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July 14 | Daily COVID-19 LST Report

CLIMATE:

· An opinion article by Swiss physicians titled “Is Clinical Effectiveness in the Eye of the Beholder?” warns against the implementation of treatments with unsound and incomplete evidence, arguing they may violate the principle of non-maleficence, or 'do no harm'. Hydroxychloroquine as an example of a drug that was widely adopted based off minimal in-vitro studies and unscientific promotion in the media. There is now a consensus that it does not offer therapeutic benefit and may have caused unnecessary harm through dangerous QT prolongation and diminished supply for patients with autoimmune diseases. The authors suggest that until effective treatments are proven, we should rely on social distancing and ensuring scientific journals and researchers are held to a high standard.


EPIDEMIOLOGY:

· A simulation model estimating the possible effect widespread use of remdesivir in South Africa - where the death rate is estimated at 85%-100% among patients who cannot obtain intensive care due to the lack of available ICU beds – predicted a reduction in COVID-19 mortality by 635 to 6,862 deaths (out of a projected 36,383 to 47,820 ICU patients as estimated by the South African National COVID-19 Epidemiology model (NCEM). These results suggest that remdesivir may reduce mortality indirectly by reducing the duration of illness and freeing up ICU beds.

UNDERSTANDING THE PATHOLOGY:

· This study investigates possible resistance to fibrinolysis as an additional underlying mechanism of the hypercoagulability in COVID-19. Investigators analyzed thromboelastometry profiles from five COVID-19 patients in France both before and after recombinant plasminogen activator administration (r-tPA), compared to 5 control samples. Results revealed a longer time to fibrinolysis in the COVID-19 samples, and acute pulmonary embolism in three out of the five COVID-19 patients despite thromboprophylaxis. The authors recommend larger prospective studies to further evaluate the fibrinolytic pathways involved in COVID-19 and to identify successful treatments for coagulopathy in this setting.

· Dermatologists review a possible underlying mechanism between severe COVID-19 and obesity, particularly focusing on ACE2 downregulation in SARS-CoV-2 infection leading to increased angiotensin II (Ang II) and angiotensin II type 1 receptor axis (AT1R) activation. The authors hypothesize that increased adipose tissue, which is known to produce angiotensinogen, also increases Ang II, thus contributing to renin-angiotensin-system dysregulation. Based on this hypothesis, they suggest ACE inhibitors, ARBs, Mas receptor agonists (antagonists of angiotensin I), and recombinant ACE2 may benefit patients with COVID-19; particularly those with obesity or metabolic disease.

MANAGEMENT:

· A case series of nine COVID-19 patients presenting with neurological symptoms discovered a common MRI finding of microbleeds in an unusual distribution (most notably the corpus callosum) suggesting a mechanism of damage to the endothelium of brain vessels (thrombotic microangiopathy) by SARS-CoV-2.

· Authors from Icahn School of Medicine at Mount Sinai performed a retrospective, single-center case series of seven COVID-19 stroke patients monitored for malignant cerebral edema (MCE). They found that of the 3/7 patients who underwent decompressive hemicraniectomy (DHC), 2 had favorable outcomes, suggesting that COVID-19 patients suffering from severe stroke may benefit from DHC and should not be excluded solely due to a positive COVID-19 test.

ADJUSTING PRACTICE DURING COVID-19:

· A review from the Department of Ophthalmology at Harvard Medical School outlines the benefits of tele-ophthalmology and Artificial Intelligence (AI) for patients, physicians, and payors. Although barriers do exist (mistrust in technology, infrastructure costs, medical liability), the authors suggest that further developments in tele-ophthalmology may lead to better detection and earlier management of ocular diseases. Additional benefits include increased accessibility of care for rural patients and underserved communities, successful remote care for eye emergencies with an ophthalmologist, and improved remote screening of chronic eye diseases such as diabetic retinopathy and glaucoma.

R&D DIAGNOSIS AND TREATMENT:

· An interdisciplinary group from across the United States details the key factors that influence the Positive Predictive Value (PPV) and the Negative Predictive Value (NPV) of diagnostic testing for COVID-19, with the goal of enabling healthcare providers to better understand the implications of a positive or negative COVID-19 test result in the context of an unknown true prevalence of the disease in the population. Three key points include:

o For low disease prevalence, the sensitivity doesn't play a large role in the PPV or NPV; instead, the focus must be on having a very high specificity in order to achieve a clinically usable PPV.

o For high disease prevalence, neither the sensitivity nor the specificity has a major impact on the PPV; however, high sensitivity is needed to obtain a clinically relevant NPV, so the focus here must be identification of a test with very high sensitivity.

o In the situation where prevalence is neither low nor high, the sensitivity tends to influence the PPV and the specificity tends to influence the NPV, so increasing utility of a test in this situation can focus on improving either the sensitivity or specificity, or both.


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