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1.
Crit Care Explor ; 2(6): e0145, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-1795095

ABSTRACT

OBJECTIVE: To describe the outcomes with use of a combination of tocilizumab and methylprednisolone administered around the time of endotracheal intubation in patients with confirmed coronavirus disease 2019-associated hypoxemic respiratory failure requiring mechanical ventilation. DATA SOURCES: Retrospective chart review. STUDY SELECTION/DATA EXTRACTION: Twenty-one consecutive patients with confirmed coronavirus disease 2019-associated hypoxemic respiratory failure requiring mechanical ventilation. Initial ventilator parameters were positive end-expiratory pressure 14 cm H2o and target plateau pressure 29 cm H2o to maximize lung recruitment. Methylprednisolone (125 mg every 6hr for 24 hr with tapering to 60 mg every 12 hr) was administered shortly after patients were intubated (median 11 hr after intubation). DATA SYNTHESIS: No patient in the cohort died while hospitalized (mortality, 0%; 95% CI, 0%-18%) and 18 patients have been discharged from the acute care setting. Twenty of 21 patients (95%) have been liberated from mechanical ventilation after a median duration of 8 days (range, 4-30 d). Following 48 hours of methylprednisolone, the A-a o2 gradient decreased from 455 ± 103 to 228 ± 109 mm Hg (difference 227 ± 108 mm Hg; p < 0.01). CONCLUSIONS: Our positive experience with tocilizumab in combination with methylprednisolone started early after endotracheal intubation may be one avenue for reducing the morbidity and mortality seen with severe coronavirus disease 2019 and merits further exploration in clinical studies.

2.
Thromb J ; 18: 22, 2020.
Article in English | MEDLINE | ID: covidwho-1793931

ABSTRACT

BACKGROUND: Hospitals in the Middle East Gulf region have experienced an influx of COVID-19 patients to their medical wards and intensive care units. The hypercoagulability of these patients has been widely reported on a global scale. However, many of the experimental treatments used to manage the various complications of COVID-19 have not been widely studied in this context. The effect of the current treatment protocols on patients' diagnostic and prognostic biomarkers may thus impact the validity of the algorithms adopted. CASE PRESENTATION: In this case series, we report four cases of venous thromboembolism and 1 case of arterial thrombotic event, in patients treated with standard or intensified prophylactic doses of unfractionated heparin or low molecular weight heparin at our institution. Tocilizumab has been utilized as an add-on therapy to the standard of care to treat patients with SARS-CoV-2 associated acute respiratory distress syndrome, in order to dampen the hyperinflammatory response. It is imperative to be aware that this drug may be masking the inflammatory markers (e.g. IL6, CRP, fibrinogen, and ferritin), without reducing the risk of thrombotic events in this population, creating instead a façade of an improved prognostic outcome. However, the D-dimer levels remained prognostically reliable in these cases, as they were not affected by the drug and continued to be at the highest level until event occurrence. CONCLUSIONS: In the setting of tocilizumab therapy, traditional prognostic markers of worsening infection and inflammation, and thus potential risk of acute thrombosis, should be weighed carefully as they may not be reliable for prognosis and may create a façade of an improved prognostic outcome insteasd. Additionally, the fact that thrombotic events continued to be observed despite decrease in inflammatory markers and the proactive anticoagulative approach adopted, raises more questions about the coagulative mechanisms at play in COVID-19, and the appropriate management strategy.

3.
Lancet ; 397(10285): 1637-1645, 2021 May 01.
Article in English | MEDLINE | ID: covidwho-1655260

ABSTRACT

BACKGROUND: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. METHODS: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg-800 mg (depending on weight) given intravenously. A second dose could be given 12-24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76-0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12-1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77-0·92; p<0·0001). INTERPRETATION: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. FUNDING: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , COVID-19/drug therapy , COVID-19/therapy , Hypoxia/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/complications , COVID-19/diagnosis , COVID-19/mortality , Female , Hospital Mortality , Hospitalization , Humans , Hypoxia/diagnosis , Hypoxia/virology , Male , Middle Aged , Respiration, Artificial/statistics & numerical data , SARS-CoV-2/isolation & purification , Severity of Illness Index , Treatment Outcome , Young Adult
4.
Int Immunol ; 33(10): 515-519, 2021 09 25.
Article in English | MEDLINE | ID: covidwho-1574756

ABSTRACT

Blockade of IL-6 function by an anti-IL-6 receptor (IL-6R) antibody (tocilizumab, trade name Actemra) has been shown to be effective for the treatment of chronic autoimmune inflammatory diseases including rheumatoid arthritis. Interestingly, treatment with tocilizumab has also been found to alleviate the cytokine storm induced by chimeric antigen receptor (CAR)-T-cell therapy. Patients with serious cases of coronavirus disease 2019 (COVID-19) exhibit cytokine release syndrome (CRS), which suggested that tocilizumab might be an effective therapeutic for serious cases of COVID-19. In the first part of this short review, the therapeutic effect of tocilizumab for the disease induced by IL-6 overproduction is described. CRS induced by CAR-T-cell therapy and COVID-19 is then discussed.


Subject(s)
Arthritis/immunology , COVID-19/immunology , Interleukin-6/immunology , Receptors, Chimeric Antigen/immunology , SARS-CoV-2/immunology , Cell- and Tissue-Based Therapy/methods , Cytokine Release Syndrome/immunology , Humans
5.
Lancet Respir Med ; 9(5): 511-521, 2021 05.
Article in English | MEDLINE | ID: covidwho-1537197

ABSTRACT

BACKGROUND: Global randomised controlled trials of the anti-IL-6 receptor antibody tocilizumab in patients admitted to hospital with COVID-19 have shown conflicting results but potential decreases in time to discharge and burden on intensive care. Tocilizumab reduced progression to mechanical ventilation and death in a trial population enriched for racial and ethnic minorities. We aimed to investigate whether tocilizumab treatment could prevent COVID-19 progression in the first multicentre randomised controlled trial of tocilizumab done entirely in a lower-middle-income country. METHODS: COVINTOC is an open-label, multicentre, randomised, controlled, phase 3 trial done at 12 public and private hospitals across India. Adults (aged ≥18 years) admitted to hospital with moderate to severe COVID-19 (Indian Ministry of Health grading) confirmed by positive SARS-CoV-2 PCR result were randomly assigned (1:1 block randomisation) to receive tocilizumab 6 mg/kg plus standard care (the tocilizumab group) or standard care alone (the standard care group). The primary endpoint was progression of COVID-19 (from moderate to severe or from severe to death) up to day 14 in the modified intention-to-treat population of all participants who had at least one post-baseline assessment for the primary endpoint. Safety was assessed in all randomly assigned patients. The trial is completed and registered with the Clinical Trials Registry India (CTRI/2020/05/025369). FINDINGS: 180 patients were recruited between May 30, 2020, and Aug 31, 2020, and randomly assigned to the tocilizumab group (n=90) or the standard care group (n=90). One patient randomly assigned to the standard care group inadvertently received tocilizumab at baseline and was included in the tocilizumab group for all analyses. One patient randomly assigned to the standard care group withdrew consent after the baseline visit and did not receive any study medication and was not included in the modified intention-to-treat population but was still included in safety analyses. 75 (82%) of 91 in the tocilizumab group and 68 (76%) of 89 in the standard care group completed 28 days of follow-up. Progression of COVID-19 up to day 14 occurred in eight (9%) of 91 patients in the tocilizumab group and 11 (13%) of 88 in the standard care group (difference -3·71 [95% CI -18·23 to 11·19]; p=0·42). 33 (36%) of 91 patients in the tocilizumab group and 22 (25%) of 89 patients in the standard care group had adverse events; 18 (20%) and 15 (17%) had serious adverse events. The most common adverse event was acute respiratory distress syndrome, reported in seven (8%) patients in each group. Grade 3 adverse events were reported in two (2%) patients in the tocilizumab group and five (6%) patients in the standard care group. There were no grade 4 adverse events. Serious adverse events were reported in 18 (20%) patients in the tocilizumab group and 15 (17%) in the standard care group; 13 (14%) and 15 (17%) patients died during the study. INTERPRETATION: Routine use of tocilizumab in patients admitted to hospital with moderate to severe COVID-19 is not supported. However, post-hoc evidence from this study suggests tocilizumab might still be effective in patients with severe COVID-19 and so should be investigated further in future studies. FUNDING: Medanta Institute of Education and Research, Roche India, Cipla India, and Action COVID-19 India.


Subject(s)
Antibodies, Monoclonal, Humanized , COVID-19 , Cytokine Release Syndrome , Receptors, Interleukin-6/antagonists & inhibitors , Respiratory Distress Syndrome , SARS-CoV-2/isolation & purification , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/complications , COVID-19/immunology , COVID-19/mortality , COVID-19/therapy , Critical Care/methods , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Drug Monitoring/methods , Female , Humans , Immunologic Factors/administration & dosage , Immunologic Factors/adverse effects , India , Male , Middle Aged , Mortality , Respiration, Artificial/methods , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/etiology , Severity of Illness Index , Treatment Outcome
6.
Clin Transl Sci ; 14(6): 2146-2151, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526353

ABSTRACT

Tocilizumab is an IL-6 receptor antagonist with the ability to suppress the cytokine storm in critically ill patients infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). We evaluated patients treated with tocilizumab for a SARS-CoV-2 infection who were admitted between March 13, 2020, and April 16, 2020. This was a multicenter study with data collected by chart review both retrospectively and concurrently. Parameters evaluated included age, sex, race, use of mechanical ventilation (MV), usage of steroids and vasopressors, inflammatory markers, and comorbidities. Early dosing was defined as a tocilizumab dose administered prior to or within 1 day of intubation. Late dosing was defined as a dose administered > 1 day after intubation. In the absence of MV, the timing of the dose was related to the patient's date of admission only. We evaluated 145 patients. The average age was 58.1 years, 64% were men, 68.3% had comorbidities, and 60% received steroid therapy. Disposition of patients was 48.3% discharged and 29.3% died, of which 43.9% were African American. MV was required in 55.9%, of which 34.5% died. Avoidance of MV (P = 0.002) and increased survival (P < 0.001) was statistically associated with early dosing. Tocilizumab therapy was effective at decreasing mortality and should be instituted early in the management of critically ill patients with coronavirus disease 2019) COVID-19).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , COVID-19/therapy , Cytokine Release Syndrome/therapy , Respiration, Artificial/statistics & numerical data , COVID-19/immunology , COVID-19/mortality , COVID-19/virology , Critical Illness/mortality , Critical Illness/therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/virology , Female , Hospital Mortality , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/immunology , Severity of Illness Index , Time Factors , Time-to-Treatment , Treatment Outcome
7.
J Clin Med ; 10(8)2021 Apr 09.
Article in English | MEDLINE | ID: covidwho-1526827

ABSTRACT

Despite direct viral effect, the pathogenesis of coronavirus disease 2019 (COVID-19) includes an overproduction of cytokines including interleukin 6 (IL-6). Therefore, tocilizumab (TOC), a monoclonal antibody against IL-6 receptors, was considered as a possible therapeutic option. Patients were selected from the SARSTer database, containing 2332 individuals with COVID-19. Current study included 825 adult patients with moderate to severe course. Analysis was performed in 170 patients treated with TOC and 655 with an alternative medication. The end-points of treatment effectiveness were death rate, need for mechanical ventilation, and clinical improvement. Patients treated with TOC were balanced compared to non-TOC regarding gender, age, BMI, and prevalence of coexisting conditions. Significant effect of TOC on death was demonstrated in patients with baseline IL-6 > 100 pg/mL (hazard ratio [HR]: 0.21, 95% confidence interval [CI]: 0.08-0.57). The best effectiveness of TOC was achieved in patients with a combination of baseline IL-6 > 100 pg/mL and either SpO2 ≤ 90% (HR: 0.07) or requiring oxygen supplementation (HR: 0.18). Tocilizumab administration in COVID-19 reduces mortality and speeds up clinical improvement in patients with a baseline concentration of IL-6 > 100 pg/mL, particularly if they need oxygen supplementation owing to the lower value of SpO2 ≤ 90%.

8.
Curr Pharm Des ; 27(41): 4223-4231, 2021.
Article in English | MEDLINE | ID: covidwho-1502208

ABSTRACT

Coronavirus disease-2019 (COVID-19) is a respiratory tract infection accompanied by severe or fatal pneumonia-like symptoms and sometimes death. It has posed to be an ongoing global health emergency caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to a sudden outbreak and a large number of infections and deaths, it became a major concern all over the world. The options available as effective therapeutics should be urgently exercised to handle this pandemic. So far, no specific and accurate anti- SARS-CoV-2 treatment is recommended because of the absence of sufficient clinical evidence. In such cases, the clinical use of available drugs is always considered to be on top priority. A broad-spectrum antiviral agent, remdesivir, is found effective in many cases and recommended by many clinicians in many countries. This drug acts as a potential inhibitor of viral RNA-dependent RNA polymerase protein and thus likely to be efficacious in SARS-CoV-2 infection. Tocilizumab is currently recommended by many hospitals as an alternative treatment for critically ill COVID-19 patients. Tocilizumab has been administered to control cytokine storms that occur due to the release of proinflammatory cytokine, including interleukin 6. Chloroquine and hydroxychloroquine are also used in hospitals to handle severe COVID-19 patients. Currently, plasma therapy has been exercised as a therapeutic alternative, especially to handle severe COVID-19 patients. In addition, herbal medicines are expected to play a significant role in the control and prevention of COVID-19. All these therapeutic options have their advantages and limitations. This review highlights the therapeutic potential of these available drugs, along with their mechanism of action and shortcomings. We have provided detailed information on available therapeutic options, which have proved to be effective in improving clinical symptoms of severe COVID-19 patients.


Subject(s)
Antiviral Agents , COVID-19 , Antiviral Agents/therapeutic use , COVID-19/therapy , Cytokine Release Syndrome , Humans , Hydroxychloroquine , Immunization, Passive , Pandemics , Phytotherapy
9.
Front Med (Lausanne) ; 7: 571597, 2020.
Article in English | MEDLINE | ID: covidwho-1488435

ABSTRACT

The COVID-19 disease is an unprecedented international public health emergency and considerably impacts the global economy and health service system. While awaiting the development of an effective vaccine, searching for the therapy for severe or critical COVID-19 patients is essential for reducing the mortality and alleviating the tension of the health service system. Cytokine release syndrome (CRS) induced by elevated interleukin-6 was recognized to underscore the pathology of severe COVID-19 patients. Inhibiting CRS by agents suppressing IL-6 may relieve symptoms, shorten the hospital stay and reduce the need for oxygen therapy. Although evidence from randomized, double-blinded clinical trials is still lacking, the IL-6R inhibitor tocilizumab (TCZ) has shown some clinical benefits in the treatment of severe COVID-19 patients and have been included in clinical guidelines. In this review, we focused on the possible mechanisms of TCZ in the treatment of CRS and highlighted some significant considerations in the use of TCZ to treat COVID-19 patients.

10.
J Transl Med ; 18(1): 405, 2020 10 21.
Article in English | MEDLINE | ID: covidwho-1477432

ABSTRACT

BACKGROUND: Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. METHODS: A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. RESULTS: In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P = 0.52) and 22.4% (97.5% CI: 17.2-28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. CONCLUSIONS: Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adult , Aged , Aged, 80 and over , Betacoronavirus/immunology , COVID-19 , Cohort Studies , Coronavirus Infections/epidemiology , Female , Humans , Italy/epidemiology , Male , Middle Aged , Mortality , Off-Label Use , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Treatment Outcome , Validation Studies as Topic
11.
Infect Control Hosp Epidemiol ; : 1-4, 2021 May 14.
Article in English | MEDLINE | ID: covidwho-1428666

ABSTRACT

We evaluated adverse drug events (ADEs) by chart review in a random national sample of 428 veterans with coronavirus disease 2019 (COVID-19) who received tocilizumab (n = 173 of 428). ADEs (median time, 5 days) occurred in 51 of 173 (29%) and included hepatoxicity (n = 29) and infection (n = 13). Concomitant medication discontinuation occurred in 22% of ADE patients; mortality was 39%.

12.
Rev Esp Geriatr Gerontol ; 55(5): 286-288, 2020.
Article in Spanish | MEDLINE | ID: covidwho-1386531

ABSTRACT

INTRODUCTION: Cytokine storm syndrome (CTS) is a serious complication of patients with SARS-CoV-2 infection. Treatment and evolution in octogenarians are not well defined. Our objective is to describe its clinical characteristics, the treatments and its clinical evolution. PATIENTS AND METHOD: Retrospective observational study of consecutive patients admitted in the period between March 23 and April 12, 2020 with confirmed SARS-CoV-2 infection, with pneumonia by radiological study or chest tomography, whith STC criteria and who received treatment. We classified patients as those who received only glucocorticoid (GC) pulses, or GC and tocilizumab pulses. We determined serum levels of ferritin, CRP and D-dimers. The final variable was survival. RESULTS: 21 patients, (80-88 years). The mean ferritin was 1056 microg/L (317-3,553), CRP 115.8mg/dL (22-306) and D-dimers 2.9m/L (0.45-17.5). All patients received GC pulses and in 2 cases simultaneously tocilizumab. The mean follow-up time was 13.7 days (8-21). The overall mortality was 38.1% (8/21 patients). The 2 patients who received tocilizumab died. The deceased had significantly higher levels of ferritin (1,254 vs. 925microg/L; P=.045) and CRP (197.6 vs. 76mg / dL; P=.007). At the end of the follow-up, a decrease in the biochemical parameters was observed with ferritin of 727microg/L, CRP of 27mg/dl and D-dimers of 1.18mg/L. In 13/21 patients (61.9%), the CTS was controlled without the need to add other treatments. CONCLUSIONS: STC mortality from SARS-CoV-2 is high despite treatment. A greater inflammatory response was associated with a higher mortality. Although it seems that the early use of GC pulses could control it, and the use of other treatments such as tocilizumab shouldo be, with the study design and its limitations, this conclusion cannot be stablished.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Coronavirus Infections/complications , Coronavirus Infections/immunology , Cytokines/immunology , Glucocorticoids/therapeutic use , Immunoproliferative Disorders/drug therapy , Immunoproliferative Disorders/virology , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , Aged, 80 and over , COVID-19 , Female , Humans , Male , Pandemics , Retrospective Studies , Syndrome
13.
Cureus ; 13(4): e14480, 2021 Apr 14.
Article in English | MEDLINE | ID: covidwho-1389786

ABSTRACT

We present a 68-year-old male patient with persistent and complicated SARS-CoV-2 infection who was diagnosed with acute myeloid leukemia (AML). The patient suffered from fever, cough and progressive dyspnea for 10 days and he was admitted to the intensive care unit due to respiratory failure and cytokine release syndrome (CRS). Despite a transient improvement of CRS by the implementation of supportive care, including also the administration of recombinant tissue plasminogen activator (rt-PA) and tocilizumab, his clinical course worsened over time. Thus, a bone marrow aspiration was performed revealing the presence of myeloblasts in a proportion of 32% and flow cytometry confirmed the diagnosis of AML-M1 according to FAB classification. Re-evaluation of peripheral blood tests revealed that the patient was admitted with anemia and thrombocytopenia that were never recovered during hospitalization. Due to the patient's poor clinical condition, no chemotherapy was applied, and he died of sepsis and multi-organ failure two days later. This case suggests that in all patients with a persistent and/or complicated infection, even during pandemics, the presence of an underlying hematologic malignancy should always be taken into consideration.

14.
Rev Esp Quimioter ; 34(4): 337-341, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1317435

ABSTRACT

OBJECTIVE: The study aims to describe characteristics and clinical outcome of patients with SARS-CoV-2 infection that received siltuximab according to a protocol that aimed to early block the activity of IL-6 to avoid the progression of the inflammatory flare. METHODS: Retrospective review of the first 31 patients with SARS-CoV-2 treated with siltuximab, in Hospital Clinic of Barcelona or Hospital Universitario Salamanca, from March to April 2020 with positive polymerase-chain reaction (PCR) from a nasopharyngeal swab. RESULTS: The cohort included 31 cases that received siltuximab with a median (IQR) age of 62 (56-71) and 71% were males. The most frequent comorbidity was hypertension (48%). The median dose of siltuximab was 800 mg ranging between 785 and 900 mg. 7 patients received siltuximab as a salvage therapy after one dose of tocilizumab. At the end of the study, a total of 26 (83.9) patients had been discharged alive and the mortality rate was 16.1% but only 1 out of 24 that received siltuximab as a first line option (4%). CONCLUSIONS: Siltuximab is a well-tolerated alternative to tocilizumab when administered as a first line option in patients with COVID-19 pneumonia within the first 10 days from symptoms onset and high C-reactive protein.


Subject(s)
Antibodies, Monoclonal/therapeutic use , COVID-19/drug therapy , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , C-Reactive Protein/analysis , COVID-19/mortality , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Disease Progression , Female , Humans , Hypertension/complications , Interleukin-6/antagonists & inhibitors , Interleukin-6/blood , Male , Middle Aged , Retrospective Studies , Salvage Therapy , Treatment Outcome
15.
Int J Biol Sci ; 17(8): 2124-2134, 2021.
Article in English | MEDLINE | ID: covidwho-1271048

ABSTRACT

The efficacy of tocilizumab on the prognosis of severe/critical COVID-19 patients is still controversial so far. We aimed to delineate the inflammation characteristics of severe/critical COVID-19 patients and determine the impact of tocilizumab on hospital mortality. Here, we performed a retrospective cohort study which enrolled 727 severe or critical inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Huoshenshan Hospital (Wuhan, China), among which 50 patients received tocilizumab. This study confirmed that most recovered patients manifested relatively normal inflammation levels at admission, whereas most of the deceased cases presented visibly severe inflammation at admission and even progressed into extremely aggravated inflammation before their deaths, proved by some extremely high concentrations of interleukin-6, procalcitonin, C-reactive protein and neutrophil count. Moreover, based on the Cox proportional-hazards models before or after propensity score matching, we demonstrated that tocilizumab treatment could lessen mortality by gradually alleviating excessive inflammation and meanwhile continuously enhancing the levels of lymphocytes within 14 days for severe/critical COVID-19 patients, indicating potential effectiveness for treating COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Inflammation/drug therapy , SARS-CoV-2 , Aged , Aged, 80 and over , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/mortality , COVID-19/physiopathology , Comorbidity , Female , Humans , Inflammation/blood , Interleukin-6/blood , Length of Stay/statistics & numerical data , Leukocyte Count , Male , Middle Aged , Neutrophils , Procalcitonin/blood , Propensity Score , Proportional Hazards Models , Retrospective Studies
16.
J Investig Med High Impact Case Rep ; 9: 23247096211019557, 2021.
Article in English | MEDLINE | ID: covidwho-1262488

ABSTRACT

An outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2, initially in December 2019 at Wuhan, China, subsequently spread around the world. We describe a case series of COVID-19 patients treated at our academic medical center with focus on cytokine storm and potential therapeutic role of tocilizumab. A 59-year-old female admitted for shortness of breath (SOB), productive cough, fever, and nausea in the setting of COVID-19 pneumonia. Oxygen saturation was 81% necessitating supplemental oxygen. She was transferred to intensive care unit (ICU) for worsening hypoxia; intubated and received tocilizumab following which her oxygen requirements improved. A 52-year-old female admitted from an outside hospital with SOB, intubated for worsening hypoxia, in the setting of COVID-19 pneumonia. She received tocilizumab 400 mg intravenous for 2 doses on ICU admission, with clinical improvement. A 56-year-old female hospitalized with worsening SOB, fever, and cough for 8 days saturating 88% on room air in the setting of COVID-19 pneumonia. Worsening hypoxia necessitated high flow nasal cannula. She was transferred to the ICU where she received 2 doses of tocilizumab 400 mg intravenous. She did not require intubation and was transitioned to nasal cannula. A hyperinflammatory syndrome may cause a life-threatening acute respiratory distress syndrome in patients with COVID-19 pneumonia. Tocilizumab is the first marketed interleukin-6 blocking antibody, and through targeting interleukin-6 receptors likely has a role in treating cytokine storm. We noted clinical improvement of patients treated with tocilizumab.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/complications , Cytokine Release Syndrome/drug therapy , Receptors, Interleukin-6/antagonists & inhibitors , Respiratory Distress Syndrome/drug therapy , COVID-19/diagnostic imaging , COVID-19/drug therapy , Critical Care , Cytokine Release Syndrome/diagnostic imaging , Cytokine Release Syndrome/etiology , Female , Humans , Lung/diagnostic imaging , Middle Aged , Oxygen Inhalation Therapy , Pennsylvania , Respiratory Distress Syndrome/diagnostic imaging , SARS-CoV-2 , Trauma Centers
17.
Open Access Emerg Med ; 13: 207-211, 2021.
Article in English | MEDLINE | ID: covidwho-1256176

ABSTRACT

BACKGROUND: Anticoagulant therapy for patients with severe coronavirus disease (COVID-19) pneumonia is considered to improve the hypercoagulable and inflammatory state. However, bleeding complications should also be considered. CASE PRESENTATION: A 77-year-old man with a history of falls was diagnosed with COVID-19. Owing to his severe condition, he was intubated and transferred to our hospital for intensive care. Favipiravir, tocilizumab, unfractionated heparin, and ART-123 were administered to treat COVID-19 and manage the antithrombotic prophylaxis for paroxysmal atrial fibrillation (Af). On the 6th day after admission, a hematoma was noted on the left chest wall. Computed tomography (CT) revealed multiple hematomas, including hematomas on his chest wall and obturatorius internus muscle. Emergency angiography transcatheter embolization (TAE) was performed. The patient was transferred to another hospital 23 days after TAE, without complications. CONCLUSION: Our findings show that anticoagulation therapy and a history of falls induced multiple hematomas in a COVID-19 patient and that the condition was managed with TAE. When anticoagulants are considered in the management of Af and COVID-19 associated coagulopathy, it is necessary to closely monitor potential bleeding complications.

18.
Cell Transplant ; 30: 9636897211021008, 2021.
Article in English | MEDLINE | ID: covidwho-1255859

ABSTRACT

The coronavirus pandemic is one of the most significant public health events in recent history. Currently, no specific treatment is available. Some drugs and cell-based therapy have been tested as alternatives to decrease the disease's symptoms, length of hospital stay, and mortality. We reported the case of a patient with a severe manifestation of COVID-19 in critical condition who did not respond to the standard procedures used, including six liters of O2 supplementation under a nasal catheter and treatment with dexamethasone and enoxaparin in prophylactic dose. The patient was treated with tocilizumab and an advanced therapy product based on umbilical cord-derived mesenchymal stromal cells (UC-MSC). The combination of tocilizumab and UC-MSC proved to be safe, with no adverse effects, and the results of this case report prove to be a promising alternative in the treatment of patients with severe acute respiratory syndrome due to SARS-CoV-2.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/therapy , Mesenchymal Stem Cell Transplantation , COVID-19/drug therapy , COVID-19/virology , Combined Modality Therapy , Humans , Immunophenotyping , Karyotyping , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Middle Aged , RNA, Viral/analysis , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Thorax/diagnostic imaging , Tomography, X-Ray Computed , Umbilical Cord/cytology , Viral Load
19.
Radiol Med ; 126(9): 1170-1180, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1252205

ABSTRACT

PURPOSE: To evaluate CT and laboratory changes in COVID-19 patients treated with tocilizumab, compared to a control group, throughout a combined semiquantitative and texture analysis of images. MATERIALS AND METHODS: From March 11 to April 20, 2020, 57 SARS-CoV-2 positive patients were retrospectively compared: group T (n = 30) receiving tocilizumab and group non-T (n = 27) undergoing only antivirals/antimalarials. Chest-CT and laboratory findings were analyzed before and after treatment. CT evaluation included both semiquantitative scoring and texture analysis of all parenchymal lesions. Survival and recovery analyses were also provided with Kaplan-Meier method. RESULTS: In group T, no significant differences were found for CT score after treatment, while several texture features significantly changed, including mean attenuation (p < 0.0001), skewness (p < 0.0001), entropy (p = 0.0146) and higher-order parameters, suggesting considerable fading of parenchymal lesions. PaO2/FiO2 mean value significantly increased after treatment, from 240 ± 93 to 363 ± 107 (p = 0.0003), with parallel decrease in inflammatory biomarkers (CRP, D-dimer and LDH). In group non-T, CT scoring, texture and laboratory parameters showed significant worsening at follow-up. Findings were clinically associated with opposite trends between two groups, with reduction of severe cases in group T (from 21/30 to 5/30; p < 0.0001) as compared to a significant worsening in group non-T (severe cases increasing from 6/27 to 14/27; p = 0.0473). Probability of discharge was significantly higher in group T (p < 0.0001), as well as survival rate, although not statistically significant. CONCLUSIONS: Our results suggest the potential role of CT texture analysis for assessing response to treatment in COVID-19 pneumonia, using Tocilizumab, as compared to semiquantitative evaluation, providing insight into the intrinsic parenchymal changes.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Lung/diagnostic imaging , Receptors, Interleukin-6/antagonists & inhibitors , Tomography, X-Ray Computed , Adult , Aged , Aged, 80 and over , COVID-19/diagnostic imaging , COVID-19/mortality , Female , Humans , Kaplan-Meier Estimate , Lung/pathology , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Survival Analysis , Treatment Outcome
20.
Transplantation ; 105(6): 1372-1380, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1249353

ABSTRACT

BACKGROUND: The magnitude and kinetics of severe acute respiratory syndrome coronavirus 2-specific cell-mediated immunity (SARS-CoV-2-CMI) in kidney transplant (KT) recipients remain largely unknown. METHODS: We enumerated SARS-CoV-2-specific interferon-γ-producing CD69+ CD4+ and CD8+ T cells at months 4 and 6 from the diagnosis of coronavirus disease 2019 (COVID-19) in 21 KT recipients by intracellular cytokine staining. Overlapping peptides encompassing the SARS-CoV-2 spike (S) glycoprotein N-terminal 1- to 643-amino acid sequence and the membrane protein were used as stimulus. SARS-CoV-2 IgG antibodies targeting the S1 protein were assessed by ELISA at month 6. RESULTS: Detectable (≥0.1%) SARS-CoV-2-specific CD4+ T-cell response was found in 57.1% and 47.4% of patients at months 4 and 6. Corresponding rates for CD8+ T cells were 19.0% and 42.1%, respectively. Absolute SARS-CoV-2-specific T-cell counts increased from month 4 to month 6 in CD8+ (P = 0.086) but not CD4+ subsets (P = 0.349). Four of 10 patients with any detectable response at month 4 had lost SARS-CoV-2-CMI by month 6, whereas 5 of 9 patients mounted SARS-CoV-2-CMI within this period. All but 2 patients (89.5%) tested positive for SARS-CoV-2 IgG. Patients lacking detectable SARS-CoV-2-specific CD4+ response by month 6 were more likely to be under tacrolimus (100.0% versus 66.7%; P = 0.087) and to have received tocilizumab for the previous COVID-19 episode (40.0% versus 0.0%; P = 0.087). CONCLUSIONS: Although still exploratory and limited by small sample size, the present study suggests that a substantial proportion of KT recipients exhibited detectable SARS-CoV-2-CMI after 6 months from COVID-19 diagnosis.


Subject(s)
COVID-19/immunology , Immunity, Cellular , Immunocompromised Host , Kidney Transplantation/adverse effects , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , COVID-19/blood , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19 Testing , Female , Follow-Up Studies , Graft Rejection/immunology , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/adverse effects , Interferon-gamma/metabolism , Male , Middle Aged , Transplant Recipients
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