scholarly journals Current advances in pharmacological treatments for patients with COVID-19

2021 ◽  
Vol 64 (5) ◽  
pp. 375-385
Author(s):  
Sun Bean Kim ◽  
Joon-Sup Yeom
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Treatment Approach ◽  
Severe Disease ◽  
Late Phase ◽  
Mortality Benefit ◽  
Pharmacological Treatments ◽  
The Us ◽  
Risk Of Progression ◽  
Clinical Benefits ◽  
Drug Treatments

Since the coronavirus disease 2019 (COVID-19) outbreak, more than 150 million people in over 200 countries have been infected, with over 3 million people dying due to it, as of May 1, 2021. Many researchers are working continuously to find effective drug treatments for COVID-19; however, the optimal treatment approach remains unclear. In this article, current advances in pharmacological treatments for patients with COVID-19 are discussed. Data obtained from recent studies indicate a mortality benefit with the administration of dexamethasone or adjunctive tocilizumab and potential clinical benefits with remdesivir (with or without baricitinib). Several monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 have been developed. The US Food and Drug Administration issued two emergency use authorizations: one for bamlanivimab/etesevimab and another for casirivimab/imdevimab for patients with mild to moderate COVID-19, at high risk of progression to severe disease and/or hospitalization. The pathogenesis of COVID-19 indicates that antiviral treatments would be most beneficial in the early phase of the infection that is primarily driven by replication of severe acute respiratory syndrome coronavirus 2, whereas immunosuppressive/anti-inflammatory therapies are likely to be more beneficial during the late phase of the infection, when the disease is driven by an exaggerated immune/inflammatory response to the virus that causes tissue damage.

scholarly journals Mifepristone as Bridge or Adjunct Therapy in the Management of Challenging Cushing Disease Cases

2021 ◽  
Vol 14 ◽  
pp. 117955142199410
Author(s):  
Alice Y Chang ◽  
Sasan Mirfakhraee ◽  
Elizabeth E King ◽  
Jennifer U Mercado ◽  
Diane M Donegan ◽  
...  
Keyword(s):  
Cushing Syndrome ◽  
Severe Disease ◽  
Disease Recurrence ◽  
Adjunctive Treatment ◽  
Therapeutic Trial ◽  
Cushing Disease ◽  
The Us ◽  
Clinical Benefits ◽  
Effects Of Radiation ◽  
Bridge Therapy

Establishing a definitive diagnosis of Cushing disease (CD), given its clinical and biochemical heterogeneity, initiating effective treatment to control the effects of hypercortisolism, and managing recurrence are challenging disease aspects to address. Mifepristone is a competitive glucocorticoid receptor antagonist that is approved in the US by the Food and Drug Administration to control hyperglycemia secondary to endogenous hypercortisolism (Cushing syndrome) in patients who have glucose intolerance or type 2 diabetes mellitus and have failed surgery or are not candidates for surgery. Herein, we describe 6 patients with CD who received mifepristone as adjunct/bridge therapy in the following clinical settings: to assess clinical benefits of treatment for suspected recurrent disease, to control hypercortisolism preoperatively for severe disease, to control hypercortisolism during the COVID-19 pandemic, and to provide adjunctive treatment to radiation therapy. The patients were treated at multiple medical practice settings. Mifepristone treatment in each of the described cases was associated with clinical improvements, including improvements in overall glycemia, hypertension, and weight loss. In addition, in one case where biochemical and radiological evidence of disease recurrence was uncertain, clinical improvement with mifepristone pointed toward likely disease recurrence. Adverse events associated with mifepristone reported in the 6 cases were consistent with those previously reported in the pivotal trial and included cortisol withdrawal symptoms, antiprogesterone effects (vaginal bleeding), hypothyroidism (treated with levothyroxine), and hypokalemia (treated with spironolactone). These cases show how mifepristone can potentially be utilized as a therapeutic trial in equivocal cases of CD recurrence; as a presurgical treatment strategy, particularly during the COVID-19 pandemic; and as bridge therapy, while awaiting the effects of radiation.

scholarly journals Extrapulmonary manifestations and complications of severe acute respiratory syndrome coronavirus 2 infection: a systematic review

2021 ◽  
Author(s):  
J Cho ◽  
J Lee ◽  
CH Sia ◽  
CS Koo ◽  
BYQ Tan ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Respiratory Symptoms ◽  
Case Reports ◽  
Meta Analysis ◽  
Severe Disease ◽  
Late Phase ◽  
Cardiac Injury ◽  
Gastrointestinal Symptoms ◽  
Case Series ◽  
Venous Thromboembolic Events

Introduction: We aimed to describe the extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including their frequency, onset with respect to respiratory symptoms, pathogenesis and association with disease severity. Methods: We searched the MEDLINE and Embase databases for SARS-CoV-2-related studies. Meta-analysis, observational studies, case series and case reports published in English or Chinese between 1 January and 1 May 2020 were included. Reports with only paediatric or obstetric cases were excluded. Results: 169 articles were included. Early manifestations (preceding respiratory symptoms until Day 6 of onset) included olfactory and gustatory disturbance (self-reported in up to 68% and 85% of cases, respectively), gastrointestinal symptoms (up to 65.9%) and rash (up to 20.4%). From Day 7 onwards, hypercytokinaemia, paralleled multi-organ complications including acute cardiac injury (pooled incidence of 17.7% in 1,412 patients, mostly with severe disease and 17.4% mortality), kidney and liver injury (up to 17% and 33%, respectively) and thrombocytopenia (up to 30%). Hypercoagulability resulted in venous thromboembolic events in up to 31% of all patients. Uncommon disease presentation and complications comprised Guillain-Barré syndrome, rhabdomyolysis, otitis media, meningoencephalitis and spontaneous pneumomediastinum. Conclusion: Although the systemic manifestations of SARS-CoV-2 infection are variegated, they are deeply interwoven by shared mechanisms. Two phases of extrapulmonary disease were identified: (a) an early phase with possible gastrointestinal, ocular and cutaneous involvement and (b) a late phase characterised by multiorgan dysfunction and clinical deterioration. A clear, multidisciplinary consensus to define and approach thromboinflammation and cytokine release syndrome in SARS-CoV-2 is needed.

The Unparalleled Growth of COVID-19 Publications (Preprint)

2020 ◽  
Author(s):  
Paul Fontelo ◽  
Mrigendra Bastola ◽  
Craig Locatis ◽  
Fang Liu
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Evidence Base ◽  
Research Papers ◽  
Global Pandemic ◽  
The Us ◽  
International Collaborative ◽  
Number Of Publications ◽  
Collaborative Publishing

UNSTRUCTURED The global pandemic of COVID-19 has generated an unprecedented number of research papers from clinicians and scientists worldwide. We searched PubMed for articles on coronaviruses from 1970 to June 2020. Surges of publications occurred in 2003 from SARS and, again in 2012 from MERS. Although the name COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was only announced by WHO in February 2020, the number of publications has already exceeded 16000 by June this year. China and the US lead in publications, but a significant number also come from countries hardest hit by the illness. International collaborative publishing is significant. Since these publications are generally free to access worldwide, it provides a rich evidence base for clinicians and scientists combatting the COVID-19 pandemic.

scholarly journals Effective use of monoclonal antibodies for treatment of persistent COVID-19 infection in a patient on rituximab

2021 ◽  
Vol 14 (8) ◽  
pp. e243469
Author(s):  
Carlos X Rabascall ◽  
Becky X Lou ◽  
Brianne Navetta-Modrov ◽  
Stella S Hahn
Keyword(s):  
Monoclonal Antibodies ◽  
Symptom Onset ◽  
Severe Disease ◽  
Therapeutic Window ◽  
Immunosuppressed Patient ◽  
Unique Case ◽  
Risk Of Progression ◽  
Immunosuppressed Patients ◽  
Effective Use ◽  
Potential Use

As we are over a year into the COVID-19 pandemic, we have made many forward strides in therapeutics. These treatments, such as monoclonal antibodies, have help mitigate the detrimental and often fatal consequences of COVID-19. The current indication for the use of monoclonal antibodies is mild to moderate COVID-19 infection within 10 days of symptom onset in those who are at high risk of progression to severe disease. However, their role in patients with prolonged symptoms is not clear. We present a unique case of monoclonal antibodies use after 54 days of symptom onset in an immunosuppressed patient with persistent COVID-19 infection despite standard treatment. This case illustrates the potential use of monoclonal antibodies outside of the current recommended therapeutic window in immunosuppressed patients, who may have difficulty with viral clearance.

scholarly journals CD169/SIGLEC1 is expressed on circulating monocytes in COVID-19 and expression levels are associated with disease severity

Infection ◽  
2021 ◽  
Author(s):  
Jan-Moritz Doehn ◽  
Christoph Tabeling ◽  
Robert Biesen ◽  
Jacopo Saccomanno ◽  
Elena Madlung ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Disease Severity ◽  
Clinical Studies ◽  
Viral Infections ◽  
Severe Disease ◽  
Type I Interferons ◽  
Type I ◽  
Interferon Signaling ◽  
Expression Levels

AbstractCoronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Type I interferons are important in the defense of viral infections. Recently, neutralizing IgG auto-antibodies against type I interferons were found in patients with severe COVID-19 infection. Here, we analyzed expression of CD169/SIGLEC1, a well described downstream molecule in interferon signaling, and found increased monocytic CD169/SIGLEC1 expression levels in patients with mild, acute COVID-19, compared to patients with severe disease. We recommend further clinical studies to evaluate the value of CD169/SIGLEC1 expression in patients with COVID-19 with or without auto-antibodies against type I interferons.

scholarly journals Distorted TCR repertoires define multisystem inflammatory syndrome in children

2021 ◽  
Author(s):  
Amna Malik ◽  
Eszter N. Tóth ◽  
Michelle S. Teng ◽  
Jacob Hurst ◽  
Eleanor Watt ◽  
...  
Keyword(s):  
T Cell ◽  
Severe Acute Respiratory Syndrome ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
High Confidence ◽  
T Cell Clones ◽  
Severity Of Disease ◽  
Cell Clones ◽  
Inflammatory Syndrome ◽  
Independent Expansion

While the majority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) display mild or no symptoms, rare individuals develop severe disease presenting with multisystem inflammatory syndrome (MIS-C). The reason for variable clinical manifestations is not understood. Here, we carried out TCR sequencing and conducted comparative analyses of TCR repertoires between children with severe (n=12) or mild (n=8) COVID-19. We compared these repertoires with unexposed individuals (samples collected pre-COVID-19 pandemic: n=8) and with the Adaptive Biotechnologies MIRA dataset, which includes over 135,000 high-confidence SARS-CoV-2-specific TCRs. We show that the repertoires of severely ill children are characterised by the expansion of TRBV11-2 chains with high junctional and CDR3 diversity. Moreover, the CDR3 sequences of TRBV11-2 clones shift away from SARS-CoV-2 specific T cell clones, resulting in distorted TCR repertoires. In conclusion, our study reports that CDR3-independent expansion of TRBV11-2+ cells, lacking SARS-CoV-2 specificity, defines severity of disease in children.

scholarly journals Systemic sclerosis and the COVID-19 pandemic: World Scleroderma Foundation preliminary advice for patient management

2020 ◽  
Vol 79 (6) ◽  
pp. 724-726 ◽  
Author(s):  
Marco Matucci-Cerinic ◽  
Cosimo Bruni ◽  
Yannick Allanore ◽  
Massimo Clementi ◽  
Lorenzo Dagna ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Severe Acute Respiratory Syndrome ◽  
Clinical Immunology ◽  
Patient Management ◽  
Severe Disease ◽  
Immunosuppressive Treatment ◽  
Disease Course ◽  
Clinical Questions ◽  
Frequent Presence

Due to the frequent presence of interstitial lung disease and widespread use of immunosuppressive treatment, systemic sclerosis (SSc) patients may be considered at risk for a more severe disease course and higher mortality when they develop Severe Acute Respiratory Syndrome - Coronavirus - 2 (SARS-CoV-2) virus infection. Therefore, with World Scleroderma Foundation endorsement, experts from different specialties including rheumatology, virology and clinical immunology gathered virtually to answer to the main practical clinical questions regarding SARS-CoV-2 infection coming from both patients and physicians. This preliminary advice is aligned with other national and international recommendations, adapted for SSc patients.

scholarly journals In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

2020 ◽  
Vol 71 (15) ◽  
pp. 732-739 ◽  
Author(s):  
Xueting Yao ◽  
Fei Ye ◽  
Miao Zhang ◽  
Cheng Cui ◽  
Baoying Huang ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Safety Profile ◽  
Late Phase ◽  
Vero Cells ◽  
Lung Fluid ◽  
Pbpk Models ◽  
Physiologically Based Pharmacokinetic ◽  
Autoimmune Conditions ◽  
Dosing Regimens

Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first broke out in 2019 and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late phase in critically ill patients with SARS-CoV-2. Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection. Methods The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2–infected Vero cells. Physiologically based pharmacokinetic (PBPK) models were implemented for both drugs separately by integrating their in vitro data. Using the PBPK models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens to explore the most effective regimen while considering the drug’s safety profile. Results Hydroxychloroquine (EC50 = 0.72 μM) was found to be more potent than chloroquine (EC50 = 5.47 μM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached 3 times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance. Conclusions Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro.

scholarly journals Differences in Antibody Kinetics and Functionality Between Severe and Mild Severe Acute Respiratory Syndrome Coronavirus 2 Infections

2020 ◽  
Vol 222 (8) ◽  
pp. 1265-1269 ◽  
Author(s):  
Ger Rijkers ◽  
Jean-Luc Murk ◽  
Bas Wintermans ◽  
Bieke van Looy ◽  
Marcel van den Berge ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Antibody Response ◽  
Geometric Mean ◽  
Severe Disease ◽  
Immunoglobulin A ◽  
Virus Neutralization ◽  
Neutralization Titer ◽  
Humoral Immune ◽  
Leave Of Absence ◽  
Antibody Kinetics

Abstract We determined and compared the humoral immune response in patients with severe (hospitalized) and mild (nonhospitalized) coronavirus disease 2019 (COVID-19). Patients with severe disease (n = 38) develop a robust antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including immunoglobulin G and immunoglobulin A antibodies. The geometric mean 50% virus neutralization titer is 1:240. SARS-CoV-2 infection was found in hospital personnel (n = 24), who developed mild symptoms necessitating leave of absence and self-isolation, but not hospitalization; 75% developed antibodies, but with low/absent virus neutralization (60% with titers <1:20). While severe COVID-19 patients develop a strong antibody response, mild SARS-CoV-2 infections induce a modest antibody response. Long-term monitoring will show whether these responses predict protection against future infections.

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