Reviews that trace how expert opinions and dogma evolved over time into scientific fact are critical in helping those of us in that field to rethink how we know what we think we know. However, I believe that this manuscript suffers from two major problems.

First, this manuscript really treads a lot of the same ground as reference 51 (https://royalsocietypublishing.org/doi/10.1098/rsfs.2021.0049), which was written by some of the current authors. They purport to have different aims, as stated in the Abstracts (ref. 51, to examine the historical underpinnings of the droplet/aerosol dichotomy and the origin of the 5 µm threshold between them, and this manuscript, to explore Chapin’s “major error”: “that ease of infection in close proximity is associated exclusively with large “sprayborne” droplets that fall to the ground quickly…leading to systematic errors in the interpretation of research evidence on transmission”), but they heave fairly close to each other in both topic and language, e.g.:

Ref. 51: “During the first few months of the COVID-19 pandemic in early 2020, the World Health Organization (WHO) and other public health agencies downplayed the airborne or aerosol transmission route, recognizing it as a potential route for transmission only during certain medical procedures such as intubation. By the end of March 2020, the WHO posted on social media, ‘FACT: COVID-19 is NOT airborne’, and said that stating otherwise was ‘misinformation’ [2].”

This manuscript: “The WHO emphatically declared on March 28, 2020 that SARS-CoV-2 was not airborne (except in the case of very specific so-called “aerosol-generating medical procedures”) and that it was “misinformation” to say otherwise (3).”

Ref. 51: “Because of his reputation and the successful implementation of contact-infection-prevention practices in a new hospital in Providence, Chapin's 1910 publication, ‘The sources and modes of infection,’ quickly became a popular guide for public health officials and remained a seminal text for decades [39].”

This manuscript: “He summarized the evidence of transmission of different diseases in his 1910 seminal book, "The Sources and Modes of Infection" (57). Based on his own success with infection prevention, he conceptualized "contact infection," i.e. infection by germs that did not come from the environment, but came from other people through direct contact or close proximity.”

Ref 51: “In 1951, Langmuir noted that although ‘[a] large amount of highly suggestive experimental data has been accumulated…, [t]he application of these engineering methods to the control of naturally occurring disease in general population groups […] has been most disappointing. It remains to be proved that airborne infection is an important mode of spread of naturally occurring disease’ [42].”

This manuscript: “In 1951, Langmuir stated, "It remains to be proved that airborne infection is an important mode of spread of naturally occurring disease” (70).”

Ref. 51: “In an early paper, the Wellses note that some rejected a theory of airborne transmission because the term ‘revive[d] the ancient and exploded theory of miasmas’ [37]. They clearly recognized the perception that a theory of airborne transmission could be viewed as regressive, re-embracing obsolete ideas of ‘bad air’.

This manuscript: “…the Wellses were accused of a retrograde approach to science which sought to bring back the miasma theory (64).”

And so on. It isn’t obvious to me that this manuscript stands on its own as a new and independent piece, even though it is longer and more fleshed out with additional historical references. The many similarities and parallels between them make this current manuscript feel derivative of the authors’ earlier review.

Second, I think the authors need to decide what kind of piece it is. Is it a “historical analysis of transmission research” (line 58), a systematic and unbiased examination suitable for a scientific journal to publish as a Review? Or is it an attempt to feed public health agencies some humble pie? Particularly in the introduction and the last few pages, the writing style reads more like the latter, as though the authors have a chip on their shoulder when they choose provocative or deprecating words that overstate the evidence. For instance, starting on line 103: “By the time these CONFUSING PARTIAL ADMISSIONS were made by both organizations, the evidence for airborne transmission was OVERWHELMING, and many scientists and medical doctors were FLATLY STATING that airborne transmission was not just a possible mode of transmission, but the PREDOMINANT MODE (15) (emphases mine).” In reference 15, the authors actually wrote, in considerably more nuanced language, “Ten streams of evidence collectively support THE HYPOTHESIS that SARS-CoV-2 is transmitted primarily by the airborne route,” and “There is consistent, strong evidence that SARS-CoV-2 spreads by airborne transmission. Although other routes can contribute, we BELIEVE that the airborne route is LIKELY to be dominant (emphases mine).” Ref. 15's authors did not flatly state that SARS-CoV-2 “IS” predominantly transmitted by aerosol particles, as the manuscript excerpt above seems to imply.

Another example (line 87): “…many scientists who stated that airborne transmission was a significant contributor (e.g. 4, 5, 6).” Any scientist who stated, in March 2020, that airborne transmission “WAS” a significant contributor to SARS-CoV-2 transmission should check their capacity for epistemic humility. At that point, it was simply too early, and the evidence too thin, for anyone of a scientific bent to proclaim “is” rather than “could be.” Again, the references for this sentence actually used more nuanced language than the authors here do, e.g., “Unfortunately, the truth is that we have only a rudimentary knowledge of several aspects of infection spread, including on one critical aspect of the SARS-CoV-2 virus: how THIS virus transmits (emphases theirs)” and “To summarize, based on the trend in the increase of infections, and understanding the basic science of viral infection spread, we strongly BELIEVE that the virus is LIKELY to be spreading through the air (emphases mine)” from ref. 4.

Medicine – and I consider public health/infection prevention to be within the medical sciences orbit – is unlike many other sciences. It has been said that changing standards of care in medicine is like turning around a battleship, but I think that comparison is too unkind to battleships. Though evidence-based medicine has revolutionized medical thinking in the past several decades, received wisdom and empiricism remain prevalent (and arguably necessary) because there are so many more questions than we have time or funding to answer in more “scientific” ways. It is critically important to document the historical progression of science and opinion that culminated in inaccurate/incomplete/unnuanced “received wisdom” about respiratory disease transmission, which was applied to SARS-CoV-2 when actual evidence was in short supply. But it should not be a polemic. Yes, public health officials may have been dogmatic, and perhaps even rude, in their dismissal of the authors’ attempts to get them to acknowledge the possibility of transmission over longer distances/time scales (“…aerosol scientists, who were rebuffed and systematically excluded from key committees…,” line 558), but a review article is not a forum for airing even legitimate grievances. It will not serve to enlighten those public health officials, nor other medical professionals who act upon received wisdom without realizing that it is eminence-based rather than evidence-based. It is a valuable exercise to summarize how we come to believe that things must be a certain way, when that belief is built on an actually rather fragile foundation, but this piece will serve that goal better if the authors also practice more epistemic humility when pointing out the mistaken observations and interpretations of others.

Specific comments:

Lines 518-521, “As just one example, colleagues report that they would write a research proposal to fund a study of airborne transmission, and the anonymous peer-reviews would come back saying "airborne transmission is not important, therefore we should not fund this proposal”: Unreferenced, anonymous anecdotes are better suited for opinion pieces rather than reviews.

Line 641, “infections affecting only the lower respiratory tract, e.g. MERS-CoV, as this implies that transmission must occur through (small) aerosols”: This is a factual error. MERS-CoV can infect cells along the length of the respiratory tract, although evidence suggests that the lungs are more productively infected (have higher viral loads) than nasal epithelium (e.g., PMIDs 24837403, 32565134). The pathogenicity of MERS-CoV may result mainly from its productive infection of the lungs, impairing gas exchange and damaging fragile alveoli, but its infectiousness is not limited to the lungs. This is in contrast to obligate airborne pathogens like Mycobacterium tuberculosis or Legionella pneumophila, whose main target cells (alveolar macrophages) are only found deep in the lungs. Unlike MERS-CoV, those bacteria simply cannot initiate infection in cell types found elsewhere along the respiratory tract, so they have to be small enough to get to the alveoli (although MTB can spread to other tissues either hematogenously or via the airways after gaining a foothold in the lung).

Please see the attached file.