Virtuous circulations in the COVID-19 universe

Written by Nobel Laureate Professor Peter Doherty

Across the world, the normal circulation of human beings has been massively disrupted by the fact that the SARS-CoV-2 virus is carried in and transmitted by us. International travel is way down, along with the local traffic of everyday life that takes us via highways, public transit systems, lanes and minor paths to the nooks and crannies of social interaction. Our workplaces, schools and universities, theatres and concert halls, cafes, clubs and pubs, and so forth, have been largely empty. Other essential forms of circulation have been less compromised: food supplies have been maintained and, though some shortages have led to what we might think of as minor “toilet paper wars”, that has been remedied as manufacturers switched their focus.

Of course, we leave out of that satisfactory food supply equation the one billion or so (of 7.6 billion) human beings who don’t, under ‘normal’ circumstances, get enough to eat - or the right kind of food to eat - each day. Beginning to ramp up in mid-February 2020, it was mid-April before global deaths from COVID-19 exceeded those from malnutrition, and mid-May before they passed the top-gun, malaria. Both malnutrition and malaria principally kill children in the poor countries.

In that grim statistic, COVID-19 is an add-on, not an either/or. And, while restrictions imposed in our efforts to deal with the pandemic have limited the physical movements of us, we are globally connected via the internet, which also allows us to be paid and pay our bills and, for many, to continue to work or study. Still, we have all become acutely aware that the normal circulation of people is important for psychological wellbeing. Medicine focuses on the mechanistic basis of maintaining what 19th century physician and physiologist Claude Bernard described as our ‘milieu interieur’. As we address that for COVID-19, our thoughts also turn to the ‘milieu exterieur’ of human social contact, and how that optimally operates.

When it comes to the language of medicine, the word ‘circulation’ means the blood and vascular system. Pumped around the body by the heart, the blood travels via our internal highways and byways, the arteries, arterioles, capillaries, venules and veins to carry essential materials to the 37.2 trillion or so cells that make up our tissues and organs. And, while we are generally less conscious of its existence, our continued good health also depends on another internal circulation, the lymphatic system. The lymphatics have no separate pump, with the lymph being ‘squeezed on’ from tissues as our body muscles tense and relax with normal human movement. The lack of that causes our ankles to swell on a long distance flight, or creates other problems if we are bed-ridden.

Formed as a transudate that exits the vasculature from the blood capillaries, the interstitial fluid that bathes our cells brings in nutrients and carries waste products away as it cumulates to be channelled, as lymph, via the thin-walled lymphatics. In mammals like us, the lymph then flows into (afferent) and out of (efferent) small, creamy white nodules called lymph nodes. We all know these as the ‘glands’ in our neck that swell-up and become painful when we have a sore throat or a respiratory infection, or in our armpit or groin if an arm or leg develops a boil or carbuncle.

The reason the lymph nodes suddenly increase in size during the course of an infection is that they are recruiting massive numbers of white blood cells in order to find the rare lymphocytes that can respond specifically to an incoming pathogen. Together, the dispersed lymph nodes comprise the secondary lymphoid tissue, the main ‘organ’ of immunity. We will be hearing a great deal about that as we go on with this COVID-19 discussion.

Lymph exiting the nodes in the efferent lymphatics flows ultimately into the ‘great drains’ of the thoracic duct and the right lymphatic duct that, in turn, discharge into the jugular or right subclavian veins located just above the heart. The heart’s right ventricle pumps the merged streams of blue venous blood and clear, colourless lymph through the microcirculation of the lungs where, at the terminal alveoli, the carbinohaemoglobin-carrying red blood cells (RBCs) send the carbon dioxide (CO2) waste product of our energy metabolism back into the airways to be breathed out. At the same time, the RBCs take-in the life-giving oxygen (O2) that is essential for energy generation. The more powerful left ventricle then drives these ‘refreshed’ RBCs, marked by the bright red of oxyhemoglobin, out into the arterial blood supply that fuels the body.

Our exhaled air becomes part of the atmospheric circulation that is central to the continuity of life on earth. The CO2 from our lungs is taken up by plants (including phytoplankton) where energy from the sun drives the process of photosynthesis that provides the plant with the carbon it needs and, at the same time, replenishes the atmospheric O2 that we, and other air-breathing life forms require. The air has been a lot cleaner during the time of COVID-19, but that’s a discussion for a different time.