro. METHOD: Articles were identified through a literature search until 31 May 2021, in PubMed, Web of Science and Google Scholar. RESULTS: Sixty-three studies were included. To date, most studies showed that the viral mutations, especially the D614G variant, correlate with a higher infectivity than the wild-type virus. However, the evidence of the association between viral mutation and severity of the disease is scant. A SARS-CoV-2 variant with a 382-nucleotide deletion was associated with less severe infection in patients. The 11,083G > U mutation was significantly associated with asymptomatic patients. By contrast, ORF1ab 4715L and S protein 614G variants were significantly more frequent in patients from countries where high fatality rates were also reported. The current evidence showed that variants of concern have led to increased infectivity and deteriorating epidemiological situations. However, the relation between this variant and severity of COVID-19 infection was contradictory. CONCLUSION: The COVID-19 pandemic continues to spread worldwide. It is necessary to anticipate large clinical cohorts to evaluate the virulence and transmissibility of SARS-CoV-2 mutants.

16.
Clin Microbiol Infect ; 27(10): 1516.e1-1516.e6, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1240263

ABSTRACT

OBJECTIVES: To compare the clinical and epidemiological aspects associated with different predominant lineages circulating in Marseille from March 2020 to January 2021. METHODS: In this single-centre retrospective cohort study, characteristics of patients infected with four different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were documented from medical files. The outcome was the occurrence of clinical failure, defined as hospitalization (for outpatients), transfer to the intensive care unit (inpatients) and death (all). RESULTS: A total of 254 patients were infected with clade 20A (20AS), 85 with Marseille-1 (M1V), 190 with Marseille-4 (M4V) and 211 with N501Y (N501YV) variants. 20AS presented a bell-shaped epidemiological curve and nearly disappeared around May 2020. M1V reached a very weak peak, then disappeared after six weeks. M4V appeared in July presented an atypical wave form for 7 months. N501YV has only recently appeared. Compared with 20AS, patients infected with M1V were less likely to report dyspnoea (adjusted odds ratio (OR) 0.50, p 0.04), rhinitis (aOR 0.57, p 0.04) and to be hospitalized (aOR 0.22, p 0.002). Patients infected with M4V were more likely to report fever than those with 20AS and M1V (aOR 2.49, p < 0.0001 and aOR 2.30, p 0.007, respectively) and to be hospitalized than those with M1V (aOR 4.81, p 0.003). Patients infected with N501YV reported lower rate of rhinitis (aOR 0.50, p 0.001) and anosmia (aOR 0.57, p 0.02), compared with those infected with 20AS. A lower rate of hospitalization was associated with N501YV infection compared with 20AS and M4V (aOR 0.33, p < 0.0001 and aOR 0.27, p < 0.0001, respectively). CONCLUSIONS: The four lineages have presentations that differ from one another, epidemiologically and clinically. This supports SARS-CoV-2 genomic surveillance through next-generation sequencing.


Subject(s)
COVID-19/epidemiology , COVID-19/pathology , SARS-CoV-2/pathogenicity , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/mortality , Child , Child, Preschool , Female , France/epidemiology , Genotype , Hospitalization , Humans , Infant , Infant, Newborn , Intensive Care Units , Male , Middle Aged , Odds Ratio , Retrospective Studies , SARS-CoV-2/classification , SARS-CoV-2/genetics , Severity of Illness Index , Young Adult
18.
Int J Infect Dis ; 106: 228-236, 2021 May.
Article in English | MEDLINE | ID: covidwho-1207034

ABSTRACT

BACKGROUND: In Marseille, France, following a first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in March-May 2020, a second epidemic phase occurred from June, involving 10 new variants. The Marseille-4 variant caused an epidemic that started in August and is still ongoing. METHODS: The 1038 SARS-CoV-2 whole genome sequences obtained in our laboratory by next-generation sequencing with Illumina technology were analysed using Nextclade and nextstrain/ncov pipelines and IQ-TREE. A Marseille-4-specific qPCR assay was implemented. Demographic and clinical features were compared between patients with the Marseille-4 variant and those with earlier strains. RESULTS: Marseille-4 harbours 13 hallmark mutations. One leads to an S477N substitution in the receptor binding domain of the spike protein targeted by current vaccines. Using a specific qPCR, it was observed that Marseille-4 caused 12-100% of SARS-CoV-2 infections in Marseille from September 2020, being involved in 2106 diagnoses. This variant was more frequently associated with hypoxemia than were clade 20A strains before May 2020. It caused a re-infection in 11 patients diagnosed with different SARS-CoV-2 strains before June 2020, suggesting either short-term protective immunity or a lack of cross-immunity. CONCLUSIONS: Marseille-4 should be considered as a major SARS-CoV-2 variant. Its sudden appearance points towards an animal reservoir, possibly mink. The protective role of past exposure and current vaccines against this variant should be evaluated.


Subject(s)
COVID-19/genetics , Genome, Viral , Mutation , SARS-CoV-2/genetics , Whole Genome Sequencing , Animals , COVID-19/virology , Epidemics , France/epidemiology , Humans , Mink/virology , Molecular Epidemiology , Phylogeny , Reinfection/virology
19.
Microb Drug Resist ; 27(3): 281-290, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1137930

ABSTRACT

The coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2, has recently emerged worldwide. In this context, there is an urgent need to identify safe and effective therapeutic strategies for treatment of such highly contagious disease. We recently reported promising results of combining hydroxychloroquine and azithromycin as an early treatment option. Although ongoing clinical trials are challenging the efficacy of this combination, many clinicians claim the authorization to or have already begun to use it to treat COVID-19 patients worldwide. The aim of this article is to share pharmacology considerations contributing to the rationale of this combination, and to provide safety information to prevent toxicity and drug-drug interactions, based on available evidence.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Hydroxychloroquine/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacology , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Antiviral Agents/pharmacology , Azithromycin/administration & dosage , Azithromycin/adverse effects , Azithromycin/pharmacology , Dose-Response Relationship, Drug , Drug Interactions , Drug Therapy, Combination , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Hydroxychloroquine/pharmacology , SARS-CoV-2
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