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Background: COVID-19 pandemic still pose a substantial threat worldwide despite increasing vaccine availability. Patients with haematological malignancies have been shown to have increased risk of contracting COVID-19 and are more susceptible to develop severe illness from SARS-CoV- 2 infection. The immune response to vaccines is impaired in patients with haematological malignancy due to underlying disease or antineoplastic therapies. The monoclonal-antibody combination, Evusheld is composed of tixagevimab and cilgavimab, two neutralising antibodies against SARS-CoV- 2. It has been shown to be safe and have efficacy for the prevention of COVID-19. Our aim of study is to describe the incidence and outcome of breakthrough COVID-19 infection among patients who received Evusheld in our centre and analyse the factors that possibly increase the risk of breakthrough infection. Material(s) and Method(s): A retrospective review of all adult patients with haematological malignancy who received tixagevimab/ cilgavimab 150/150 mg injection in Hospital Pulau Pinang from 1 July 2022 to 31 August 2022 with a follow-up period to 30 November 2022 was conducted. Demographic data, clinical characteristics and outcome will be retrieved from patient's medical records. Data were analysed using Statistical Package for Social Sciences software (version 21.0). Result(s): A total of 96 patients (50 males and 46 females) received tixagevimab/cilgavimab injection during the study period with a median age of 61 years (range 19-82). Majority of them were diagnosed with multiple myeloma (42.7%), followed by lymphoma (33.3%) and leukaemia (24%). One third of them had history of therapy with monoclonal antibody and 20% had haematopoietic stem cell transplantation. No major adverse effects of tixagevimab/cilgavimab injection were noted among the study population. Of the 12 patients (12.5%) who had COVID-19 infection, all of them had mild infection;three were asymptomatic and six patients received Paxlovid antiviral therapy. The median time from tixagevimab/cilgavimab to the onset of COVID-19 infection was 35 days (range 5-97 days). The mean age of patients with breakthrough COVID-19 infection were older compared to those without breakthrough infection but was not statistically significant. The incidence of breakthrough COVID-19 infection was not affected by type of haematological malignancy, history of monoclonal antibody therapy or COVID-19 vaccination. Discussion and Conclusion(s): Our findings showed that tixagevimab/cilgavimab was safe and effective in preventing COVID-19- related morbidity and mortality among patients with haematological malignancy during the study period. However, the limitation is the lack of access to whole genome sequencing for detection of resistant variants for breakthrough infections.
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Therapy with neutralizing monoclonal antibodies (mAbs) is particularly relevant during COVID-19 outbreaks in patients at high risk of severe disease, including kidney transplant recipients (KTRs). Objective(s): to evaluate the efficacy and safety of neutralizing mAbs in KTRs with mild to moderate COVID-19. Materials and methods. The retrospective study included 99 KTRs who received inpatient treatment for COVID-19 between September 1 and December 31, 2021. Patients were 52.0 +/- 11.5 years old (M, 47.5%). Bamlanivimab/etesevimab combination drug at a dose of 700/1400 mg was used as mAbs. To evaluate the efficacy of mAbs therapy, two groups of patients were identified. Group 1 consisted of 33 KTRs who received mAbs as one of the therapy components, while group 2 consisted of 66 patients who received no mAbs. Discharge from the hospital or death was considered as the endpoint of follow-up. Results. In group 1, after the use of mAb, progression of pulmonary process was observed less frequently than in the control group with CT1-2 transformation to CT3-4 (9.1% vs. 30.3%, respectively, p < 0.01). Group 1 KTRs differed significantly from group 2 - lower need for ICU and ventilator care (6.1% vs. 27.3% and 3% vs. 19.8%, respectively). The groups were comparable by sex, age, body mass index, Charlson Comorbidity Index (CCI) and time after kidney transplant (KTx) at the onset of the disease and by aseline blood biochemistry parameter values at the time of hospitalization. Only C-reactive protein (CRP) and fibrinogen values were higher in the non-mAbs patients who were hospitalized later in the course of the disease (7.7 +/- 3.2 days versus 4.6 +/- 1.6 days in group 1, p < 0.001). The frequency of prescription of other therapies did not differ between the compared groups. Use of mAbs significantly reduced mortality from 19.7% in KTRs in group 2 to 3% in group 1 without adverse effect on graft function. Conclusion. The use of mAbs therapy in the early stages of COVID-19 in KTRs is safe, it prevents severe COVID-19, and reduces the incidence of adverse outcomes.Copyright © 2023 Russian Transplant Society. All rights reserved.
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Background/Aims The immune response to SARS-CoV-2 is known to be reduced in the immunocompromised. However, extent to which immunity is affected by immunosuppression in specific disease cohorts remains poorly characterised. Furthermore, implications of the ongoing vaccination booster programme require further study. Individuals with lupus nephritis (LN) require prolonged high-dose immunosuppression in order to maintain disease control, rendering them important to study in this context. We evaluated SARS-CoV-2 nucleocapsid and spike antibody response in this cohort during the Spring/Summer 2022 booster vaccine campaign. Nucleocapsid antibody indicates previous infection whilst spike antibody indicates previous infection and/or vaccination response. Titre of spike antibody to prevent infection is not known, but presence of antibodies is likely to protect against severe disease. Methods SARS-CoV-2 spike and nucleocapsid antibody were measured in adult patients with LN attending a tertiary centre rheumatology clinic. Data was collected retrospectively on disease, immunosuppression, vaccine status and history of natural exposure. Results 35 cases of LN were investigated, of which LN III, IV and V were predominant biopsy diagnoses. Regarding immunosuppressants, the Eurolupus Cyclophosphamide protocol had been used in the majority of patients to achieve initial control, with 3/35 patients still receiving pulsed courses at data collection. 18/35 were on Mycophenolate Mofetil;a further 13/35 had previously received this. 31/35 took at least 5mg Prednisolone daily;25/35 took Hydroxychloroquine;7/35 took Azathioprine;7/35 had previously been on Methotrexate, 3/35 took Tacrolimus;1/35 took Ciclosporin. Regarding B-cell depleting monoclonal antibody therapy, 13/35 had received Rituximab and 8/35 were receiving Belimumab. Antibody levels were measured between 4 weeks and 13 months after last dose of vaccination;mean duration was 6 months. 11/35 had confirmed COVID-19 infection;a further 8/35 reported a possible history. Of the 35, 32 (91%) had mounted detectable SARS-CoV-2 spike antibody above the bottom 10% of assay detection, indicating some immunity to vaccination or natural exposure. 20 (57%) had detectable nucleocapsid antibody, suggesting natural infection with antibody response. Only 2 (6%) had not mounted any antibody response. Of note, neither were fully vaccinated: one had 1 vaccination with blood test 8 months subsequent;one had 2 vaccinations with blood test 7 months subsequent. The latter was also notably on haemodialysis. All who received 3+ vaccinations had detectable spike antibody responses, as well as 75% of those who had received 2 vaccinations. Conclusion Our study is the first analysis, to our knowledge, of SARS-CoV-2 antibody response in a LN cohort. Whilst neutralising capacity and level of antibody providing protection remains under research, these findings provide at least some reassurance that individuals with LN on immunosuppression are capable of mounting an immune response against SARS-CoV-2. Further work is required to establish extent and duration of protection with serial vaccinations in this cohort.
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Intro: Patients receiving B-cell depleting or inhibiting therapies (BCDT), such as anti-CD20 monoclonal antibodies (CD20-MAB), are at risk for severe COVID-19. BCDT decreases production of neutralizing antibodies, causing delayed viral clearance and prolonged viral shedding. Passive antibody therapy (PAT), including COVID-19 convalescent plasma (CCP) and monoclonal antibodies (MAB), is hypothesized to be an effective Findings: * At the time of treatment, all patients (19/19) receiving CCP were hospitalized compared with10/53 patients treated with MAB. 2/10(20%) hospitalized patients treated with MAB died, compared with 3/19(15%) treated with CCP. **5/43 patients treated outpatient with MAB were hospitalized for COVID following CCP/MAB treatment with no COVID related deaths. Conclusion(s): Our data suggest that patients with COVID-19 who received BCDT within the last year may have improved outcomes after treatment with MAB or CCP. Elderly patients with >3 comorbidities and underlying hematological malignancy who contracted COVID-19 within 30 days of last BCDT had increased morbidity and mortality. To improve clinical outcomes, passive antibody therapy should be administered prior to the development of severe disease requiring hospitalization. Further prospective studies and comparisons to COVID-19 patients that did not receive MAB or CCP are needed to help confirm this association.Copyright © 2023
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BACKGROUND: Monoclonal antibody (MAB) treatments for COVID-19 received Emergency Use Authorization in the United States. METHODS: We used surveillance data from Rhode Island to conduct a retrospective, statewide cohort study to estimate the effectiveness of MABs for preventing hospitalization and death during periods when Alpha and Delta variants were predominant. RESULTS: From 1/17/2021-10/26/2021, 285 long-term congregate care (LTCC) residents and 3,113 non-congregate patients met our eligibility criteria and received MAB; they were matched to 285 and 6,226 controls, respectively. Among LTCC residents, 8.8% (25/285) of patients who received MAB were hospitalized or died compared to 25.3% (72/285) of those who did not receive MAB (adjusted difference=16.7%, 95% confidence interval CI=11.0-22.3%). Among non-congregate patients, 4.5% (140/3,113) of patients who received MAB were hospitalized or died compared to 11.8% (737/6,226) of those who did not receive MAB (adjusted difference=7.2%, 95% CI=6.0-8.4%). CONCLUSIONS: Administration of MABs led to an absolute reduction in hospitalization or death during periods when Alpha and Delta variants were predominant.
Subject(s)
COVID-19 , Humans , Cohort Studies , Retrospective Studies , SARS-CoV-2 , Hospitalization , Antibodies, Monoclonal/therapeutic useABSTRACT
Purpose of study The COVID-19 pandemic led to an unprecedented rapid transmission of healthcare information. This information was critical to enact frequently changing patient care protocols and to inform staff about redistribution of hospital resources at New York University Langone Hospital- Long Island. In this investigation, we analyze our hospital clinicians' methods of mass communication to front-line health care workers, with particular interest in assessing how communication was informed by real-time clinical findings. At the height of the pandemic (March 25th- April 15th), a mass broadcast email disseminated daily from the Director of Pulmonary and Critical Care was effective in informing treatment protocols that were clinically observed to improve patient outcomes. We analyzed over thirty broadcast emails and identified three major categories of information that were routinely addressed and/or updated: (i) reallocation of resources, (ii) clinical protocol changes, (iii) recommended lab tests for monitoring patient clinical course. We also interviewed key hospital clinicians and administrators on their experience working during the height of the pandemic. We found treatment protocols in these emails included information regarding the use of steroids and monoclonal antibody therapy, ventilators, and patient repositioning. In addition, the hospital's first autopsy results on COVID related deaths gave further insight into the disease process and manner of death for many patients (diffuse alveolar damage and evidence of hypercoagulability). So, too, did clinical findings around this time support what was seen grossly on autopsy-patients with more severe disease often presented with serial d-dimer levels >6x the normal limit. The information through these different conduits was synthesized and subsequently communicated in the aforementioned mass emails as an anticoagulation treatment protocol. Through continuous input of data, this protocol was updated and adjusted over the course of three weeks. We found that real-time communication amongst hospital staff regarding patient treatment protocols was a dynamic process that required synthesis of lab values, autopsy findings, and observed response to treatments. Successful treatment of patients depended on continuous review and communication of this information. Methods used The COVID-19 pandemic led to an unprecedented rapid transmission of healthcare information. This information was critical to enact frequently changing patient care protocols and to inform staff about redistribution of hospital resources at New York University Langone Hospital-- Long Island. In this investigation, we analyze our hospital clinicians' methods of mass communication to front-line health care workers, with particular interest in assessing how communication was informed by real-time clinical findings. At the height of the pandemic (March 25th- April 15th), a mass broadcast email disseminated daily from the Director of Pulmonary and Critical Care was effective in informing treatment protocols that were clinically observed to improve patient outcomes. Summary of results We analyzed over thirty broadcast emails and identified three major categories of information that were routinely addressed and/or updated: (i) reallocation of resources, (ii) clinical protocol changes, (iii) recommended lab tests for monitoring patient clinical course. We also interviewed key hospital clinicians and administrators on their experience working during the height of the pandemic. We found treatment protocols in these emails included information regarding the use of steroids and monoclonal antibody therapy, ventilators, and patient repositioning. In addition, the hospital's first autopsy results on COVID related deaths gave further insight into the disease process and manner of death for many patients (diffuse alveolar damage and evidence of hypercoagulability). So, too, did clinical findings around this time support what was seen grossly on autopsy- patients with more severe disease often presented with seri l d-dimer levels >6x the normal limit. The information through these different conduits was synthesized and subsequently communicated in the aforementioned mass emails as an anticoagulation treatment protocol. Through continuous input of data, this protocol was updated and adjusted over the course of three weeks. Conclusions We found that real-time communication amongst hospital staff regarding patient treatment protocols was a dynamic process that required synthesis of lab values, autopsy findings, and observed response to treatments. Successful treatment of patients depended on continuous review and communication of this information.
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Background: Given effectiveness of SARS-CoV-2 vaccines and outpatient antiviral and monoclonal antibody therapy for reducing progression to severe COVID-19, we sought to estimate the impact of these interventions on risk of hospitalization following SARS-CoV-2 infection in a large US healthcare system. Method(s): All patients >=18 of age in the UNC Health system, with first positive SARS-CoV-2 RT-PCR test or U07.1 ICD-10-CM (diagnosis date) during 07/01/2021- 05/31/2022, were included. The outcome was first hospitalization with U07.1 ICD-10-CM primary diagnosis <=14 days after SARS-CoV-2 diagnosis date. SARS-CoV-2 vaccinations were included if received >=14 days prior to diagnosis. Outpatient therapies were included if administered after diagnosis date and before hospital admission. Age, gender, race, ethnicity, and comorbidities associated with COVID-19 (using ICD-10-CM, if documented >=14 days prior to diagnosis date) were also evaluated. Risk ratios for hospitalization were estimated using generalized linear models, and predictors identified using extreme gradient boosting using feature influence with Shapley additive explanations algorithm. Result(s): The study population included 54,886 patients, 41% men and 27% >=60 years of age. One-third of SARS-CoV-2 diagnoses occurred July-December 2021 and 67% December-May 2022 (predominantly Delta and Omicron variants, respectively). Overall 7.0% of patients were hospitalized for COVID-19, with median hospitalization stay of 5 days (IQR: 3-9). 32% and 12% of patients received >=1 SARS-CoV-2 vaccine dose and outpatient therapy, respectively. Unadjusted and age-adjusted hospitalization risk decreased with vaccination and outpatient therapy (TABLE). Comparing patients who received 3 vaccine doses versus none we observed a 66% relative reduction in risk, with stronger association for more recent vaccination. For patients who received nirmatrelvir/ ritonavir versus no therapy we observed a 99% relative reduction in risk. In predictive models, older age was the most influential predictor of being hospitalized with COVID-19, while vaccination and outpatient therapy were the most influential factors predicting non-hospitalization. Conclusion(s): The impact of recent SARS-CoV-2 vaccination and outpatient antiviral and monoclonal antibody therapy on reducing COVID-19 hospitalization risk was striking in this large healthcare system covering Delta and Omicron variant timeframes. SARS-CoV-2 vaccinations and outpatient therapeutics are critical for preventing severe COVID-19. Unadjusted and age-adjusted risk ratios for hospitalization among patients with SARS-CoV-2.
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The COVID-19 pandemic has significantly changed the understanding of the safety profile of therapies for immunoinflammatory rheumatic diseases (IRDs). This is primarily due to the negative impact of a number of basic anti-inflammatory drugs (DMARDs) and biological DMARDs on the course and outcomes of a new coronavirus infection. A number of studies have shown that anti-B-cell therapy (rituximab) gave a statistically significant increase in the risk of severe COVID-19 and an increase in mortality. At the same time, the analysis of real clinical practice data dictated the need to establish a number of restrictions on the use of certain classes of biological DMARDs and to search for alternative therapy programs to maintain control over disease activity. Purpose of the study - to evaluate the efficacy and safety of the drug Artlegia (olokizumab), solution for subcutaneous injection, 160 mg/ml - 0.4 ml, manufactured by R-Pharm JSC, Russia) for the treatment of patients with rheumatoid arthritis in real clinical practice after switching with rituximab during the COVID-19 pandemic. Materials and methods. The study included 14 patients with a confirmed diagnosis of rheumatoid arthritis (RA), who were previously on rituximab therapy at a dose of 1000-500 mg twice with an interval of 2 weeks, who received at least one course of therapy with this drug. As RA worsened, patients were switched to olokizumab against the background of standard DMARDs. At 4, 8, 12 weeks after the switch, the severity of pain was assessed on the VAS scale, the number of painful and swollen joints (TJC28 and TSC28), the level of acute phase markers of inflammation, the DAS28 disease activity index calculated using ESR and CRP, and the CDAI (clinical activity index), functional state index HAQ, as well as assessment of the safety profile of therapy. Results. Data analysis was performed using median values (Me) were used for data analysis. A significant decrease of TJC28 was after the injection of olokizumab (Artlegia) in 8 and 12 weeks (Me baseline = 10;Me 8 weeks = 4;Me 12 weeks = 4;p<0.05) and a decrease of TSC28 in 4, 8 and 12 weeks (Me baseline = 9;Me 4 weeks = 3.5;Me 8 weeks = 2.5;Me 12 weeks = 2.0;p<0.05). Laboratory markers of inflammation showed a decrease in CRP and ESR levels after 4 weeks of treatment (CRP: Me baseline = 21, Me 4 weeks = 1 (p<0.05);ESR: Me baseline = 31, Me 4 weeks = 7 (p<0.05)). Positive dynamics persisted at 8 and 12 weeks (CRP: Me 8 weeks = 1, Me 12 weeks = 0;ESR: Me 8 weeks = 4, Me 12 weeks = 5). The level of CRP by the fourth week 4 became within the normal range, regardless of the initial values. All activity indices improved from the fourth week in each evaluation period compared to baseline: DAS28-ESR: Me baseline = 5.52, Me 4 weeks = 3.59, Me 8 weeks = 3.33, Me 12 weeks = 3.22 (p<0.05);DAS28-CRP: Me baseline = 5.39, Me 4 weeks = 3.71, Me 8 weeks = 3.35, Me 12 weeks = 3.45 (p<0.05);CDAI: Me baseline = 28.5, Me 4 weeks = 18.0, Me 8 weeks = 16.5, Me 12 weeks = 16.0 (p<0.05). All patients showed a reduction in pain (VAS scale) by week 8. The functional status of patients, according to the HAQ index, showed a significant decrease only by the 12th week of the study: Me baseline = 1.62, Me 12 weeks = 1.31 (p<0.05). Conclusion. The study found that switching from rituximab to olokizumab was effective and safe during the COVID-19 pandemic.Copyright © 2023 Ima-Press Publishing House. All rights reserved.
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Globalization and high-speed means of transportation contribute to the spread of infections dangerous to humans. Airborne pathogens have pandemic potential as currently shown in case of the novel coronavirus SARS-CoV-2. Natural focal Lassa fever (LF) common in West African countries, in 35 cases was registered in non-endemic geographical areas because any person infected with Lassa virus (LASV) is a long-term source of infection (up to two months). Cases of person-to-person infection in endemic territories are described. In Germany, the facts of secondary virus transmission from patients to doctors have been recorded during the examination and blood collection from an apparently healthy person as well as during the autopsy of a deceased subjects due to severe LF course. Nonspecific malaise symptoms in LF are also characteristic of numerous other diseases common on the African continent, e.g., malaria and typhoid fever or viral infections such as yellow fever, Chikungunya, dengue and Zika, monkey pox and Ebola virus disease. In this regard, there may be similar dermatological manifestations. Timely detection of cases and differential diagnosis are crucial to ensure safe patient care and use of affordable antiviral therapy for LL provided by the drug Ribavirin. Research methods for studying LASV use polymerase chain reaction (PCR) for detecting viral RNA, electron microscopy, isolation of infectious virus cultured sensitive cells, indirect immunofluorescence reaction, enzyme immunoassay (ELISA) and immuno-chromatographic assays for the detection of antibodies and/or antigen as well as immunoblotting. Currently, test kits based on molecular and genetic methods are mainly used for LF laboratory diagnostics. Since the 1980s, ribavirin has been used to treat patients with LF. The serum accumulation of the drug in large quantities causes hemolysis, development of anemia and impaired renal function. In this regard, treatment options are being considered with decline in its concentration due to combined use with other antiviral drugs. A search for new therapeutic agents capable of inhibiting viral replication at disease early stage has been in progress due to lack of any approved vaccines.
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Objectives: To describe the implementation of an ED-based program to offer monoclonal antibody therapy to patients with mild-moderate COVID-19 disease. Background(s): Monoclonal antibody therapy (MOAB) has recently emerged as a treatment for mild to moderate COVID-19, potentially preventing those with underlying conditions from progressing to severe illness and hospitalization. Further, as EDs are the primary point of health care access for many at-risk individuals, offering MOAB in the ED may increase availability of treatment options for patients from traditionally underserved communities. Method(s): A retrospective chart review was conducted of patients 12 years and above who received treatment in our urban, academic, community hospital. Patients 12 years and older were screened for eligibility during ED visits or during follow-up calls providing positive test results. Staff was trained on specific consent, infusion, monitoring, and documentation procedures adherent to MOAB administration under the Emergency Use Authorization. Patients were contacted following MOAB and queried regarding symptom resolution and healthcare utilization. Data regarding patient demographics, ED course, and 7-day unscheduled visits were collected. Result(s): In this ongoing quality improvement initiative, from December 2020 to March 2021, there were 26,229 patient encounters at the pilot ED site. 84 patients were provided MOAB, 87% Bamlanivimab and 13% Bamlanivimab/Etesevimab. Patients had a mean age of 52.3 years (SD 24.4);21% were 12-17 years of age and 37% were >65 years old. 52% were male. 33% self-reported as Caucasian, 19% Black, 18% Asian/Pacific Islander, 21% as other, and 9% were unknown. 17% identified as Latinx. 19% of patients were insured by Medicaid, 36% Medicare, 39% commercially insured, and 6% were uninsured. Patients had symptoms a median of 3 days prior to MOAB. After age (46%), the most commonly reported eligibility criteria was obesity (20%), followed by hypertension (11%) and immunocompromised state (11%). 74% of infusions were administered during nights and weekends. No infusion reactions occurred. 8% returned to an ED within 7 days of MOAB, 5% were hospitalized. No patients required ICU admission or died. Conclusion(s): ED-based MOAB has been safely implemented and may be an effective treatment for patients with mild to moderate COVID-19. Health-system wide expansion of this program may provide opportunities to offer this life-saving therapy to underserved populations with poor access to care.Copyright © 2023
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T-lineage acute lymphoblastic leukemia (T-ALL) is curable for most children and adolescent and young adult patients with contemporary frontline chemotherapy regimens. During the past decade, improved survival rates have resulted from the optimization of frontline chemotherapy regimens, the use of minimal residual disease (MRD) assessment for evaluating a patient's risk for relapse, and the intensification of treatment based on the persistence of MRD. Optimization of initial therapy is critical because relapsed T-ALL after initial intensive chemotherapy is incurable for most adult patients. Current T-ALL salvage chemotherapy regimens are minimally effective, and unlike in B-cell ALL, there are no approved antibody therapies or chimeric antigen receptor T-cell therapies for relapsed disease. Immunotherapy and small-molecule inhibitors are beginning to be tested in relapsed T-ALL and have the potential to advance the treatment. Until effective salvage strategies are discovered, however, intensive frontline therapy is required for cure. In this article I review the current frontline chemotherapy regimens for adult patients with T-ALL, summarize the novel targeted and immune therapeutics currently in early-phase clinical trials, and outline how these therapies are helping to define an optimal approach for T-ALL.Copyright © 2022 by The American Society of Hematology.
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As of April 2022, the Mater Hospital serves 190 patients who have been the recipient of a lung transplant in Ireland. During the COVID-19 pandemic, solid organ transplant was recognised as a risk factor for progression to severe disease. In January 2022, the European Medicines Agency (EMA) approved the use of Sotrovimab for high risk patients. Sotrovimab is a monoclonal antibody which neutralises SARS-CoV-2 with recent data showing efficacy in reducing the risk of progression to severe disease in high risk patients . We aim to describe our patient cohort and the rates of COVID-19 infection seen before and after the introduction of monoclonal antibody therapy. While likely reflecting emerging variants resulting in less severe disease, we observe variation in morbidity and mortality in this time. From March 2020 to April 2022, 116 post-lung transplant patients tested positive for COVID-19 infection. This represents 61% of our overall population. Since January 2022, coinciding with the surge of the omicron variant, 57 patients contracted COVID-19. 47 were deemed to be suitable for treatment with 10 presenting outside the window for therapeutic intervention. 3.5% (n=2) required ICU admission and 2 died directly as a result of COVID-19. Prior to this, 58 patients contracted COVID-19, 31 of which (53.5%) required hospital admission with 18 (58%) requiring ICU admission. Overall we saw 13 deaths representing 22.4% of this group and 6.8% of the overall population.
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During the treatment of critically ill COVID-19 patients it has been revealed that the neutralizing monoclonal antibodies against 2019-nCoV have the advantages of high specificity, high purity, and can be prepared in a large scale, which are expected to be a effective preparation for clinical use. This article introduces the way of 2019-nCoV invasion into the host cells, the major variants of novel coronavirus, and the mechanism of action of anti-2019-nCoV monoclonal antibodies, as well as the progress of research and development of their preparation in major pharmaceutical companies, to provide reference for scientific research and clinical application.Copyright © Chinese Journal of Clinical Infectious Diseases.All rights reserved.
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The objective was to evaluate real-world effectiveness of sotrovimab, a monoclonal antibody (mAb) for the treatment of high-risk outpatients with COVID-19, in reducing the risk of mortality or hospitalization during the SARS-CoV-2 Delta and initial Omicron variant waves in the US. A retrospective analysis was conducted of de-identified, high-risk patients diagnosed with COVID-19 (index date) from 1 September 2021 to 28 February 2022 in the FAIR Health FH NPIC claims database. Patients were divided into 2 cohorts based on claimed procedural codes: treated with sotrovimab and not treated with any mAb (no mAb). Facility-reported mortality ("mortality"), all cause hospitalizations and intensive care unit (ICU) admissions <=30 days of index were identified. Multivariable logistic regression was conducted to estimate the risk of 30-day mortality or hospitalization, adjusting for demographic and clinical factors. Of the high-risk COVID-19 patients identified,13,140 were treated with sotrovimab and 1,283,284 received no mAb therapy. In the no mAb cohort, 0.59% died and 5.74% were hospitalized (of whom 30% in ICU). In the sotrovimab cohort, 0.08% died and 2.50% were hospitalized (of whom 15% in ICU). After adjusting for potential confounders, sotrovimab treatment was associated with 85% reduced odds of 30-day mortality (OR: 0.15, 95% CI: 0.08-0.31) and 61% reduced odds of 30-day hospitalization or mortality (OR: 0.39, 95% CI: 0.35-0.44) among high-risk COVID-19 patients. In this US real-world study of high-risk COVID-19 patients during the Delta and initial Omicron waves, treatment with sotrovimab was associated with reduced odds of mortality and hospitalization compared to no mAb treatment.
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Coronavirus disease 2019 (COVID-19) is an acute respiratory tract infection causing a pandemic that emerged in 2019 initially in China involving 13.8% cases with severe, and 6.1% with critical course and later throughout the globe. Vaccines or antiviral medications are yet to be used to prevent or treat infections of Human Coronavirus (HCoV). The much-discovered HCoV found in 2003, SARS-COVID-19, which caused respiratory syndrome, has special pathogenesis as it causes respiratory tract infection. The coronavirus spike protein's association with its host cell receptor complement is crucial in deciding the virus infectivity, tissue tropism and species variety. SARS, COVID-19, infects human cells by binding to angiotensin-converting enzyme 2 (ACE2) receptor and uses the TMPRSS2 cell protease to activate it. Lungs are most affected by COVID-19 as host cells are accessed by the virus through ACE2, which is most abundant in alveolar cells of the lungs. Special attention and efforts should be given in reducing transmission in vulnerable populations, including infants, health care providers and the elderly. COVID 19, is the main causative agent of potentially lethal disease and is of significant concern for global public health and in pandemics which was highlighted in this review.Copyright © 2021 Bentham Science Publishers.
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Antibody therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have been approved in many countries, with most being developed based on the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 has an exceptional ability to mutate under the pressure of host immunity, especially the immune-dominant spike protein of the virus, which is the target of both antibody drugs and vaccines. Given the continuous evolution of the virus and the identification of critical mutation sites, the World Health Organization (WHO) has named 5 variants of concern (VOCs): 4 are previously circulating VOCs, and 1 is currently circulating (Omicron). Due to multiple mutations in the spike protein, the recently emerged Omicron and descendent lineages have been shown to have the strongest ability to evade the neutralizing antibody (NAb) effects of current antibody drugs and vaccines. The development and characterization of broadly neutralizing antibodies (bNAbs) will provide broad strategies for the control of the sophisticated virus SARS-CoV-2. In this review, we describe how the virus evolves to escape NAbs and the potential neutralization mechanisms that associated with bNAbs. We also summarize progress in the development of bNAbs against SARS-CoV-2, human coronaviruses (CoVs) and other emerging pathogens and highlight their scientific and clinical significance.
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BACKGROUND: Monoclonal antibodies represent one option for treatment of COVID-19 early after infection. Although large clinical trials have been successfully conducted, real world data are needed to obtain a realistic assessment of the assumed effect on hospitalization rates. METHODS: For this retrospective, observational study, clinical data were collected in 2021 from outpatients (402) as well as hospitalized patients (350) receiving monoclonal antibodies Bamlanivimab, Casirivimab/Imdevimab or Etesevimab/Bamlanivimab. These data were compared with data from a control group of patients not receiving antibodies because admission to the hospital was too late for this therapy. RESULTS: Both groups showed a comparable spectrum of risk factors. Due to the late hospitalization of control patients, a higher frequency of severe symptoms, such as fever, dyspnea, syncope and lower viral load, were observed. CRP and leukocytes counts were also higher in the untreated group. Most importantly, hospitalization time was significantly shorter and the number of deaths was also lower in the treated group. CONCLUSIONS: Apparently, the application of anti-SARS-CoV-2 antibodies reduced the work load of our hospital as shown by the shorter hospitalization time and lower number of COVID-19-related deaths.
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The aim of this randomized, controlled trial is to determine whether anti-SARS-CoV-2 hyperimmune globulin protects against severe COVID-19 in severely immunocompromised, hospitalized, COVID-19 patients. Patients were randomly assigned to receive anti-SARS-CoV-2 hyperimmune globulin (COVIG) or intravenous immunoglobulin without SARS-CoV-2 antibodies. Severe COVID-19 was observed in two out of ten (20%) patients treated with COVIG compared to seven out of eight (88%) in the IVIG control group (p = 0.015, Fisher's exact test). COVIG may be a valuable treatment in severely immunocompromised, hospitalized, COVID-19 patients and should be considered when no monoclonal antibody therapies are available. The trial was registered at www.trialregister.nl (#NL9436).
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The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic named coronavirus disease 2019 (COVID-19) that has become the greatest worldwide public health threat of this century. Recent studies have unraveled numerous mysteries of SARS-CoV-2 pathogenesis and thus largely improved the studies of COVID-19 vaccines and therapeutic strategies. However, important questions remain regarding its therapy. In this review, the recent research advances on COVID-19 mechanism are quickly summarized. We mainly discuss current therapy strategies for COVID-19, with an emphasis on antiviral agents, neutralizing antibody therapies, Janus kinase inhibitors, and steroids. When necessary, specific mechanisms and the history of therapy are present, and representative strategies are described in detail. Finally, we discuss key outstanding questions regarding future directions of the development of COVID-19 treatment.
Subject(s)
COVID-19 , Humans , SARS-CoV-2 , COVID-19 Vaccines , COVID-19 Drug Treatment , Antiviral Agents/pharmacologyABSTRACT
The burden of morbidity and mortality from SARS-CoV-2 infection is especially significant in heart transplant patients who are at higher risk for poor outcomes owing to immunosuppression, blunted response to vaccination, and multiple comorbid conditions. Over the last 3 years the therapeutic landscape for COVID-19 has evolved and our drug armamentaria continues to expand. With these advancements comes a time of great hope to mitigate significant illness from SARS - CoV - 2 infection. However, as with many emerging frontiers, the administration of novel therapeutics to a complex patient population remains challenging. We present a patient case encountered at our institution that highlights the need for increased awareness of nuances while managing COVID-19 infection in a heart transplant recipient.