Covid-19 – salt loss, blood clots and treatments

Salt dysregulation and blood clotting in vital organs, like lungs and heart, are two of the features in severe cases of the Coronavirus disease 2019 (Covid-19), that is caused by the SARS-CoV-2 (virus).

Some viruses are activated by proteolytic cleaving, by human proteases inside the body. Proteases are proteins that can cut other proteins at specific sequences to make them more or less active, and thus regulate processes in the body. The new coronavirus, SARS-CoV-2, binds to proteases with its spike proteins, to get the spike proteins cut, in order for the virus to infect the cells (Hoffmann et al, 2020). Several human proteases can activate the virus, but when the proteases are bound to the viruses they are doing less of their normal job. Consequently, specific serine protease inhibitors can reduce the SARS-CoV-2 inection (Hoffmann et al, 2020). That might be a powerfull treatment against Covid-19, although it first has to be controlled that such medication doesn’t worsen any symptoms.

One function that might suffer from the reduced protease activity during Covid-19 is the sodium channel, ENaC, which needs proteases to be activated. With less functioning sodium channels, sodium and water can be trapped in the lung alveoli and reduce the gas exchange function of the lungs (Anand et al, 2020). Indeed, autopsy studies show that the lungs, and to some extent the heart, are much heavier in persons that have passed away due to Covid-19, than the normal weight of these organs (Youd and Moore, 2020).

The sodium channel is also responsible for reabsorption of sodium in the kidneys and the intestine (Anand et al, 2020), why Covid-19 symptoms include increased loss of sodium and water in the urine and feces. The loose stool experienced in Covid-19 might be due to reduced uptake of sodium from the intestines.

Most people eat more than enough of table salt (sodium chloride), but especially those abiding by a low salt diet might be at risk of getting too little sodium during Covid-19 (Post et al, 2020). The consequences could be too low blood pressure and possibly lower performance of muscles and nerves. This could be difficult for the heart, especially if the body, as in some severe cases, has both reduced blood pressure, reduced oxygenation and blood clotting problem on top of that. Eating moderately more salt might be helpful to quickly improve the feeling of low blood pressure, weakness over the heart, the strange weakness in the body, accompanied with slight dizziness, as those Covid-19 symptoms might be caused by sodium deficiency. In severe cases, healthcare or nursing homes might have to keep track of the sodium level and make sure that the patients get enough sodium.

There might be reduced level of calcium in the blood as well, during Covid-19 (Lippi et al, 2020), with probably mild effects, although so many processes in the body rely on calcium at some point.

Another severe, but fairly rare, symptom of Covid-19, is the formation of many small blood clots, in the small blood vessels of infected organs, primarily the lungs, heart and kidneys. The exact causation of the blood clots is still under investigation, but seems to be caused by disturbances of the endothelial cells (Iba et al, 2020; Martin-Rojas et al, 2020; O’Sullivan et al, 2020). Endothelial cells are the inner cells that line the blood vessels. Anticoagulation therapy and thrombolysis have somewhat, but limited, protective effect (Blasi et al, 2020).

A third feature of the SARS-CoV-2 virus is intussusceptive angiogenesis, where endothelial cells rearrange, so that additional capillary connections form (Ackermann et al, 2020), but that might not be a detrimental thing.

Since a SARS-CoV-2 infection can have such an impact on the body, even in some cases where the symptoms at first seem mild, it’s reasonable to try to avoid getting exposed to the virus. There are evidence that the amount of exposure to the virus has an impact on the severity of the infection. Unfortunately, based on anecdotal stories, the antibodies (the immunesystem’s targeted missiles) against the virus, might disappear a few months after an infection or vaccination, or they might not effectively stop recurrent infections. This raises questions on how often and when we need renewed vaccination shots, perhaps once or more per year and possibly before attending big events. The vaccines are however way, way milder to the body than the actual live virus, for an overwhelming portion of people and getting vaccinated is, beside a protection for oneself, also a prevention from being a spreader of SARS-CoV-2 to more vulnerable people. Extra cautious routines in nursing homes and hospitals might have to be permanented and people might have to continue to use masks in public, whenever they feel any slight infection. The future will tell.

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References:

Ackermann et al, 2020
Maximilian Ackermann et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 2020; 383:120-128.

Anand et al, 2020
Praveen Anand et al. SARS-CoV-2 strategically mimics proteolytic activation of human ENaC. eLife. 2020; 9:e58603

Blasi et al, 2020
Annabel Blasi et al. In vitro hypercoagulability and ongoing in vivo activation of coagulation and fibrinolysis in COVID-19 patients on anticoagulation. J Thrombosis and Haemostasis. 2020; 18(10):2646-53.

Hoffmann et al, 2020
Markus Hoffmann et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020; 181(2):271-80.

Iba et al, 2020
Toshiaki Iba et al. The unique characteristics of COVID-19 coagulopathy. Crit Care. 2020; 24(360)

Lippi et al, 2020
Giuseppe Lippi et al. Electrolyte imbalances in patients with severe coronavirus disease 2019 (COVID-19). Ann Clin Biochem. 2020; 57(3):262-5.

Martin-Rojas et al, 2020
Reyes Maria Martin-Rojas et al. COVID-19 coagulopathy: An in-depth analysis of the coagulation system. Eur J Haematol. 2020; 105(6):741-50.

O’Sullivan et al, 2020
Jamie M O’Sullivan et al. Endothelial cells orchestrate COVID-19 coagulopathy. Lancet Haematology. 2020; 7(8):E553-5.

Post et al, 2020
Adrian Post et al. Sodium status and kidney involvement during COVID-19 infection. Virus Research. 2020; 286:198034.

Youd and Moore, 2020
Esther Youd, Luiza Moore. COVID-19 autopsy in people who died in community settings: the first series. J. Clinical Pathology. 2020; 73(12):840-844.