Publications by authors named "Samira Fafi-Kremer"

104 Publications

Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies.

Nat Med 2021 Mar 26. Epub 2021 Mar 26.

Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 and B.1.351 variants were first identified in the United Kingdom and South Africa, respectively, and have since spread to many countries. These variants harboring diverse mutations in the gene encoding the spike protein raise important concerns about their immune evasion potential. Here, we isolated infectious B.1.1.7 and B.1.351 strains from acutely infected individuals. We examined sensitivity of the two variants to SARS-CoV-2 antibodies present in sera and nasal swabs from individuals infected with previously circulating strains or who were recently vaccinated, in comparison with a D614G reference virus. We utilized a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection. Sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G. In contrast, after 9 months, convalescent sera had a mean sixfold reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351. Sera from 19 individuals vaccinated twice with Pfizer Cominarty, longitudinally tested up to 6 weeks after vaccination, were similarly potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Neutralizing titers increased after the second vaccine dose, but remained 14-fold lower against B.1.351. In contrast, sera from convalescent or vaccinated individuals similarly bound the three spike proteins in a flow cytometry-based serological assay. Neutralizing antibodies were rarely detected in nasal swabs from vaccinees. Thus, faster-spreading SARS-CoV-2 variants acquired a partial resistance to neutralizing antibodies generated by natural infection or vaccination, which was most frequently detected in individuals with low antibody levels. Our results indicate that B1.351, but not B.1.1.7, may increase the risk of infection in immunized individuals.
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http://dx.doi.org/10.1038/s41591-021-01318-5DOI Listing
March 2021

SARS-Cov-2 Seroprevalence in a French Kidney Transplant Center Located Within a "High Risk" Zone.

Transplantation 2021 Mar 22. Epub 2021 Mar 22.

Department of Nephrology and Transplantation, Strasbourg University Hospital, Strasbourg, France INSERM U1109, LabEx TRANSPLANTEX Strasbourg, France Department of Virology, Strasbourg University Hospital, Strasbourg, France.

Background: Data on SARS-CoV-2 seroprevalence in kidney transplant recipients (KTR) remain rare. We sought to shed further light on this issue by conducting a single-center study in a kidney transplant center located in one of the France's highest risk zone (Grand Est) for Covid-19 during the initial disease outbreak.

Method: To this aim, we used a survey approach coupled with systematic investigation of SARS-CoV-2 serology in a cohort of 1390 KTR.

Results: SARS-CoV-2 serologies were available for 780 survey respondents, among whom 48 had anti-SARS-CoV-2 antibodies (total seroprevalence: 6.2%). Thirty-five of the 48 seropositive KTR had previously received a diagnosis of Covid-19, whereas the remaining 13 patients were not known to be infected (8 asymptomatic cases). Specifically, 18.7% of seropositive KTR and 1.1% of the entire cohort were asymptomatic. Household exposure was found to markedly increase the risk of SARS-CoV-2 transmission.

Conclusion: Our findings demonstrate that the overall SARS-CoV-2 seroprevalence in KTR living in one of the France's highest risk zone for Covid-19 during the first French lockdown was as low as 6.3%. A rapid and strict implementation of protective measures could have significantly mitigated virus spread even in an area of high virus circulation.
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http://dx.doi.org/10.1097/TP.0000000000003766DOI Listing
March 2021

Sex differences in the evolution of neutralizing antibodies to SARS-CoV-2.

J Infect Dis 2021 Mar 7. Epub 2021 Mar 7.

CHU de Strasbourg, Laboratoire de virologie, F-67091 Strasbourg, France.

We measured Anti-Spike (S), Nucleoprotein (N) and neutralizing antibodies (NAbs) in sera from 308 RT-qPCR + healthcare workers with mild disease, collected at two time-points up to 6 months after symptom onset. At Month 1 (M1), anti-S and N antibody levels were higher in males > 50 years or with a body mass index (BMI) > 25. At M3-6, anti-S and anti-N antibodies were detected in 99% and 59% of individuals, respectively. Anti-S antibodies and NAbs declined faster in males than in females, independently of age and BMI, suggesting an association of sex with evolution of the humoral response.
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http://dx.doi.org/10.1093/infdis/jiab127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989436PMC
March 2021

Multiplex assays for the identification of serological signatures of SARS-CoV-2 infection: an antibody-based diagnostic and machine learning study.

Lancet Microbe 2021 Feb 21;2(2):e60-e69. Epub 2020 Dec 21.

Malaria: Parasites and Hosts Unit, Department of Parasites and Insect Vectors, Institut Pasteur, Paris, France.

Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces an antibody response targeting multiple antigens that changes over time. This study aims to take advantage of this complexity to develop more accurate serological diagnostics.

Methods: A multiplex serological assay was developed to measure IgG and IgM antibody responses to seven SARS-CoV-2 spike or nucleoprotein antigens, two antigens for the nucleoproteins of the 229E and NL63 seasonal coronaviruses, and three non-coronavirus antigens. Antibodies were measured in serum samples collected up to 39 days after symptom onset from 215 adults in four French hospitals (53 patients and 162 health-care workers) with quantitative RT-PCR-confirmed SARS-CoV-2 infection, and negative control serum samples collected from healthy adult blood donors before the start of the SARS-CoV-2 epidemic (335 samples from France, Thailand, and Peru). Machine learning classifiers were trained with the multiplex data to classify individuals with previous SARS-CoV-2 infection, with the best classification performance displayed by a random forests algorithm. A Bayesian mathematical model of antibody kinetics informed by prior information from other coronaviruses was used to estimate time-varying antibody responses and assess the sensitivity and classification performance of serological diagnostics during the first year following symptom onset. A statistical estimator is presented that can provide estimates of seroprevalence in very low-transmission settings.

Findings: IgG antibody responses to trimeric spike protein (S) identified individuals with previous SARS-CoV-2 infection with 91·6% (95% CI 87·5-94·5) sensitivity and 99·1% (97·4-99·7) specificity. Using a serological signature of IgG and IgM to multiple antigens, it was possible to identify infected individuals with 98·8% (96·5-99·6) sensitivity and 99·3% (97·6-99·8) specificity. Informed by existing data from other coronaviruses, we estimate that 1 year after infection, a monoplex assay with optimal anti-S IgG cutoff has 88·7% (95% credible interval 63·4-97·4) sensitivity and that a four-antigen multiplex assay can increase sensitivity to 96·4% (80·9-100·0). When applied to population-level serological surveys, statistical analysis of multiplex data allows estimation of seroprevalence levels less than 2%, below the false-positivity rate of many other assays.

Interpretation: Serological signatures based on antibody responses to multiple antigens can provide accurate and robust serological classification of individuals with previous SARS-CoV-2 infection. This provides potential solutions to two pressing challenges for SARS-CoV-2 serological surveillance: classifying individuals who were infected more than 6 months ago and measuring seroprevalence in serological surveys in very low-transmission settings.

Funding: European Research Council. Fondation pour la Recherche Médicale. Institut Pasteur Task Force COVID-19.
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http://dx.doi.org/10.1016/S2666-5247(20)30197-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837364PMC
February 2021

SARS-CoV-2 viral load in nasopharyngeal swabs in the emergency department does not predict COVID-19 severity and mortality.

Acad Emerg Med 2021 03 5;28(3):306-313. Epub 2021 Feb 5.

INSERM (French National Institute of Health and Medical Research, UMR 1260, Regenerative NanoMedicine (RNM), Fédération de Médecine Translationnelle (FMTS), University of Strasbourg, Strasbourg, France.

Introduction: The ongoing COVID-19 pandemic has led to devastating repercussions on health care systems worldwide. This viral infection has a broad clinical spectrum (ranging from influenza-like disease, viral pneumonia, and hypoxemia to acute respiratory distress syndrome requiring prolonged intensive care unit stays). The prognostic impact of measuring viral load on nasopharyngeal swab specimens (by reverse transcriptase polymerase chain reaction [RT-PCR]) is yet to be elucidated.

Methods: Between March 3 and April 5, 2020, we conducted a retrospective study on a cohort of COVID-19 patients (mild or severe disease) who were hospitalized after presenting to the emergency department (ED) and had at least one positive nasopharyngeal swab during their hospital stay. We led our study at the University Hospitals of Strasbourg in the Greater East region of France, one of the pandemic's epicenters in Europe.

Results: We have collected samples from a cohort of 287 patients with a confirmed diagnosis of COVID-19 who were included in our study. Nearly half of them (50.5%) presented a mild form of the disease, while the other half (49.5%) presented a severe form, requiring mechanical ventilation. Median (interquartile range) viral load on the initial upper respiratory swab at admission was 4.76 (3.29-6.06) log copies/reaction. When comparing survivors and nonsurvivors, this viral load measurement did not differ according to subgroups (p = 0.332). Additionally, we have found that respiratory viral load measurement was predictive of neither in-hospital mortality (adjusted odds ratio [AOR] = 1.05, 95% confidence interval [CI] = 0.85 to 1.31, p = 0.637) nor disease severity (AOR = 0.88, 95% CI = 0.73 to 1.06, p = 0.167).

Conclusion: Respiratory viral load measurement on the first nasopharyngeal swab (by RT-PCR) during initial ED management is neither a predictor of severity nor a predictor of mortality in SARS-CoV-2 infection. Host response to this viral infection along with the extent of preexisting comorbidities might be more foretelling of disease severity than the virus itself.
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http://dx.doi.org/10.1111/acem.14217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014851PMC
March 2021

D-Dimers Level as a Possible Marker of Extravascular Fibrinolysis in COVID-19 Patients.

J Clin Med 2020 Dec 24;10(1). Epub 2020 Dec 24.

Division of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, 67000 Strasbourg, France.

Background And Objective: Host defence mechanisms to counter virus infection include the activation of the broncho-alveolar haemostasis. Fibrin degradation products secondary to extravascular fibrin breakdown could contribute to the marked increase in D-Dimers during COVID-19. We sought to examine the prognostic value on lung injury of D-Dimers in non-critically ill COVID-19 patients without thrombotic events.

Methods: This study retrospectively analysed hospitalized COVID-19 patients classified according to a D-Dimers threshold following the COVID-19 associated haemostatic abnormalities (CAHA) classification at baseline and at peak (Stage 1: D-Dimers less than three-fold above normal; Stage 2: D-Dimers three- to six-fold above normal; Stage 3: D-Dimers six-fold above normal). The primary endpoint was the occurrence of critical lung injuries on chest computed tomography. The secondary outcome was the composite of in-hospital death or transfer to the intensive care unit (ICU).

Results: Among the 123 patients included, critical lung injuries were evidenced in 8 (11.9%) patients in Stage 1, 6 (20%) in Stage 2 and 15 (57.7%) in Stage 3 ( = 0.001). D-Dimers staging at peak was an independent predictor of critical lung injuries regardless of the inflammatory burden assessed by CRP levels (OR 2.70, 95% CI (1.50-4.86); < 0.001) and was significantly associated with increased in-hospital death or ICU transfer (14.9 % in Stage 1, 50.0% in Stage 2 and 57.7% in Stage 3 ( < 0.001)). D-Dimers staging at peak was an independent predictor of in-hospital death or ICU transfer (OR 2.50, CI 95% (1.27-4.93); = 0.008).

Conclusions: In the absence of overt thrombotic events, D-Dimers quantification is a relevant marker of critical lung injuries and dismal patient outcome.
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http://dx.doi.org/10.3390/jcm10010039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795726PMC
December 2020

Persistence of SARS-CoV-2 antibodies in kidney transplant recipients.

Am J Transplant 2020 Dec 28. Epub 2020 Dec 28.

Department of Nephrology and Transplantation, Strasbourg University Hospital, Strasbourg, France.

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http://dx.doi.org/10.1111/ajt.16469DOI Listing
December 2020

Evaluation of Humoral Immunity to SARS-CoV-2: Diagnostic Value of a New Multiplex Addressable Laser Bead Immunoassay.

Front Microbiol 2020 26;11:603931. Epub 2020 Nov 26.

Normandie University, UNIROUEN, INSERM, U1234, Rouen, France.

Despite efforts to develop anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody (Ab) immunoassays, reliable serological methods are still needed. We developed a multiplex addressable laser bead immunoassay (ALBIA) to detect and quantify anti-Spike S1 and nucleocapsid N Abs. Recombinant S1 and N proteins were bound to fluorescent beads (ALBIA-IgG-S1/N). Abs were revealed using class-specific anti-human Ig Abs. The performances of the test were analyzed on 575 serum samples including 192 from SARS-CoV-2 polymerase chain reaction-confirmed patients, 13 from seasonal coronaviruses, 70 from different inflammatory/autoimmune diseases, and 300 from healthy donors. Anti-S1 IgM were detected by monoplex ALBIA-IgM-S1. Comparison with chemiluminescent assays or enzyme-linked immunosorbent assays was performed using commercial tests. Multiplex ALBIA-IgG-S1/N was effective in detecting and quantifying anti-SARS-CoV-2 IgG Abs. Two weeks after first symptoms, sensitivity and specificity were 97.7 and 98.0% (anti-S1), and 100 and 98.7% (anti-N), respectively. Agreement with commercial tests was good to excellent, with a higher sensitivity of ALBIA. ALBIA-IgG-S1/N was positive in 53% of patients up to day 7, and in 75% between days 7 and 13. For ALBIA-IgM-S1, sensitivity and specificity were 74.4 and 98.7%, respectively. Patients in intensive care units had higher IgG Ab levels (Mann-Whitney test, < 0.05). ALBIA provides a robust method for exploring humoral immunity to SARS-CoV-2. Serology should be performed after 2 weeks following first symptoms, when all COVID-19 (coronavirus disease 2019) patients had at least one anti-S1 or anti-N IgG Ab, illustrating the interest of a multiplex test.
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http://dx.doi.org/10.3389/fmicb.2020.603931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726470PMC
November 2020

Inadequate Immune Humoral Response against JC Virus in Progressive Multifocal Leukoencephalopathy Non-Survivors.

Viruses 2020 12 2;12(12). Epub 2020 Dec 2.

Virology Laboratory, Strasbourg University Hospitals, 67000 Strasbourg, France.

JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML) in immunosuppressed patients. There is currently no effective specific antiviral treatment and PML management relies on immune restoration. Prognosis markers are crucially needed in this disease because of its high mortality rate. In this work, we investigated the compartmentalization of JCV strains as well as the humoral neutralizing response in various matrices to further understand the pathophysiology of PML and define markers of survival. Four patients were included, of which three died in the few months following PML onset. Cerebrospinal fluid (CSF) viral loads were the highest, with plasma samples having lower viral loads and urine samples being mostly negative. Whether at PML onset or during follow-up, neutralizing antibody (NAb) titers directed against the same autologous strain (genotype or mutant) were the highest in plasma, with CSF titers being on average 430-fold lower and urine titers 500-fold lower at the same timepoint. Plasma NAb titers against autologous genotype or mutant were lower in non-survivor patients, though no neutralization "blind spot" was observed. The surviving patient was followed up until nine months after PML onset and presented, at that time, an increase in neutralizing titers, from 38-fold against the autologous genotype to around 200-fold against PML mutants. Our results suggest that patients' humoral neutralizing response against their autologous strain may play a role in PML outcome, with survivors developing high NAb titers in both plasma and CSF.
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http://dx.doi.org/10.3390/v12121380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761562PMC
December 2020

The BASIC Score: A Useful Tool to Identify Patients at High Risk of Early Progression to Severe Coronavirus Disease 2019.

Open Forum Infect Dis 2020 Oct 1;7(10):ofaa405. Epub 2020 Sep 1.

CHU de Strasbourg, Department of Infectious and Tropical Diseases, Strasbourg, France.

We developed a score, with easily accessible data (age, sex, body mass index, dyspnea, inflammatory parameters), to predict the risk of rapid progression to severe coronavirus disease 2019. Using a cutoff of >6 points, the negative predictive value was 87%.
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http://dx.doi.org/10.1093/ofid/ofaa405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499730PMC
October 2020

Intrafamilial Exposure to SARS-CoV-2 Associated with Cellular Immune Response without Seroconversion, France.

Emerg Infect Dis 2021 01 1;27(1). Epub 2020 Dec 1.

We investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies and T-cell responses against SARS-CoV-2 and human coronavirus (HCoV) 229E and OC43 in 11 SARS-CoV-2 serodiscordant couples in Strausbourg, France, in which 1 partner had evidence of mild coronavirus disease (COVID-19) and in 10 unexposed healthy controls. Patients with confirmed COVID-19 were considered index patients and their partners close contacts. All index patients displayed positive SARS-CoV-2-specific antibody and T-cell responses that lasted up to 102 days after symptom onset. All contacts remained seronegative for SARS-CoV-2; however, 6 reported COVID-19 symptoms within a median of 7 days after their partners, and 4 of those showed a positive SARS-CoV-2-specific T-cell response against 3 or 4 SARS-CoV-2 antigens that lasted up to 93 days after symptom onset. The 11 couples and controls displayed positive T-cell responses against HCoV-229E or HCoV-OC43. These data suggest that exposure to SARS-CoV-2 can induce virus-specific T-cell responses without seroconversion.
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http://dx.doi.org/10.3201/eid2701.203611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774579PMC
January 2021

Cerebrospinal Fluid Features in Patients With Coronavirus Disease 2019 and Neurological Manifestations: Correlation with Brain Magnetic Resonance Imaging Findings in 58 Patients.

J Infect Dis 2021 02;223(4):600-609

Service d'Imagerie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Background: Neurological manifestations are common in patients with coronavirus disease 2019 (COVID-19), but little is known about pathophysiological mechanisms. In this single-center study, we examined neurological manifestations in 58 patients, including cerebrospinal fluid (CSF) analysis and neuroimaging findings.

Methods: The study included 58 patients with COVID-19 and neurological manifestations in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction screening and on CSF analysis were performed. Clinical, laboratory, and brain magnetic resonance (MR) imaging data were retrospectively collected and analyzed.

Results: Patients were mostly men (66%), with a median age of 62 years. Encephalopathy was frequent (81%), followed by pyramidal dysfunction (16%), seizures (10%), and headaches (5%). CSF protein and albumin levels were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient, suggesting impaired blood-brain barrier integrity. CSF-specific immunoglobulin G oligoclonal band was found in 5 patients (11%), suggesting an intrathecal synthesis of immunoglobulin G, and 26 patients (55%) presented identical oligoclonal bands in serum and CSF. Four patients (7%) had a positive CSF SARS-CoV-2 reverse-transcription polymerase chain reaction. Leptomeningeal enhancement was present on brain MR images in 20 patients (38%).

Conclusions: Brain MR imaging abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV-2 detection in CSF remained scanty.
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http://dx.doi.org/10.1093/infdis/jiaa745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798956PMC
February 2021

Progressive multifocal leukoencephalopathy: MRI findings in HIV-infected patients are closer to rituximab- than natalizumab-associated PML.

Eur Radiol 2020 Nov 6. Epub 2020 Nov 6.

Hôpitaux Universitaires de Strasbourg, Service d'imagerie 2, Hôpital de Hautepierre, Strasbourg, France.

Objectives: To compare brain MRI findings in progressive multifocal leukoencephalopathy (PML) associated to rituximab and natalizumab treatments and HIV infection.

Materials And Methods: In this retrospective, multicentric study, we analyzed brain MRI exams from 72 patients diagnosed with definite PML: 32 after natalizumab treatment, 20 after rituximab treatment, and 20 HIV patients. We compared T2- or FLAIR-weighted images, diffusion-weighted images, T2*-weighted images, and contrast enhancement features, as well as lesion distribution, especially gray matter involvement.

Results: The three PML entities affect U-fibers associated with low signal intensities on T2*-weighted sequences. Natalizumab-associated PML showed a punctuate microcystic appearance in or in the vicinity of the main PML lesions, a potential involvement of the cortex, and contrast enhancement. HIV and rituximab-associated PML showed only mild contrast enhancement, punctuate appearance, and cortical involvement. The CD4/CD8 ratio showed a trend to be higher in the natalizumab group, possibly mirroring a more efficient immune response.

Conclusion: Imaging features of rituximab-associated PML are different from those of natalizumab-associated PML and are closer to those observed in HIV-associated PML.

Key Points: • Nowadays, PML is emerging as a complication of new effective therapies based on monoclonal antibodies. • Natalizumab-associated PML shows more inflammatory signs, a perivascular distribution "the milky way," and more cortex involvement than rituximab- and HIV-associated PML. • MRI differences are probably related to higher levels of immunosuppression in HIV patients and those under rituximab therapy.
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http://dx.doi.org/10.1007/s00330-020-07362-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644389PMC
November 2020

SARS-CoV-2 viral dynamics in immunocompromised patients.

Am J Transplant 2021 04 31;21(4):1667-1669. Epub 2020 Oct 31.

Fédération de Médecine Translationnelle, INSERM U1109, LabEx TRANSPLANTEX, Strasbourg, France.

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http://dx.doi.org/10.1111/ajt.16353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675471PMC
April 2021

Biomarkers of Cytokine Release Syndrome Predict Disease Severity and Mortality From COVID-19 in Kidney Transplant Recipients.

Transplantation 2021 01;105(1):158-169

Department of Nephrology and Transplantation, University Hospital, Strasbourg, France.

Background: Data on coronavirus disease 2019 (COVID-19) in immunocompromised kidney transplant recipients (KTR) remain scanty. Although markers of inflammation, cardiac injury, and coagulopathy have been previously associated with mortality in the general population of patients with COVID-19, their prognostic impact amongst KTR with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has not been specifically investigated.

Methods: We conducted a cohort study of 49 KTR who presented with COVID-19. Clinical and laboratory risk factors for severe disease and mortality were prospectively collected and analyzed with respect to outcomes. The study participants were divided into 3 groups: (1) mild disease manageable in an outpatient setting (n = 8), (2) nonsevere disease requiring hospitalization (n = 21), and (3) severe disease (n = 20).

Results: Gastrointestinal manifestations were common at diagnosis. The 30-day mortality rate in hospitalized patients was 19.5%. Early elevations of C-reactive protein (>100 mg/L) and interleukin-6 (>65 ng/L) followed by increases in high-sensitivity troponin I (>30 ng/L) and D-dimer (>960 ng/mL) were significantly associated with severe disease and mortality. Viral load did not have prognostic significance in our sample, suggesting that outcomes were chiefly driven by a cytokine release syndrome (CRS).

Conclusions: Regular monitoring of CRS biomarkers in KTR with COVID-19 is paramount to improve clinical outcomes.
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http://dx.doi.org/10.1097/TP.0000000000003480DOI Listing
January 2021

Remdesivir failure with SARS-CoV-2 RNA-dependent RNA-polymerase mutation in a B-cell immunodeficient patient with protracted Covid-19.

Clin Infect Dis 2020 Sep 28. Epub 2020 Sep 28.

Sorbonne Université, Inserm IPLESP, Infectious Diseases Department, Saint-Antoine Hospital, APHP, Paris - France.

SARS-CoV-2 is a new pandemic virus for which Remdesivir is the only antiviral available. We report the occurrence of a mutation in the RdRP (D484Y) following failure of remdesivir in a 76-year-old woman with a post-rituximab B-cell immunodeficiency and persistent SARS-CoV-2 viremia. Cure was reached after supplementation with convalescent plasma.
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http://dx.doi.org/10.1093/cid/ciaa1474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543308PMC
September 2020

Evaluation of the performance of SARS-CoV-2 serological tools and their positioning in COVID-19 diagnostic strategies.

Diagn Microbiol Infect Dis 2020 Dec 21;98(4):115181. Epub 2020 Aug 21.

Laboratoire de Virologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; INSERM, UMR_S1109, LabEx TRANSPLANTEX, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Fédération Hospitalo-Universitaire (FHU) OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France. Electronic address:

Rapid and accurate diagnosis is crucial for successful outbreak containment. During the current coronavirus disease 2019 (COVID-19) public health emergency, the gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis is the detection of viral RNA. Additional diagnostic methods õenabling the detection of current or past SARS-CoV-2 infection would be highly beneficial. We assessed 2 immunochromatographic lateral flow assays (LFA-1, LFA-2) and 2 enzyme-linked immunosorbent assay kits (IgA/IgG ELISA-1, IgM/IgG ELISA-2) using 325 samples: serum samples from polymerase chain reaction-confirmed COVID-19 hospitalized patients (n = 55) and healthcare workers (n = 143) and 127 samples from negative controls. Diagnostic performances were assessed according to days after symptom onset (dso) and the antigenic format used by manufacturers. Clinical sensitivities varied greatly among the assays, showing poor mutual agreement. After 15 dso, ELISA-1 (Euroimmun) and LFA-1 (Biosynex) combining IgM and IgG detection showed the best performances. A thorough selection of serological assays for the detection of ongoing or past infections is advisable.
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http://dx.doi.org/10.1016/j.diagmicrobio.2020.115181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441068PMC
December 2020

In-depth virological assessment of kidney transplant recipients with COVID-19.

Am J Transplant 2020 11 12;20(11):3162-3172. Epub 2020 Sep 12.

Department of Virology, Strasbourg University Hospital, Strasbourg, France.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely, causing coronavirus disease 2019 (COVID-19) and significant mortality. However, data on viral loads and antibody kinetics in immunocompromised populations are lacking. We aimed to determine nasopharyngeal and plasma viral loads via reverse transcription-polymerase chain reaction and SARS-CoV-2 serology via enzyme-linked immunosorbent assay and study their association with severe forms of COVID-19 and death in kidney transplant recipients. In this study, we examined hospitalized kidney transplant recipients with nonsevere (n = 21) and severe (n = 19) COVID-19. SARS-CoV-2 nasopharyngeal and plasma viral load and serological response were evaluated based on outcomes and disease severity. Ten recipients (25%) displayed persistent viral shedding 30 days after symptom onset. The SARS-CoV-2 viral load of the upper respiratory tract was not associated with severe COVID-19, whereas the plasma viral load was associated with COVID-19 severity (P = .010) and mortality (P = .010). All patients harbored antibodies during the second week after symptom onset that persisted for 2 months. We conclude that plasma viral load is associated with COVID-19 morbidity and mortality, whereas nasopharyngeal viral load is not. SARS-CoV-2 shedding is prolonged in kidney transplant recipients and the humoral response to SARS-CoV-2 does not show significant impairment in this series of transplant recipients.
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http://dx.doi.org/10.1111/ajt.16251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436721PMC
November 2020

Delirium and encephalopathy in severe COVID-19: a cohort analysis of ICU patients.

Crit Care 2020 08 8;24(1):491. Epub 2020 Aug 8.

Hôpitaux Universitaires de Strasbourg, Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil, 1, place de l'Hôpital, F-67091, Strasbourg, Cedex, France.

Background: Neurotropism of SARS-CoV-2 and its neurological manifestations have now been confirmed. We aimed at describing delirium and neurological symptoms of COVID-19 in ICU patients.

Methods: We conducted a bicentric cohort study in two French ICUs of Strasbourg University Hospital. All the 150 patients referred for acute respiratory distress syndrome due to SARS-CoV-2 between March 3 and May 5, 2020, were included at their admission. Ten patients (6.7%) were excluded because they remained under neuromuscular blockers during their entire ICU stay. Neurological examination, including CAM-ICU, and cerebrospinal fluid analysis, electroencephalography, and magnetic resonance imaging (MRI) were performed in some of the patients with delirium and/or abnormal neurological examination. The primary endpoint was to describe the incidence of delirium and/or abnormal neurological examination. The secondary endpoints were to describe the characteristics of delirium, to compare the duration of invasive mechanical ventilation and ICU length of stay in patients with and without delirium and/or abnormal neurological symptoms.

Results: The 140 patients were aged in median of 62 [IQR 52; 70] years old, with a median SAPSII of 49 [IQR 37; 64] points. Neurological examination was normal in 22 patients (15.7%). One hundred eighteen patients (84.3%) developed a delirium with a combination of acute attention, awareness, and cognition disturbances. Eighty-eight patients (69.3%) presented an unexpected state of agitation despite high infusion rates of sedative treatments and neuroleptics, and 89 (63.6%) patients had corticospinal tract signs. Brain MRI performed in 28 patients demonstrated enhancement of subarachnoid spaces in 17/28 patients (60.7%), intraparenchymal, predominantly white matter abnormalities in 8 patients, and perfusion abnormalities in 17/26 patients (65.4%). The 42 electroencephalograms mostly revealed unspecific abnormalities or diffuse, especially bifrontal, slow activity. Cerebrospinal fluid examination revealed inflammatory disturbances in 18/28 patients, including oligoclonal bands with mirror pattern and elevated IL-6. The CSF RT-PCR SARS-CoV-2 was positive in one patient. The delirium/neurological symptoms in COVID-19 patients were responsible for longer mechanical ventilation compared to the patients without delirium/neurological symptoms. Delirium/neurological symptoms could be secondary to systemic inflammatory reaction to SARS-CoV-2.

Conclusions And Relevance: Delirium/neurological symptoms in COVID-19 patients are a major issue in ICUs, especially in the context of insufficient human and material resources.

Trial Registration: NA.
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http://dx.doi.org/10.1186/s13054-020-03200-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414289PMC
August 2020

Serologic responses to SARS-CoV-2 infection among hospital staff with mild disease in eastern France.

EBioMedicine 2020 Sep 31;59:102915. Epub 2020 Jul 31.

Institut Pasteur, Emerging Diseases Epidemiology Unit, Paris, France; Conservatoire National des Arts et Métiers, PACRI Unit, Paris, France.

Background: The serologic response of individuals with mild forms of SARS-CoV-2 infection is poorly characterized.

Methods: Hospital staff who had recovered from mild forms of PCR-confirmed SARS-CoV-2 infection were tested for anti-SARS-CoV-2 antibodies using two assays: a rapid immunodiagnostic test (99.4% specificity) and the S-Flow assay (~99% specificity). The neutralizing activity of the sera was tested with a pseudovirus-based assay.

Findings: Of 162 hospital staff who participated in the investigation, 160 reported SARS-CoV-2 infection that had not required hospital admission and were included in these analyses. The median time from symptom onset to blood sample collection was 24 days (IQR: 21-28, range 13-39). The rapid immunodiagnostic test detected antibodies in 153 (95.6%) of the samples and the S-Flow assay in 159 (99.4%), failing to detect antibodies in one sample collected 18 days after symptom onset (the rapid test did not detect antibodies in that patient). Neutralizing antibodies (NAbs) were detected in 79%, 92% and 98% of samples collected 13-20, 21-27 and 28-41 days after symptom onset, respectively (P = 0.02).

Interpretation: Antibodies against SARS-CoV-2 were detected in virtually all hospital staff sampled from 13 days after the onset of COVID-19 symptoms. This finding supports the use of serologic testing for the diagnosis of individuals who have recovered from SARS-CoV-2 infection. The neutralizing activity of the antibodies increased overtime. Future studies will help assess the persistence of the humoral response and its associated neutralization capacity in recovered patients.

Fundings: The funders had no role in study design, data collection, interpretation, or the decision to submit the work for publication.
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http://dx.doi.org/10.1016/j.ebiom.2020.102915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502660PMC
September 2020

Intravenous immunoglobulin as a preventive strategy against BK virus viremia and BKV-associated nephropathy in kidney transplant recipients-Results from a proof-of-concept study.

Am J Transplant 2021 01 27;21(1):329-337. Epub 2020 Aug 27.

Service de Néphrologie et Transplantation, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

BK virus (BKV) replication occurs frequently in kidney transplant recipients (KTR), potentially leading to BKV-associated nephropathy (BKVAN) and graft loss. Patients with high titers of BKV-neutralizing antibodies (NAbs) are protected against BKV replication, and intravenous immunoglobulin (IVIg) infusion can increase NAb titers. We investigated whether early IVIg administration prevents BKV replication in patients with low NAb titers (<4 log against the BKV-specific genotype). Based on NAb titers on the day of transplantation, KTR followed in the Strasbourg University Hospital (n = 174) were retrospectively divided into the following 3 risk categories for BKV replication: (1) patients with low NAb titers ("high-risk") who received IVIg for the first 3 posttransplant months (n = 44), (2) patients with low NAb titers ("high-risk") who did not undergo IVIg treatment (n = 41), and (3) patients with high NAb titers ("low-risk") who did not receive IVIg (n = 89). At 12 posttransplant months, the incidence of BKV viremia in the high-risk group treated with IVIg (6.8%) was similar to that observed in the low-risk group (10.1%) and markedly lower than that of the untreated high-risk group (36.6%; P < .001). Similar results were observed with regard to BKVAN. We conclude that IVIg may be a valuable strategy for preventing BKV replication.
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http://dx.doi.org/10.1111/ajt.16233DOI Listing
January 2021

Neurologic and neuroimaging findings in patients with COVID-19: A retrospective multicenter study.

Neurology 2020 09 17;95(13):e1868-e1882. Epub 2020 Jul 17.

From the Hôpitaux Universitaires de Strasbourg (S.K., F.L., S.B., F.-D.A., T.W.), Service d'imagerie 2, Hôpital de Hautepierre; Engineering Science, Computer Science and Imaging Laboratory (S.K., N.M.), UMR 7357, University of Strasbourg-CNRS; Service de Neurologie (M. Anheim), Hôpitaux Universitaires de Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (M. Anheim), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Illkirch; Fédération de Médecine Translationnelle de Strasbourg (M. Anheim), Université de Strasbourg; Hôpitaux universitaires de Strasbourg (H.M., F.M., J.H.), Service de Médecine Intensive Réanimation, Nouvel Hôpital Civil; INSERM (French National Institute of Health and Medical Research) (H.M., F.M.), UMR 1260, Regenerative Nanomedicine, Fédération de Médecine Translationnelle de Strasbourg; Médecine Intensive-Réanimation (M.S., F.S.), Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg; Service de Neuroradiologie (H.O., F.B., J.M.), Hôpitaux Civils de Colmar; Service d'Imagerie (A. Khalil, A.G.), Unité de Neuroradiologie, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat Claude Bernard; Université Paris Diderot (A. Khalil), Paris; Service de Neurologie (S. Carré, C.L.), Centre Hospitalier de Haguenau; Service de Radiologie (M. Alleg), Centre Hospitalier de Haguenau; Service de Neuroradiologie, (E.S., R.A., F.Z.) Hôpital Central, CHU de Nancy; CHIC Unisanté (L.J., P.N., Y.T.M.), Hôpital Marie Madeleine, Forbach; Neuroimaging Department (G.H., J. Benzakoun, C.O., G. Boulouis, M.E.-G., B.K.), GHU Paris Psychiatrie et Neurosciences, Hôpital Sainte-Anne, Université de Paris, INSERM U1266, F-75014; CHU Rennes (J.-C.F., B.C.-N.), Department of Neuroradiology; CHU Rennes (A.M.), Medical Intensive Care Unit; Department of Neuroradiology (P.-O.C., F.R., P.T.), University Hospital of Dijon, Hôpital François Mitterrand; Service de Radiologie (C.B.), CHU de Saint-Etienne; Service de Réanimation (X.F.), CH de Roanne; Service de Neuroradiologie (G.F., S.S.), CHU de Limoges; Radiology Department (I.d.B., G. Bornet), Hôpital Privé d'Antony; Department of Diagnostic and Interventional Neuroradiology (H.D.), University Hospital, Nantes; Neuroradiology Department (J. Berge), CHU de Bordeaux; Service de Neuroradiologie (A. Kazémi), CHU de Lille; Assistance Publique Hôpitaux de Paris (N.P.), Service de Neuroradiologie, Hôpital Pitié-Salpêtrière; Sorbonne Université (N.P.), Univ Paris 06, UMR S 1127, CNRS UMR 7225, ICM, F-75013; Service de Neuroradiologie Diagnostique (A.L.), Foundation A. Rothschild Hospital, Paris; EA CHIMERE 7516 (J.-M.C.), Université de Picardie Jules Verne; Service de NeuroRadiologie, pôle Imagerie Médicale, Centre Hospitalo-Universitaire d'Amiens; Hôpitaux Universitaires de Strasbourg (P.-E.Z., M.M.), UCIEC, Pôle d'Imagerie, Strasbourg; Observatoire Français de la Sclérose en Plaques (J.-C.B.), Lyon; Nephrology and Transplantation Department (S. Caillard), Hôpitaux Universitaires de Strasbourg; Inserm UMR S1109 (S. Caillard), LabEx Transplantex, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg; Hôpitaux Universitaires de Strasbourg (O.C., P.M.M.), Service d'Anesthésie-Réanimation, Nouvel Hôpital Civil; Hôpitaux Universitaires de Strasbourg (S.F.-K.), Laboratoire de Virologie Médicale; Radiology Department (M.O.), Nouvel Hôpital Civil, Strasbourg University Hospital; CHU de Strasbourg (N.M.), Service de Santé Publique, GMRC, F-67091 Strasbourg; Immuno-Rhumatologie Moléculaire (S.F.-K., J.H.), INSERM UMR_S1109, LabEx TRANSPLANTEX, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg; MRI Center (F.C.), Centre Hospitalier Lyon Sud, Hospices Civils de Lyon; and Université Lyon 1 (F.C.), CREATIS-LRMN, CNRS/UMR/5220-INSERM U630, Villeurbanne, France.

Objective: To describe neuroimaging findings and to report the epidemiologic and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with neurologic manifestations.

Methods: In this retrospective multicenter study (11 hospitals), we included 64 patients with confirmed COVID-19 with neurologic manifestations who underwent a brain MRI.

Results: The cohort included 43 men (67%) and 21 women (33%); their median age was 66 (range 20-92) years. Thirty-six (56%) brain MRIs were considered abnormal, possibly related to severe acute respiratory syndrome coronavirus. Ischemic strokes (27%), leptomeningeal enhancement (17%), and encephalitis (13%) were the most frequent neuroimaging findings. Confusion (53%) was the most common neurologic manifestation, followed by impaired consciousness (39%), presence of clinical signs of corticospinal tract involvement (31%), agitation (31%), and headache (16%). The profile of patients experiencing ischemic stroke was different from that of other patients with abnormal brain imaging: the former less frequently had acute respiratory distress syndrome ( = 0.006) and more frequently had corticospinal tract signs ( = 0.02). Patients with encephalitis were younger ( = 0.007), whereas agitation was more frequent for patients with leptomeningeal enhancement ( = 0.009).

Conclusions: Patients with COVID-19 may develop a wide range of neurologic symptoms, which can be associated with severe and fatal complications such as ischemic stroke or encephalitis. In terms of meningoencephalitis involvement, even if a direct effect of the virus cannot be excluded, the pathophysiology seems to involve an immune or inflammatory process given the presence of signs of inflammation in both CSF and neuroimaging but the lack of virus in CSF.

Clinicaltrialsgov Identifier: NCT04368390.
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http://dx.doi.org/10.1212/WNL.0000000000010112DOI Listing
September 2020

Coronavirus disease 2019 3 months after hematopoietic stem cell transplant: A pediatric case report.

Pediatr Blood Cancer 2020 09 6;67(9):e28545. Epub 2020 Jul 6.

Department of Pediatric Onco-Hematology, Hautepierre University Hospital, Strasbourg, France.

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http://dx.doi.org/10.1002/pbc.28545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361236PMC
September 2020

SARS-CoV-2 Pneumonia in Hospitalized Asthmatic Patients Did Not Induce Severe Exacerbation.

J Allergy Clin Immunol Pract 2020 Sep 27;8(8):2600-2607. Epub 2020 Jun 27.

Chest Diseases Department, Strasbourg University Hospital, Strasbourg, France; Public Health Department, Strasbourg University Hospital, Strasbourg, France; EA 3070 Federation of Translational Medicine, FHU Homicare, University of Strasbourg, Strasbourg, France. Electronic address:

Background: Viral infections are known to exacerbate asthma in adults. Previous studies have found few patients with asthma among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia cases. However, the relationship between SARS-CoV-2 infection and severe asthma exacerbation is not known.

Objective: To assess the frequency of asthma exacerbation in patients with asthma hospitalized for SARS-CoV-2 pneumonia and compare symptoms and laboratory and radiological findings in patients with and without asthma with SARS-CoV-2 pneumonia.

Methods: We included 106 patients between March 4 and April 6, 2020, who were hospitalized in the Chest Diseases Department of Strasbourg University Hospital; 23 had asthma. To assess the patients' asthma status, 3 periods were defined: the last month before the onset of COVID-19 symptoms (p1), prehospitalization (p2), and during hospitalization (p3). Severe asthma exacerbations were defined according to Global INitiative for Asthma guidelines during p1 and p2. During p3, we defined severe asthma deterioration as the onset of breathlessness and wheezing requiring systemic corticosteroids and inhaled β2 agonist.

Results: We found no significant difference between patients with and without asthma in terms of severity (length of stay, maximal oxygen flow needed, noninvasive ventilation requirement, and intensive care unit transfer); 52.2% of the patients with asthma had Global INitiative for Asthma step 1 asthma. One patient had a severe exacerbation during p1, 2 patients during p2, and 5 patients were treated with systemic corticosteroids and inhaled β2 agonist during p3.

Conclusions: Our results demonstrate that patients with asthma appeared not to be at risk for severe SARS-CoV-2 pneumonia. Moreover, SARS-CoV-2 pneumonia did not induce severe asthma exacerbation.
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http://dx.doi.org/10.1016/j.jaip.2020.06.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320869PMC
September 2020

Coronavirus disease 2019 in pregnancy was associated with maternal morbidity and preterm birth.

Am J Obstet Gynecol 2020 12 15;223(6):914.e1-914.e15. Epub 2020 Jun 15.

Department of Obstetrics and Gynecology, Strasbourg University Hospitals, Strasbourg, France.

Background: Despite the mainly reassuring outcomes for pregnant women with coronavirus disease 2019 reported by previous case series with small sample sizes, some recent reports of severe maternal morbidity requiring intubation and of maternal deaths show the need for additional data about the impact of coronavirus disease 2019 on pregnancy outcomes.

Objective: This study aimed to report the maternal characteristics and clinical outcomes of pregnant women with coronavirus disease 2019.

Study Design: This retrospective, single-center study includes all consecutive pregnant women with confirmed (laboratory-confirmed) or suspected (according to the Chinese management guideline [version 7.0]) coronavirus disease 2019, regardless of gestational age at diagnosis, admitted to the Strasbourg University Hospital (France) from March 1, 2020, to April 3, 2020. Maternal characteristics, laboratory and imaging findings, and maternal and neonatal outcomes were extracted from medical records.

Results: The study includes 54 pregnant women with confirmed (n=38) and suspected (n=16) coronavirus disease 2019. Of these, 32 had an ongoing pregnancy, 1 had a miscarriage, and 21 had live births: 12 vaginal and 9 cesarean deliveries. Among the women who gave birth, preterm deliveries were medically indicated for their coronavirus disease 2019-related condition for 5 of 21 women (23.8%): 3 (14.3%) before 32 weeks' gestation and 2 (9.5%) before 28 weeks' gestation. Oxygen support was required for 13 of 54 women (24.1%), including high-flow oxygen (n=2), noninvasive (n=1) and invasive (n=3) mechanical ventilation, and extracorporeal membrane oxygenation (n=1). Of these, 3, aged 35 years or older with positive test result for severe acute respiratory syndrome coronavirus 2 using reverse transcription polymerase chain reaction, had respiratory failure requiring indicated delivery before 29 weeks' gestation. All 3 women were overweight or obese, and 2 had an additional comorbidity.

Conclusion: Coronavirus disease 2019 in pregnancy was associated with maternal morbidity and preterm birth. Its association with other well-known risk factors for severe maternal morbidity in pregnant women with no infection, including maternal age above 35 years, overweight, and obesity, suggests further studies are required to determine whether these risk factors are also associated with poorer maternal outcome in these women.
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http://dx.doi.org/10.1016/j.ajog.2020.06.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294260PMC
December 2020

Brain MRI Findings in Severe COVID-19: A Retrospective Observational Study.

Radiology 2020 11 16;297(2):E242-E251. Epub 2020 Jun 16.

From the Hôpitaux Universitaires de Strasbourg, Service d'Imagerie 2, Hôpital de Hautepierre, Strasbourg, France (S.K.).

Background Brain MRI parenchymal signal abnormalities have been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Purpose To describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe coronavirus disease 2019 (COVID-19) infection. Materials and Methods This was a retrospective study of patients evaluated from March 23, 2020, to April 27, 2020, at 16 hospitals. Inclusion criteria were () positive nasopharyngeal or lower respiratory tract reverse transcriptase polymerase chain reaction assays, () severe COVID-19 infection defined as a requirement for hospitalization and oxygen therapy, () neurologic manifestations, and () abnormal brain MRI findings. Exclusion criteria were patients with missing or noncontributory data regarding brain MRI or brain MRI showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. Categorical data were compared using the Fisher exact test. Quantitative data were compared using the Student test or Wilcoxon test. < .05 represented a significant difference. Results Thirty men (81%) and seven women (19%) met the inclusion criteria, with a mean age of 61 years ± 12 (standard deviation) (age range, 8-78 years). The most common neurologic manifestations were alteration of consciousness (27 of 37, 73%), abnormal wakefulness when sedation was stopped (15 of 37, 41%), confusion (12 of 37, 32%), and agitation (seven of 37, 19%). The most frequent MRI findings were signal abnormalities located in the medial temporal lobe in 16 of 37 patients (43%; 95% confidence interval [CI]: 27%, 59%), nonconfluent multifocal white matter hyperintense lesions seen with fluid-attenuated inversion recovery and diffusion-weighted sequences with variable enhancement, with associated hemorrhagic lesions in 11 of 37 patients (30%; 95% CI: 15%, 45%), and extensive and isolated white matter microhemorrhages in nine of 37 patients (24%; 95% CI: 10%, 38%). A majority of patients (20 of 37, 54%) had intracerebral hemorrhagic lesions with a more severe clinical presentation and a higher admission rate in intensive care units (20 of 20 patients [100%] vs 12 of 17 patients without hemorrhage [71%], = .01) and development of the acute respiratory distress syndrome (20 of 20 patients [100%] vs 11 of 17 patients [65%], = .005). Only one patient had SARS-CoV-2 RNA in the cerebrospinal fluid. Conclusion Patients with severe coronavirus disease 2019 and without ischemic infarcts had a wide range of neurologic manifestations that were associated with abnormal brain MRI scans. Eight distinctive neuroradiologic patterns were described. © RSNA, 2020.
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http://dx.doi.org/10.1148/radiol.2020202222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301613PMC
November 2020