Coagulopathy associated with COVID-19 – Perspectives &amp; Preventive strategies using a biological response modifier Glucan

Ikewaki, Nobunao; Rao, K. S.; Durant-Archibold, Armando A.; Iwasaki, Masanori; Senthilkumar, Rajappa; Preethy, Senthilkumar; Katoh, Shojiro; Abraham, Samuel JK

doi:10.1186/s12959-020-00239-6

Cited by 22 publications

(27 citation statements)

References 56 publications

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“…COVID-19 associated alterations of hemostasis is multifactorial including systemic inflammation and activation of the complement system [ 10 , 11 ]. According to Iba et al [ 12 ], thrombus formation in COVID-19 patients is caused by four major factors: first, COVID-19 induces a cytokine storm which activates coagulation.…”

Section: Discussionmentioning

confidence: 99%

“…It is also an acute phase reactant produced in the liver and fibrinogen levels can therefore be a useful monitoring tool of the inflammatory state [ 20 ]. As mentioned above, the infection with coronavirus induces a cytokine storm [ 11 ] and interleukin-6 is a major initiator of the acute phase response [ 21 , 22 ]. Ranucci et al described a significant association of interleukin-6 with fibrinogen levels [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

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Coronavirus-induced coagulopathy during the course of disease

et al. 2020

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Background A significant proportion of patients with coronavirus disease 19 (COVID-19) suffer from excessive coagulation activation and coagulopathy which is associated with an increased risk of venous and arterial thromboembolism and adverse outcome. Our study investigates coagulation markers and the incidence of thromboembolic events in COVID-19 patients receiving recommended anticoagulation strategies. Methods In a retrospective single-center analysis at the University Hospital Zurich, Switzerland, we investigated 31 adult COVID-19 patients between April 6th and May 13th, 2020 and with at least one laboratory assessment of the coagulation markers prothrombin time/Quick, thrombin time, fibrinogen and D-dimers. For antithrombotic prophylaxis low-molecular-weight-heparin or unfractionated heparin was administered and two patients with heparin-induced thrombocytopenia received argatroban. Results We analyzed 31 patients (68% male, mean age 60± SD 15 years). 22 (71%) of these required intensive care unit treatment, 5 (16%) were hospitalized in a ward, and 4 (13%) were outpatients. Mean fibrinogen levels were markedly elevated to 6.4± SD 1.8g/l, with a peak in the third week of the disease and no significant decrease over time. D-dimers were elevated to a mean value of 5.1±4.4mg/l with peak levels of 6.8±5.3mg/l in the fourth week of disease, and a subsequent decrease. Platelet count (308±136G/l) and PT/Quick (85±22%) showed no significant changes over time. Sensitivity analyses for patients treated in the ICU showed that D-dimer levels were higher in this group. The results of other sensitivity analyses were comparable. Thromboembolic events were diagnosed in 4 (13%) patients and 5 (16%) patients died during the observation period. Conclusion We find coagulation alterations in COVID-19 patients indicating significant hypercoagulability. These alterations are visible despite antithrombotic treatment, and peak around week 3–4 of the disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Coronavirus-induced coagulopathy during the course of disease

et al. 2020

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“…Tissue damage that contributes to multiple organ failure in severe COVID-19 patients is attributed to defective stimulation of the immune system leading to a condition of sustained inflammation-the cytokine storm, which involves excessive and uncontrollable release of inflammatory cytokines [2][3][4]. Symptomatic COVID-19 patients possibly exhibit a baseline state of inflammation, which allows the virus to escape the immune system and take over cellular processes in human cells to promote its replication [8][9][10]. Particularly, it alters the metabolism of key immune cells such as monocytes and macrophages to be highly glycolytic [10]-glucose metabolism dysfunction promotes viral growth [10] and potentiates inflammation [11][12][13].…”

Section: Overviewmentioning

confidence: 99%

Approaches to Nutritional Screening in Patients with Coronavirus Disease 2019 (COVID-19)

Ali

Kunugi

2021

IJERPH

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Malnutrition is common among severe patients with coronavirus disease 2019 (COVID-19), mainly elderly adults and patients with comorbidities. It is also associated with atypical presentation of the disease. Despite the possible contribution of malnutrition to the acquisition and severity of COVID-19, it is not clear which nutritional screening measures may best diagnose malnutrition in these patients at early stages. This is of crucial importance given the urgency and rapid progression of the disease in vulnerable groups. Accordingly, this review examines the available literature for different nutritional screening approaches implemented among COVID-19 patients, with a special focus on elderly adults. After a literature search, we selected and scrutinized 14 studies assessing malnutrition among COVID-19 patients. The Nutrition Risk Screening 2002 (NRS-2002) has demonstrated superior sensitivity to other traditional screening measures. The controlling nutritional status (CONUT) score, which comprises serum albumin level, cholesterol level, and lymphocytes count, as well as a combined CONUT-lactate dehydrogenase-C-reactive protein score expressed a predictive capacity even superior to that of NRS-2002 (0.81% and 0.92% vs. 0.79%) in midlife and elder COVID-19 patients. Therefore, simple measures based on routinely conducted laboratory investigations such as the CONUT score may be timely, cheap, and valuable alternatives for identifying COVID-19 patients with high nutritional risk. Mini Nutritional Assessment (MNA) was the only measure used to detect residual malnutrition and high malnutrition risk in remitting patients—MNA scores correlated with hypoalbuminemia, hypercytokinemia, and weight loss. Older males with severe inflammation, gastrointestinal symptoms, and pre-existing comorbidities (diabetes, obesity, or hypertension) are more prone to malnutrition and subsequently poor COVID-19 prognosis both during the acute phase and during convalescence. Thus, they are in need of frequent nutritional monitoring and support while detecting and treating malnutrition in the general public might be necessary to increase resilience against COVID-19.

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“… 34 In addition, AFO-202 β-glucan has been suggested to be beneficial in decreasing the risk of coagulopathy due to the presence of a dysregulated inflammatory system in COVID-19 patients, especially in vulnerable individuals based on race (Caucasians, African Americans and Hispanics), people with comorbidities, including diabetes, hypertension, and cardiovascular diseases, pregnant women. 35 …”

Section: Afo-202 β-Glucanmentioning

confidence: 99%

β-glucans: wide-spectrum immune-balancing food-supplement-based enteric (β-WIFE) vaccine adjuvant approach to COVID-19

Ikewaki

Iwasaki

Kurosawa

et al. 2021

Human Vaccines & Immunotherapeutics

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Conventional vaccines to combat COVID-19 through different approaches are at various stages of development. The complexity of COVID-19 such as the potential mutations of the virus leading to antigenic drift and the uncertainty on the duration of the immunity induced by the vaccine have hampered the efforts to control the COVID-19 pandemic. Thus, we suggest an alternative interim treatment strategy based on biological response modifier glucans such as the Aureobasidium pullulans AFO-202-derived β-glucan, which has been reported to induce trained immunity, akin to that induced by the Bacille Calmette-Guérin vaccine, by epigenetic modifications at the central level in the bone marrow. These β-glucans act as pathogen-associated molecular patterns, activating mucosal immunity by binding with specific pathogen recognition receptors such as dectin-1 and inducing both the adaptive and innate immunity by reaching distant lymphoid organs. β-Glucans have also been used as immune adjuvants for vaccines such as the influenza vaccine. Therefore, until a conventional vaccine is widely available, an orally consumable vaccine adjuvant that acts like biosimilars, termed as the wide-spectrum immune-balancing food-supplement-based enteric (β-WIFE) vaccine adjuvant approach, with well-reported safety is worth in-depth investigation and can be considered for a clinical trial.

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Coagulopathy associated with COVID-19 – Perspectives & Preventive strategies using a biological response modifier Glucan

Cited by 22 publications

References 56 publications

Coronavirus-induced coagulopathy during the course of disease

Coronavirus-induced coagulopathy during the course of disease

Approaches to Nutritional Screening in Patients with Coronavirus Disease 2019 (COVID-19)

β-glucans: wide-spectrum immune-balancing food-supplement-based enteric (β-WIFE) vaccine adjuvant approach to COVID-19

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