Mild Clinical Course of COVID-19 in 3 Patients Receiving Therapeutic Monoclonal Antibodies Targeting C5 Complement for Hematologic Disorders

Araten, David J.; Belmont, H. Michael; Schaefer-Cutillo, Julia; Iyengar, Arjun; Mattoo, Aprajita; Reddy, Ramachandra C.

doi:10.12659/ajcr.927418

Cited by 22 publications

(21 citation statements)

References 9 publications

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“…During admission he also required red blood cells (RBC) transfusion (3 units) and progressively recovered. (9)(10)(11)(12)(13)(14)(15)(16). Patients were mostly women (63% females, 37% males), with a wide age range (19 to 77 years).…”

Section: Case Descriptionmentioning

confidence: 99%

Complement Mediated Hemolytic Anemias in the COVID-19 Era: Case Series and Review of the Literature

et al. 2021

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The complex pathophysiologic interplay between SARS-CoV-2 infection and complement activation is the subject of active investigation. It is clinically mirrored by the occurrence of exacerbations of complement mediated diseases during COVID-19 infection. These include complement-mediated hemolytic anemias such as paroxysmal nocturnal hemoglobinuria (PNH), autoimmune hemolytic anemia (AIHA), particularly cold agglutinin disease (CAD), and hemolytic uremic syndrome (HUS). All these conditions may benefit from complement inhibitors that are also under study for COVID-19 disease. Hemolytic exacerbations in these conditions may occur upon several triggers including infections and vaccines and may require transfusions, treatment with complement inhibitors and/or immunosuppressors (i.e., steroids and rituximab for AIHA), and result in thrombotic complications. In this manuscript we describe four patients (2 with PNH and 2 with CAD) who experienced hemolytic flares after either COVID-19 infection or SARS-Cov2 vaccine and provide a review of the most recent literature. We report that most episodes occurred within the first 10 days after COVID-19 infection/vaccination and suggest laboratory monitoring (Hb and LDH levels) in that period. Moreover, in our experience and in the literature, hemolytic exacerbations occurring during COVID-19 infection were more severe, required greater therapeutic intervention, and carried more complications including fatalities, as compared to those developing after SARS-CoV-2 vaccine, suggesting the importance of vaccinating this patient population. Patient education remains pivotal to promptly recognize signs/symptoms of hemolytic flares and to refer to medical attention. Treatment choice should be based on the severity of the hemolytic exacerbation as well as of that of COVID-19 infection. Therapies include transfusions, complement inhibitor initiation/additional dose in the case of PNH, steroids/rituximab in patients with CAD and warm type AIHA, plasma exchange, hemodialysis and complement inhibitor in the case of atypical HUS. Finally, anti-thrombotic prophylaxis should be always considered in these settings, provided safe platelet counts.

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Section: Case Descriptionmentioning

confidence: 99%

Complement Mediated Hemolytic Anemias in the COVID-19 Era: Case Series and Review of the Literature

et al. 2021

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“…Thus, it is not surprising that several groups have initiated small clinical trials using various anti-complement strategies. One of the first studies came from Mastigllo et al, with some success [99][100][101][102] . These patients were not as severely ill as might be expected and had only moderately elevated CRPs that did fall after treatment and all recovered after 14 days.…”

Section: Potential Therapies For Abrogating Complement Signaling In Covid-19mentioning

confidence: 99%

“…One of the first studies came from Mastaglio et al, who treated a case of severe ARDS in a COVID‐19 pneumonia patient with the complement C3 inhibitor AMY‐101 93 . Diurno et al treated four COVID‐19 patients with the C5 blocking monoclonal antibody eculizumab with some success 99 – 102 . These patients were not as severely ill as might be expected and had only moderately elevated C‐reactive proteins that did fall after treatment and all recovered after 14 days.…”

Section: Potential Therapies For Abrogating Complement Signaling In Covid‐19mentioning

confidence: 99%

Mechanisms of SARS‐CoV‐2‐induced lung vascular disease: potential role of complement

et al. 2021

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The outbreak of COVID-19 disease, caused by SARS-CoV-2 beta-coronovirus, urges a focused search for the underlying mechanisms and treatment options. The lung is the major target organ of COVID-19, wherein the primary cause of mortality is hypoxic respiratory failure, resulting from acute respiratory distress syndrome, with severe hypoxemia, often requiring assisted ventilation. While similar in some ways to acute respiratory distress syndrome secondary to other causes, lungs of some patients dying with COVID-19 exhibit distinct features of vascular involvement, including severe endothelial injury and cell death via apoptosis and/or pyroptosis, widespread capillary inflammation, and thrombosis. Furthermore, the pulmonary pathology of COVID-19 is characterized by focal inflammatory cell infiltration, impeding alveolar gas exchange resulting in areas of local tissue hypoxia, consistent with potential amplification of COVID-19 pathogenicity by hypoxia. Vascular endothelial cells play essential roles in both innate and adaptive immune responses, and are considered to be “conditional innate immune cells” centrally participating in various inflammatory, immune pathologies. Activated endothelial cells produce cytokines/chemokines, dynamically recruit and activate inflammatory cells and platelets, and centrally participate in pro-thrombotic processes (thrombotic microangiopathies). Initial reports presented pathological findings of localized direct infection of vascular endothelial cells with SARS-CoV-2, yet emerging evidence does not support direct infection of endothelial or other vascular wall cell and thus widespread endothelial cell dysfunction and inflammation may be better explained as secondary responses to epithelial cell infection and inflammation. Endothelial cells are also actively engaged in a cross-talk with the complement system, the essential arm of innate immunity. Recent reports present evidence for complement deposition in SARS-CoV-2-damaged lung microcirculation, further strengthening the idea that, in severe cases of COVID-19, complement activation is an essential player, generating destructive hemorrhagic, capillaritis-like tissue damage, clotting, and hyperinflammation. Thus, complement-targeted therapies are actively in development. This review is intended to explore in detail these ideas.

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“…Monoclonal antibodies are most effective when given early in infection. 2 , 3 , 4 The BLAZE‐1 study reported SARS‐CoV‐2 viral load reductions at day 11 post‐infusion of three escalating doses of BAM or one dose of the combination of BAM and etesevimab in a phase 2/3 clinical trial. 5 In the BLAZE‐1 trial, a significant difference in the secondary endpoint that evaluated reduction in hospitalizations was found to be associated with combination treatment compared with placebo.…”

Section: Introductionmentioning

confidence: 99%

Bamlanivimab use in mild‐to‐moderate COVID‐19 disease: A matched cohort design

et al. 2021

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Background: Bamlanivimab (LY-CoV555; BAM), a monoclonal antibody therapy for mild-to-moderate Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2), has been granted an Emergency Use Authorization (EUA) in the United States. Our goal was to determine if BAM prevented emergency department (ED) visits, hospitalizations for SARS-CoV-2, or death within 60 days of a positive SARS-CoV-2 viral test. Setting and Participants: Patients (N=2,107) eligible to receive BAM from November 1 to December 31, 2020, were identified. Eligible patients had mild-to-moderate SARS-CoV-2 disease, a positive SARS-CoV-2 test, and risk factor(s) for progression to severe SARS-CoV-2 infection. All patients were reviewed for subsequent ED visits, subsequent hospitalization, and death. Intervention: A total of 144 of 2,107 patients with mild-to-moderate SARS-CoV-2 received BAM. Patient propensity matching was performed for BAM administration to get two discrete groups of patients; those who received BAM (n=117) and those who did not (n=117). Continuous variables are presented as median and interquartile range (IQR). Discrete variables are presented as counts and proportions. Results: Patients (n=234) were matched, 117 in each group. Median (IQR) age was 72 (65-80) years.Forty-seven percent of patients were male. Twenty-one patients who received BAM were subsequently seen in the ED compared to 34 untreated patients (18.0% vs. 29.1%; P = 0.045).Fourteen BAM-treated patients were subsequently hospitalized post-BAM infusion compared to 27 untreated patients (12.0% vs. 23.1%; P = 0.025). Finally, there were no mortalities in the BAM group, however, eleven patients in the untreated group died (0.0% vs. 9.4%; P < 0.001). The number needed to treat (NNT) is 11 patients to prevent one mortality event.Conclusions: BAM infusion for mild-to-moderate SARS-CoV-2 infection in outpatients significantly prevented subsequent ED visits, hospitalizations, and death from SARS-CoV-2.

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Mild Clinical Course of COVID-19 in 3 Patients Receiving Therapeutic Monoclonal Antibodies Targeting C5 Complement for Hematologic Disorders

Cited by 22 publications

References 9 publications

Complement Mediated Hemolytic Anemias in the COVID-19 Era: Case Series and Review of the Literature

Complement Mediated Hemolytic Anemias in the COVID-19 Era: Case Series and Review of the Literature

Mechanisms of SARS‐CoV‐2‐induced lung vascular disease: potential role of complement

Bamlanivimab use in mild‐to‐moderate COVID‐19 disease: A matched cohort design

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