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1.
Hemasphere ; 6(5): e0711, 2022 May.
Article in English | MEDLINE | ID: covidwho-1795006

ABSTRACT

Data on outcome of patients with mantle cell lymphoma (MCL) and COVID-19 infection are limited. The European MCL (EMCL) registry is a centralized registry of the EMCL network, collecting real-world information about treatments and disease courses. During the COVID-19 pandemic, additional data on MCL patients with COVID-19 infection were collected, aiming to identify risk factors for mortality from COVID-19. In our retrospective, multicenter, international study, we collected data from 63 MCL patients with a median age of 64 years (range, 44-84) in 9 countries with evidence of a COVID-19 infection between February 2020 and October 2021. The overall mortality rate was high (44.4%), especially in hospitalized patients (61%) and in patients with need for intensive care unit care (94%). Patients receiving rituximab had significantly poorer survival than patients not receiving rituximab (P = 0.04). Our data highlight the importance of prevention strategies and underline the need for effective vaccination in this vulnerable cohort.

2.
HemaSphere ; 6(5), 2022.
Article in English | EuropePMC | ID: covidwho-1787481

ABSTRACT

Data on outcome of patients with mantle cell lymphoma (MCL) and COVID-19 infection are limited. The European MCL (EMCL) registry is a centralized registry of the EMCL network, collecting real-world information about treatments and disease courses. During the COVID-19 pandemic, additional data on MCL patients with COVID-19 infection were collected, aiming to identify risk factors for mortality from COVID-19. In our retrospective, multicenter, international study, we collected data from 63 MCL patients with a median age of 64 years (range, 44–84) in 9 countries with evidence of a COVID-19 infection between February 2020 and October 2021. The overall mortality rate was high (44.4%), especially in hospitalized patients (61%) and in patients with need for intensive care unit care (94%). Patients receiving rituximab had significantly poorer survival than patients not receiving rituximab (P = 0.04). Our data highlight the importance of prevention strategies and underline the need for effective vaccination in this vulnerable cohort.

3.
Front Public Health ; 10: 816848, 2022.
Article in English | MEDLINE | ID: covidwho-1776012

ABSTRACT

Convalescent plasma therapy has been described as an attractive approach to treat critically ill patients with COVID-19 (Coronavirus disease 2019). The selection of convalescent plasma donors (CPD) is commonly based on neutralizing antibody titer. A better understanding of the quality of immune responses following COVID-19 will enable the optimization of convalescent donors' selection in convalescent plasma programs. The involvement of SARS-CoV-2 specific T cells in the induction and persistence of high affinity anti-SARS-CoV-2 neutralizing antibody is still poorly investigated. In this study, 115 CPD who presented SARS-CoV-2 and who were eligible for plasma donation were included. Comprehensive analysis of T cells together with humoral responses were performed in regards of sex, age and blood group type. High frequency of T cell responses against SARS-CoV-2 related protein such as spike glycoprotein (80.0%), nucleocapsid (NCAP) (70.4%) and membrane protein (VME1) (74.8%) were detected in CPD by ex vivo IFN-γ and TNF-α ELISpot assays. Among CPD responders, most exhibited poly-specific T cell responses (75%) defined by the ability to mount responses against at least two SARS-CoV-2 antigens. We found a positive correlation between the magnitude and the poly-specificity of anti-SARS-CoV-2 T cell responses in CPD. Notably, both the magnitude and poly-specificity of SARS-CoV-2 T cell responses were highly correlated with neutralizing antibody titer in CPD. The present study highlights that the poly-specificity and strength of SARS-CoV-2 specific T cell responses predicts neutralizing antibody titer following COVID-19. These observations show the interest to combine T cell assays and antibody titer for the selection of CPD and to a latter extend to assess COVID-19 vaccine efficacy in at-risk patients.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , COVID-19/therapy , COVID-19 Vaccines , Humans , Immunization, Passive
4.
Leukemia ; 36(4): 1025-1034, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1773952

ABSTRACT

Patients with hematological malignancy and COVID-19 display a high mortality rate. In such patients, immunosuppression due to underlying disease and previous specific treatments impair humoral response, limiting viral clearance. Thus, COVID-19 convalescent plasma (CCP) therapy appears as a promising approach through the transfer of neutralizing antibodies specific to SARS-CoV-2. We report the effect of CCP in a cohort of 112 patients with hematological malignancy and COVID-19 and a propensity score analysis on subgroups of patients with B-cell lymphoid disease treated (n = 81) or not (n = 120) with CCP between May 1, 2020 and April 1, 2021. The overall survival of the whole cohort was 65% (95% CI = 56-74.9) and 77.5% (95% CI = 68.5-87.7) for patients with B-cell neoplasm. Prior anti-CD20 monoclonal antibody therapy was associated with better overall survival, whereas age, high blood pressure, and COVID-19 severity were associated with a poor outcome. After an inverse probability of treatment weighting approach, we observed in anti-CD20-exposed patients with B-cell lymphoid disease a decreased mortality of 63% (95% CI = 31-80) in the CCP-treated group compared to the CCP-untreated subgroup, confirmed in the other sensitivity analyses. Convalescent plasma may be beneficial in COVID-19 patients with B-cell neoplasm who are unable to mount a humoral immune response.


Subject(s)
COVID-19 , Neoplasms , Antibodies, Viral , COVID-19/therapy , Humans , Immunization, Passive , Propensity Score , SARS-CoV-2
5.
EClinicalMedicine ; 46: 101362, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1757291

ABSTRACT

Background: In moderate-to-severe COVID-19 pneumonia, dexamethasone (DEX) and tocilizumab (TCZ) reduce the occurrence of death and ventilatory support. We investigated the efficacy and safety of DEX+TCZ in an open randomized clinical trial. Methods: From July 24, 2020, through May 18, 2021, patients with moderate-to-severe COVID-19 pneumonia requiring oxygen (>3 L/min) were randomly assigned to receive DEX (10 mg/d 5 days tapering up to 10 days) alone or combined with TCZ (8 mg/kg IV) at day 1, possibly repeated with a fixed dose of 400 mg i.v. at day 3. The primary outcome was time from randomization to mechanical ventilation support or death up to day 14, analysed on an intent-to-treat basis using a Bayesian approach. ClinicalTrials.gov number, NCT04476979. Findings: A total of 453 patients were randomized, 3 withdrew consent, 450 were analysed, of whom 226 and 224 patients were assigned to receive DEX or TCZ+DEX, respectively. At day 14, mechanical ventilation or death occurred in 32/226 (14%) and 27/224 (12%) in the DEX and TCZ+DEX arms, respectively (hazard ratio [HR] 0·85, 90% credible interval [CrI] 0·55 to 1·31). At day 14, the World health Organization (WHO) clinical progression scale (CPS) was significantly improved in the TCZ+DEX arm (OR 0·69, 95% CrI, 0·49 to 0.97). At day 28, the cumulative incidence of oxygen supply independency was 82% in the TCZ+DEX arms and 72% in the DEX arm (HR 1·36, 95% CI 1·11 to 1·67). On day 90, 24 deaths (11%) were observed in the DEX arm and 18 (8%) in the TCZ+DEX arm (HR 0·77, 95% CI 0·42-1·41). Serious adverse events were observed in 25% and 21% in DEX and TCZ+DEX arms, respectively. Interpretation: Mechanical ventilation need and mortality were not improved with TCZ+DEX compared with DEX alone. The safety of both treatments was similar. However, given the wide confidence intervals for the estimate of effect, definitive interpretation cannot be drawn. Funding: Programme Hospitalier de Recherche Clinique [PHRC COVID-19-20-0151, PHRC COVID-19-20-0029], Fondation de l'Assistance Publique - Hôpitaux de Paris (Alliance Tous Unis Contre le Virus) and from Fédération pour la Recherche Médicale" (FRM). Tocilizumab was provided by Roche.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-312304

ABSTRACT

Background: In moderate-to-severe COVID-19 pneumonia, dexamethasone (DEX) and tocilizumab (TCZ) reduce the occurrence of death and ventilatory support. The efficacy and safety of combining the two drugs remains to be investigated.Methods: Patients with moderate-to-severe COVID-19 pneumonia (WHO class 5) requiring oxygen (>3 L/min) were randomly assigned to receive DEX (10mg/d 5 days tapering up to 10 days) alone or combined with TCZ (8mg/kg IV) at day 1 possibly repeated with a fixed dose of 400 mg i.v at day 3. The primary outcome was time from randomization to mechanical ventilation support or death up to day 14, analyzed on an intent-to-treat basis using a Bayesian approach.Findings: A total of 453 patients were randomized, 3 withdrew consent, 450 were analyzed of whom 226 and 224 patients were assigned to receive DEX or TCZ+DEX, respectively. At day 14, mechanical ventilation or death occurred in 32/226 (14%) and 27/224 (12%) in the DEX and TCZ+DEX arms, respectively (Hazard ratio (HR) [90% credible interval (CrI)], 0.85 [0.55-1.31]). At day 14, WHO CPS scale was significantly improved in the TCZ+DEX arm (OR 0.69, (95% CrI, 0.49 to 0.97). On day 90, 24 deaths (11%) were observed in the DEX arm and 18 (8%) in the TCZ+DEX arm (HR 0.77, 95% CI 0.42-1.41). Patients with at least one serious adverse event were observed in 25 and 21% in DEX and TCZ+DEX arms, respectively.Interpretation: Mechanical ventilation need and mortality were not improved with combination of TCZ and DEX compared with DEX alone. The safety of both treatments was similar. However, given the wide confidence intervals for the estimate of effect, the findings do not allow for a definitive interpretation.Trial Registration: ClinicalTrials.gov number, NCT04476979.Funding: Funded by PHRCDeclaration of Interest: None to declare. Ethical Approval: The CORIMUNO Cohort and all embedded trials (i.e. trials using data collected in the CORIMUNO cohort) were approved by an ethics committee (CPP Île-de-France VI) and relevant authorities.

7.
Eur Respir J ; 2022 Feb 03.
Article in English | MEDLINE | ID: covidwho-1673901

ABSTRACT

QUESTION: To determine whether anti-IL-6 Receptors improve outcomes of critically ill patients with COVID-19 pneumonia. PATIENTS AND METHODS: Two cohort-embedded, investigator-initiated, multicenter, open-label, Bayesian randomised controlled clinical trials. Patients were randomly assigned to receive either usual care (UC) or UC+Tocilizumab (TCZ) 8 mg/kg (TOCI-2 trial), or UC or UC+ Sarilumab (SARI) 200 mg (SARI-2 trial), both intravenously on day 1 (D1) and on D3 if clinically indicated. RESULTS: Between 31 March and 20 April 2020, 97 patients were randomised in the TOCI-2 trial, to receive UC (n=46) or UC+TCZ (n=51). At day 14, numbers of patients who did not need NIV, MV and alive with TCZ or UC were similar (47% versus 42%, median posterior hazard ratio [HR] 1.19, 90% CrI, 0.71 to 2.04), with a posterior probability of HR>1 of 71.4%.Between 27 March and 4 April 2020, 91 patients were randomised in the SARI-2 trial, to receive UC (n=41) or UC+SARI (n=50). At day 14, numbers of patients who did not need NIV, MV and alive with SARI or UC were similar (38% versus 33%, median posterior hazard ratio [HR] 1.05, 90% CrI, 0.55 to 2.07), with a posterior probability of HR>1 of 54.9%.Overall, the risk of death up to day 90 was: UC+TCZ versus UC (24% versus 30%, HR 0.67 [0.30 to 1.49]); UC+SARI versus UC (29% versus 39%, (HR 0.74 ([0.35 to 1.58]). Both TCZ and SARI increased serious infectious events. CONCLUSION: In critically ill patients with COVID-19, anti-IL-6 Receptors did not significantly increase the number of patients alive without any NIV, MV by D14. TRIAL REGISTRATION: ClinicalTrials.gov numbers: (NCT04331808 and NCT04324073).

8.
Clin Infect Dis ; 73(12): 2368-2369, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1597440
9.
SSRN; 2021.
Preprint in English | SSRN | ID: ppcovidwho-291971

ABSTRACT

Patients with hematological malignancies and COVID-19 display a high mortality rate. In such patients, immunosuppression due to underlying disease and previous specific treatment impairs humoral response, limiting viral clearance. Thus, COVID-19 convalescent plasma (CCP) therapy appears to be a promising approach through the transfer of neutralizing antibodies specific to SARS-CoV-2.Our study reports the effect of CCP in a cohort of patients with hematological malignancies and COVID-19 between 1 May 2020 and 1 April 2021. Overall, 112 hospitalized patients with severe COVID-19 (83 B-cell neoplasm, 19 plasma cell neoplasm, and 10 myeloid neoplasm) were included. The overall survival of the whole cohort was 65% [56–74.9] and 77.5% [68.5–87.7] for patients with B-cell neoplasm. Prior anti-CD20 monoclonal antibodies therapy was associated with better overall survival whereas age, high blood pressure, and COVID-19 severity were associated with a poor outcome after CCP transfusion. A retrospective analysis in the subgroup of COVID-19 patients with B-cell neoplasm treated with CCP (n=81) was compared to a similar group of patients (n=120) treated only with standard of care. An inverse probability of treatment weighting (IPTW) approach, performed to limit confusion and immortality bias, revealed a decreased mortality of 63% (95% CI=31%–80%) in the main analysis and 50% (95% CI=28%–66%) in the overall population of the CCP-treated group of patients with similar findings in the other sensitivity analyses.Convalescent plasma may be beneficial in COVID-19 patients with B-cell neoplasm who are unable to mount a humoral immune response. Comparing CCP to other passive immunotherapy approaches such as anti-SARS-CoV-2 monoclonal antibodies is warranted.

10.
Mucosal Immunol ; 15(2): 198-210, 2022 02.
Article in English | MEDLINE | ID: covidwho-1493071

ABSTRACT

As the COVID-19 pandemic is still ongoing, and considering the lack of efficacy of antiviral strategies to this date, and the reactive hyperinflammation leading to tissue lesions and pneumonia, effective treatments targeting the dysregulated immune response are more than ever required. Immunomodulatory and immunosuppressive drugs have been repurposed in severe COVID-19 with contrasting results. The heterogeneity in the timing of treatments administrations could be accountable for these discrepancies. Indeed, many studies included patients at different timepoints of infection, potentially hiding the beneficial effects of a time-adapted intervention. We aim to review the available data on the kinetics of the immune response in beta-coronaviruses infections, from animal models and longitudinal human studies, and propose a four-step model of severe COVID-19 timeline. Then, we discuss the results of the clinical trials of immune interventions with regards to the timing of administration, and finally suggest a time frame in order to delineate the best timepoint for each treatment.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/therapy , Immunosuppressive Agents/administration & dosage , Immunotherapy , SARS-CoV-2/drug effects , Animals , Antiviral Agents/adverse effects , COVID-19/diagnosis , COVID-19/immunology , COVID-19/virology , Drug Administration Schedule , Host-Pathogen Interactions , Humans , Immunosuppressive Agents/adverse effects , Immunotherapy/adverse effects , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Time Factors , Treatment Outcome
11.
Sci Transl Med ; 14(628): eabj7521, 2022 Jan 19.
Article in English | MEDLINE | ID: covidwho-1483988

ABSTRACT

The drivers of critical coronavirus disease 2019 (COVID-19) remain unknown. Given major confounding factors such as age and comorbidities, true mediators of this condition have remained elusive. We used a multi-omics analysis combined with artificial intelligence in a young patient cohort where major comorbidities were excluded at the onset. The cohort included 47 "critical" (in the intensive care unit under mechanical ventilation) and 25 "non-critical" (in a non-critical care ward) patients with COVID-19 and 22 healthy individuals. The analyses included whole-genome sequencing, whole-blood RNA sequencing, plasma and blood mononuclear cell proteomics, cytokine profiling, and high-throughput immunophenotyping. An ensemble of machine learning, deep learning, quantum annealing, and structural causal modeling were used. Patients with critical COVID-19 were characterized by exacerbated inflammation, perturbed lymphoid and myeloid compartments, increased coagulation, and viral cell biology. Among differentially expressed genes, we observed up-regulation of the metalloprotease ADAM9. This gene signature was validated in a second independent cohort of 81 critical and 73 recovered patients with COVID-19 and was further confirmed at the transcriptional and protein level and by proteolytic activity. Ex vivo ADAM9 inhibition decreased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uptake and replication in human lung epithelial cells. In conclusion, within a young, otherwise healthy, cohort of individuals with COVID-19, we provide the landscape of biological perturbations in vivo where a unique gene signature differentiated critical from non-critical patients. We further identified ADAM9 as a driver of disease severity and a candidate therapeutic target.


Subject(s)
COVID-19 , ADAM Proteins , Artificial Intelligence , Humans , Intensive Care Units , Membrane Proteins , Respiration, Artificial , SARS-CoV-2
12.
Ann Rheum Dis ; 81(1): 34-40, 2022 01.
Article in English | MEDLINE | ID: covidwho-1462913

ABSTRACT

OBJECTIVES: To update the EULAR points to consider (PtCs) on the use of immunomodulatory therapies in COVID-19. METHODS: According to the EULAR standardised operating procedures, a systematic literature review up to 14 July 2021 was conducted and followed by a consensus meeting of an international multidisciplinary task force. The new statements were consolidated by formal voting. RESULTS: We updated 2 overarching principles and 12 PtC. Evidence was only available in moderate to severe and critical patients. Glucocorticoids alone or in combination with tocilizumab are beneficial in COVID-19 cases requiring oxygen therapy and in critical COVID-19. Use of Janus kinase inhibitors (baricitinib and tofacitinib) is promising in the same populations of severe and critical COVID-19. Anti-SARS-CoV-2 monoclonal antibodies and convalescent plasma may find application in early phases of the disease and in selected subgroups of immunosuppressed patients. There was insufficient robust evidence for the efficacy of other immunomodulators with further work being needed in relation to biomarker-based stratification for IL-1 therapy CONCLUSIONS: Growing evidence supports incremental efficacy of glucocorticoids alone or combined with tocilizumab/Janus kinase inhibitors in moderate to severe and critical COVID-19. Ongoing studies may unmask the potential application of other therapeutic approaches. Involvement of rheumatologists, as systemic inflammatory diseases experts, should be encouraged in clinical trials of immunomodulatory therapy in COVID-19.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Glucocorticoids/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Azetidines/therapeutic use , Consensus Development Conferences as Topic , Drug Therapy, Combination , Humans , Immunomodulation , Piperidines/therapeutic use , Purines/therapeutic use , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , SARS-CoV-2 , Sulfonamides/therapeutic use
14.
JAMA ; 326(6): 499-518, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1413703

ABSTRACT

Importance: Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm. Objective: To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes. Data Sources: Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts. Study Selection: Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria. Data Extraction and Synthesis: In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality. Main Outcomes and Measures: The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days. Results: A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P < .001) for tocilizumab and 1.08 (95% CI, 0.86-1.36; P = .52) for sarilumab. The summary ORs for the association with mortality compared with usual care or placebo in those receiving corticosteroids were 0.77 (95% CI, 0.68-0.87) for tocilizumab and 0.92 (95% CI, 0.61-1.38) for sarilumab. The ORs for the association with progression to invasive mechanical ventilation or death, compared with usual care or placebo, were 0.77 (95% CI, 0.70-0.85) for all IL-6 antagonists, 0.74 (95% CI, 0.66-0.82) for tocilizumab, and 1.00 (95% CI, 0.74-1.34) for sarilumab. Secondary infections by 28 days occurred in 21.9% of patients treated with IL-6 antagonists vs 17.6% of patients treated with usual care or placebo (OR accounting for trial sample sizes, 0.99; 95% CI, 0.85-1.16). Conclusions and Relevance: In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality. Trial Registration: PROSPERO Identifier: CRD42021230155.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Interleukin-6/antagonists & inhibitors , Aged , COVID-19/complications , COVID-19/mortality , COVID-19/therapy , Cause of Death , Coinfection , Disease Progression , Drug Therapy, Combination , Female , Glucocorticoids/therapeutic use , Hospitalization , Humans , Male , Middle Aged , Prospective Studies , Randomized Controlled Trials as Topic , Respiration, Artificial
17.
JAMA Intern Med ; 181(7): 1020-1021, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1168786
18.
J Allergy Clin Immunol Pract ; 9(6): 2139-2144, 2021 06.
Article in English | MEDLINE | ID: covidwho-1163976

ABSTRACT

Mastocytosis is a neoplasm characterized by an accumulation of mast cells in various organs and increased risk for severe anaphylaxis in patients with concomitant allergies. Coronavirus disease 2019 (COVID-19) is a pandemic that is associated with a relatively high rate of severe lung disease and mortality. The mortality is particularly high in those with certain comorbidities and increases with age. Recently, several companies have developed an effective vaccination against COVID-19. Although the reported frequency of severe side effects is low, there is an emerging discussion about the safety of COVID-19 vaccination in patients with severe allergies and mastocytosis. However, even in these patients, severe adverse reactions are rare. We therefore recommend the broad use of COVID-19 vaccination in patients with mastocytosis on a global basis. The only well-established exception is a known or suspected allergy against a constituent of the vaccine. Safety measures, including premedication and postvaccination observation, should be considered in all patients with mastocytosis, depending on the individual personal risk and overall situation in each case. The current article provides a summary of published data, observations, and expert opinion that form the basis of these recommendations.


Subject(s)
Anaphylaxis , COVID-19 , Mastocytosis , Anaphylaxis/epidemiology , COVID-19 Vaccines , Humans , Mast Cells , Mastocytosis/epidemiology , SARS-CoV-2 , United States , Vaccination
19.
Ann Rheum Dis ; 2021 Feb 05.
Article in English | MEDLINE | ID: covidwho-1066833

ABSTRACT

OBJECTIVES: Severe systemic inflammation associated with some stages of COVID-19 and in fatal cases led therapeutic agents developed or used frequently in Rheumatology being at the vanguard of experimental therapeutics strategies. The aim of this project was to elaborate EULAR Points to consider (PtCs) on COVID-19 pathophysiology and immunomodulatory therapies. METHODS: PtCs were developed in accordance with EULAR standard operating procedures for endorsed recommendations, led by an international multidisciplinary Task Force, including rheumatologists, translational immunologists, haematologists, paediatricians, patients and health professionals, based on a systemic literature review up to 15 December 2020. Overarching principles (OPs) and PtCs were formulated and consolidated by formal voting. RESULTS: Two OPs and fourteen PtCs were developed. OPs highlight the heterogeneous clinical spectrum of SARS-CoV-2 infection and the need of a multifaceted approach to target the different pathophysiological mechanisms. PtCs 1-6 encompass the pathophysiology of SARS-CoV-2 including immune response, endothelial dysfunction and biomarkers. PtCs 7-14 focus on the management of SARS-CoV-2 infection with immunomodulators. There was evidence supporting the use of glucocorticoids, especially dexamethasone, in COVID-19 cases requiring oxygen therapy. No other immunomodulator demonstrated efficacy on mortality to date, with however inconsistent results for tocilizumab. Immunomodulatory therapy was not associated with higher infection rates. CONCLUSIONS: Multifactorial pathophysiological mechanisms, including immune abnormalities, play a key role in COVID-19. The efficacy of glucocorticoids in cases requiring oxygen therapy suggests that immunomodulatory treatment might be effective in COVID-19 subsets. Involvement of rheumatologists, as systemic inflammatory diseases experts, should continue in ongoing clinical trials delineating optimal immunomodulatory therapy utilisation in COVID-19.

20.
Blood ; 136(20): 2290-2295, 2020 11 12.
Article in English | MEDLINE | ID: covidwho-950941

ABSTRACT

Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. Within 48 hours of transfusion, all but 1 patient experienced an improvement of clinical symptoms. The inflammatory syndrome abated within a week. Only 1 patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in all 9 evaluated patients. In 3 patients, virus-specific T-cell responses were analyzed using T-cell enzyme-linked immunospot assay before convalescent plasma transfusion. All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti-SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2.


Subject(s)
Antibodies, Viral/immunology , B-Lymphocytes/pathology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Immune Sera/administration & dosage , Lymphopenia/therapy , Pneumonia, Viral/immunology , Adult , Aged , B-Lymphocytes/immunology , Blood Component Transfusion , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/therapy , Coronavirus Infections/virology , Female , France , Hematologic Neoplasms/complications , Humans , Immunization, Passive , Lymphopenia/etiology , Lymphopenia/pathology , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , SARS-CoV-2
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