Covid-19: acquired acute porphyria hypothesis
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Abstract
Pandemic Covid-19 pneumonia, of SARS-CoV-2 aetiology, presents an existential threat to health care systems globally. Multiple
therapeutic and prophylactic agents are currently undergoing clinical trial, including 23 clinical trials of (hydroxy)chloroquine in China.
While progress towards a curative agent or vaccine is promising, the principal limiting factor in public health emergency is time, and
therefore a pre-existing licensed therapeutic would offer reprieve to health care systems operating at the edge of capacity. In this brief
communication, the author argues that Covid-19 has high probability of being more than a disease of pneumonia, and that critical Covid-19
patients may be experiencing a form of acquired acute porphyria. Readily available interventions exist to treat acute porphyria and the
position is advanced that urinalysis of critical Covid-19 patients would diagnose this pathology.
Erythrocytes are strongly implicated in the pathophysiology of Covid-19. Wuhan University researchers argue that the role of erythrocytes in
the pathophysiology of Covid-19 is under-estimated; the co-efficient of variation of red blood cell distribution width (RDW) is predictive of
severity of disease state (Gong 2020). Elevated RDW is correlated with reduced erythrocyte turnover; red blood cells become smaller as they
age and the delay in clearance expands the low-volume tail of the volume distribution (Patel 2015). Suppressed erythrocyte turnover may
indicate erythropoietic distress and function as a compensatory mechanism to maintain circulating red blood cell levels (Patel 2015). Excess
porphyrins in red blood cells can precipitate cell lysis and development of hemolytic anaemia (Sassa 2006). Macaques infected with SARS-CoV2 also have decreased red blood cell numbers (Munster 2020) and susceptibility to SARS-CoV-2 appears to be determined by blood group;
blood group A is most affected whereas blood group O seems to be protected (Yang 2020). This finding is concordant with previous studies
showing that susceptibility to the 2003 strain of SARS-CoV was determined by blood group (Guillon 2008). Preliminary evidence suggests that
CD147, the determinant of the Ok blood group system, binds the spike protein of SARS-CoV-2 (Wang 2020). Incidentally, CD147 functions as an
essential receptor for erythrocyte invasion by Plasmodium falciparum (Crosnier 2011). Blockade of CD147 abrogates the normal recirculation
of erythrocytes, from the spleen into the general circulation, leading to selective trapping of red blood cells in the spleen as development of a
form of anaemia (Coste 2001). Autopsy of deceased Covid-19 patients reveals that the spleen is significantly reduced in size. Reduction in
spleen size would be expected in the event that the spleen has emptied its reserve of erythrocytes into the circulation as part of a normal
physiological response to anaemia (Dale 2016).