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9 pages, 2827 KiB

Open AccessArticle

Third Early “Booster” Dose Strategy in France of bnt162b2 SARS-CoV-2 Vaccine in Allogeneic Hematopoietic Stem Cell Transplant Recipients Enhances Neutralizing Antibody Responses

by Abdelhakim Ahmed-Belkacem, Rabah Redjoul, Rozenn Brillet, Nazim Ahnou, Mathieu Leclerc, Dennis Salomón López-Molina, Alexandre Soulier, Aurélie Gourgeon, Christophe Rodriguez, Sébastien Maury, Jean-Michel Pawlotsky and Slim Fourati

Viruses 2022, 14(9), 1928; https://doi.org/10.3390/v14091928 - 30 Aug 2022

Cited by 5 | Viewed by 1810

Abstract

Immunocompromised individuals generally fail to mount efficacious immune humoral responses following vaccination. The emergence of SARS-CoV-2 variants of concern has raised the question as to whether levels of anti-spike protein antibodies achieved after two or three doses of the vaccine efficiently protect against [...] Read more.

Immunocompromised individuals generally fail to mount efficacious immune humoral responses following vaccination. The emergence of SARS-CoV-2 variants of concern has raised the question as to whether levels of anti-spike protein antibodies achieved after two or three doses of the vaccine efficiently protect against breakthrough infection in the context of immune suppression. We used a fluorescence-based neutralization assay to test the sensitivity of SARS-CoV-2 variants (ancestral variant, Beta, Delta, and Omicron BA.1) to the neutralizing response induced by vaccination in highly immunosuppressed allogeneic HSCT recipients, tested after two and three doses of the BNT162b2 vaccine. We show that neutralizing antibody responses to the Beta and Delta variants in most immunocompromised HSCT recipients increased after three vaccine doses up to values similar to those observed in twice-vaccinated healthy adults and were significantly lower against Omicron BA.1. Overall, neutralization titers correlated with the amount of anti-S-RBD antibodies measured by means of enzyme immunoassay, indicating that commercially available assays can be used to quantify the anti-S-RBD antibody response as a reliable surrogate marker of humoral immune protection in both immunocompetent and immunocompromised individuals. Our findings support the recommendation of additional early vaccine doses as a booster of humoral neutralizing activity against emerging variants, in HSCT immunocompromised patients. In the context of Omicron circulation, it further emphasizes the need for reinforcement of preventive measures including the administration of monoclonal antibodies in this high-risk population. Full article

(This article belongs to the Special Issue SARS-CoV-2 Research in France)

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14 pages, 893 KiB

Open AccessArticle

SARS-CoV-2 Genomic Characteristics and Clinical Impact of SARS-CoV-2 Viral Diversity in Critically Ill COVID-19 Patients: A Prospective Multicenter Cohort Study

by Slim Fourati, Etienne Audureau, Romain Arrestier, Stéphane Marot, Claire Dubois, Guillaume Voiriot, Charles-Edouard Luyt, Tomas Urbina, Julien Mayaux, Anne-Marie Roque-Afonso, Tài Pham, Luce Landraud, Benoit Visseaux, Damien Roux, Raphael Bellaiche, Anne-Sophie L’honneur, Zakaria Ait Hamou, Ségolène Brichler, Stéphane Gaudry, Maud Salmona, Raphaël Clere-Jehl, Elie Azoulay, Laurence Morand-Joubert, Anne-Geneviève Marcelin, Marie-Laure Chaix, Diane Descamps, Armand Mekontso Dessap, Christophe Rodriguez, Jean-Michel Pawlotsky and Nicolas de Prost Show full author list Hide full author list

Viruses 2022, 14(7), 1529; https://doi.org/10.3390/v14071529 - 13 Jul 2022

Cited by 5 | Viewed by 1651

Abstract

The SARS-CoV-2 variant of concern, α, spread worldwide at the beginning of 2021. It was suggested that this variant was associated with a higher risk of mortality than other variants. We aimed to characterize the genetic diversity of SARS-CoV-2 variants isolated from patients [...] Read more.

The SARS-CoV-2 variant of concern, α, spread worldwide at the beginning of 2021. It was suggested that this variant was associated with a higher risk of mortality than other variants. We aimed to characterize the genetic diversity of SARS-CoV-2 variants isolated from patients with severe COVID-19 and unravel the relationships between specific viral mutations/mutational patterns and clinical outcomes. This is a prospective multicenter observational cohort study. Patients aged ≥18 years admitted to 11 intensive care units (ICUs) in hospitals in the Greater Paris area for SARS-CoV-2 infection and acute respiratory failure between 1 October 2020 and 30 May 2021 were included. The primary clinical endpoint was day-28 mortality. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing (Illumina COVIDSeq). In total, 413 patients were included, 183 (44.3%) were infected with pre-existing variants, 197 (47.7%) were infected with variant α, and 33 (8.0%) were infected with other variants. The patients infected with pre-existing variants were significantly older (64.9 ± 11.9 vs. 60.5 ± 11.8 years; p = 0.0005) and had more frequent COPD (11.5% vs. 4.1%; p = 0.009) and higher SOFA scores (4 [3–8] vs. 3 [2–4]; 0.0002). The day-28 mortality was no different between the patients infected with pre-existing, α, or other variants (31.1% vs. 26.2% vs. 30.3%; p = 0.550). There was no association between day-28 mortality and specific variants or the presence of specific mutations. At ICU admission, the patients infected with pre-existing variants had a different clinical presentation from those infected with variant α, but mortality did not differ between these groups. There was no association between specific variants or SARS-CoV-2 genome mutational pattern and day-28 mortality. Full article

(This article belongs to the Special Issue SARS-CoV-2 Research in France)

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21 pages, 2146 KiB

Open AccessArticle

Translation of SARS-CoV-2 gRNA Is Extremely Efficient and Competitive despite a High Degree of Secondary Structures and the Presence of an uORF

by Lionel Condé, Omran Allatif, Théophile Ohlmann and Sylvain de Breyne

Viruses 2022, 14(7), 1505; https://doi.org/10.3390/v14071505 - 8 Jul 2022

Cited by 9 | Viewed by 3072

Abstract

The SARS-CoV-2 infection generates up to nine different sub-genomic mRNAs (sgRNAs), in addition to the genomic RNA (gRNA). The 5′UTR of each viral mRNA shares the first 75 nucleotides (nt.) at their 5′end, called the leader, but differentiates by a variable sequence (0 [...] Read more.

The SARS-CoV-2 infection generates up to nine different sub-genomic mRNAs (sgRNAs), in addition to the genomic RNA (gRNA). The 5′UTR of each viral mRNA shares the first 75 nucleotides (nt.) at their 5′end, called the leader, but differentiates by a variable sequence (0 to 190 nt. long) that follows the leader. As a result, each viral mRNA has its own specific 5′UTR in term of length, RNA structure, uORF and Kozak context; each one of these characteristics could affect mRNA expression. In this study, we have measured and compared translational efficiency of each of the ten viral transcripts. Our data show that most of them are very efficiently translated in all translational systems tested. Surprisingly, the gRNA 5′UTR, which is the longest and the most structured, was also the most efficient to initiate translation. This property is conserved in the 5′UTR of SARS-CoV-1 but not in MERS-CoV strain, mainly due to the regulation imposed by the uORF. Interestingly, the translation initiation mechanism on the SARS-CoV-2 gRNA 5′UTR requires the cap structure and the components of the eIF4F complex but showed no dependence in the presence of the poly(A) tail in vitro. Our data strongly suggest that translation initiation on SARS-CoV-2 mRNAs occurs via an unusual cap-dependent mechanism. Full article

(This article belongs to the Special Issue SARS-CoV-2 Research in France)

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12 pages, 1450 KiB

Open AccessArticle

Kinetics of the SARS-CoV-2 Antibody Avidity Response Following Infection and Vaccination

by Laura Garcia, Tom Woudenberg, Jason Rosado, Adam H. Dyer, Françoise Donnadieu, Delphine Planas, Timothée Bruel, Olivier Schwartz, Thierry Prazuck, Aurélie Velay, Samira Fafi-Kremer, Isabella Batten, Conor Reddy, Emma Connolly, Matt McElheron, Sean P. Kennelly, Nollaig M. Bourke, Michael T. White and Stéphane Pelleau

Viruses 2022, 14(7), 1491; https://doi.org/10.3390/v14071491 - 8 Jul 2022

Cited by 13 | Viewed by 3638

Abstract

Serological assays capable of measuring antibody responses induced by previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been critical tools in the response to the COVID-19 pandemic. In this study, we use bead-based multiplex assays to measure IgG and IgA [...] Read more.

Serological assays capable of measuring antibody responses induced by previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been critical tools in the response to the COVID-19 pandemic. In this study, we use bead-based multiplex assays to measure IgG and IgA antibodies and IgG avidity to five SARS-CoV-2 antigens (Spike (S), receptor-binding domain (RBD), Nucleocapsid (N), S subunit 2, and Membrane-Envelope fusion (ME)). These assays were performed in several cohorts of healthcare workers and nursing home residents, who were followed for up to eleven months after SARS-CoV-2 infection or up to six months after vaccination. Our results show distinct kinetic patterns of antibody quantity (IgG and IgA) and avidity. While IgG and IgA antibody levels waned over time, with IgA antibody levels waning more rapidly, avidity increased with time after infection or vaccination. These contrasting kinetic patterns allow for the estimation of time since previous SARS-CoV-2 infection. Including avidity measurements in addition to antibody levels in a classification algorithm for estimating time since infection led to a substantial improvement in accuracy, from 62% to 78%. The inclusion of antibody avidity in panels of serological assays can yield valuable information for improving serosurveillance during SARS-CoV-2 epidemics. Full article

(This article belongs to the Special Issue SARS-CoV-2 Research in France)

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18 pages, 8361 KiB

Open AccessArticle

Evolution of Neuroimaging Findings in Severe COVID-19 Patients with Initial Neurological Impairment: An Observational Study

by François Lersy, Caroline Bund, Mathieu Anheim, Mary Mondino, Vincent Noblet, Shirley Lazzara, Clelie Phillipps, Olivier Collange, Walid Oulehri, Paul-Michel Mertes, Julie Helms, Hamid Merdji, Maleka Schenck, Francis Schneider, Julien Pottecher, Céline Giraudeau, Agathe Chammas, François-Daniel Ardellier, Seyyid Baloglu, Khalid Ambarki, Izzie Jacques Namer and Stéphane Kremer Show full author list Hide full author list

Viruses 2022, 14(5), 949; https://doi.org/10.3390/v14050949 - 1 May 2022

Cited by 11 | Viewed by 2257

Abstract

Background and Objectives: Cerebral complications related to the COVID-19 were documented by brain MRIs during the acute phase. The purpose of the present study was to describe the evolution of these neuroimaging findings (MRI and FDG-PET/CT) and describe the neurocognitive outcomes of these [...] Read more.

Background and Objectives: Cerebral complications related to the COVID-19 were documented by brain MRIs during the acute phase. The purpose of the present study was to describe the evolution of these neuroimaging findings (MRI and FDG-PET/CT) and describe the neurocognitive outcomes of these patients. Methods: During the first wave of the COVID-19 outbreak between 1 March and 31 May 2020, 112 consecutive COVID-19 patients with neurologic manifestations underwent a brain MRI at Strasbourg University hospitals. After recovery, during follow-up, of these 112 patients, 31 (initially hospitalized in intensive care units) underwent additional imaging studies (at least one brain MRI). Results: Twenty-three men (74%) and eight women (26%) with a mean age of 61 years (range: 18–79) were included. Leptomeningeal enhancement, diffuse brain microhemorrhages, acute ischemic strokes, suspicion of cerebral vasculitis, and acute inflammatory demyelinating lesions were described on the initial brain MRIs. During follow-up, the evolution of the leptomeningeal enhancement was discordant, and the cerebral microhemorrhages were stable. We observed normalization of the vessel walls in all patients suspected of cerebral vasculitis. Four patients (13%) demonstrated new complications during follow-up (ischemic strokes, hypoglossal neuritis, marked increase in the white matter FLAIR hyperintensities with presumed vascular origin, and one suspected case of cerebral vasculitis). Concerning the grey matter volumetry, we observed a loss of volume of 3.2% during an average period of approximately five months. During follow-up, the more frequent FDG-PET/CT findings were hypometabolism in temporal and insular regions. Conclusion: A minority of initially severe COVID-19 patients demonstrated new complications on their brain MRIs during follow-up after recovery. Full article

(This article belongs to the Special Issue SARS-CoV-2 Research in France)

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11 pages, 302 KiB

Open AccessArticle

Two Years and Four Time Points: Description of Emotional State and Coping Strategies of French University Students during the COVID-19 Pandemic

by Elodie Charbonnier, Aurélie Goncalves, Cécile Puechlong, Lucile Montalescot and Sarah Le Vigouroux

Viruses 2022, 14(4), 782; https://doi.org/10.3390/v14040782 - 10 Apr 2022

Cited by 10 | Viewed by 1925

Abstract

While it is now clear that the COVID-19 pandemic has had a major impact on the mental health of individuals, especially the most vulnerable ones such as students, we have very little knowledge about the long-term consequences. The objective of this study was [...] Read more.

While it is now clear that the COVID-19 pandemic has had a major impact on the mental health of individuals, especially the most vulnerable ones such as students, we have very little knowledge about the long-term consequences. The objective of this study was to compare the mental health and coping of French university students during the different phases of the pandemic in the first 2 years. To this end, French university students were evaluated at four time points: during France’s first lockdown (April–May 2020; n_T1 = 1357), the period after lockdown (June 2020; n_T2 = 309), 1 year after the first lockdown, which was also a lockdown period (April–May 2021; n_T1′ = 2569); and 1 year after the end of the first unlock (June 2021; n_T2′ = 1136). Anxiety and depressive symptoms, coping and concerns were measured. In order to compare scores between the lockdown and unlock periods within the same year, paired samples t-tests were performed. To compare scores between the 2 years for different participants, independent samples t-tests were conducted. Our results showed that maladaptive strategies, concerns and symptoms were higher during lockdown periods, compared with unlock periods. In addition, symptom levels were higher in the second year of the pandemic compared with the first one. These argue that the psychological effects of COVID-19 were exacerbated by lockdowns but also by time. This highlights the need for more attention to be paid to students’ mental health. Full article

(This article belongs to the Special Issue SARS-CoV-2 Research in France)

10 pages, 857 KiB

Open AccessArticle

Low T Cell Responsiveness in the Early Phase of COVID-19 Associates with Progression to Severe Pneumonia in Kidney Transplant Recipients

by Marion Cremoni, Sébastien Cuozzo, Emanuela Martinuzzi, Susana Barbosa, Nadia Ben Hassen, Filippo Massa, Elisa Demonchy, Matthieu Durand, Olivier Thaunat, Vincent Esnault, Moglie Le Quintrec, Sophie Caillard, Nicolas Glaichenhaus and Antoine Sicard

Viruses 2022, 14(3), 542; https://doi.org/10.3390/v14030542 - 5 Mar 2022

Cited by 3 | Viewed by 1836

Abstract

Kidney transplant (KT) recipients are at increased risk of developing severe forms of COVID-19. Little is known about the immunological mechanisms underlying disease severity in these patients receiving T-cell targeting immunosuppressive drugs. We investigated the relationship between T cell responsiveness at the beginning [...] Read more.

Kidney transplant (KT) recipients are at increased risk of developing severe forms of COVID-19. Little is known about the immunological mechanisms underlying disease severity in these patients receiving T-cell targeting immunosuppressive drugs. We investigated the relationship between T cell responsiveness at the beginning of the infection and the risk of subsequent progression to respiratory failure. We performed a multicentric prospective study in KT recipients with a positive RT-PCR COVID-19 test and only mild symptoms at inclusion. Blood samples were collected at baseline in a cell culture system containing T cell stimuli. We assessed T cell responsiveness by computing the ratio between the levels of Th1, Th2, Th17 and Treg cytokines produced after polyclonal stimulation and the number of blood lymphocytes. We then used an unsupervised classification approach to stratify patients into low and high T cell responders and a penalized logistic regression to evaluate the association between T cell responsiveness and progression to severe pneumonia. Forty-five patients were included. All patients who progressed to severe pneumonia (24.4%, n = 11) were low T cell responders at baseline (p = 0.01). In multivariate analysis, low T cell responsiveness at baseline was the main risk factor for subsequent progression to severe pneumonia. This study provides novel insights into the mechanisms underlying COVID-19 severity in organ transplant recipients and data of interest to clinicians managing immunosuppressive drugs in these patients. Full article

(This article belongs to the Special Issue SARS-CoV-2 Research in France)

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Review

Jump to: Research

9 pages, 269 KiB

Open AccessReview

Can the COVID-19 Pandemic Improve the Management of Solid Organ Transplant Recipients?

by Arnaud Del Bello, Olivier Marion, Jacques Izopet and Nassim Kamar

Viruses 2022, 14(9), 1860; https://doi.org/10.3390/v14091860 - 24 Aug 2022

Viewed by 2233

Abstract

Increased mortality due to SARS-CoV-2 infection was observed among solid organ transplant patients. During the pandemic, in order to prevent and treat COVID-19 infections in this context, several innovative procedures and therapies were initiated within a short period of time. A large number [...] Read more.

Increased mortality due to SARS-CoV-2 infection was observed among solid organ transplant patients. During the pandemic, in order to prevent and treat COVID-19 infections in this context, several innovative procedures and therapies were initiated within a short period of time. A large number of these innovations can be applied and expanded to improve the management of non-COVID-19 infectious diseases in solid organ transplant patients and in the case of a future pandemic. In this vein, the present paper reviews and discusses medical care system adaptation, modification of immunosuppression, adjuvant innovative therapies, the role of laboratory expertise, and the prevention of infections as examples of such innovations. Full article

(This article belongs to the Special Issue SARS-CoV-2 Research in France)

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