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In March 2020, the World Health Organization (WHO) declared that the COVID-19 outbreak can be characterized as a pandemic. Human-to-human transmission of the SARS-CoV-2 virus may initially be blamed as the first cause of spread, but can an infection be contracted by ingestion of contaminated food or touching contaminated food surfaces? Recently cold-chain food contamination has been indicated as a possible source of many human cases in China. However, the risk of a food-related COVID-19 infection is still debated since the virus may reach people through a fresh product or packaging, which have been touched/sneezed on by infected people. This review summarizes the most recent evidence on the zoonotic origin of the pandemic, reports the main results regarding the transmission of SARS-CoV-2 through food or a food chain, as well as the persistence of the virus at different environmental conditions and surfaces. Emphasis is also posed on how to manage the risk of food-related COVID-19 spread and potential approaches that can reduce the risk of SARS-CoV-2 contamination.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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Background: SARS-COV-2 anti-Spike IgG response following mRNA vaccination (BNT162b2) is suboptimal and highly variable in MM patients. Patients and Methods: We report here a single-institution retrospective analysis of 127 consecutive patients with symptomatic MM (71 males, 56 females), [median age 69.5 years (range 45-85)], 63 patients with untreated MM and 64 patients with MM refractory to one or more previous treatment lines. Myeloma therapies included PI+IMiD combos, IMiD-based regimens, PI-based regimens, anti-CD38 mAb-based therapies, antibody-drug conjugates (Belantamab Mafodotin monotherapy), dexamethasone and high dose melphalan. Anti-spike IgG antibody were detected also in 50 healthy volunteers. Patients with symptomatic MM and healthy controls received two dose of COVID-19 mRNA vaccine (Pfizer BioNTech) on days 1 and 21 between 29 April and 15 May 2021. Patients with prior history of SARS-CoV-2 were excluded from analysis. Quantitative determination of anti-spike S1/S2 IgG antibody was performed at 4 weeks from vaccination completion (LIAISONR SARS-COV-2 S1/S2 IgG, LIAISONR). It was previously established a threshold >15 AU/ml of anti-Spike IgG which was related to neutralizing activity of anti-SARS-COV-2 antibodies. Results: Sixty-five out of 127 patients were evaluable for response. Antispike IgG antibody were detected in 50/65 (76.9%) MM patients, defined as responders [177 AU/mL (range 26.4 - 1430)]. 23.1% of MM patients, defined as non-responders, failed to respond at two doses of COVID-19 mRNA vaccine [3.8 AU/mL (range 0.65 - 9.33)]. Seroprotection rate at cutoff of 15 AU/mL was 100% in controls [249 AU/mL (range 104 - 2430)]. No statistically significant differences were found between the two subgroups of patients for myeloma disease phase (relapse/refractory MM vs. untreated symptomatic MM), LDH, residual gammaglobulin levels, WBC, ANC, lymphocytic response, age and sex (Tab. 2). Conversely, plasmacytosis, B2M and haemoglobin concentration were associated with a different response to vaccine. Patients with extreme plasmacytosis (60.0 20.3 vs. 28.218.8 meanSD;p <0.001) (Tab. 2) had a mean titer less than 15 AU/ml of anti-Spike IgG compared with patients with a low plasmacytosis, who, conversely, showed significantly higher mean titers of anti-Spike IgG. B2M was significantly higher in non-responders compared to responders (4.6 4.1 vs. 3.23.6 mean SD;p = 0.006) (Tab. 2). Haemoglobin value was significantly lower in non-responders compared to responders (10.8 1.8 vs. 12.11.8 mean SD;p = 0.008) (Tab. 2). Multivariate analysis confirmed the bone marrow infiltration pattern and haemoglobin value as statistically significant variables. In addition, in the present cohort, the myeloma treatment, including high-dose melphalan and autologous stem cell transplantation, have not been associated with SARS-CoV-2 infection. Conclusions: In our experience, significant fraction of MM patients (23.1%) does not developed any detectable anti-Spike IgG after two dose of COVID-19 mRNA vaccine. Lack of IgG response associated with three statistically significant variables: extreme plasmacytosis, B2M, and haemoglobin concentration. In the subgroup of patients with good response to vaccine, after a median follow-up of 7 months from second dose of COVID-19 mRNA vaccine, no cases of COVID-19 occurred. .
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The ongoing COVID-19 pandemic is the first epidemic in human history in which digital contact tracing has been deployed at a global scale. Tracking and quarantining all the contacts of individuals who test positive for a virus can help slow down an epidemic, but the impact of contact tracing is severely limited by the generally low adoption of contact-tracing apps in the population. We derive here an analytical expression for the effectiveness of contact-tracing app installation strategies in a susceptible-infected-recovered (SIR) model on a given contact graph. We propose a decentralized heuristic to improve the effectiveness of contact tracing under fixed adoption rates, which targets a set of individuals to install contact-tracing apps and can be easily implemented. Simulations on a large number of real-world contact networks confirm that this heuristic represents a feasible alternative to the current state of the art. © 2022 authors. Published by the American Physical Society. Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.
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We sought to determine parameters of the acute phase response, a feature of innate immunity activated by infectious noxae and cancer, deranged by Covid-19 and establish oncological indices' prognostic potential for patients with concomitant cancer and Covid-19. Between 27/02 and 23/06/2020, OnCovid retrospectively accrued 1,318 consecutive referrals of patients with cancer and Covid-19 aged 18 from the U.K., Spain, Italy, Belgium, and Germany. Patients with myeloma, leukemia, or insufficient data were excluded. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and prognostic index (PI) were evaluated for their prognostic potential, with the NLR, PLR, and PNI risk stratifications dichotomized around median values and the pre-established risk categorizations from literature utilized for the mGPS and PI. 1,071 eligible patients were randomly assorted into a training set (TS, n=529) and validation set (VS, n=542) matched for age (67.9±13.3 TS, 68.5±13.5 VS), presence of 1 comorbidity (52.1% TS, 49.8% VS), development of 1 Covid-19 complication (27% TS, 25.9% VS), and active malignancy at Covid-19 diagnosis (66.7% TS, 61.6% VS). Among all 1,071 patients, deceased patients tended to categorize into poor risk groups for the NLR, PNI, mGPS, and PI (P<0.0001) with a return to pre-Covid-19 diagnosis NLR, PNI, and mGPS categorizations following recovery (P<0.01). In the TS, higher mortality rates were associated with NLR>6 (44.6% vs 28%, P<0.0001), PNI<40 (46.6% vs 20.9%, P<0.0001), mGPS (50.6% for mGPS2 vs 30.4% and 11.4% for mGPS1 and 0, P<0.0001), and PI (50% for PI2 vs 40% for PI1 and 9.1% for PI0, P<0.0001). Findings were confirmed in the VS (P<0.001 for all comparisons). Patients in poor risk categories had shorter median overall survival [OS], (NLR>6 30 days 95%CI 1-63, PNI<40 23 days 95%CI 10-35, mGPS2 20 days 95%CI 8-32, PI2 23 days 95%CI 1-56) compared to patients in good risk categories, for whom median OS was not reached (P<0.001 for all comparisons). The PLR was not associated with survival. Analyses of survival in the VS confirmed the NLR (P<0.0001), PNI (P<0.0001), PI (P<0.01), and mGPS (P<0.001) as predictors of survival. In a multivariable Cox regression model including all inflammatory indices and pre-established prognostic factors for severe Covid-19 including sex, age, comorbid burden, malignancy status, and receipt of anti-cancer therapy at Covid-19 diagnosis, the PNI was the only factor to emerge with a significant hazard ratio [HR] in both TS and VS analysis (TS HR 1.97, 95%CI 1.19-3.26, P=0.008;VS HR 2.48, 95%CI 1.47- 4.20, P=0.001). We conclude that systemic inflammation drives mortality from Covid-19 through hypoalbuminemia and lymphocytopenia as measured by the PNI and propose the PNI as the OnCovid Inflammatory Score (OIS) in this context.
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Background: Over a third of pts with 1L DLBCL do not respond to, or relapse after, rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP;[Sarkozy and Sehn. Ann Lymphoma 2019]). Despite recent advances, pts with R/R NHL have limited curative options. Glofitamab (Glofit) is a novel, T-cell-engaging bispecific antibody with a 2:1 molecular configuration that allows bivalent binding to CD20 on B cells and monovalent binding to CD3 on T cells. Unlike other CD20xCD3 bispecific antibodies, this format uniquely enables combination with anti-CD20 antibodies, including rituximab. Glofit monotherapy induces high response rates in R/R B-cell NHL (Hutchings et al. J Clin Oncol 2021). We present results of the ongoing NP40126 study (NCT03467373), designed to assess the feasibility and safety of Glofit + R-CHOP in R/R NHL (dose-escalation phase) and 1L DLBCL (safety run-in phase). Methods: R/R NHL dose-escalation: Pts (Eastern Cooperative Oncology Group performance status [ECOG PS] 0-2) received increasing Glofit doses in separate cohorts (70µg, 1800µg, 10mg and 30mg) plus standard R-CHOP for 6-8 cycles (each 21-day). To mitigate CRS risk, R- or obinutuzumab (G)-CHOP was given in Cycle (C)1, with the aim of tumor debulking. Glofit was given from C2 onwards. For 70µg and 1800µg cohorts, fixed-dose Glofit was given on C2 Day (D)8 and onwards. For 10mg and 30mg cohorts, step-up dosing was used to further mitigate CRS risk (2.5mg C2D8, 10mg C2D15, target dose C3D8 and onwards). Optional Glofit maintenance was permitted (every 2 months for <2 years;dose-escalation phase only). 1L DLBCL safety run-in: Pts (ECOG PS 0-3) received Glofit 30mg plus standard R-CHOP for 6-8 cycles (each 21-day). Pts received R-CHOP in C1;Glofit step-up dosing began in C2 (2.5mg C2D8, 10mg C2D15, 30mg C3D8 and onwards). Response rates were assessed by PET-CT (Lugano criteria;[Cheson et al. J Clin Oncol 2014]). CRS events were graded by ASTCT criteria [Lee et al. Biol Blood Marrow Transplant 2019]. Results: R/R NHL dose-escalation: At data cut-off (June 10, 2021), 31 pts (23 follicular lymphoma [FL];6 transformed FL;1 marginal-zone lymphoma;1 mantle-cell lymphoma) had received Glofit with R/G-CHOP. Median age was 62 years, median prior lines of therapy was 2 (range: 1-5). In efficacy-evaluable pts (n=31), after a median 9.0 months' (range: 0-29) follow-up, the overall response rate (ORR) was 90% (n=28) and complete response rate (CRR) was 77% (n=24). Median duration of response was not reached. The Figure shows change in tumor size. Grade (Gr) ≥3 adverse events (AEs) occurred in 28 (90%) pts, serious AEs in 21 (68%) pts and CRS in 17 (55%) pts (mostly low grade;majority after the first 2.5mg Glofit dose;Table). One (3%) pt had a Gr 5 AE (COVID-19 pneumonia not related to study treatment). AEs led to Glofit dose modification/interruption in 2 (6%) pts and Glofit withdrawal in 1 (3%) pt. Neurologic AEs (NAEs) occurred in 20 (65%) pts: Gr 1-2 (16 pts, 52%);Gr 3 (4 pts, 13%). Immune effector cell-associated neurotoxicity syndrome (ICANS)-like AEs were uncommon;a serious AE was reported in 1 pt only (Gr 3 epilepsy during the maintenance phase;resolved in 3 days). Neutropenia occurred in 24 (77%) pts. Median dose intensity was 100% for all R-CHOP components. 1L DLBCL safety run-in: At data cut-off, 13 pts were enrolled (safety population);of these, 4 pts received Glofit 30mg with R-CHOP and were efficacy-evaluable. Median age was 68 years, all pts had Ann Arbor Stage 3/4 disease. At interim assessment (C3), CRR was 100% (4/4). Of 13 pts, 1 (8%) had a CRS event (Gr 1 with fever only) after the first 2.5mg Glofit dose;no other CRS events observed. Gr ≥3 AEs occurred in 8 (62%) pts and Gr ≥3 AEs related to Glofit in 1 (8%) pt only. One (8%) pt had a serious AE and 1 (8%) pt had a Gr 5 AE (infusion-related reaction related to rituximab on C1D1). No AEs led to Glofit or R-CHOP dose interruptions. NAEs occurred in 3 (23%) pts (all Gr 1-2;none were ICANS-like). Neutropenia occurred in 6 (46%) pts. Median dose intensity was 10 % for all R-CHOP components. Conclusions: Initial data show that Glofit + R-CHOP has tolerable safety in R/R NHL and 1L DLBCL. R-CHOP dose intensity was maintained in all pts. The very low CRS rate and no neurotoxicity in 1L DLBCL may render Glofit particularly suitable for the outpatient setting without the need for hospitalization. Updated data, including end-of-treatment responses from the 1L DLBCL safety run-in phase, will be presented. [Formula presented] Disclosures: Ghosh: Seattle Genetics: Consultancy, Honoraria, Speakers Bureau;Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau;Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau;AbbVie: Honoraria, Speakers Bureau;Karyopharma: Consultancy, Honoraria;AstraZeneca: Consultancy, Honoraria, Speakers Bureau;ADC Therapeutics: Consultancy, Honoraria;Adaptive Biotech: Consultancy, Honoraria;TG Therapeutics: Consultancy, Honoraria, Research Funding;Genmab: Consultancy, Honoraria;Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau;Epizyme: Honoraria, Speakers Bureau;Incyte: Consultancy, Honoraria;Janssen: Consultancy, Honoraria, Speakers Bureau;Genentech: Research Funding. Townsend: Celgene (Bristol-Myers Squibb): Consultancy, Honoraria;F. Hoffmann-La Roche Ltd: Consultancy, Honoraria. Dickinson: Amgen: Honoraria;Celgene: Research Funding;Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau;Takeda: Research Funding;Gilead Sciences: Consultancy, Honoraria, Speakers Bureau;MSD: Consultancy, Honoraria, Research Funding, Speakers Bureau;Janssen: Consultancy, Honoraria;Bristol-Myers Squibb: Consultancy, Honoraria;Roche: Consultancy, Honoraria, Other: travel, accommodation, expenses, Research Funding, Speakers Bureau. Topp: Celgene: Consultancy, Research Funding;Janssen: Consultancy;Universitatklinikum Wurzburg: Current Employment;Kite, a Gilead Company: Consultancy, Research Funding;Novartis: Consultancy;Roche: Consultancy, Research Funding;Gilead: Research Funding;Regeneron: Consultancy, Research Funding;Macrogeniecs: Research Funding;Amgen: Consultancy, Research Funding. Santoro: Sandoz: Speakers Bureau;Eli-Lilly: Speakers Bureau;Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;AstraZeneca: Speakers Bureau;Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Celgene: Speakers Bureau;Amgen: Speakers Bureau;AbbVie: Speakers Bureau;Roche: Speakers Bureau;BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Eisai: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Takeda: Speakers Bureau;Sanofi: Consultancy;Arqule: Consultancy, Speakers Bureau;Novartis: Speakers Bureau;Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;MSD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Crump: Novartis: Membership on an entity's Board of Directors or advisory committees;Kyte/Gilead: Membership on an entity's Board of Directors or advisory committees;Epizyme: Research Funding;Roche: Research Funding. Morschhauser: Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;Genentech, Inc.: Consultancy;Genmab: Membership on an entity's Board of Directors or advisory committees;Roche: Consultancy, Speakers Bureau;BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees;Chugai: Honoraria;Incyte: Membership on an entity's Board of Directors or advisory committees;Servier: Consultancy;AstraZenenca: Membership on an entity's Board of Directors or advisory committees;Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees;F. Hoffmann-La Roch Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Celgene: Membership on an entity's Board of Directors or advisory committees;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria. Mehta: Kite/Gilead;Roche-Genetech;Celgene/BMS;Oncotartis;Innate Pharmaceuticals;Seattle Genetics;Incyte;Takeda;Fortyseven Inc/Gilead;TG Therapeutics;Merck;Juno Pharmaceuticals/BMS: Research Funding;Seattle Genetics;Incyte;TG Therapeutics: Consultancy;Seattle Genetics;Incyte;TG Therapeutics: Membership on an entity's Board of Directors or advisory committees. Panchal: F. Hoffmann-La Roche Ltd: Current Employment. Wu: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Barrett: Roche Products Ltd: Current Employment;F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Humphrey: Roche: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Qayum: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Hutchings: Novartis: Research Funding;Janssen: Honoraria, Research Funding;Incyte: Research Funding;Genentech: Honoraria, Research Funding;Celgene: Research Funding;Takeda: Consultancy, Honoraria, Research Funding;Roche: Consultancy, Honoraria, Research Funding;Genmab: Consultancy, Honoraria, Research Funding. OffLabel Disclosure: Glofitamab is a full-length, humanized immunoglobulin G1 bispecific antibody with a 2:1 molecular format that facilitates bivalent binding to CD20 on B-cells, and monovalent binding to CD3 on T-cells. Glofitamab redirects T cells to engage and eliminate malignant B cells. Glofitamab is an investigational agent. Rituximab (Rituxan) is aCD20-directed cytolytic antibody indicated for the treatment of adult pts with: relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL as a single agent;previously untreated follicular, CD20-positive, B-cell NHL in combination with first-line chemotherapy (chemo) and, in pts achieving a CR or PR to a rituximab product in combination with chemo, as single-agent maintenance therapy;non-progressing (including stable disease), low-grade, CD20 positive, B-cell NHL as a single agent after first-line CVP chemo;previously untreated diffuse large B-cell, CD20-positive, NHL in combination with CHOP or other anthracycline-based chemo regimens;previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide.
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Background: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is an effective option for the treatment of relapsed/refractory diffuse large B-cell lymphoma. In order to control lymphoma progression during the manufacturing period, a bridge therapy regimen is required for most patients. Radiotherapy (RT) may be used for patients with localized chemorefractory disease as a bridge therapy. Patients: Here we report a case series of 6 patients (1 primary mediastinal, PMBCL, and 5 diffuse large B-cell lymphoma, DLBCL) treated with radiotherapy as bridge to CAR-T. (Figure 1 summarizes the treatment history). Four patients received tisagenlecleucel (tisa-cel), and one axicabtagene- ciloleucel (axi-cel);one patient died before reinfusion of CAR-T. Results: The dose of RT was 30 Gy in 15 fractions, the site was mediastinum for pt 001, abdominal adenopathy for pt 002, 003 and 005, inguinal adenopathy for pt 004, laterocervical adenopathy for pt 006). Median volume of irradiation was 210 ml (avg. 270 ml, min 79,6 ml, max 635 ml). Response to bridging RT was achieved in 3/ patients (2 PR, 1 CR), one patient had stable disease, and one patient ha disease progression at the time of CAR-T infusion. One patient died for severe Covid19 pneumonia before receiving the planned CART infusion. The outcome is favorable at the time of writing for all infused patient but one, who died for progression 3 months after infusion (the one with progressive disease at the time of infusion). Toxicity was manageable, with no grade 3-4 CRS;maximum CRS grade was 2 in 3 cases. Only one patient receiving axi-cel needed admission at ICU for grade 4 ICANS, with complete resolution after treatment with high dose steroids. Conclusions: We showed in this report that RT is feasible and effective as bridging therapy for patients with localized disease before CAR-T therapy.
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BACKGROUND AND AIMS: Many studies are available that reported a higher risk of COVID-19 disease among patients on dialysis or with kidney transplantation, and the poor outcome of COVID-19 in these patients. Patients in conservative therapy for chronic kidney disease (CKD) have received lower attention, therefore little is known about how COVID-19 may affect this population. The aim of this study was to analyse the COVID-19 incidence and mortality in CKD patients followed up in an integrated healthcare program, living in a small area of Northern Italy. METHOD: The study population included CKD patients from the Emilia-Romagna Prevention of Progressive Renal Insufficiency (PIRP) project, followed up in the 4 nephrology units (Ravenna, Forlì, Cesena and Rimini) of AUSL Romagna (Italy) and alive at 1.01.2020. All patients were in conservative therapy and none of them had initiated dialysis or received kidney transplantation. The hospital discharge database was used to identify patients hospitalized with COVID-19 up to 31.07.2020, and the mortality database was used to assess mortality among patients with COVID-19 at the same date. Multivariable logistic regression was used to identify predictors of COVID- 19 disease, and Kaplan-Meier survival analysis to identify predictors of COVID-19 mortality. Excess mortality of 2020 compared to mortality in 2015-19 in the PIRP cohort was also estimated. RESULTS: COVID-19 incidence among CKD patients was 4.09% (193/4716 patients), while in the general population it was 0.46% (5,195/1,125,574). COVID-19 was more likely in CKD patients with older age (Odds Ratio=1.038), cardiovascular comorbidities (OR=2.217), COPD (OR=1.559) and less likely in patients living in the province of Ravenna (OR=0.468), that was hit later by the first wave of pandemic compared to the other areas of AUSL Romagna. Baseline eGFR was lower in CKD patients with COVID-19 (31.7 vs. 35.8 ml/min/1.73 m2), but this difference did not reach statistical significance (p=0.066). As of 31.07.2020, the crude mortality rate among CKD patients with COVID-19 was 44.6% (86/193), compared to 4.7% (215/ 4523) in CKD patients without COVID-19 and to 14.5% (4289/29670) in the general population with COVID-19 of the Emilia-Romagna region. Factors associated with mortality of CKD patients with COVID-19 were older age (p=0.034) and the period of COVID-19 onset (p=0.003). The highest crude mortality rate (71.4%) was found in CKD patients for whom COVID-19 onset occurred between 8 and 21 March. The excess mortality of January-July 2020 with respect to the average mortality of January- July 2015-19 in the PIRP cohort was +17.7%, corresponding to 77 excess deaths. March-April was the period with the highest excess mortality (+69.8%), while in January-February a 15.9% lower mortality was observed with respect to the corresponding months of the five previous years. CONCLUSION: In our study, including a cohort of regularly followed up CKD patients, the risk of COVID-19 disease and of COVID-19 related mortality was comparable, or even somewhat higher, to that observed in patients on dialysis and those who received kidney transplantation. The incidence of COVID-19 in CKD patients was higher in the areas of AUSL Romagna earlier affected by the pandemic wave, whereas mortality rates were similar across all areas. CKD patients represent a population very vulnerable to COVID-19 disease, and their protection should be highly prioritized in the models of care and prevention measures.
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Background: The use of cytokine-blocking agents has been proposed to modulate the inflammatory response in patients with COVID-19. Tocilizumab and anakinra were included in the local protocol as an optional treatment in critically ill patients with acute respiratory distress syndrome (ARDS) by SARS-CoV-2 infection. This cohort study evaluated the effects of therapy with cytokine blocking agents on in-hospital mortality in COVID-19 patients requiring mechanical ventilation and admitted to intensive care unit. Methods: The association between therapy with tocilizumab or anakinra and in-hospital mortality was assessed in consecutive adult COVID-19 patients admitted to our ICU with moderate to severe ARDS. The association was evaluated by comparing patients who received to those who did not receive tocilizumab or anakinra and by using different multivariable Cox models adjusted for variables related to poor outcome, for the propensity to be treated with tocilizumab or anakinra and after patient matching. Results: Sixty-six patients who received immunotherapy (49 tocilizumab, 17 anakinra) and 28 patients who did not receive immunotherapy were included. The in-hospital crude mortality was 30,3% in treated patients and 50% in non-treated (OR 0.77, 95% CI 0.56-1.05, p=0.069). The adjusted Cox model showed an association between therapy with immunotherapy and in-hospital mortality (HR 0.40, 95% CI 0.19-0.83, p=0.015). This protective effect was further confirmed in the analysis adjusted for propensity score, in the propensity-matched cohort and in the cohort of patients with invasive mechanical ventilation within 2 hours after ICU admission. Conclusions: Although important limitations, our study showed that cytokine-blocking agents seem to be safe and to improve survival in COVID-19 patients admitted to ICU with ARDS and the need for mechanical ventilation.