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Global Public Health in COVID-19: Pandemic Research from University Hospital Institute Méditerranée Infection

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Epidemiology & Public Health".

Deadline for manuscript submissions: closed (31 October 2021)

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Prof. Dr. Philippe Parola

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Guest Editor

University Hospital Institute Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13005 Marseille, France
Interests: medical entomology; ticks & tick-borne diseases; fleas & flea-borne diseases; lice & tick-borne diseases; emerging infectious diseases; vector borne diseases; tropical medicine; rickettsiology

Dr. Corneliu Petru Popescu

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Guest Editor

Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
Interests: emerging infectious diseases; tropical medicine; travel medicine; virology; central nervous system infections; zoonoses; COVID-19

Special Issue Information

Dear Colleagues,

SARS-CoV-2 spread rapidly in 2020, and the global pandemic of coronavirus disease 2019 (COVID-19) has since resulted in considerable unexpected mortality in Europe and America. Interestingly, one year after the first cases were detected in Africa, the mortality was still low in many countries of the continent, far below predictions. The COVID-19 public health impact has also been much lower in Asia. COVID-19 ranges from asymptomatic infection to acute respiratory distress syndrome with multisystem involvement, particularly in older individuals and individuals with co-morbidities. Specific clinical signs have also been described. Dramatic efforts have been made to develop diagnosis tests and make them available. Treatment options for COVID‐19, including drug repositioning (also called drug repurposing, involving the investigation of existing drugs for new therapeutic purposes) has resulted in passionate academic debate.

Regrouping patient care, diagnostics, research, and development, the University Hospital Institute Méditerranée Infection (IHU-MI) in Marseille France has been built to contain and understand contagion and fight emerging infectious diseases in a well-designed building. The principle of the IHU-MI is technological capacity, also in terms of human resources and applications, support of students, connections with southern countries through win-win collaborations, autonomy, and speed of decisions.

This Special Issue aims to offer a place to report some of the work carried out in the IHU-MI and welcomes original clinical research and reviews on COVID-19 pathogenesis, diagnosis, and management from international teams.

Prof. Dr. Philippe Parola
Dr. Corneliu Petru Popescu
Guest Editor

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Keywords

SARS-CoV-2
COVID-19
Emerging infectious diseases
Point-of-care
Drug repositioning
Diagnostic tools
Clinical features
Treatment

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Published Papers (11 papers)

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Research

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17 pages, 1803 KiB

Open AccessArticle

Consequences of the COVID-19 Outbreak Lockdown on Non-Viral Infectious Agents as Reported by a Laboratory-Based Surveillance System at the IHU Méditerranée Infection, Marseille, France

by Lanceï Kaba, Audrey Giraud-Gatineau, Marie-Thérèse Jimeno, Jean-Marc Rolain, Philippe Colson, Didier Raoult and Hervé Chaudet

J. Clin. Med. 2021, 10(15), 3210; https://doi.org/10.3390/jcm10153210 - 21 Jul 2021

Cited by 5 | Viewed by 2100

Abstract

The objective of this paper is to describe the surveillance system MIDaS and to show how this system has been used for evaluating the consequences of the French COVID-19 lockdown on the bacterial mix of AP-HM and the antibiotic resistance. MIDas is a kind of surveillance activity hub, allowing the automatic construction of surveillance control boards. We investigated the diversity and resistance of bacterial agents from respiratory, blood, and urine samples during the lockdown period (from week 12 to 35 of 2020), using the same period of years from 2017 to 2019 as control. Taking into account the drop in patient recruitment, several species have exhibited significant changes in their relative abundance (either increasing or decreasing) with changes up to 9%. The changes were more important for respiratory and urine samples than for blood samples. The relative abundance in respiratory samples for the whole studied period was higher during the lockdown. A significant increase in the percentage of wild phenotypes during the lockdown was observed for several species. The use of the MIDaS syndromic collection and surveillance system made it possible to efficiently detect, analyze, and follow changes of the microbiological population as during the lockdown period. Full article

(This article belongs to the Special Issue Global Public Health in COVID-19: Pandemic Research from University Hospital Institute Méditerranée Infection)

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9 pages, 1230 KiB

Open AccessArticle

In Vitro Evaluation of the Antiviral Activity of Methylene Blue Alone or in Combination against SARS-CoV-2

by Mathieu Gendrot, Priscilla Jardot, Océane Delandre, Manon Boxberger, Julien Andreani, Isabelle Duflot, Marion Le Bideau, Joel Mosnier, Isabelle Fonta, Sébastien Hutter, Bernard La Scola and Bruno Pradines

J. Clin. Med. 2021, 10(14), 3007; https://doi.org/10.3390/jcm10143007 - 6 Jul 2021

Cited by 9 | Viewed by 4640

Abstract

A new severe acute respiratory syndrome coronavirus (SARS-CoV-2) causing coronavirus diseases 2019 (COVID-19), which emerged in Wuhan, China in December 2019, has spread worldwide. Currently, very few treatments are officially recommended against SARS-CoV-2. Identifying effective, low-cost antiviral drugs with limited side effects that are affordable immediately is urgently needed. Methylene blue, a synthesized thiazine dye, may be a potential antiviral drug. Antiviral activity of methylene blue used alone or in combination with several antimalarial drugs or remdesivir was assessed against infected Vero E6 cells infected with two clinically isolated SARS-CoV-2 strains (IHUMI-3 and IHUMI-6). Effects both on viral entry in the cell and on post-entry were also investigated. After 48 h post-infection, the viral replication was estimated by RT-PCR. The median effective concentration (EC₅₀) and 90% effective concentration (EC₉₀) of methylene blue against IHUMI-3 were 0.41 ± 0.34 µM and 1.85 ± 1.41 µM, respectively; 1.06 ± 0.46 µM and 5.68 ± 1.83 µM against IHUMI-6. Methylene blue interacted at both entry and post-entry stages of SARS-CoV-2 infection in Vero E6 cells as retrieved for hydroxychloroquine. The effects of methylene blue were additive with those of quinine, mefloquine and pyronaridine. The combinations of methylene blue with chloroquine, hydroxychloroquine, desethylamodiaquine, piperaquine, lumefantrine, ferroquine, dihydroartemisinin and remdesivir were antagonist. These results support the potential interest of methylene blue to treat COVID-19. Full article

(This article belongs to the Special Issue Global Public Health in COVID-19: Pandemic Research from University Hospital Institute Méditerranée Infection)

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11 pages, 839 KiB

Open AccessArticle

Hydroxychloroquine and Azithromycin Treatment of Hospitalized Patients Infected with SARS-CoV-2 in Senegal from March to October 2020

by Fabien Taieb, Khardiata Diallo Mbaye, Billo Tall, Ndèye Aïssatou Lakhe, Cheikh Talla, Daouda Thioub, Amadou Moustapha Ndoye, Daye Ka, Aboubacry Gaye, Viviane Marie-Pierre Cissé Diallo, Ndongo Dia, Pape Samba Ba, Mamadou Cissé, Moustapha Diop, Cheikh Tidiane Diagne, Louise Fortes, Mamadou Diop, Ndèye Maguette Fall, Fatoumata Diène Sarr, Margarite Diatta, Mamadou Aliou Barry, Aboubakar Sidikh Badiane, Abdoulaye Seck, Philippe Dubrous, Ousmane Faye, Inès Vigan-Womas, Cheikh Loucoubar, Amadou Alpha Sall and Moussa Seydi Show full author list Hide full author list

J. Clin. Med. 2021, 10(13), 2954; https://doi.org/10.3390/jcm10132954 - 30 Jun 2021

Cited by 7 | Viewed by 10711

Abstract

As of today, little data is available on COVID-19 in African countries, where the case management relied mainly on a treatment by association between hydroxychloroquine (HCQ) and azithromycin (AZM). This study aimed to understand the main clinical outcomes of COVID-19 hospitalized patients in Senegal from March to October 20202. We described the clinical characteristics of patients and analysed clinical status (alive and discharged versus hospitalized or died) at 15 days after Isolation and Treatment Centres (ITC) admission among adult patients who received HCQ plus AZM and those who did not receive this combination. A total of 926 patients were included in this analysis. Six hundred seventy-four (674) (72.8%) patients received a combination of HCQ and AZM. Results showed that the proportion of patient discharge at D15 was significantly higher for patients receiving HCQ plus AZM (OR: 1.63, IC 95% (1.09–2.43)). Factors associated with a lower proportion of patients discharged alive were: age ≥ 60 years (OR: 0.55, IC 95% (0.36–0.83)), having of at least one pre-existing disorder (OR: 0.61, IC 95% (0.42–0.90)), and a high clinical risk at admission following NEWS score (OR: 0.49, IC 95% (0.28–0.83)). Few side effects were reported including 2 cases of cardiac rhythmic disorders in the HCQ and AZM group versus 13 in without HCQ + AZM. An improvement of clinical status at 15 days was found for patients exposed to HCQ plus AZM combination. Full article

(This article belongs to the Special Issue Global Public Health in COVID-19: Pandemic Research from University Hospital Institute Méditerranée Infection)

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17 pages, 1503 KiB

Open AccessArticle

Evaluation of Strategies to Fight COVID-19: The French Paradigm

by Audrey Giraud-Gatineau, Philippe Gautret, Philippe Colson, Hervé Chaudet and Didier Raoult

J. Clin. Med. 2021, 10(13), 2942; https://doi.org/10.3390/jcm10132942 - 30 Jun 2021

Cited by 3 | Viewed by 11190

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. Full article

(This article belongs to the Special Issue Global Public Health in COVID-19: Pandemic Research from University Hospital Institute Méditerranée Infection)

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10 pages, 956 KiB

Open AccessArticle

COVID-19 Management at IHU Méditerranée Infection: A One-Year Experience

by Philippe Brouqui, Michel Drancourt, Didier Raoult and on behalf of the IHU Task Force

J. Clin. Med. 2021, 10(13), 2881; https://doi.org/10.3390/jcm10132881 - 29 Jun 2021

Cited by 2 | Viewed by 4776

Abstract

Background: The Hospital-University Institute (IHU) Méditerranée Infection features a 27,000 square meter building hosting 700 employees and 75 hospitalized patients in the center of Marseille, France. Method: Previous preparedness in contagious disease management allowed the IHU to manage the COVID-19 outbreak by continuing adaptation for optimal diagnosis, care and outcome. We report here the output of this management. Results: From 5 March 2020, and 26 April 2021, 608,313 PCR tests were provided for 424,919 patients and 44,089 returned positive. A total of 23,390 patients with COVID-19 were followed at IHU with an overall case fatality ratio of 1.7%. Of them 20,270 were followed as outpatients with an overall CFR of 0.17%. We performed 24,807 EKG, 5759 low dose CT Scanner, and 18,344 serology. Of the 7643 nasopharyngeal samples inoculated in cell cultures 3317 (43.3%) yielded SARS-Cov-2 isolates. Finally, 7370 SARS-Cov-2 genomes were analyzed, allowing description of the first genetic variants and their implication in the epidemiologic curves. Continuous clinical care quality evaluation provided the opportunity for 155 publications allowing a better understanding of the disease and improvement of care and 132 videos posted on the IHU Facebook network, totaling 60 million views and 390,000 followers, and dealing with COVID-19, outbreaks, epistemology, and ethics in medicine. Conclusions: During this epidemic, IHU Méditerranée Infection played the role for which it has been created; useful clinical research to guarantee a high-quality diagnostic and care for patient and a recognized expertise. Full article

(This article belongs to the Special Issue Global Public Health in COVID-19: Pandemic Research from University Hospital Institute Méditerranée Infection)

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7 pages, 976 KiB

Open AccessArticle

Isolation of Viable SARS-CoV-2 Virus from Feces of an Immunocompromised Patient Suggesting a Possible Fecal Mode of Transmission

by Julie Dergham, Jeremy Delerce, Marielle Bedotto, Bernard La Scola and Valérie Moal

J. Clin. Med. 2021, 10(12), 2696; https://doi.org/10.3390/jcm10122696 - 18 Jun 2021

Cited by 37 | Viewed by 4212

Abstract

(1) Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) excretion in stools is well documented by RT-PCR, but evidences that stools contain infectious particles are scarce. (2) Methods: After observing a Corona Virus 2019 Disease (COVID-19) epidemic cluster associated with a ruptured sewage pipe, we search for such a viable SARS-CoV-2 particle in stool by inoculating 106 samples from 46 patients. (3) Results: We successfully obtained two isolates from a unique patient with kidney transplantation under immunosuppressive therapy who was admitted for severe diarrhea. (4) Conclusions: This report emphasizes that SARS-CoV-2 is an enteric virus, and infectious virus particles can be isolated from the stool of immune-compromised patients like, in our case, kidney transplant recipient. Immune-compromised patients are likely to have massive multiplication of the virus in the gastrointestinal tract and this report suggests possible fecal transmission of SARS-CoV-2. Full article

(This article belongs to the Special Issue Global Public Health in COVID-19: Pandemic Research from University Hospital Institute Méditerranée Infection)

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5 pages, 532 KiB

Open AccessCommunication

Rapid Isothermal Amplification for the Buccal Detection SARS-CoV-2 in the Context of Out-Patient COVID-19 Screening

by Amar Bouam, Jean-Jacques Vincent, Elisabeth Le Glass, Lionel Almeras, Pierre-Yves Levy, Hervé Tissot-Dupont, Jean-Christophe Lagier, Pierre-Edward Fournier, Didier Raoult and Michel Drancourt

J. Clin. Med. 2021, 10(12), 2643; https://doi.org/10.3390/jcm10122643 - 16 Jun 2021

Viewed by 2654

Abstract

A commercially available isothermal amplification of SARS-CoV-2 RNA was applied to self-collected saliva samples using dry dental cotton rolls, which were held in the mouth for two minutes. Of 212 tests, isothermal amplification yielded three (0.14%) invalid results, 120 (56.6%) positive results and 89 (42%) negative results. Compared to reference RT-PCR assays routinely performed simultaneously on nasopharyngeal swabs, excluding the three invalid isothermal amplification assays and one RT-PCR invalid assay, these figures indicated that 119/123 (96.7%) samples were positive in both methods and 85/85 samples were negative in both methods. Four positive buccal swabs which were missed by the isothermal amplification, exhibited Ct values of 26–34 in reference RT-PCR assays. Positive isothermal amplification detection was achieved in less than 10 min. Supervision of the self-sampling procedure was key to achieve these performances. These data support the proposal to use the protocol reported in this paper, including supervised buccal self-sampling, to screen people suspected of having COVID-19 at the point of care. Full article

(This article belongs to the Special Issue Global Public Health in COVID-19: Pandemic Research from University Hospital Institute Méditerranée Infection)

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10 pages, 2176 KiB

Open AccessArticle

Contagion Management at the Méditerranée Infection University Hospital Institute

by Pierre-Edouard Fournier, Sophie Edouard, Nathalie Wurtz, Justine Raclot, Marion Bechet, Christine Zandotti, Véronique Filosa, Didier Raoult and Florence Fenollar

J. Clin. Med. 2021, 10(12), 2627; https://doi.org/10.3390/jcm10122627 - 15 Jun 2021

Cited by 2 | Viewed by 3225

Abstract

The Méditerranée Infection University Hospital Institute (IHU) is located in a recent building, which includes experts on a wide range of infectious disease. The IHU strategy is to develop innovative tools, including epidemiological monitoring, point-of-care laboratories, and the ability to mass screen the population. In this study, we review the strategy and guidelines proposed by the IHU and its application to the COVID-19 pandemic and summarise the various challenges it raises. Early diagnosis enables contagious patients to be isolated and treatment to be initiated at an early stage to reduce the microbial load and contagiousness. In the context of the COVID-19 pandemic, we had to deal with a shortage of personal protective equipment and reagents and a massive influx of patients. Between 27 January 2020 and 5 January 2021, 434,925 nasopharyngeal samples were tested for the presence of SARS-CoV-2. Of them, 12,055 patients with COVID-19 were followed up in our out-patient clinic, and 1888 patients were hospitalised in the Institute. By constantly adapting our strategy to the ongoing situation, the IHU has succeeded in expanding and upgrading its equipment and improving circuits and flows to better manage infected patients. Full article

(This article belongs to the Special Issue Global Public Health in COVID-19: Pandemic Research from University Hospital Institute Méditerranée Infection)

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Review

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15 pages, 1615 KiB

Open AccessReview

A Possible Role of Remdesivir and Plasma Therapy in the Selective Sweep and Emergence of New SARS-CoV-2 Variants

by Philippe Colson, Christian A. Devaux, Jean-Christophe Lagier, Philippe Gautret and Didier Raoult

J. Clin. Med. 2021, 10(15), 3276; https://doi.org/10.3390/jcm10153276 - 24 Jul 2021

Cited by 16 | Viewed by 3912

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. Full article

(This article belongs to the Special Issue Global Public Health in COVID-19: Pandemic Research from University Hospital Institute Méditerranée Infection)

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35 pages, 1041 KiB

Open AccessReview

SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence

by Thi Loi Dao, Van Thuan Hoang, Philippe Colson, Jean Christophe Lagier, Matthieu Million, Didier Raoult, Anthony Levasseur and Philippe Gautret

J. Clin. Med. 2021, 10(12), 2635; https://doi.org/10.3390/jcm10122635 - 15 Jun 2021

Cited by 35 | Viewed by 4525

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. Full article

(This article belongs to the Special Issue Global Public Health in COVID-19: Pandemic Research from University Hospital Institute Méditerranée Infection)

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11 pages, 1479 KiB

Open AccessReview

Low Dose Chest CT and Lung Ultrasound for the Diagnosis and Management of COVID-19

by Julie Finance, Laurent Zieleskewicz, Paul Habert, Alexis Jacquier, Philippe Parola, Alain Boussuges, Fabienne Bregeon and Carole Eldin

J. Clin. Med. 2021, 10(10), 2196; https://doi.org/10.3390/jcm10102196 - 19 May 2021

Cited by 11 | Viewed by 6276

Abstract

Background: The COVID-19 pandemic has provided an opportunity to use low- and non-radiating chest imaging techniques on a large scale in the context of an infectious disease, which has never been done before. Previously, low-dose techniques were rarely used for infectious diseases, despite the recognised danger of ionising radiation. Method: To evaluate the role of low-dose computed tomography (LDCT) and lung ultrasound (LUS) in managing COVID-19 pneumonia, we performed a review of the literature including our cases. Results: Chest LDCT is now performed routinely when diagnosing and assessing the severity of COVID-19, allowing patients to be rapidly triaged. The extent of lung involvement assessed by LDCT is accurate in terms of predicting poor clinical outcomes in COVID-19-infected patients. Infectious disease specialists are less familiar with LUS, but this technique is also of great interest for a rapid diagnosis of patients with COVID-19 and is effective at assessing patient prognosis. Conclusions: COVID-19 is currently accelerating the transition to low-dose and “no-dose” imaging techniques to explore infectious pneumonia and their long-term consequences. Full article

(This article belongs to the Special Issue Global Public Health in COVID-19: Pandemic Research from University Hospital Institute Méditerranée Infection)

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