Covid-19. Where have we been, and where are we headed?

There have been surprisingly, some good things that have come from SARS Corona Virus 2, and the disease it causes Covid -19.

A few days ago I was sent a link to an intriguing piece of electronic music based on the peptide sequence of the SARS spike protein. It turns out that many good scientists are also well grounded in music. The structure and function of the virus is widely known; to the point that it inspires music.

Within weeks of the emergence of the epidemic in China, laboratories around the world were reporting its entire molecular structure. The extent of international co-operation in science is now extra-ordinary and global collaboration is the new normal. While Peer Reviewed publications remain the absolute gold standard and across the world scientists are submitting their papers to journals, but at the same time uploading them to websites to which other scientists have free access. So almost in real time scientists can communicate by phone, skype, zoom on interesting developments in the field. This is historic, and a template we may need for the interesting times which might lie ahead.

Corona viruses are common, and apart from the SARS of 2002-3, gave us little more than a cold. Most of these “Cold” viruses had receptors in the upper airway and made us sneeze and splutter. The spike protein of SARS Corona virus 2 is a problem. In the brilliant representations in colour taken from electron micrographs, the spikes are the purple quills sticking out of the bluish blob. But its human receptors lie deep in the lung, in the very apparatus which keeps life-giving oxygen in our blood. The air we breathe enters the fine little sacs call alveoli in our lungs where gas exchange occurs. These alveoli are lined by two kinds of cells, pneumocytes. Type 1 are large flattened cells that are the lining which helps gas exchange. And then there are type 2 cells which are small and squeezed in between them. These carry the receptor for the spike protein, the ACE receptor.

These cells have a function, of course. They produce a protein which has surfactant properties. So when we breathe in our lungs expand, and when we breathe out our alveoli collapse and the walls would stick together without surfactant. Which it does in Covid -19 patients. But more problematically the spike allows viral RNA to enter the type 2 pneumocyte, and take over its reproductive apparatus to produce copies of virus as the cell disintegrates. As it does so it releases chemicals that cause severe inflammation. Inflammation causes fluid and both pro and anti-inflammatory products that accumulate around the alveolus. The fluid laden alveolus by now is no longer doing its job. Patients suffer from a lack of oxygen, and the lungs begin to congest and respiration fails.

The final devastating stage is when these bits of virus, combined with inflammatory and inti-inflammatory molecules escape into the circulation. They lodge in all parts of the body and set up secondary centres of inflamammation (the cytokine storm). The end is nigh!

There does not seem to be any other receptor that this virus is evolved for. It is, of course,  an obvious target for a vaccine. Other approaches target the stages of virus replication.  There are several dozen well funded projects underway, all underpinned by the insights of international collaboration.

Like other RNA viruses, SARS Coronavirus 2 is itself continuously changing. The main secret for its evolutionary success of course, is the Spike Protein, and this will be at its best while the going is good for it, as it is at present in many parts of the world. Other bits of it are changing, and allow us to map the changing face of the pandemic. The American virus is very similar to the Wuhan variety. But not identical.

So the R number (the number of people who are infected by a single patient) is key. It is as important from where I write in Cairns as it is in Sri Lanka. The initial R was thought to be between 1 and 2, then as it progressed through Europe and the US, to between 2 and 3, possibly higher. This translates to that exponential part of the curve describing cases and deaths. The mechanisms used to flatten this curve are part of the toolkit of traditional Public Health. From social distancing, vigorous contact tracing, to a complete shutdown of the economy and borders.

When it dips to less than 1 the curve points downward and can then get to the baseline of Zero Transmission. At this point the virus has nowhere to go and dies out. This seemed to occur during the Spanish Flu where several American cities had good statistics where the baseline was reached. It was also seen with the last SARS Coronavirus epidemic in 2002/2003.

The Chinese did a remarkable Public Health job in Wuhan. They locked down and isolated this city of 11 million, an economic powerhouse. In Europe and North America leaders were simply disbelieving, and delayed these severe measures. The results have been painful to see. The Public Health principle is, if you delay extreme measures by a day, you extend viral transmission a week.

So, while it is hard medicine, when taken as directed it has the potential to eradicate the virus. A vaccine will take too long to develop. It will not be an answer to this pandemic.

This also tells us that these R statistics vary in time and place. In Australia, a vast country there are large numbers of Postal Areas where not a single case of Covid-19 has been reported. In Cape York, thankfully, where many indigenous Australians live no cases have been recorded. The whole of Sri Lanka will fit six times over into Cape York.

We are now moving into the era of rapid testing for Covid-19, and blood tests that will help us to understand what immunity means. Does the development of antibodies in the blood mean immunity and if so for how long? We have never been able to manufacture a successful vaccine for Corona viruses, so there is no certainty about this.

I recently heard Prof. Ian Frazer, who developed the vaccine for Human Papilloma Virus, being interviewed on the prospects of a vaccine for SARS Covid-19, and he was quite guarded. Flu vaccines are no more than 50 or 60% effective. BCG has been resurrected for an international trial. I have never understood quite how it works against certain manifestations of TB, but we do know it has some other interesting effects, with bladder cancer for instance.

The potential market for anti-virals has also exploded, particularly with the repurposing of drugs used for other conditions. Drugs used for HIV and for Ebola.

Hydrochloroquine has been recommended by a President. Early trials are being reported. Some drug candidates have already fallen by the wayside.

But the other truth we need to bear in mind is that we have lived with viruses, and indeed continue to live within pandemics.

Take influenza A H1N. It takes a steady toll on Australians every year, 18,000 hospitalisations and 2-3000 deaths. Measles; a 100,000 deaths internationally every year. Dengue in Sri Lanka about 100,000 cases every year and 400 deaths (I know, I was nearly one of them!). What about the big one? 1 million per year internationally, and counting over 30 years, HIV/AIDS? Social Distancing? Travel Bans? Shut Down of economies? Not likely.

So as societies we come to terms with what is around us. From time to time extreme measures are taken which have the support of the public. The Chinese were praised when they clamped down on Wuhan. They even boarded up apartment blocks. Much of Europe chose to disregard the horseman galloping toward them. History will show that some countries managed this badly. The tragedy of the United States highlights the calamity where ignorance and hubris lead the life of nations.

So what else good has happened?

We have got better at using technology at work, and shifted a great deal online. As an educator I see a great possibility for novel educational strategies.

The environment gets a breather, as does nitric oxide pollution of the atmosphere. Certainly we produce less CO2 sitting at home; and many say that this is important.

I have watched on line, many birds returning to gardens in Colombo. I would like to get back.

(The writer is Associate Professor of Surgery, Cairns Clinical School, James Cook University,  Cairns, Australia)

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