covid: aerosol spread, worse with variants; masks important

 A couple of articles have just come out on airborne transmissibility of SARS-CoV-2. The first study quantifies airborne viral transmission (see covid more aerosol spread clininfdis2021 in dropbox, or doi.org/10.1093/cid/ciab691)

 

Details: 

-- 22 patients PCR-positive Covid-19 patients in Singapore were recruited for evaluation of respiratory aerosols, divided into coarse (>5 µm) and fine (≤5 µm) aerosols

-- 19 (86%) male, median age 38, 5 (23%) asymptomatic

-- symptoms: fever (10 people), rhinorrhea (8), sore throat (6), cough (5)

-- almost all had PCR Ct values in the mid-teens, one asymptomatic had Ct 22 (these represent very high viral loads), and another had Ct 33 (lower viral load, on day 3 of diagnosis, though unclear how long they had been positive given lack of symptoms)

-- patients were seated and their expiratory breath was sampled, with 30 minutes of tidal breathing, 15 minutes of talking, and 15 minutes of singing

 

Results: 

-- 13 people (59%) emitted detectable levels of SARS-CoV-2 in respiratory aerosols, including 3 asymptomatic and one presymptomatic patient.

    -- expiratory viral loads range from 63 to5821 gene copies per participant (ie, high person-to-person variation)

    -- no difference in aerosolized virus when controlling for age, viral load at time of initial presentation, or SARS-CoV-2 variant: non-variant of concern or interest (4 people), Alpha (4), Beta (8), Kappa (3), Delta (1)

-- fine versus coarse aerosols: 85% of the viral load detected was from fine aerosols

-- detectable RNA was more often found in those earlier in their illness; two participants sampled on day 3 of illness accounted for 52% of the total viral load

 

--virus emitted by exhalation process:

    -- breathing for 30 minutes: coarse aerosol had RNA viral load 897; fine aerosol had 1062 (overall 6% of emitted virus)

    -- talking: coarse aerosol 868; fine 11,788 (overall 41% of emitted virus)

    -- singing: coarse aerosol 2762; fine 13,653 (overall 53% of emitted virus)

    -- only 6 people (27%) emitted virus from all expiratory activities

        --so, 94% of SARS-CoV-2 RNA copies were emitted by talking and singing

-- BUT, 7 participants emitted more virus from talking than singing

-- viral cultures were done of fine aerosol samples only, and all were negative

 

Commentary: 

-- coarse aerosols (>5 µm) deposit particles in the upper airway, whereas fine aerosols (≤5 µm) deposit particles lower in the respiratory tract

-- the data has been somewhat mixed as to which aerosol is more likely to create Covid-19 disease, though more often the fine aerosols have been implicated

-- this study found that more than half the patients emitted detectable levels of SARS-CoV-2  RNA in respiratory aerosols, and this included three asymptomatic and one presymptomatic person

-- the study also confirmed a very high viral load early in the disease

-- the viral transmission was much higher with talking and singing versus breathing, with seven people actually having higher viral loads with talking than singing

-- it is unclear why the virus emitted was not culturable, though there was a relatively low viral load, (other studies have suggested there needs to be a much higher viral load to culture the virus), and there were no simultaneous respiratory samples. In addition, neutralizing antibodies typically appear five days after symptom onset, and these might have neutralized large quantities of virus and decreased the likelihood of its being culturable

 

Limitations:

--small study in one area of one country, and mostly younger males, all limiting generalizability

--73% were not infected with variants of concern or interest.  Too small numbers of concerning variants (other than Alpha) to determine aerosol-shedding patterns by variant type

-- unclear how to interpret the relative risk of viral transmission by talking versus singing, given that they did not measure voice amplitude

-- though, as noted, there was no virus that was able to be cultured; this does not mean that people were not contagious. The mechanics of viral cultures may lead to live virus not being able to be cultured. And, the quantity of virus that might be transmitted decreases dramatically over a short period of time after infection; therefore, even those with low viral titers might have been super-spreaders a few days prior

 

So, this study adds to prior studies regarding the aerosolization of potentially transmissible SARS-CoV-2 virus, this time quantifying the amount of virus exhaled by tidal breathing, talking, or singing. The study does reinforce the importance of using masks and physical distancing to decrease person-to-person transmission, as well as the importance of high-efficiency particulate air (HEPA) filters. The quantitation from this study also allows for determining appropriate specific interventions to decrease virus transmission e.g. using air curtains to help isolate the audience from singers

 

 

The other study suggested more efficient aerosol spread (ie more dangerous) with variants of concern (see

covid aerosol more efficient spread medrix2021, or doi.org/10.1101/2021.08.13.21261989, accepted for publication by Clinical Infectious Diseases (see https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab797/6370149 )

 

Details: 

-- 49 patients seronegative for SARS-CoV-2, from May 2020 thru April 2021, who were a mean of 3.8 days after developing Covid-19

    -- 37% female, mean age 24, 82% white, BMI 25, chronic respiratory illness 24%, ever-smokers 4%

    -- all cases were either asymptomatic or had only mild symptoms

        -- symptoms:  loss of taste or smell 27%, minimal other symptoms; oxygen saturation 98%

        -- asymptomatic cases were picked up through weekly pooled saliva testing of volunteers, or frequent testing of close contacts

    -- four (8%) were infected with the Alpha variant, none with the Delta or other variants

-- patients were tested for blood, saliva, mid-turbinate and fomite swabs (swabs of the computer or

 phone), as well as 30-minute breath samples while vocalizing, both with and without masks

-- primary outcome: quantification and sequencing of viral RNA, cultured virus, and assayed sera for spike and  anti-receptor binding domain antibodies

 

Results: 

-- SARS-CoV-2 RNA detected in:

    -- fine aerosol (≤5 µm): 45% of samples

    -- coarse aerosol (>5 µm): 31%

    -- fomites: 65%

    -- these numbers reflect overall samples as well as  for the four Alpha-variant cases

        -- viral RNA in aerosols was greatest 2 to 5 days after either the onset of symptoms or the first positive test

        -- there was a significant correlation between the viral load in the mid-turbinate samples and  the viral load of aerosols

 

-- each of the Alpha variant cases had detectable viral RNA in all mid-turbinate swabs, 99% of saliva, 49% of fomite, and 19% of coarse-aerosol and 31% of fine-aerosol samples

    -- the concentrations of viral RNA were higher for each of these with Alpha variants vs the rest (there were too few concerning variants to compare appropriately)

 -- Alpha-variant: 43-fold increase (6.6 to 280-fold) in fine aerosol viral RNA as compared to earlier non-Alpha viruses

    -- 18-fold increase (3.4 to 92-fold) increase adjusting for viral RNA in saliva, swabs, and other potential confounders

-- effect of masks on SARS-CoV-2  RNA detection, adjusting for the number of coughs during a sampling session:

    -- fine aerosol (≤5 µm): decreased by 48% (3-72%)

    -- coarse aerosol (>5 µm): decreased by 77% (51-89%)

        -- of note, there was no difference between cloth and surgical masks, even comparing those that were single-layer homemade cloth masks versus KN95 masks

 

-- Virus cultures:

    -- positive in 68% of mid-turbinate samples and 32% of 62 saliva samples

    -- fine aerosol: none were culture positive while not wearing masks and two (3%) from those wearing masks were culture positive, including one in a person with Alpha variant. Fomite and coarse aerosol samples were negative on culture

 

Commentary: 

-- the study does suggest that the SARS-CoV-2 virus is evolving into being more efficiently transmissible, as evidenced by the Alpha variant, with 10-100 times the viral loads detected.

-- The study also showed that masks are protective of viral spread, though to a limited degree; and this study also confirmed culturable live virus, not just viral RNA concentrations (which could reflect nonviable virus)

-- as with prior studies employing loose fitting facemasks (including surgical masks and others used in this study), masks were more effective preventing spread of coarse aerosols

    -- masks worked equally well in the few participants who had the Alpha variant

-- though this small study did not find any difference between types of masks used, there is pretty clear benefit from more tight-fitting masks having more effective air filtration (see https://www.medrxiv.org/content/10.1101/2020.12.31.20249101v1 )

 

Limitations:

-- the study was limited by the small number of participants, especially with the Alpha variant, which was the new variant at that time. it is likely that some newer variants will be similarly more transmissible, especially since Delta already seems to be about 50% more transmissible than Alpha (see https://asm.org/Articles/2021/July/How-Dangerous-is-the-Delta-Variant-B-1-617-2 ), and the newer variants, such as C.1.1, is accruing even more mutations beyond those of the Alpha and Delta variants (see http://gmodestmedblogs.blogspot.com/2021/09/covid-troublesome-new-variant-lurking.html )

-- this study may have missed the most important time of viral transmission, since they tested people several days after symptom onset

-- this study was performed over many months, and the types of facemasks changed significantly over the course of the study

-- only young people on a single university campus were evaluated, limiting generalizability to older people as well as those with significant comorbidities, smoking history, those living in other areas/countries with different sociodemographic backgrounds, etc

-- it is still unclear what the gold standard is for assessing viral transmissibility: for example, in this study they found that respiratory aerosols may be more transmissible than what is found in mid-turbinate sampling, confirming a prior study suggesting that human bronchial airway epithelium may be more susceptible to infection than what is found in laboratory-based cell cultures (see https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001006 )

    -- also, because samples were frozen after collection and prior to culture, it is possible that some people with more dilute aerosol specimens might have been culture-negative, despite live virus being present

 

So, these studies do suggest that facemasks do help in preventing spread of SARS-CoV-2. However, a couple of points:

-- the protection from facemasks is incomplete, reinforcing the importance of vaccination and other mitigation strategies

-- but, given that even postvaccination there may well be transmissible virus (though less frequently than without vaccination), this study does reinforce that even vaccinated people should use facemasks in areas of increased transmissibility.

    -- In particular, I am concerned that in the winter with its associated increased gatherings indoors, population adherence to indoor masking will be quite small, given the misery of the last 1.5 years and attendant covid-fatigue

    -- This may be particularly a problem as newer variants develop with likely increased transmissibility, increasing the likelihood of spreading Covid. Especially to those who have waning immunity or a less robust immunologic response to the vaccines

geoff

 

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