Systematic review and meta-analysis of the clinical effectiveness of tixagevimab/cilgavimab for prophylaxis of COVID-19 in immunocompromised patients

Immunocompromised patients, such as those with a haematological malignancy, are at higher risk of SARS-CoV-2 infection, severe outcomes and mortality. Tixagevimab/cilgavimab is a monoclonal antibody combination which binds to the SARS-CoV-2 spike protein. The PROVENT phase III clinical trial reported that tixagevimab/cilgavimab prophylaxis significantly reduced the risk of COVID-19 infection in immunocompromised participants. However, the trial was conducted before the Omicron variant became prevalent. This systematic review and meta-analysis provide an up-to-date summary of the real-world effectiveness of tixagevimab/cilgavimab in immunocompromised patients, including patients with haematological malignancies. Clinical studies from 1 January 2021 to 1 October 2022, which reported breakthrough COVID-19 infections after tixagevimab/cilgavimab, were included. COVID-19-related hospitalisations, intensive care admissions and mortality were also assessed. A meta-analysis was performed to ascertain overall clinical effectiveness. Eighteen studies, with 25 345 immunocompromised participants, including 5438 patients with haematological pathologies, were included in the review. The overall clinical effectiveness of tixagevimab/cilgavimab against COVID-19 breakthrough infection, hospitalisation, intensive care admission and COVID-19-specific mortality was 40.54%, 66.19%, 82.13% and 92.39%, respectively. This review highlights the clinical effectiveness of tixagevimab/cilgavimab at reducing COVID-19 infection and severe outcomes for immunosuppressed individuals, including patients with a haematological malignancy, during the Omicron-predominant era. Real-world studies are important to provide ongoing certainty of the clinical benefit for immunocompromised patients against new SARS-CoV-2 variants.     

Clinical outcomes and risk factors for severe COVID-19 in patients with haematological disorders receiving chemo- or immunotherapy

Haematology patients receiving chemo- or immunotherapy are considered to be at greater risk of COVID-19-related morbidity and mortality. We aimed to identify risk factors for COVID-19 severity and assess outcomes in patients where COVID-19 complicated the treatment of their haematological disorder. A retrospective cohort study was conducted in 55 patients with haematological disorders and COVID-19, including 52 with malignancy, two with bone marrow failure and one immune-mediated thrombotic thrombocytopenic purpura (TTP). COVID-19 diagnosis coincided with a new diagnosis of a haematological malignancy in four patients. Among patients, 82% were on systemic anti-cancer therapy (SACT) at the time of COVID-19 diagnosis. Of hospitalised patients, 37% (19/51) died while all four outpatients recovered. Risk factors for severe disease or mortality were similar to those in other published cohorts. Raised C-reactive protein at diagnosis predicted an aggressive clinical course. The majority of patients recovered from COVID-19, despite receiving recent SACT. This suggests that SACT, where urgent, should be administered despite intercurrent COVID-19 infection, which should be managed according to standard pathways. Delay or modification of therapy should be considered on an individual basis. Long-term follow-up studies in larger patient cohorts are required to assess the efficacy of treatment strategies employed during the pandemic.     

SARS-CoV-2 primary and breakthrough infections in patients with cancer: Implications for patient care

Initial reports of SARS-CoV-2 caused COVID-19 suggested that patients with malignant diseases were at increased risk for infection and its severe consequences. In order to provide early United States population-based assessments of SARS-CoV-2 primary infections in unvaccinated patients with hematologic malignancies or cancer, and SARS-CoV-2 breakthrough infections in vaccinated patients with hematologic malignancies or cancer, we conducted retrospective studies using two, unique nationwide electronic health records (EHR) databases. Using these massive databases to provide highly statistically significant data, our studies demonstrated that, compared to patients without malignancies, risk for COVID-19 was increased in patients with all cancers and with all hematologic malignancies. Risks varied with specific types of malignancy. Patients with hematologic malignancies or cancer were at greatest risk for COVID-19 during the first year after diagnosis. Risk for infection was increased for patients 65 years and older, compared to younger patients and among Black patients compared to white patients.When patients with hematologic malignancies or cancer were vaccinated against SARS-CoV-2, their risk for breakthrough infections was decreased relative to primary infections but remained elevated relative to vaccinated patients without malignancies. Compared to vaccinated patients without malignancies, vaccinated patients with hematologic malignancy or cancer showed increased risk for infection at earlier post vaccination time points. As with primary infections, risk for breakthrough infections was greatest in patients during their first year of hematologic malignancy or cancer. There were no signs of racial disparities among vaccinated patients with hematologic malignancies or cancer. These results provide the population basis to understand the significance of subsequent immunologic studies showing relative defective and delayed immunoresponsiveness to SARS-CoV-2 vaccines among patients with hematologic malignancies and cancers. These studies further provide the basis for recommendations regarding COVID-19 vaccination, vigilance and maintaining mitigation strategies in patients with hematologic malignancies and cancers.     

Haematological manifestations of COVID-19: From cytopenia to coagulopathy

Emerging data from the management of patients with coronavirus disease 2019 (COVID-19) suggests multi-systemic involvement, including the hemopoietic system. The haematological manifestations of COVID-19 include blood count anomalies notably lymphopenia and neutrophilia which are of prognostic significance. Hyperferritinemia and elevated lactate dehydrogenase have also been associated with increased mortality. Furthermore, there is considerable evidence of a distinct coagulopathy associated with COVID-19 characterised by elevated D-dimers and an increased risk of thrombotic events. This comprehensive review summarises the latest evidence from published studies and discusses the implications of the various haematological manifestations of COVID-19 with a view to guiding clinical management and risk stratification in this rapidly evolving pandemic.     

Managing the front-line treatment for diffuse large B cell lymphoma and high-grade B cell lymphoma during the COVID-19 outbreak

The COVID-19 pandemic has dramatically challenged care for cancer patients, especially those with active treatment who represent a vulnerable population for SARS-CoV-2 infection. Aggressive lymphoid neoplasms, such as diffuse large B cell lymphoma and high-grade B cell lymphoma, need to be treated without delay in order to get the best disease outcome. Because of that, our clinical practice was changed to minimise the risk of SARS-CoV-2 infection while continuing haematological treatment. In this report, we analyse the management of front-line therapy in 18 patients during the COVID-19 outbreak, as well as the results of the implemented measures in their outcome.     

Is COVID-19 a high risk factor for lung cancer?: A protocol for systematic review and meta-analysis

Introduction:COVID-19 has become a common threat to global human health and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Some asymptomatic patients with early-stage lung cancer who have COVID-19 receive surgical treatment but develop severe pneumonia and other complications or even experience postoperative death, and they may have a worse prognosis compared with healthy individuals infected with COVID-19. However, there is no evidence that COVID-19 is a risk factor for lung cancer patients. This systematic review aims to evaluate the incidence and prognosis of COVID-19 in lung cancer patients and provide evidence-based medical support for clinical treatment.Methods:We will search 6 medical databases to identify eligible studies published from the establishment of the database to the present. The quality of the included literature will be evaluated using the bias risk assessment tool in Cochrane 5.1.0, and a meta-analysis will be performed using Stata 14.0. Heterogeneity will be statistically assessed using χ² tests.Results:The study will integrate existing research findings to investigate the prevalence and severity rate of patients with lung cancer infected with SARS-CoV-2 and analyze the prognosis and adverse clinical outcomes in patients with or without COVID-19.Conclusion:The results of this study provide evidence to support whether COVID-19 is a risk factor for lung cancer and provide guidance for clinical prevention and treatment based on the evidence obtained in light of the unpredictable threat posed by COVID-19.Ethics and dissemination:Ethics approval is not required for this systematic review as it will involve the collection and analysis of secondary data. The results of the review will be reported in international peer-reviewed journals.PRORPERO registration number:CRD42020195967.     

Management of patients with Intestinal Bowel Disease and COVID-19: A review of current evidence and future perspectives

The COVID-19 pandemic has been a challenge for countries and health professionals worldwide. Viral entry by ACE-2 receptor and an excessive activation of the immune system are key to understand both incidence and severity of disease. Inflammatory Bowel Disease (IBD) represents a special condition associated with an inordinate response of the immune system to external agents. IBD treatments have been associated to an increased risk of bacterial and viral infections. This has raised the question of possible higher incidence and severity of COVID-19 infection in IBD patients. Several papers have been published during this year of pandemic to answer that question. Moreover, COVID-19 vaccination offers great promise in controlling infection in patients with IBD. Based on current evidence, patients with IBD do not have a higher incidence of COVID-19 than the general population, and they do not have worse disease evolution. Advanced age and presence of a greater number of comorbidities have been associated with worse outcomes, similar to the general population. Corticosteroids are associated to an increased risk of COVID-19 infection, higher hospitalization rate and higher risk of severe COVID-19. 5-ASA/Sulfasalazine and Thiopurines have a possible increased risk of severe COVID-19, although studies are lacking. On the other hand, Anti-TNF may have a possible protective effect. It is recommended to maintain the treatment. Anti-IL-12/23, anti-integrins and tofacitinib have results comparable to anti-TNF. Based on the efficacy, expert recommendations, and the absence of other evidence, it is recommended that patients with IBD be vaccinated.     

COVID-19 infection in patients with haematological malignancies: A single-centre survey in the latest Omicron wave in China

As the COVID-19 variant Omicron surge in Beijing, China, a better understanding of risk factors for adverse outcomes may improve clinical management in patients with haematological malignancies (HM) diagnosed with COVID-19. The study sample includes 412 cases, mainly represented by acute leukaemia, chronic myeloid leukaemia (CML), plasma cell disorders and lymphoma and chronic lymphocytic leukaemia. COVID-19 pneumonia was observed in 10.4% (43/412) of patients, and severe/critical illness was observed in 5.3% (22/412). Among the 86 cases with advanced malignancies, 17.6% (12/86) of patients developed severe/critical COVID-19, which was significantly higher than reported in patients with stable malignancies (9/326, 2.70%, p < 0.001). Similarly, the advanced malignancy cohort had a higher mortality rate (9/86, 10.5% vs. 0/326, 0%, p < 0.001) and a poor 30-day overall survival (OS) compared with the stable malignancy cohort (74.2% vs. 100.0%, p < 0.0001). Overall, nine patients (2.2%) died. The primary cause of death was progressive HM in four patients and a combination of both COVID-19 and HM in five patients. In the multivariable analysis, over 65 years of age, comorbidities and advanced malignancy were correlated with severe/critical COVID-19 in HM patients. This study sheds light on the poor outcomes among COVID-19 HM patients with the leading cause of advanced malignancy.     

Management of COVID-19 patients with chronic liver diseases and liver transplants

The epidemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has increasingly attracted worldwide concern. Liver damage or dysfunction occurred in patients with COVID-19 (mainly characterized by moderately elevated serum aspartate aminotransferase levels). However, it is not yet clear whether the COVID-19-related liver injury is mainly caused by the virus infection, potentially hepatotoxic drugs, or other coexisting conditions. Progression of pre-existing chronic liver disease (CLD) may be the underlying mechanism of liver injury. Although COVID-19 patients with CLD, such as nonalcoholic fatty liver disease, liver cirrhosis, and liver cancer, have been deemed at increased risk for serious illness in many studies, little is known about the impact of CLD on the natural history and outcome of COVID-19 patients. Thereby, based on the latest evidence from case reports and case series, this paper discusses the clinical manifestations, treatment, prognosis, and management of the COVID-19 patients with different CLD. This article also reviews the effect of COVID-19 on liver transplantation patients (LT), hoping to work for future prevention, management, and control measures of COVID-19. However, due to the lack of relevant research, most of them are still limited to the theoretical stage, further study of COVID-19 and CLD needs to be improved in the future.     

The racial/ethnic and sociocultural aspects of the pandemic in rheumatology

The disproportionate impact of coronavirus-2019 (COVID-19) on communities of color is gaining global attention. Current research demonstrates that historically marginalized populations are experiencing disproportionate levels of SARS-Cov-2 infection and adverse clinical outcomes. However, research examining whether COVID-19 outcomes vary by race and ethnicity within the rheumatic disease population is limited. This paper will review data showing how SARS-CoV-2 infection has differentially affected racial and ethnic minorities in the general population and those with rheumatic disease. We will also highlight disparities in rheumatic disease risk and severity that existed prior to the pandemic, and discuss recent work examining severe outcomes of COVID-19 in rheumatic disease patients by race and ethnicity. Finally, we propose several actionable steps for the rheumatology community to address COVID-19 health disparities, which may have long-term effects on patients with rheumatic disease.     

COVID-19 and the Liver: Lessons Learnt from the EAST and the WEST,A Year Later

Globally, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus) has been a major cause for significant morbidity and mortality. Since the start of the pandemic, several hepato-biliary manifestations in coronavirus disease 2019 (COVID-19) have been described and unique considerations raised. The review aims to summarize the pathogenesis and hepato-biliary manifestations in COVID-19 and discuss the similarities, contrasting features and disease-specific management across a range of hepato-biliary diseases from the EAST and the WEST. Published studies and regional society guidelines from the EAST and the WEST were comprehensively reviewed and summarized. A wide range of hepato-biliary manifestations, including the infrequent and chronic manifestation of cholangiopathy, has been observed in COVID-19. The pathogenesis of liver injury is multifactorial and with scant evidence for a direct SARS-CoV-2 infection of the liver. Patients with non-alcoholic fatty liver disease, cirrhosis, and liver cancer are potentially at increased risk for severe COVID-19, and there are unique considerations in chronic hepatitis B or C, hepatocellular carcinoma, and in those immunosuppressed such as autoimmune hepatitis or liver transplant recipients. With the surges in SARS-CoV-2 infection, liver transplant activity has variably been impacted. Preliminarily, SARS-CoV-2 vaccines appear to be safe in those with chronic liver disease and in transplant recipients, while emerging data suggest the need for a third dose in immunosuppressed patients. In conclusion, patients with chronic liver disease, particularly cirrhosis, and liver transplant recipients, are vulnerable to severe COVID-19. Over the past year, several unique considerations have been highlighted across a spectrum of hepato-biliary diseases. Vaccination is strongly recommended for those with chronic liver disease and liver transplant recipients.     

Management of Heart Failure,Durable Left Ventricular Assist Device,and Heart Transplant Patients in the COVID-19 Era

Our world is facing recurrent waves of coronavirus disease 2019 (COVID-19) with the emergence of more infectious strains of the novel coronavirus, SARS-CoV-2. Multiple studies have established that heart failure (HF) patients are at high risk of severe disease and poor outcomes with COVID-19. Management of COVID-19 in patients with HF, heart transplant, and those supported with durable left ventricular assist devices present an arduous challenge due to underlying complex health conditions and overlap of symptoms. Based on available data, this review outlines the management of this vulnerable patient population who either present with COVID-19 with preexisting HF or with de novo HF from COVID-19.     

Systemic Inflammation May Induce Cardiac Injury in COVID-19 Patients Including Children and Adolescents Without Underlying Cardiovascular Diseases: A Systematic Review

Coronavirus disease 2019(COVID-19) is an ongoing global pandemic with a daily increasing number of affected individuals and a relatively high mortality rate. COVID-19 patients that develop cardiac injury are at increased risk of a worse clinical course with higher rates of mortality. Increasing amounts of evidence suggest that a system-wide inflammatory response and a cytokine storm mediated type syndrome plays a crucial role in disease progression. This systematic review investigates the possible role of hyperinflammation in inducing cardiac injury as one of the severe complications of COVID-19. A systematic literature search was performed using PubMed, Embase and Scopus databases to identify relevant clinical studies that investigated cardiovascular injury manifestations and reported inflammatory and cardiac biomarkers in COVID-19 patients. Only 29 studies met our inclusion criteria and the majority of these studies demonstrated significantly elevated inflammatory and cardiac blood markers. It was evident that underlying cardiovascular diseases may increase the risk of developing cardiac injury. However, many COVID-19 patients included in this review, developed different types of cardiac injury without having any underlying cardiovascular diseases. Furthermore, many of these patients were either children or adolescents. Therefore, age and comorbidities may not always be the two main risk factors that dictate the severity and outcome of COVID-19. Further investigations are required to understand the underlying mechanisms of pathogenicity as an urgent requirement to develop the appropriate treatment and prevention strategies. These strategies may specifically target hyperinflammation as a suspected driving factor for some of the severe complications of COVID-19.     

Dysregulation of Protein S in COVID-19

Coronavirus Disease 2019 (COVID-19) has been widely associated with increased thrombotic risk, with many different proposed mechanisms. One such mechanism is acquired deficiency of protein S (PS), a plasma protein that regulates coagulation and inflammatory processes, including complement activation and efferocytosis. Acquired PS deficiency is common in patients with severe viral infections and has been reported in multiple studies of COVID-19. This deficiency may be caused by consumption, degradation, or clearance of the protein, by decreased synthesis, or by binding of PS to other plasma proteins, which block its anticoagulant activity. Here, we review the functions of PS, the evidence of acquired PS deficiency in COVID-19 patients, the potential mechanisms of PS deficiency, and the evidence that those mechanisms may be occurring in COVID-19.     

Non-alcoholic fatty liver disease and clinical outcomes in patients with COVID-19: A comprehensive systematic review and meta-analysis

BackgroundNon-alcoholic fatty liver disease (NAFLD) patients represent a vulnerable population that may be susceptible to more severe COVID-19. Moreover, not only the underlying NAFLD may influence the progression of COVID-19, but the COVID-19 may affect the clinical course of NAFLD as well. However, comprehensive evidence on clinical outcomes in patients with NAFLD is not well characterized.ObjectivesTo systematically review and meta-analysis the evidence on clinical outcomes in NAFLD patients with COVID-19.MethodsMEDLINE, EMBASE, and Cochrane Central were searched from inception through November 2020. Epidemiological studies assessing the clinical outcomes in COVID-19 patients with NAFLD were included. Newcastle-Ottawa Scale (NOS) was used to assess study quality. Generic inverse variance method using RevMan was used to determine the pooled estimates using the random-effects model.ResultsFourteen studies consisting of 1851 NAFLD patients, were included. Significant heterogeneity was observed among the studies, and studies were of moderate to high quality [mean, (range):8 (6, 8)]. For NAFLD patients, the adjusted odds ratio (aOR) for the severe COVID-19 was 2.60 (95%CI:2.24–3.02; p < 0.001) (studies,n:8), aOR for admission to ICU due to COVID-19 was 1.66 (95%CI:1.26–2.20; p < 0.001) (studies,n:2), and aOR for mortality for was 1.01 (95%CI:0.65–1.58; p = 0.96) (studies,n:2).ConclusionsAn increased risk of severe COVID-19 infection and admission to ICU due to COVID-19 with no difference in mortality was observed between NAFLD and non-NAFLD patients. Future studies should include the mortality outcome to conclusively elucidate the impact of NAFLD in patients with COVID-19.     

Severe acute exacerbation of HCV infection in cancer patients who undergo chemotherapy without antiviral prophylaxis

No guidelines have been developed for the management of HCV‐infected cancer patients receiving chemotherapy. The current study aimed to investigate the incidence of severe acute exacerbation of HCV infection in cancer patients receiving chemotherapy and to search for risk factors predicting severe acute exacerbation of HCV infection. This retrospective cohort study reviewed the clinical data of the cancer patients receiving chemotherapy in our institute from August 2012 to December 2017. Incidences of severe acute exacerbation of HCV infection in different kinds of cancers were assessed, and risk factors were analysed. Cancer patients with HCV infection (n = 306) had a higher frequency of severe acute liver injury (2.3% vs 0.7%; P = .003) than those without HCV infection (n = 4419). The incidence of severe acute exacerbation in HCV‐infected haematological cancer patients was higher than that in those with HCC and non‐HCC solid tumours (9.4% vs 1.9% and 1.1%). Rituximab‐containing chemotherapy and haematological malignancy were the risk factors related to the acute exacerbation (P < .001 and P = .004, respectively). None of the patients with severe acute HCV flares developed hepatic decompensation or mortality. However, 57.1% of them discontinued chemotherapy due to liver dysfunction. In conclusion, HCV infection increases the risk of acute severe liver injury in cancer patients undergoing chemotherapy. Rituximab‐containing chemotherapy and haematological malignancy are the risk factors related to severe acute exacerbation of HCV infection in cancer patients undergoing chemotherapy. Pre‐chemotherapy HCV testing is therefore mandatory before rituximab‐containing chemotherapy for the treatment of haematological malignancy.     

Australian and New Zealand consensus statement on the management of lymphoma,chronic lymphocytic leukaemia and myeloma during the COVID‐19 pandemic

The COVID‐19 pandemic poses a unique challenge to the care of patients with haematological malignancies. Viral pneumonia is known to cause disproportionately severe disease in patients with cancer, and patients with lymphoma, myeloma and chronic lymphocytic leukaemia are likely to be at particular risk of severe disease related to COVID‐19. This statement has been developed by consensus among authors from Australia and New Zealand. We aim to provide supportive guidance to clinicians making individual patient decisions during the COVID‐19 pandemic, in particular during periods that access to healthcare resources may be limited. General recommendations include those to minimise patient exposure to COVID‐19, including the use of telehealth, avoidance of non‐essential visits and minimisation of time spent by patients in infusion suites and other clinical areas. This statement also provides recommendations where appropriate in assessing indications for therapy, reducing therapy‐associated immunosuppression and reducing healthcare utilisation in patients with specific haematological malignancies during the COVID‐19 pandemic. Specific decisions regarding therapy of haematological malignancies will need to be individualised, based on disease risk, risks of immunosuppression, rates of community transmission of COVID‐19 and available local healthcare resources.     

新型冠状病毒肺炎心血管并发症研究现状

新型冠状病毒肺炎是由严重急性呼吸综合征冠状病毒2引起的一种传染性疾病,目前的临床证据表明,新型冠状病毒肺炎合并基础心血管系统疾病的患者死亡风险明显增加,大部分患者在病程中会发生心肌炎、心肌损伤、心律失常和心肌病等。该文主要阐述新型冠状病毒肺炎心血管并发症的研究现状。     

The Immunology of SARS-CoV-2 Infection and Vaccines in Solid Organ Transplant Recipients

Since its outbreak in December 2019, the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to an enormous rise in scientific response with an excess of COVID-19-related studies on the pathogenesis and potential therapeutic approaches. Solid organ transplant (SOT) recipients are a heterogeneous population with long-lasting immunosuppression as a joining element. Immunocompromised patients are a vulnerable population with a high risk of severe infections and an increased infection-related mortality rate. It was postulated that the hyperinflammatory state due to cytokine release syndrome during severe COVID-19 could be alleviated by immunosuppressive therapy in SOT patients. On the other hand, it was previously established that T cell-mediated immunity, which is significantly weakened in SOT recipients, is the main component of antiviral immune responses. In this paper, we present the current state of science on COVID-19 immunology in relation to solid organ transplantation with prospective therapeutic and vaccination strategies in this population.