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Noninvasive ventilation (NIV) by helmet or mask is increasingly being used for treatment of patients with acute hypoxemic respiratory failure (ARF) of varied etiologies. Although the first significant data of benefit from NIV comes from studies performed in Intensive Care Units, subsequently these methodologies have been used with increasing frequency in Emergency Departments and Medical Wards. Despite the overall success of NIV, failure rates still occur in clinical settings such as for acute asthma, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and severe pneumonia. Acceptance of the interface by the patient is crucial for successful treatment. Poor cooperation with the interface from onset of treatment will hamper NIV effectiveness. That’s why interface choice is essential from the beginning. Offering various interface models and sizes may enhance compliance for those who might not adapt well to one but might comply with another. In this context, the role of a properly trained nursing staff becomes essential for the success of NIV. Helmet and mask NIV are recommended treatments for hypoxemic ARF in general. Recent data on avoidance of intubation and improvement in outcomes are conflicting for patients with moderate or severe ARDS, for which further investigations are needed. In COVID-19 respiratory failure, healthcare professionals not only have to determine the best treatment, but also eliminate virus transmission. The administration of NIV via helmet or mask seems to improve oxygenation and decrease need for intubation for patients with COVID-19 pneumonia in hypoxemic ARF. Just as importantly, with COVID-19 being extremely contagious, it is vital to adhere to the infection control measures of the policies of hospitals, health departments, recommendations from WHO and the Centers for Disease Control and Prevention to limit viral transmission during NIV therapy. © 2022 by Nova Science Publishers, Inc. All rights reserved.
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Background: Patients with systemic autoimmune diseases (SADs) are often treated with drugs that interfere with the immune system and previous data showed a reduced seroconversion rate after anti-SARS-CoV2 vaccine in these subjects compared to healthy controls1. Administration of a booster dose of the vaccine could be particularly important in these patients, but data available to date are still scarce. Objectives: To evaluate the antibody response to the booster dose of mRNA SARS-CoV2 vaccine in patients with SADs and to compare it to the response after completion of the frst vaccination course. Secondly, to fnd possible correlations between a low antibody titre and patients' clinical features, with special regard to ongoing immunosuppressive therapies. Methods: Consecutive patients with an established diagnosis of SADs undergoing SARS-CoV2 vaccine were prospectively enrolled from January 2021;among them, we selected the patients who received the third vaccination dose between September and December 2021. Demographic and clinical data were collected at enrolment (sex, age, diagnosis, disease duration, ongoing therapies, previous SARS-CoV2 infection, presence of hypogammaglobulinemia);the last three elements were reassessed at each follow-up visit. Blood samples were collected 4 weeks both after the second (W4a) and the third (W4b) dose of the vaccine;a minority of patients was also tested 12 weeks after the second dose (W12). IgG antibodies to SARS-CoV2 receptor-binding domain (RBD) and neutralizing antibodies inhibiting the interaction between RBD and angiotensin converting enzyme 2 were evaluated. IgG anti-RBD were detected by solid phase assay on plates coated with recombinant RBD, while neutralising antibodies by using the kit SPIA (Spike Protein Inhibition Assay). Cut-off values were defned as the 97.5th percentile of a pre-vaccine healthy population. Statistical analysis was performed using IBM SPSS Statistics 20 and GraphPad Prism statistical packages. P values <0.05 were considered signifcant. Results: Forty-five patients (95.6% female;mean age ±SD 55.6±14.1 years;mean disease duration 12.9±10.6 years) were enrolled. Diagnosis was in most cases connective tissue disease (31/45, 68.9%), followed by infammatory arthritis (11/45, 24.4%) and systemic vasculitis (3/45, 6.7%). Two patients (4.4%) had a previous SARS-CoV2 infection and three had hypogammaglobulinemia (6.7%). At the time of the second dose, 18/45 patients were treated with glucocorticoids (GCs) [mean daily 6-methylprednisolone (6MP) dose 3.9 mg (min. 2, max. 14)], 17/45 with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and 12/45 with biologic DMARDs (bDMARDs). At the third dose administration, 19/45 patients were treated with GCs [mean daily 6MP dose 4.1 mg (min. 1.5, max. 10)], 18/45 with csDMARDs and 13/45 with bDMARDs. Anti-RBD IgG were positive in 42/45 patients (93.3%) at W4a, in 16/18 (88.9%) at W12 and in 42/45 (93.3%) at W4b. Neutralizing antibodies were present in 38/45 patients (84.4%) at W4a, in 14/18 (77.8%) at W12 and in 42/45 (93.3%) at W4b. Both anti-RBD IgG titers and neutralizing antibody titers signifcantly increased after the third dose if compared to W4a (p<0.0001 both) (Figure 1). Interestingly, of the 7 patients who had not developed an adequate neutralizing antibody response after the frst vaccination course, 5 mounted an adequate titer after the booster. Two non-responder patients were both on combination therapy (one with low dose of GCs plus mycophenolate mofetil, the other with methotrexate and infiximab). Conclusion: Our data suggest that in patients with SADs there is a decline in the antibody titers developed after COVID-19 vaccination, however the booster dose is effective in restoring an adequate antibody titre. These data consolidate the importance of a booster dose of COVID-19 vaccination in patients with SADs to aid in the generation of an immune response.
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Background: Growing evidence from in vitro and clinical studies have highlighted important similarities between severe COVID-19 and rapidly progressive interstitial lung diseases (ILD) occurring in systemic autoimmune disorders. These data supported the use of anti-rheumatic drugs, baricitinib and glucocor-ticoids, for the treatment of COVID-19 pneumonia. Objectives: To compare mortality rate and infammatory response in critically ill COVID-19 patients treated with either a 'rheumatologic approach' based on baricitinib plus pulse steroids (BPS) or with a 'conventional approach' (Standard of Care, SoC). Methods: In this retrospective study, we enrolled patients admitted to the Intensive Care Unit (ICU) with CT-proven SARS-CoV2 pneumonia, from September 2020 to April 2021. Demographic, laboratory, and clinical data were collected at the admission to ICU and after one week of treatment. SoC included dexameth-asone 6 to 8 mg daily plus remdesivir (+/-antibiotics and hydroxychloroquine);BPS approach was based on baricitinib 4 mg daily for 10-14 days plus 6-methyl-prednisolone pulses (250-500 mg) for three consecutive days followed by rapid tapering. The primary endpoint was the intra-ICU mortality rate;the secondary endpoint was the change in infammatory biomarkers at week 1 after treatment. Results: We enrolled a total of 210 consecutive patients with SARS-CoV2 pneumonia (male 61.4%, mean age 66.6 ± 10.9 years);137/210 (male 59.8%, mean age 66.3 ± 11.9 years) were treated with SoC and 73/210 (male 64.3%, mean age 67.3 ± 8.8 years) with BPS. At admission in ICU, all patients presented lag time from the frst symptom of SARS-CoV2 infection ≤ 10 days, laboratory biomarkers' alterations suggestive of hyper-infammatory response (CRP 10.8 ± 11.9 mg/dL, ferritin 1238 ± 1005 μ g/L, fbrinogen 575 ± 173 mg/dL, LDH 385 ± 152 U/L) and severe respiratory failure, requiring non-invasive or invasive ventilatory support. Lung-CT pattern showed multiple and diffuse areas of ground glass opacities, septal thickening, and/or consolidation. No statistically signifcant differences were found between SoC and BPS groups in terms of demographic, laboratory, and clinical features at enrolment. 59/210 (28.1%) patients died during ICU hospitalization (mean ICU length of stay 14.6 ± 9.6 days). Mortality rate in the BPS group (13/73, 17.8%) resulted signifcantly lower compared to that in the SoC group (46/137, 33.6%) (p= 0.016). Furthermore, patients in the BPS group had signifcantly lower levels of CRP (BPS=1.9 ± 2.8 vs SoC 6.1 ± 7.3, p<0.001) and fbrinogen (BPS=335 ± 108 vs SoC 453 ± 172, p<0.001) at one week after the start of treatment. Conclusion: Our real-life experience, in an ICU setting, showed that baricitinib and pulse steroids combination was associated with a lower mortality rate paralleled by a prompt reduction of infammatory biomarkers. These results shed new light on the possible usefulness of baricitinib for the treatment of rapidly progressive ILD in patients with systemic autoimmunity and hyper-infammation.
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Background: Since the COVID-19 vaccination campaign was launched all over Europe, there has been general agreement on how benefts of SARS-CoV2 vaccines outweigh the risks in patients with rare connective tissue diseases (rCTDs). Yet, there is still limited evidence regarding safety and efficacy of such vaccines in these patients, especially in the long-term. For this reason, in the framework of ERN-ReCONNET, an observational long-term study (VACCINATE) was designed in order to explore the long-term outcome of COVID-19 vaccination in rCTDs patients. The consent form was developed thanks to the involvement of the ERN ReCONNET ePAG Advocates (European Patients Advocacy Group). Objectives: To evaluate the safety profile of COVID-19 vaccination in rCTDs patients and the potential impact on disease activity. Primary endpoints were the prevalence of adverse events (AEs) and of disease exacerbations post-vaccination. Secondary endpoints were the proportion of serious adverse events (SAEs) and adverse events of special interest for COVID-19 (adapted from https://bright-oncollaboration.us/wp-content/uploads/2021/01/SO2-D2.1.2-V1.2-COVID-19- AESI-update-23Dec2020-review-fnal.pdf) Methods: The frst ad-interim analysis of the VACCINATE study involved 9 ERN-ReCONNET Network centres. Patients over 18 years of age with a known rCTD and who received vaccine against COVID-19 were eligible for recruitment. Demographic data and diagnoses were collected at the time of enrolment, while the appearance of AEs and potential disease exacerbations were monitored after one week from each vaccination dose, and then after 4, 12 and 24 weeks from the second dose. A disease exacerbation was defned as at least one of the following: new manifestations attributable to disease activity, hospital-ization, increase in PGA from previous evaluation, addition of corticosteroids or immunosuppressants. Results: A cohort of 300 patients (261 females, mean age 52, range 18-85) was recruited. Systemic lupus erythematosus (44%) and systemic sclerosis (16%) were the most frequent diagnoses, followed by Sjogren's syndrome (SS,12%), idiopathic infammatory myositis (IMM,10%), undifferentiated connective tissue disease (UCTD,8%), mixed connective tissue disease (MCTD,4%), Ehlers-Dan-los's syndrome (EDS,4%), antiphospholipid syndrome (APS,2%). AEs appearing 7 days after the frst and second doses were reported in 93 (31%) and 96 (32%) patients respectively, mainly represented by fatigue, injection site reaction, headache, fever and myalgia. Otitis, urticaria, Herpes Simplex-related rash, stomatitis, migraine with aura, vertigo, tinnitus and sleepiness were reported with very low frequency. Less than 2% of patients experienced AEs within 24 weeks from the second dose. No SAEs or AEs of special interest were observed in the study period. There were 25 disease exacerbations (8%), 7 of which severe. The highest number of exacerbations was observed after 4 weeks from the second dose (12 within week 4, 6 within week 12 and 7 within week 24). Disease exacerbation was most frequent in patients with EDS (33%) and MCTD (25%). Conclusion: This preliminary analysis shows that COVID-19 vaccination is safe in rCTDs patients. AEs appear most often early after vaccination and are usually mild. Disease exacerbations are not frequent, but can be potentially severe and tend to occur most frequently within the frst month after vaccination. Exacerbations can also occur 3-6 months after vaccination, although a causal relationship with the vaccination remains to be established. Our present data underline the importance of long-term observational studies.
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Background: the pathogenesis of severe COVID-19 involves the deregulated activation of different compartments of immunothrombosis, which are otherwise important for pathogen eradication and tissue repair. Coagulation activation, angiogenesis and alterations of endothelial barrier (EB) are elements of immunothrombosis that have been shown to be involved in the pathogenesis of COVID-19. Angiopoietins (Ang) 1 and 2 and their receptor Tie2 and VEGF-A are well-known pro-angiogenic mediators that, during inflammation also mediate EB disruption. Recently, it has also been demonstrated that the Ang/Tie2 pathway is involved in coagulation activation. Here we explored whether increased levels of angiogenesis/EB regulators (which have been previously associated with disease severity in COVID-19) are also associated with both EB disruption and coagulation activation in this condition. Methods: the study population consisted of 30 patients with COVID-19 confirmed by RT-PCR and presenting typical CT findings admitted due to hypoxemia. Thirty sex- and age-matched healthy individuals were recruited at the same time, from the same geographic region. Patients were part of a clinical trial (REBEC: U1111-1250-1843) but samples were obtained before any study intervention, within 24 hours from diagnosis confirmation. Circulating levels of angiogenesis/EB regulation mediators and coagulation biomarkers were measured by commercial assays (immunological or functional). Monolayers of endothelial cells from umbilical veins (HUVECs) or lung (HULECs) were used for measurement of EB integrity using an impedance sensor system (ECIS, Electric Cell-substrate Impedance Sensing System). Cells were stimulated with serum from patients or healthy individuals and EB integrity was continuously monitored for 36 hours. Clinical outcomes were obtained from the digital medical records. Results: mean length of hospital stay (LOS) was 12.9 ± 9.8 days. Twelve patients (40%) required intensive care (ICU) and 28/30 patients survived. Mean D-dimer was 3,609 ± 14,440 ng/mL. Circulating levels of Ang1, Ang2, sTie2 and VEGF-A were all significantly increased in patients compared to healthy individuals (Ang1: 463.2 ± 194.6 vs 237.4 ± 104.9 pg/mL, p<0.0001;Ang2: 1,926 (1,275 - 3,134) vs 1,215 (9 - 1,440 pg/mL), p<0.0001;Tie2: 10,753 ± 2,377 vs 8,603 ± 1,851 pg/mL, p<0.0001 and VEGF-A: 94.7 (73.4 - 116.0) vs 45.9 (39.7 - 57.0 pg/mL), p<0.0001.). In contrast, soluble VE-cadherin levels were decreased in patients compared to healthy individuals (1,234 ± 318 vs 1,539 ± 363 ng/mL, P=0.001). Serum from COVID-19 patients induced decreases of EB integrity in monolayers of both HUVECs and HULECs as early as 15 minutes, lasting up to 5 hours after stimulation (figure 1). The magnitude of EB disruption was correlated with clinically relevant outcomes such as time of ICU stay and LOS (figure 1). Interestingly, levels of Ang1, Ang2 and soluble VE-cadherin levels were also significantly correlated with the magnitude of EB disruption, as well as with biomarkers of coagulation activation such as fibrinogen, Von Willebrand Factor antigen levels, PAI-1, P-selectin and urokinase receptor (uPAR). Conclusions: Ang-1/Ang-2 mediated Tie2 signaling has been shown to be important for the fine regulation of barrier integrity and coagulation activation at the endothelial level, which are two critical elements of immunothrombosis. Our results provide evidence supporting that the interplay between these processes can play a role in the mechanisms driving COVID-19 severity, and suggest that targeting the Ang/Tie2 and VEGF-A pathways could be attractive strategies to modulate not only changes of the alveolar-capillary barrier, but also of coagulation activation in COVID-19. Figure 1. In (a), endothelial barrier (EB) integrity of HUVEC monolayers upon stimulation by serum from COVID-19 patients and healthy individuals (n=27-30 per group). The lower the normalized resistance, the higher the magnitude of EB disruption. Significant differences (* to ****) are evident from 15 min to 5 hours (An va corrected for multiple comparisons). In the lower panels, the correlation of EB disruption with clinically relevant outcomes such as length of hospital stay (b) and days of intensive care (c) are shown. Negative correlations (Spearman test) indicate that the magnitude of EB disruption is associated with worse outcomes. [Formula presented] Disclosures: No relevant conflicts of interest to declare.
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In this paper, ARPA Lombardy presents the simulation results and a preliminary impact assesment on air quality due to the introduction of limitation and social distancing rules for contrasting the diffusion of COVID-19 disease. A specific data flux and methodology have been developed on the base of the most recent emission inventory available for the Lombardy region and algorithms, ad hoc built up for the study, to estimate the primary emission variations of the main atmospheric pollutant, potentially affected by the anti-COVID rules. Two emission scenarios have been identified:”BAU”, defined as business as usual, and”COVID”, defined as the situation expected during the period. The main emission estimates on a daily base have been used as input in the chemical transport model FARM for evaluating the impact of lockdown on air quality in Lombardy. Simulated data have been also assimilated with measurements in 2020 and measured data in the three previous years 2017-2019. © 2020 HARMO. All rights reserved.
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Background: Hemostasis activation is a hallmark of COVID-19, and an integral part of a broader host response known as immunothrombosis. Microvesicles (MVs) are lipid-bilayer particles released from cells, and thought to be relevant mediators of immunothrombosis, due to their capacity to transfer proteins such as tissue factor (TF) and fibrinolytic mediators between different cells. Aims: To quantify platelet, endothelial cell (EC) and red blood cell (RBC) MVs in plasma from patients with COVID-19 and to explore their association with immunothrombosis mediators. Methods: Samples were obtained from patients admitted to a COVID-19 ward as part of a clinical trial. Samples were collected at admission, before any study intervention. MVs levels were measured in double centrifuged platelet poor plasma by flow cytometry. Coagulation, fibrinolysis and endothelial activation markers were measured by functional or immunological methods. The study was approved by the IRB and all participants provided written informed consent. Results: Data were obtained from 30 patients and 30 age and sexmatched healthy individuals. Mean time from symptoms onset and length of hospital stay (LOS) were 8.1 ± 2.3 days and 12.9 ± 9.8 days respectively. Twelve patients (40%) required intensive care (ICU), and 28/30 patients survived. Mean D-dimer was 3,609 ± 14,440 ng/mL. Platelet, EC and RBC MV counts are shown in Table 1. No association was observed between MV counts and clinical markers of disease severity such as LOS (total or in ICU), oximetry, and lung CT extension score. Associations between MV counts and biomarkers of coagulation, fibrinolysis and EC activation are shown in Table 2. Conclusions: Increased levels of MV from platelets and EC were observed in COVID-19. The association of these MVs with markers of coagulation and fibrinolytic activation, and with elements of the Tie2/Ang1 pathway warrant additional studies on the contribution of these pathways to the pathogenesis of COVID-19.
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Background : Endothelial barrier (EB) disruption is an important part of immunothrombosis, allowing the access of leukocytes to inflamed tissues. Pathways involving angiopoietin (Ang) 1 and 2 and their receptor Tie2, and VEGF-A/VE-cadherin (VEC) are key regulators of EB integrity. While the association of these mediators with sepsis severity have been known for more than 15 years, it was only recently that their role in coagulation activation was described. Moreover, these proteins also mediate angiogenesis, which has been shown to be upregulated in COVID-19. Aims : To measure circulating levels of key mediators of Ang/Tie2 and VEGF-A pathways in COVID-19 patients, and to explore their association with disease severity and hemostatic activation. Methods : Samples were obtained from patients admitted to a COVID-19 ward, within 24 h from COVID-19 confirmation. EB mediator levels were measured by immunological methods (Elisa or multiplex assays). The study was approved by the IRB and all participants provided written informed consent. Results : Data were obtained from 30 patients and 30 age and sexmatched healthy individuals. Mean length of hospital stay (LOS) was 12.9 ± 9.8 days respectively, twelve patients (40%) required intensive care (ICU), and 28/30 patients survived. Mean D-dimer was 3,609 ± 14,440 ng/mL. Levels of EB mediators are shown in Table 1. Associations between these parameters with relevant clinical and laboratory markers of disease severity are shown in Table 2. Conclusions : All mediators of EB disruption were significantly elevated in COVID-19 patients. In addition, these mediators were consistently associated with proteins involved in immunothrombosis, in particular with fibrinogen, VWF:Ag, uPAR, PAI-1 and P-selectin. Clinically significant associations were observed between Ang-2 and VEGF-A and extension of lung disease (for both) and ICU stay (for VEGF-A). Additional studies are warranted to explore the crosstalk between Ang/Tie2 and VEGF-A pathways with hemostasis in COVID-19.
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Background : Hemostasis activation is considered a key pathogenic element of COVID-19, as evidenced by the frequency of lung microvascular thrombosis and of venous thromboembolism. As shown in other conditions, pathways that mediate hemostasis activation during inflammation are not necessarily the same as those that drive hemostasis in non-inflammatory states. In particular, contact system and intrinsic pathway activation have been increasingly explored as potential mediators of hemostasis activation and prothrombotic states observed in both sterile and infectious inflammatory conditions. Aims : To assess the activation of contact system and intrinsic pathway activation in COVID-19. Methods : Protease:serpin complexes were measured in plasma from inpatients with COVID-19 and healthy individuals (HI). All samples were collected within 24 h of COVID-19 diagnosis. Associations with laboratory and clinical markers of hemostasis activation and disease severity were explored. The study was approved by the IRB and all participants provided written informed consent. Results : In total, 30 patients with COVID-19 and 30 age and sex-matched HI were enrolled. Main characteristics of the study population are shown in Table 1. As expected, higher levels of classical coagulation activation parameters were observed in COVID-19 patients. Contact system and intrinsic pathway activation in COVID-19 was demonstrated by increased levels of several protease:serpin complexes (Table 2). Interestingly, a consistent and significant association was observed between FIXa:antithrombin complexes with both clinical endpoints (need of ICU admission, length of ICU stay, total length of stay and extent of lung CT alterations), and with laboratory markers of immunothrombosis (neutrophil:lymphocyte ratio, C-reactive protein, D-dimer, PAP, VWF:Ag), as well as with several other activation markers of contact system and intrinsic pathway Conclusions : Contact system and intrinsic pathway activation contribute to hemostasis activation in COVID-19. The association of FIXa:antithrombin complexes with disease severity suggests that these pathways contribute to the pathogenesis of the prothrombotic state of COVID-19.
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This study aims to quantify antibiotic consumption for suspected respiratory tract superinfections in COVID-19 patients, while investigating the associated drivers of antibiotic prescribing in light of the current signs of antibiotic overuse. Adult patients with a positive COVID-19 diagnosis admitted to a Belgian 721-bed university hospital were analyzed retrospectively (March 11th-May 4th, 2020), excluding short-term admissions (< 24 h). Antibiotic prescriptions were analyzed and quantified, using Defined Daily Doses (DDD) per admission and per 100 bed days. Possible drivers of antibiotic prescribing were identified by means of mixed effects logistic modelling analysis with backwards selection. Of all included admissions (n = 429), 39% (n = 171) were prescribed antibiotics for (presumed) respiratory tract superinfection (3.6 DDD/admission; 31.5 DDD/100 bed days). Consumption of beta-lactamase inhibitor-penicillin combinations was the highest (2.55 DDD/admission; 23.3 DDD/100 bed days). Four drivers were identified: fever on admission (OR 2.97; 95% CI 1.42-6.22), lower SpO2/FiO2 ratio on admission (OR 0.96; 95% CI 0.92-0.99), underlying pulmonary disease (OR 3.04; 95% CI 1.12-8.27) and longer hospital stay (OR 1.09; 95% CI 1.03-1.16). We present detailed quantitative antibiotic data for presumed respiratory tract superinfections in hospitalized COVID-19 patients. In addition to knowledge on antibiotic consumption, we hope antimicrobial stewardship programs will be able to use the drivers identified in this study to optimize their interventions in COVID-19 wards.
Subject(s)
COVID-19 , Superinfection , Adult , Anti-Bacterial Agents/therapeutic use , COVID-19 Testing , Drug Prescriptions , Hospitals, University , Humans , Respiratory System , Retrospective Studies , SARS-CoV-2 , Superinfection/drug therapyABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in cancer patients may vary widely dependent on the geographic area and this has significant implications for oncological care. The aim of this observational, prospective study was to assess the seroprevalence of SARS-CoV-2 IgM/IgG antibodies in solid cancer patients referred to the academic institution of the Marche Region, Italy, between 1 July and 26 October 2020 and to determine the accuracy of the rapid serological test. After performing 3767 GCCOV-402a rapid serological tests on a total of 949 patients, seroconversion was initially observed in 13 patients (1.4%). Ten (77% of the total positive) were IgG-positive, 1 (8%) were IgM-positive and 2 (15%) IgM-positive/IgG-positive. However, only 7 out of 13 were confirmed as positive at the reference serological test (true positives), thus seroprevalence after cross-checking was 0.7%. No false negatives were reported. The kappa value of the consistency analysis was 0.71. Due to rapid serological test high false positive rate, its role in assessing seroconversion rate is limited, and the standard serological tests should remain the gold standard. However, as rapid test negative predictive value is high, GCCOV-402a may instead be useful to monitor patient immunity over time, thus helping to assist ongoing vaccination programs.
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BACKGROUND: Published reports on tocilizumab in COVID-19 pneumonitis show conflicting results due to weak designs or heterogeneity in critical methodological issues. METHODS: This open-label trial, structured according to Simon's optimal design, aims to identify factors predicting which patients could benefit from anti-IL6 strategies and to enhance the design of unequivocal and reliable future randomized trials. A total of 46 patients with COVID-19 pneumonia needing of oxygen therapy to maintain SO2 > 93% and with recent worsening of lung function received a single infusion of tocilizumab. Clinical and biological markers were measured to test their predictive values. Primary end point was early and sustained clinical response. RESULTS: Twenty-one patients fulfilled pre-defined response criteria. Lower levels of IL-6 at 24 h after tocilizumab infusion (P = 0.049) and higher baseline values of PaO2/FiO2 (P = 0.008) predicted a favourable response. CONCLUSIONS: Objective clinical response rate overcame the pre-defined threshold of 30%. Efficacy of tocilizumab to improve respiratory function in patients selected according to our inclusion criteria warrants investigations in randomized trials.