In recent days much has been made about the link between High Altitude Pulmonary Edema (HAPE) and the respiratory complications of Sars-Cov-2 infection (Covid-19). On the surface it’s easy to see why. Both are potentially fatal lung diseases that develop gradually over several days and cause a staggering degree of hypoxia. Unfortunately the similarities end there. HAPE is triggered by an irregular pattern of hypoxic pulmonary vasoconstriction that leads to widespread breakdown of the alveolar capillary membrane and the flooding of airways with fluid and cells, whilst Sars-Cov-2 infection causes destruction of the endothelial lining of small airways and swelling of neighbouring connective tissue.
Sars-Cov-2 is an RNA virus that binds to the angiotensin-converting enzyme-2 (ACE-2) receptors of cells lining the upper respiratory tract. On contact with ACE-2 receptors, RNA enters the nuclei of cells and replicates before spreading to neighbouring cells. Whilst virus spread is normally limited by the immune system of the host, in a small proportion of those infected with Sars-Cov-2 this goes unchecked and spreads throughout the lungs and leads to respiratory symptoms such as cough and shortness of breath (Covid-19). Given the high level of Sars-Cov-2 transmission, this has already occurred in many thousands of patients in the UK
Patients with the sort of damage seen in Covid-19 do not benefit from conventional drugs. Pulmonary vasodilators, anticoagulants, anti-inflammatories, diuretics and anti-microbials have little to offer a sick patient and may in fact worsen the clinical picture. Unfortunately the lack of treatment options isn’t good news for those of us who work in critical care. Faced with dying patients we want to “do something” and that’s where our interest in HAPE comes in. We see a coronavirus-infected patient present with similar symptoms to HAPE and assume that nifedipine and acetazolamide will work. But (and it's a big "but"!) this overlooks the very different pathological processes that separate the two diseases - in reality drugs like these will almost certainly not work for Covid-19.
CT scans of those with Covid-19 typically show "ground glass" abnormalities in the periphery of one or both lungs (a). Whilst this is seen in a number of different lung conditions, these changes are thought to reflect damage of small airways and connective tissue swelling seen in Covid-19. As the disease develops these often develop into areas of consolidation (b). Further information on CT changes in Covid-19 can be found here.
Research has shown us that dozens (perhaps hundreds?) of interventions in critical care have made either little difference or caused significant harm to patients. This may have occurred already in those infected with Sars-Cov-2. Has the use of early mechanical ventilation, therapeutic anticoagulation and aggressive diuresis been based upon the results of clinical research or the need to “do something”?
For now, respiratory failure, irrespective of its cause, should be investigated thoroughly and treated with oxygen and the best possible supportive care. The answer is not to “do something” but simply to “do no harm”.
A recent article in High Altitude Medicine and Biology that looks at the link between HAPE and Covid-19 can be found here.
For something completely different why not take a look at this?