The SARS-CoV-2 transmission riddle - Part 3 and Architecture of Isolation 9

(revised November 2024)

This is the third post in the re-run of our Transmission Riddle series. Each post has been updated and reworked with the new evidence we could find. 

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Part 3 focuses on the catching vs infection debate that our pioneering predecessors started 80 years ago. 

The original theory was put forward by Sir Christopher Andrewes in 1942. Andrewes was no empty vessel; he was part of the trio who isolated the first human influenza virus. This was way before other agents of Influenza-like illness or acute respiratory infections had been identified. The only “kid in town” then was influenza, considered separate from the “common cold”. 

Andrewes, Dochez, Shope and the virologists of their generation knew there were other players. Still, they could not visualise them; they only let them through filters that caught bigger particles like bacteria and reproduced the illness we now call influenza-like illness or acute respiratory infection.

In his book “the Common Cold”, Andrewes explains his chain of thought. 

Numerous sudden waves of ILI have synchronised across the globe. Witness accounts date back to the Napoleonic Wars; more recent examples are below. 

The near-synchronous outbreaks (of the same agents, as we now know) thousands of miles apart could not be explained by one-to-one transmission, and clusters emerged in isolated communities. However, transmission of “pedigree colds,” as Andrewes called them, was hit and miss. In the chapter “Transmission vs Activation,”

Andrewes describes a frustrating, elaborate experiment illustrating how difficult studying transmission can be. 

 “It is well-established that polar explorers and others cut off from contact with their fellow men for some time are abnormally susceptible to catching colds when they once more rejoin civilization. 

Could we possibly get hold of such returning hyper-susceptible explorers and carry out our contact experiments on them? Alas, we could not. Returning explorers show a not unnatural interest in rejoining their families. We planned therefore, to keep the whole thing under our own control by marooning our own party of explorers on our own desert island.” 

We learnt through Dr Fraser Darling of a suitable island, Eilean nan Ron, lying one and half miles off the little port of Skerray on the north coast of Sutherland. It was just over a mile long and less than a mile wide surrounded by fairly steep cliffs but with one good landing place. The island had a number of well-built houses on it but had been abandoned by the inhabitants for economic reasons twelve years earlier. It be­longed to the Duke of Sutherland who kindly lent it to us. A few of the houses were readily made habitable and early in July 1950 a party of twelve volunteers was, not unwillingly, marooned on the island. Most of them were students from the University of Aberdeen; in charge was an ex-superintendent of police. They were to be there for three months, their summer vacation, the longest period for which we could readily obtain volunteers. They took with them all the stores and equipment they needed for their stay; and they also had a small radio transmitter and receiver with which they maintained daily con­tact with the mainland.

One man had a cold on arrival, July 8th; another case occurred on July 9th and three more on July 11th. There were no more until the isolation ended on September 19th. On that day a colleague and I landed and made contact with some of the Party to see whether any stranger, even without a cold, could introduce infection. 

Nothing having happened, another of our team arrived with five others; all had just been inoculated in Aberdeen with one of our “pedigree” colds, that is one which had been studied for some while at Salisbury [MRC Common Cold Unit]. Meanwhile the island had been divided into three, each third inhabited by a party of four islanders, who kept apart from the other two parties. Each group was exposed under different conditions to the newly arrived party, each of whom had either developed a cold already, or did so very shortly after landing. The 'colds' had arrived late in the day, but as early colds are probably the most infectious we carried out the experiment forthwith and far into the night. It was a fine night and a magnificent display of the Aurora·Borealis made the whole thing most romantic. The six invaders with colds attempted to infect the islanders in one of three ways. They occupied a room in one of the houses for three hours in the absence of the four 'natives' (party A). 

To quote the report: “During their occupation they were liberal in the way they disseminated nasal discharge on playing cards, books,·cutlery and handles of cups, letters, chairs, door-handles and tables”. They then left the room, which was aired for half­ an-hour before party A entered. The invaders then occupied a room with party B, being separated from them by a blanket stretched across the room but not quite reaching floor or ceiling. This arrangement was intended, and in fact shown by appropriate tests, to permit droplet nuclei to pass to the opposite half of the room while stopping coarse particles. Party C lived and ate with·the people with the colds for three days, allowing maximum exposure. To our intense surprise and dis­appointment, no colds developed in any of the groups. Four more people with colds arrived a few days later and were exposed to party A under conditions of 'maximum exposure'. Again no colds developed.

We then learnt, through our radio, of a crofter on the main­ land who had a cold, though not a very early, streaming one. He was exposed to Party B, talking round a fire for two periods of two hours, and this time transfer was successful, three of four of the Bs developing colds within a few days. 

In reviewing the rest we inclined to think at the time that our 'pedigree' cold strain was for some reason less effective than a naturally occurring one. In the light of later work on the multiplicity of strains of cold-viruses it seems far more likely that the islanders were resistant as a result of the little outbreak of colds a few days after their isolation began; and that by bad luck this was due to a virus of the same type as the pedigree virus used in the later test.

Though this laborious experiment failed in its main objective, it gave us some useful ideas for future work.”

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The year was 1950, and Sir Christopher blamed immunity for the failure of his elaborate isolation experiment and subsequent exposure. The “pedigree” was almost certainly rhinovirus, although its identification came later. Other transmission experiments also gave equivocal results.

So if 1 to 1 transmission was so inefficient, what did the other evidence point to?

Here’s a well-documented historical example from Antarctica, reported in the Journal of Hygiene (London).

From March 18, 1969, to December, 12 men wintered at the Adelaide Winter base when the first aircraft arrived. Six of the 12 sequentially developed symptoms and signs of a common cold after 17 weeks of complete isolation. 

No specimen, both swabs, cultures or sera, revealed exposure to a causative agent. The outbreak was studied in collaboration with Andrewes’s MRC Common Cold Unit, which ran an extensive range of tests looking for the usual agents, including coronaviridae. The recording was carried out under radio supervision by a trained physician at the base and included the recording of symptoms and meteorological and environmental conditions.

Another more modern example is that of the Argentinian trawler. Sixty-one crew members were quarantined for two weeks before sailing, and all tested negative for SARS-CoV-2. At the end of the trip, they set sail for the Antarctic fishing grounds. After about 35 days at sea with no contact (other than with the fish), they started exhibiting signs and symptoms of Covid and were quickly returned to base in Tierra del Fuego. All but a few were positive, and two were hospitalised.

How can that be? Do we have carriers no one knows about? 

In 1931 Andrewes’s friend Dick Shope from the Rockefeller Institute in New York had shown just such a mechanism of latency in swine influenza through the vehicle of earthworm eggs.

Paradoxical events such as the trawler story have existed for centuries. The name “influenza” comes from the Italian “Influenza degli astri” (influence of the planets). Our ancestors were as bewildered as we were. Influenza comes and goes without rhyme or reason; surely, the planets must be causing all this mayhem! 

The unclear role of isolation has been studied extensively, with the best-known example being the 1933 study by the aptly named Drs Paul and Freese. 

They showed that in the Spitsbergen Islands, colds died off at the end of the trading season and were reintroduced when sailing conditions allowed ships to berth again. The first to go down with a cold was usually the harbour storekeeper, the fellow with the most contact with the incoming sailors.

The Spitsbergen narrative is wholly in keeping with germ theory and our contemporary understanding of immunity and transmission. But what about the episodes of Eilean nan Ron, Argentinian trawler, and Antarctica?

This is the nub of Andrewes’s “catching vs. infection” theory: a “stripped down” version of a virus seeds by spreading widely until activated. Person-to-person transmission can take place, but it’s inefficient and hit-and-miss. What causes the problems is the activation by some external influence of the stripped-down virus.  

If you think about it, the idea that respiratory viruses live with us and activate when the time comes is a logical explanation for the worldwide presence of genetically identical viruses and their near synchronous appearance thousands of miles across.

For readers raised on germ theory and 1 to 1 transmission, we offer this riddle from the great Spanish Influenza of 1918-19. 

In 1919, the following observations were made in the BMJ by Dr Andrew Garvie, a general practitioner in good old Halifax, England: 

“But why the first case in the household was, on the average, more serious than the sporadic, and why the ‘clumping’ should occur, is difficult to understand. Casual observation might lead one to suppose that the spread was due to actual contagion from one house to another. At first I regarded it simply as due to ‘neighbourliness,’ but later on became convinced that this could only be a partial explanation of the spread. In many of the households affected in a ‘clump,’ a suggestion of being in any of the other affected houses was absolutely denied. It will further be noticed that within one particular ‘clump’ two or three houses commenced on the same date, and further, owing to the general fear of the epidemic, spread by newspaper reports and other methods, if the epidemic was known to be present in a house, the house was usually shunned by neighbours. In many cases the houses were not in direct contact but separated by the breadth of the street or by garden walls ... but why people within small radii of one another, of all ages, of different occupations, not coming in actual contact with one another, should develop synchronous attacks, still remains a mystery to me.”

Quite a history of events: Garvey's conclusion provides excellent advice:

“I am fully aware how little importance will be attached to the views expressed by those who frame regulations, but with the experience gained in over 100 cases and with many hours spent in analysing the observations made, I cannot help but express the view that if public health authorities canny be a help to the general practitioner, they should at least refrain from being a hindrance.”

Dr Garvey could see the future, unlike our present-day modellers.

In the era of modern computing, such detailed fieldwork is dispensed with, and instead, models and retrospective database analysis are the mainstays of investigation. It is no use asking overnight experts and media pundits for advice; transmission is a lot more complicated than it appears. 

However, as Garvey notes, it remains a mystery why people within a small distance from one another who do not come into contact should develop synchronous attacks.

References

Tyrrell, D. A. J. (David Arthur John). Common Colds and Related Diseases. London: Arnold, 1965. Print.

Tyrrell, D. A.J. “Common colds and related diseases.” British medical bulletin 23.2 (1967): 124–128. Web.

Andrewes, C. H. (Christopher Howard). The Common Cold. London: Weidenfeld and Nicolson, 1965. Print.

Allen TR, Bradburne AF, Stott EJ, Goodwin CS, Tyrrell DA. An outbreak of common colds at an Antarctic base after seventeen weeks of complete isolation. J Hyg (Lond). 1973 Dec;71(4):657-67. doi: 10.1017/s0022172400022920. PMID: 4520509; PMCID: PMC2130424.

Paul, J.H. & Freese, H. L. (1933). An epidemiological and bacteriological study of the 'common cold' in an isolated Arctic community (Spitzbergen). American Journal of Hygiene 17, 517.

Garvie A. The spread of influenza in an industrial area. BMJ 1919;2:519-23.