A recent Cochrane review concluded that there was insufficient evidence that masks made a difference in the pandemic. As Cochrane is a recognized contributor to evidence-based medicine, this statement created confusion among the general public as well as the healthcare community, and was widely criticised for its methodology and conclusions. Most of the articles included in the meta analysis were based on studies done prior to the pandemic. These studies are not directly applicable to the new SARS CoV2 virus that is fast-spreading through aerosols, and capable of covering the entire globe in 6 weeks.
This article discusses the current evidence about masks, in the context of the pandemic.
How do masks work?
The mechanism of action depends on the type of mask used. For example, a cloth mask might stop large droplets, but the gaps in between the cloth fibres are too wide to stop aerosols. A surgical mask on the other hand has multiple layers that are electrostatically charged, which means it can block very small particles.
N95 masks are even better because they also fit tightly on the face, not allowing air to leak along the sides.
For surgical and N95 (also called FFP2) masks, it is not just the mechanical filter that keeps particles out. There is substantial physics involved here. As air passes through the mask while breathing, particles slow down within the fibre network. The electrostatic charge on the polypropylene fibre attracts particles, trapping them. This allows efficient trapping of the smallest particles, which are even smaller than the smallest spaces between the fibres. In other words, if the N95 mask was compared to a fishing net, it has the ability to catch fish that are much smaller than the holes in the net. The definition of an N95 mask is that it filters at least 95% particles from the air that passes through it.
When the pandemic arrived, many people compared it to influenza and the common cold, which spread through large droplets. Hence, there was emphasis on cough etiquette and hand-washing. Large droplets however do not hang in the air. They drop to the ground within a few seconds.
As outlined in my article from April 10, 2020, it was found that this virus spreads by aerosols rather than large droplets (1).
COVID-19 is a new disease, known to spread rapidly in the air through smoke-like aerosols. Aerosols are essentially weightless fluid particles generated during breathing and more so while talking, singing, laughing or cheering. These mist-like fluid particles carry thousands of viruses within them. When they are breathed in by other people sharing the same room, the virus spreads. In open airy spaces they get blown away in the wind and therefore do not cause much spread, unless there is crowding.
Improving room ventilation (for example, by opening windows or by upgrading HVAC systems) can reduce the concentration of these aerosols. But it is not feasible in most places. Masks are the workable solution in such settings. Masks purify the air that we breathe individually, just like a water filter provides clean water at home - regardless of the quality of water arriving from a potentially polluted river or lake.
By blocking the two-way traffic of aerosols, the air we breathe out also gets filtered. Thus, masks also prevent us from infecting other people. The extent of asymptomatic transmission of the SARS-CoV2 virus is greater than that of Influenza, hence the benefit for universal masking in crowded indoor settings during a surge (2,3). For example, if someone is carrying the virus in their nose and throat without having symptoms, they might mingle freely instead of isolating at home. Wearing a mask will reduce the output of infectious virus particles, making it safer for other people.
What was the Cochrane study about?
On 30 January 2023, Cochrane published a meta-analysis combining 78 studies done on the topic of physical measures such as masks, hand hygiene, of which only six were conducted since the pandemic (4). Acknowledging limitations, authors declared that “wearing masks in the community probably makes little or no difference to Influenza/COVID-19 like illness”
What are the problems with the Cochrane study?
Meta analysis is a technique that aims to increase the number of subjects studied by clumping several similar studies together. The main problem with the current paper is that the individual studies were not done in a uniform format to be grouped together. Besides, a separate analysis for COVID-19 was not done. Although there is a general view that a larger sample size yields more accurate results, that applies only to studies where the methodology is carefully controlled. In fact, a smaller well-conducted study by a team of unbiased researchers could provide more reliable information than a large collage of multiple studies done in different settings by various investigators (5).
Most of the studies included in the Cochrane meta analysis addressed other respiratory viruses like Influenza, for which community mask-wearing had largely shown no benefit.
However, measuring the effectiveness of community mask-wearing has its challenges. Unlike giving a pill or an injection, mask-wearing is not a binary variable, and studies arrive at conclusions based on whether people say they wear masks or not. It is not possible to control for the technique or consistency of mask wearing behaviour in such studies.
An RCT (randomised controlled trial) basically involves randomly allocating two similar groups of people to two different types of intervention, and checking afterwards for differences in outcomes. For example, when a new drug is compared to placebo, one group of patients receives the medication, while the other receives a dummy pill. Both groups will also be receiving existing standard treatment measures, so there is no denial of care involved. At the end of the study period, if the outcome in the pill group is better than placebo, the pill is declared to be effective.
While RCT’s are helpful to decide between two comparable treatments for a particular disease, doing this for masks is not possible - for ethical reasons. For instance, it is unacceptable to ask a 58 year-old healthcare worker on immunosuppressant medication to go on the “control” (no masks) arm. The best that can be done therefore are observational and modelling studies, of which there are several indicating that masks reduce the chance of getting COVID-19 (6,7,8,9,10).
Clinical research is no doubt important, and evidence-based medicine is the way forward, serving to eliminate the risk of personal bias. However, expecting all interventions to be proven by RCT’s is not realistic. For example, we know that falling off a coconut tree carries the risk of severe injury or death, without the need for a meta-analysis or even a published case report on it.
To prove this point, the BMJ published a spoof study referring to parachutes (11). The paper, a satire, essentially says that since parachutes have not been put through randomised controlled trials (to compare with jumping off a plane without a parachute), there was no evidence that they work. “Advocates of evidence-based medicine have criticised the adoption of (parachutes) evaluated by using only observational data”. In other words, observational studies also matter, provided they are in the right context.
The Bradford Hill criteria for causation are worth recalling here. To prove that a variable A leads to outcome B, some criteria need to be met. They include biological plausibility, strength of statistical association, consistency, experimental evidence and dose-response relationship. Masks filter out small particles, and there is no doubt that COVID-19 spreads through aerosols.
In summary, some medical interventions require randomised trials to prove they are effective. A meta analysis of several well-done randomised trials can help cement the evidence and also iron out any erroneous interpretations that might have occurred in a few. But this is not the right method to evaluate masks, and a meta-analysis of studies done on masks mainly from the pre pandemic era cannot be extrapolated to the present situation.
In the setting of the pandemic, where vaccines only provide incomplete and waning protection from infection, multiple simultaneous public health measures are required to minimise the impact. This is particularly true for the vulnerable population, which includes older people as well as those with certain high risk medical conditions. At an individual level, masks are often perceived as an inconvenience especially by low risk individuals, but public health refers to the health of the community as a whole. Regarding mask wearing, the action of a low risk person might save the life of a high risk individual who is not directly known to him or her.
The paradox of public health was explained by Geoffrey Rose. Seat belts benefit the community only when they are worn by a large number of people, where only those few who meet with an accident will get the opportunity to escape death. But if we start thinking about seat belts from an individual standpoint, they do not seem to provide an immediate benefit to the person wearing it.
Public health measures for the pandemic need to be customised depending on the population, as well as the intensity of the pandemic in each geographical region from time to time.
References
1. Jayadevan R, How does the SARS-CoV2 virus really spread?
2.Byambasuren O, Cardona M, Bell K, Clark J, McLaws ML, Glasziou P. Estimating the extent of asymptomatic COVID-19 and its potential for community transmission: Systematic review and meta-analysis. J Assoc Med Microbiol Infect Dis Can. 2020 Dec 31;5(4):223-234. doi: 10.3138/jammi-2020-0030. PMID: 36340059; PMCID: PMC9602871.
3. Patrozou E, Mermel LA. Does influenza transmission occur from asymptomatic infection or prior to symptom onset? Public Health Rep. 2009 Mar-Apr;124(2):193-6. doi: 10.1177/003335490912400205. PMID: 19320359; PMCID: PMC2646474.
4. Jefferson T, Dooley L, Ferroni E, Al-Ansary LA, van Driel ML, Bawazeer GA, Jones MA, Hoffmann TC, Clark J, Beller EM, Glasziou PP, Conly JM. Physical interventions to interrupt or reduce the spread of respiratory viruses. Cochrane Database of Systematic Reviews 2023, Issue 1. Art. No.: CD006207. DOI: 10.1002/14651858.CD006207.pub6.
5. Indrayan A, Mishra A. The importance of small samples in medical research. J Postgrad Med. 2021 Oct-Dec;67(4):219-223. doi: 10.4103/jpgm.JPGM_230_21. PMID: 34845889; PMCID: PMC8706541.
6. Cowger TL, Murray EJ, Clarke J, Bassett MT, Ojikutu BO, Sánchez SM, Linos N, Hall KT. Lifting Universal Masking in Schools - Covid-19 Incidence among Students and Staff. N Engl J Med. 2022 Nov 24;387(21):1935-1946. doi: 10.1056/NEJMoa2211029. Epub 2022 Nov 9. PMID: 36351262; PMCID: PMC9743802.
7. Cheng Y, Ma N, Witt C, Rapp S, Wild PS, Andreae MO, Pöschl U, Su H. Face masks effectively limit the probability of SARS-CoV-2 transmission. Science. 2021 May 20;372(6549):1439–43. doi: 10.1126/science.abg6296. Epub ahead of print. PMID: 34016743; PMCID: PMC8168616.
8. Rader B, White LF, Burns MR, Chen J, Brilliant J, Cohen J, Shaman J, Brilliant L, Kraemer MUG, Hawkins JB, Scarpino SV, Astley CM, Brownstein JS. Mask-wearing and control of SARS-CoV-2 transmission in the USA: a cross-sectional study. Lancet Digit Health. 2021 Mar;3(3):e148-e157. doi: 10.1016/S2589-7500(20)30293-4. Epub 2021 Jan 19. PMID: 33483277; PMCID: PMC7817421.
9. Leech G, Rogers-Smith C, Monrad JT, Sandbrink JB, Snodin B, Zinkov R, Rader B, Brownstein JS, Gal Y, Bhatt S, Sharma M, Mindermann S, Brauner JM, Aitchison L. Mask wearing in community settings reduces SARS-CoV-2 transmission. Proc Natl Acad Sci U S A. 2022 Jun 7;119(23):e2119266119. doi: 10.1073/pnas.2119266119. Epub 2022 May 31. PMID: 35639701; PMCID: PMC9191667.
10.Howard J, Huang A, Li Z, Tufekci Z, Zdimal V, van der Westhuizen HM, von Delft A, Price A, Fridman L, Tang LH, Tang V, Watson GL, Bax CE, Shaikh R, Questier F, Hernandez D, Chu LF, Ramirez CM, Rimoin AW. An evidence review of face masks against COVID-19. Proc Natl Acad Sci U S A. 2021 Jan 26;118(4):e2014564118. doi: 10.1073/pnas.2014564118. PMID: 33431650; PMCID: PMC7848583.
11.Smith GC, Pell JP. Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials. BMJ. 2003 Dec 20;327(7429):1459-61. doi: 10.1136/bmj.327.7429.1459. PMID: 14684649; PMCID: PMC300808.
