The SARS-CoV-2 Transmission Riddle - Part 13 The role of airborne transmission

Controversy on airborne transmission is nothing new

The term airborne is confusing. In its current use, it appears to include a range of particles, from rather large droplets to a fine mist of aerosol. Large droplets (droplet nuclei) are generated while breathing or, more likely, coughing or shouting, whereas an aerosol is generated with instrumental procedures in and out of hospitals. 

Air, the simple air that we breathe, has also been indicated as a possible medium of transport of infectious particles. The possibility that air may be infectious has historically been a bone of contention for reasons that are more to do with social science and politics than epidemiology. 

Malaria literally means bad air in Italian, and it was thought that malarial areas were such because of the presence of swamps which produce poisonous gases causing fever, so-called miasmata.

But malaria (like influenza) were terms generally used to indicate fevers and not specific ailments.

The joker in the pack was the presence of breeding grounds for anopheles mosquitoes, which was not fully understood until Sir Ronald Ross proved transmission of the malarial parasite, and we began to distinguish the presence of various agents and to identify their action.

Centuries ago, the miasmatic theory came to be equated with opposition to germ theory or contagionism, thereby generating the polarised debate of contagionism vs anticontagionism.

To investigate whether SARS-CoV-2 could indeed be transported by air from a contagious source to a person infected with the same strain (or, more correctly, lineage in the era of gene sequencing), we carried out the usual systematic review, which we have updated to the current third version. This was initially funded by WHO, a detail which caused no end of problems.

Although 90 airborne studies we included in our initial review were carried out in healthcare settings, we immediately ran into the usual problems relating to the quality of the evidence with an added complication related to sampling. For example, 54 studies reported finding viral RNA in the air sample taken, but 69 different air samplers were used (as some studies used more than one sampler) with vast variation in sampling methods. This, coupled with weak reporting, made it difficult to distinguish between aerosol and droplet nuclei transmission routes. 

The variability further limited interpretation in reporting of patient distance from the sampler, use of protective equipment or oxygen masks by patients, time since symptom onset, patient activities (coughing and sneezing during sampling time), air movement, air conditioning sampler design, method of sampling, storage and transfer conditions. Oh, dear. 

The hospital environment is a good place to carry out this type of study as the concentration of sick people is such that researchers stand the biggest chance of retrieving a positive sample, and the chain of transmission of air is obvious but vague; it could be anywhere. 

This concept is what eventually sunk miasma theory: it was everywhere, and for a time, it could not be disproven until a contagionist pointed out that deaths for infectious diseases (cholera in this case) were no different in London streets with tanneries compared to streets with no miasmata and terrible smells. 

Contagionists were eventually also able to point to specific agents and specific routes of transmission, as in the case of anthrax, cholera and smallpox.

Viral RNA was found in air samples, especially those from ICU (as you would expect). It's worth restating that the viral RNA detected by PCR is only a tiny fragment of the virus - PCR detects  20 base pairs from a virus that has 29,000 base pairs in length. This minute fragment of RNA can attach to particulate matter and readily be found in the environment. However, the detection of RNA in the air cannot confirm transmission since only infectious virions can cause disease, but it can be a useful tool for surveillance. 

Eight studies out of 25 that attempted viral culture reported growing replication-competent viruses. A closer look at the methods and results shows that some of the so-called positive cultures were due to other circulating viruses, not SARS-CoV-2 and others had very low numbers of particles. 

For example, one study looked like it was culturing something, but the plaques demonstrating positive culture were microscopic and barely in the range of genome quantities needed to detect plaques. Another had an anecdotal statement that one specimen permitted virus culture, but there was no picture and no confirmation. 

While the presence of genetic material of SARS-CoV-2 in the air is not really surprising, it was found in concentrations which were considerably lower than those genetic materials of other agents, none of which are considered to transmit via the airborne route. In other words, the evidence for infectiousness by air is weak.

Credible airborne transmission studies are not easy to carry out. For example, air samplers could damage extracted particles, compromising their viability in vitro. Interpretation is not easy, especially when the methods used are so heterogeneous, preventing comparisons.

Proponents of the airborne route favour laboratory studies in which animals are subjected to unrealistically high concentrations of infectious viruses, and other variables, such as particle travel distance, are exaggerated. Particles generated by a human cough travel a distance of around 10 cm before it begins to dry in the air. Whereas a manikin allows consistent replication, it does not reflect the real world. For example, mannequins only face straight, whereas humans constantly move. And a manikin can expel particles at many times the distance of a human.

These experiments may be accepted as proof of concept. But they cannot be applied to the real world of crowded hospitals or wide outdoor spaces where conditions are considerably different.

The evidence is weak, but the airborne route of transmission cannot be ruled out.

Some proponents of the airborne route have few qualms about misreporting the findings of any study, which in their view, contradicts their dogma. This is an example of a Corrigendum forced by the editor on the authors of one paper who misquoted our findings after we complained.

Instead of promoting a constructive discussion, such behaviour generates polarisation, especially in a context of poor science. And the truth, as Pontius Pilate remarked, slips through your hands.

Heneghan CJ, Spencer EA, Brassey J et al. SARS-CoV-2 and the role of airborne transmission: a systematic review [version 3; peer review: 1 approved with reservations, 2 not approved]. F1000Research 2022, 10:232 (https://doi.org/10.12688/f1000research.52091.3)