CMAAO Coronavirus Facts and Myth Buster: Mucocutaneous manifestations of MIS-C; Baricitinib plus remdesivir

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With input from Dr Monica Vasudev

1210: DG Alerts: Mucocutaneous manifestations of multisystem inflammatory syndrome in children: An array of mucocutaneous findings was identified in hospitalized children with multisystem inflammatory syndrome in children (MIS-C) or suspected MIS-C during the COVID-19 pandemic, reported a case series published in JAMA Dermatology.

Of the patients assessed, 83% developed mucocutaneous changes, with the most common being conjunctival injection, palmoplantar erythema, lip hyperemia, periorbital erythema and edema, strawberry tongue, and malar erythema. Other cutaneous morphologic findings included scarlatiniform eruptions, morbilliform eruptions, urticarial eruptions, and reticulated eruptions. Among those with mucocutaneous changes, 19 patients experienced fever a mean of 2.7 days (range, 1-7 days) prior to the recognition of the first mucocutaneous finding. The duration of mucocutaneous findings ranged from hours to days (median duration, 5 days [range, 0-11 days]).

Overall, 19 patients had cardiac involvement as noted by elevated troponin and/or brain natriuretic peptide levels, while 10 had abnormal echocardiogram findings; five patients with cardiac involvement needed inotropic support. Ten patients were admitted to the intensive care unit (ICU). There appeared to be no statistically significant associations between the presence of mucocutaneous findings and cardiac dysfunction, need for inotropic support, or ICU admission, which suggests that mucocutaneous changes were not tied to disease severity in MIS-C.

Conjunctivitis, lip hyperemia or cracking, and palmoplantar erythema exhibited an even distribution across all ages; however, urticarial eruptions were noted in those below 2 years of age, and periorbital and palmoplantar edema were evident in those younger than 6 years.

[SOURCE: JAMA Dermatology]

1211:  Baricitinib plus remdesivir shows promise in treatment of COVID-19:  The combination of baricitinib, an anti-inflammatory drug, and remdesivir, an antiviral, was found to reduce the time to recovery among hospitalized COVID-19 patients, suggested clinical trial results published in the New England Journal of Medicine. The study was supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The ACTT-2 trial started on May 8, 2020 and recruited 1,033 volunteers at sites in eight countries. Participants were randomized to receive either oral baricitinib tablets and intravenous (IV) remdesivir or oral placebo tablets and IV remdesivir.

Combination of baricitinib and remdesivir reduced median time to recovery among hospitalized COVID-19 patients from 8 days to 7 days. Patients requiring high-flow oxygen or non-invasive ventilation during hospitalization were shown to obtain the largest benefit. The median time to recovery in these patients was reduced from 18 days to 10 days. Furthermore, participants’ condition at day 15 (measured by an eight-category ordinal scale which ranked the severity of their condition) was significantly improved when they received the combination therapy. Those who were given the two treatments also had slightly fewer serious adverse effects.

[Source: NIH]

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA

CMAAO Coronavirus Facts and Myth Buster: Direct oral anticoagulant use

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With input from Dr Monica Vasudev

1186: Direct oral anticoagulant use not tied to reduced risk of severe COVID-19

DG Alerts Excerpts:

Prognosis would not be altered by early outpatient DOAC initiation as per a study in Journal of Internal Medicine.

Identified as a prominent feature of severe COVID-19, managing hypercoagulability in hospitalized patients has largely been focused, with interim guidelines supporting anticoagulation, suggest researchers led by Benjamin Flam, MD, Karolinska University Hospital, Stockholm, Sweden. Pre-emptive anticoagulation before or at the time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to protect against severe disease is theoretically appealing; however, there is a lack of real-world data. Only small studies of COVID-19 patient cohorts have been conducted which have shown mixed results.

A nationwide register-based cohort study was carried out in Sweden between February and May, 2020 to ascertain if the ongoing DOAC use was linked with reduced risk of hospital admission for COVID-19, or a composite of intensive care unit (ICU) admission or death due to COVID-19.

Within the cohort, 103,703 (mean age, 73.6 years) patients had non-valvular atrial fibrillation (AF) who were DOAC users, 90% of whom were using direct factor Xa inhibitors. The comparator groups included 36,875 (mean age, 66.4 years) patients with AF with no DOAC use and 355,699 (mean age, 69.3 years) patients with cardiovascular disease (CVD) with no DOAC use.

In all, 360 hospital admissions for COVID-19 were reported among DOAC users (crude risk, 0.35%), compared to 95 among non-users with AF (0.26%) and 1,119 among non-users with CVD (0.31%).

A total of 161 composite ICU admission or death due to COVID-19 outcome events occurred among those using DOACs (crude risk, 0.16%), compared to 55 among non-users with AF (0.15%) and 473 among non-users with CVD (0.13%).

DOAC use, in comparison with non-use, was found not to be associated with reduced risk of hospital admission for COVID-19. Both outcomes appeared to be similar for both DOAC subtypes (direct thrombin inhibitor and direct factor Xa inhibitors).

The authors state that rather than directing against secondary hypercoagulability, therapies may be directed against thrombogenic inflammation or vasculopathy.

[Reference: https://onlinelibrary.wiley.com/doi/10.1111/joim.13205]

My Comments: We cannot interpolate the results as in COVID-19, it’s thrombo-inflammation and results have to be compared whether they were given early steroids or not to stop inflammation.

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA

CMAAO Coronavirus Facts and Myth Buster: Venous Thrombosis

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With input from Dr Monica Vasudev

1181: Thrombosis in COVID-19

The risk of arterial and venous thrombosis in patients with COVID-19 is a major issue.
One has to be proactive about prevention.
It is increasingly being recognized that there is a heightened risk of thrombosis in COVID-19 patients.
The risk appears to be the greatest in patients in the intensive care unit (ICU), though it is also increased in patients hospitalized with COVID-19, not in ICU.
The risk is in non-hospitalized COVID-19 patients is not known, but is much lower than hospitalized patients.
Every patient hospitalized with COVID-19 may receive some type of thromboprophylaxis. This would mainly be with anticoagulation.
A recent US registry study reported thrombotic complication rates of 2.6% in noncritically ill hospitalized patients with COVID-19 and 35.3% in critically ill patients.
The ACCP guidelines are conservative and follow the evidence base for medical patients. The ISTH guidelines, being more aggressive, recommend increased levels of anticoagulation in both ICU and hospitalized non-ICU patients and also extend prophylaxis following discharge.
[Medscape]

1182: At present, neither the ISTH nor ACCP recommend D-dimer measurement to screen for venous thromboembolism or for evaluating intensity of prophylaxis or treatment. [Medscape]]

1183: The European Medicines Agency (EMA) stated that it received applications for conditional marketing authorization for COVID-19 vaccines BNT162b2 and mRNA-1273. According to the EMA, the assessments of BNT162b2 and mRNA-1273 will “proceed under an accelerated timeline,” and the opinions on approval could be issued within weeks, based on whether the data are robust enough and complete to demonstrate the quality, safety and effectiveness of the vaccine.

1184: U.S. donor blood collected in December and early January tested positive for SARS-CoV-2 antibodies, thus pointing to an earlier arrival of SARS-CoV-2 infection than previously thought. (NPR)

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA

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