Sandbox:Usman Shah

Covid-19 Associated ARDS

Historical Perspective

• On 31 December 2019, the World Health Organization (WHO) was formally notified about a cluster of cases of pneumonia in Wuhan City.
• Ten days later, WHO was aware of 282 confirmed cases, of which four were in Japan, South Korea and Thailand
• The virus responsible was isolated on 7 January and its genome shared on 12 January.The cause of the severe acute respiratory syndrome that became known as COVID‐19 was a novel coronavirus, SARS‐CoV‐2
• ARDS is one of the most important causes of hospital and ICU admission due to COVID.
• Many autopsies studies reported ARDS to be the cause of death in patients dying due to respiratory complications of COVID.

• As of July 19 2020 the number of total cases worldwide are 14,043,176 including 597,583 deaths, reported to WHO.

Classification

Authors in a case report highlighted the nonuniformity of patients with COVID-19-associated ARDS and proposed the existence of two primary phenotypes:

• Type L (low values of elastance, pulmonary ventilation/ perfusion ratio, lung weight, and recruitability).
• Type H (high values of elastance, right-to-left shunt, lung weight, and recruitability), more consistent with typical severe ARDS.

ARDS is divided into three categories based on oxygenation index (PaO2/FiO2) on PEEP ≥ 5 cmH2O:

• mild (200 mmHg ≤ PaO2/FiO2 < 300 mmHg),
• mild-moderate (100 mmHg ≤ PaO2/FiO2 < 200 mmHg), and
• moderate-severe (PaO2/FiO2 < 100 mmHg).

Pathophysiology

• The SARS-CoV-2 virus, like the closely-related MERS and SARS coronaviruses, effects its cellular entry via attachment of its virion spike protein (a.k.a. S protein) to the angiotensin-converting enzyme 2 (ACE2) receptor.
• This receptor is commonly found on alveolar cells of the lung epithelium.It suggested that injury to the alveolar epithelial cells was the main cause of COVID-19-related ARDS.
• Cellular infection and viral replication cause activation of the inflammasome in the host cell, leading to the release of pro-inflammatory cytokines and cell death by pyroptosis with ensuing release of a damage-associated molecular pattern, further amplifying the inflammatory response.
• The cytokine storm and the deadly uncontrolled systemic inflammatory response resulting from the release of large amounts of proinflammatory cytokines including interferons and interleukins and, chemokines by immune effector cells resulting in acute inflammation within the alveolar space. The exudate containing plasma proteins, including albumin, fibrinogen, proinflammatory cytokines and coagulation factors will increase alveolar-capillary permeability and decrease the normal gas exchange and plasma proteins, including albumin, fibrinogen, proinflammatory cytokines and coagulation factors.

Covid19 healthcare worker. [1]

Classification of Waldenstrom macroglobulinemia (WM) and Related Disorders

Criteria	Symptomatic WM	Asymptomatic WM	IgM-Related Disorders	MGUS
IgM monoclonal protein	+	+	+	+
Bone marrow infiltration	+	+	-	-
Symptoms attributable to IgM	+	-	+	-
Symptoms attributable to tumor infiltration	+	-	-	-

Infra-Hisian Block Microchapters
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Epidemiology and Demographics
Risk Factors
Natural History, Complications and Prognosis
Diagnosis
Treatment
Prevention
Differentiating Infra-Hisian Block from other Diseases