key: cord-0920983-2tohg1he authors: Riediker, M.; Tsai, D.-H. title: Estimation of SARS-CoV-2 emissions from non-symptomatic cases date: 2020-05-03 journal: nan DOI: 10.1101/2020.04.27.20081398 sha: 171995ba226739b163f2866dbef682b1000976b6 doc_id: 920983 cord_uid: 2tohg1he Importance: Cases of the coronavirus disease 2019 (COVID-19) with no or mild symptoms were reported to frequently transmit the disease even without direct contact. The severe acute respiratory syndrome virus (SARS-COV-2) was found at very high concentrations in swab and sputum of such cases. Objective: We aimed to estimate virus release from such cases into different aerosol sizes by normal breathing and coughing, and what exposure can result from this in a room shared with such as case. Data Sources and Model: We combined the size-distribution of exhaled breath aerosols for coughing and normal breathing with viral sputum concentrations as approximation for lung lining liquid to obtain an estimate of emitted virus levels. The resulting emission data fed a single-compartment model of airborne concentrations in a room of 50m3, the size of a small office or medical exam room. Results: The estimated viral load in aerosols emitted by patients while breathing normally was on average 0.34 copies/cm3 and could go up to 11.5 copies/cm3. The corresponding numbers for coughing patients were 10,900 copies/cm3 and 366,000 copies/cm3, respectively, per cough. The resulting concentrations in a room with a coughing emitter were always very high, up to 2.02*10^9 copies/m3. However, also regular breathing aerosol from high emitters was predicted to lead to several thousand copies/m3. Conclusions and Relevance: These very high predicted virus concentrations may provide an explanation why for COVID-19, frequent community transmissions from non-symptomatic cases and also high infection rates in medical staff in hospital settings were reported. Our findings suggest that strict respiratory protection is needed when there is a chance to be in the same room with a patient - whether symptomatic or not - especially if this was for a prolonged time. The novel Coronavirus disease 2019 , emerged in late 2019 in Wuhan, China 1 47 from where it spread to the entire world. COVID-19 is caused by a novel type of Coronavirus, 48 the severe acute respiratory syndrome virus (SARS-COV-2) 2 . The host-receptor for SARS-49 CoV-2 was found to be Angiotensin I converting enzyme 2 (ACE2), which is present in cells of 50 the lungs and airways 3 . A large number of patients hospitalized for other reasons and also 51 an important proportion of the medical staff contracted COVID-19 4 . This is remarkable given 52 that medical professionals are trained at protecting themselves against infections. Also a 53 series of community-transmissions were reported from cases that had no apparent 54 symptoms, some even without direct contact [5] [6] [7] [8] . Correspondences about the viral load in 55 samples from COVID-19 patients having no or only mild symptoms reported very high 56 concentrations of SARS-CoV-2 in swab samples [8] [9] [10] . This raised the question whether 57 transfections could occur via the air. 58 When coughing, humans release thousands of aerosol droplets per cubic-centimeter in the 59 size range of 0.6 to 15 µm, with the droplet concentration increasing strongly with cough 60 flow rate 11 . But also normal breathing will lead to some aerosol production, which is 61 attributed to fluid film rupture in the respiratory bronchioles during inhalation leading to the 62 formation of droplets that are released during exhalation 12 . The size of these droplets is 63 mostly below 1 µm 13 . The mode of droplet generation implies that they consist of lung lining 64 liquid including dispersed viruses. Indeed, human volunteers exposed to virus-sized 65 nanoparticles show nano-scaled particles in their exhaled breath 14,15 . Also, the described 66 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 3, 2020 . . https://doi.org/10.1101 size distribution of particles emitted from coughing as well as normal respiration suggests 67 that an important proportion of them will be able to remain airborne for many hours in 68 turbulent conditions 16 . 69 This study aimed to estimate the cumulative viral load released from COVID-19 patients with 71 no to moderate symptoms in different aerosol sizes via respiration and coughing. We then 72 used this information to make a risk appraisal for the situation of a high emitter that is either 73 breathing normally or coughing in a room operated at different air exchange rates. We 74 chose a room size that is similar to a medical examination room or an office shared by two 75 to three people. 76 Concept: The release of viruses from individual patients was modeled by first calculating the viral load 79 per exhaled droplets formed during normal breathing and while coughing. The resulting size-80 distribution provided an initial estimate of the concentration of SARS-CoV-2 virus copies 81 released by a regularly breathing or coughing patient. This viral emission factor was then fed 82 into a well-mixed one-compartment model to simulate the situation in a closed room with 83 different ventilation air exchange rates. 84 Data sources: Data on the number of viral copies present in sputum was used to estimate the SARS-CoV-2 86 viral load present in the lining liquid of respiratory bronchioles in patients 9 , specifically an 87 average of 7*10^6 copies/ml with a maximum of 2.35*10^9 copies/ml (hereafter referred to 88 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. . https://doi.org/10. 1101 as "high emitters"), and 1,000 copies/ml representing a low-virus producing patient ("low 89 emitters"). 90 Exhaled aerosol size distributions and numbers were retrieved from published studies on 91 coughing 11 and healthy persons 12 . Both studies assessed the size-number distribution of 92 freshly emitted aerosols. The concentration of viral copies in each aerosol size was 93 calculated from the volume of the aerosols, the actual count number in each size and the 94 above-mentioned virus-load per ml sputum. The viral load in the actual aerosol counts in 95 each aerosol size was then used to calculate the total viral concentration. The cumulative 96 emissions in the PM10 fraction were summed up after applying the standard size 97 fractionation curves 17 to the aerosol distribution. 98 Model: A one-compartment model estimated the virus load concentration C for a perfectly mixed 100 room of volume VR of 50 m 3 with one patient as source, using the following mass-balance 101 (equation 1): 102 (1) 103 The emission rate was calculated from the concentration cPM10, the viral load in the PM10-104 size range, which are particles collected with a 50% efficiency cut-off at 10 µm aerodynamic 105 diameter; and a respiratory rate of 15 breaths per minute (RR) at a tidal volume of Vt of 500 106 ml per breath. Air exchange rates (ER) used were 1-, 3-, 10-and 20-times per hour. The virus' 107 half-life t½ of 1.1 hours was obtained from an experimental study about the persistence of 108 SARS-CoV-2 on surfaces and when airborne 18 , tested by assessing the 50% tissue culture 109 infective dose (TCID50). 110 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. . https://doi.org/10. 1101 The model for coughing was identical, except that coughing was assumed to happen every 111 30 seconds at a volume of 250 ml. 112 All statistics and models were calculated using Stata/SE 15.1 (Mac 64-bit Intel, Rev. 03 Feb 113 2020, StataCorp, College Station, TX, USA). 114 Emissions from normal breathing patients 116 To estimate the virus emissions from patients breathing normally, we first calculated the 117 viral load for the aerosol size distribution. Figure 1 shows that the highest virus load is 118 present in the largest aerosol size. The cumulative total emission per breath was 0.34 119 copies/cm 3 (air) for an average patient, and 11.5 copies/cm 3 for high emitters. The 120 cumulative emissions in the PM10 fraction were about 1/3 of these values with 0.12 121 copies/cm 3 (average) and 4.1 copies/cm 3 (high) per breath. 122 Emission from coughing patient We then estimated the virus emissions from a coughing patient ( Figure 2 ). The cumulative 124 total emission per cough was 19,400 copies/cm 3 for an average patient, and 651,315 125 copies/cm 3 for high emitters. The cumulative emissions in the PM10 fraction were about 1/2 126 of these values with 10,900 copies/cm 3 (average) and 366,000 copies/cm 3 (high) per cough. 127 To estimate the exposure of bystanders spending time in the same room as a COVID-19 129 positive person, we calculated the time-course of the viral load in the thoracic size fraction 130 for aerosols released from a high-emitter either breathing normally or coughing. Figure 3 131 shows the results for a high-emitting patient coughing frequently. 132 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. The very high virus load in exhaled respiratory aerosols proposed by our assessment may be 154 an explanation why COVID-19 was associated with much more transfections to hospital staff 155 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. . https://doi.org/10. 1101 than what was expected from SARS 4 . While having everybody wear a surgical face mask can 156 be an effective source control 22 , the protective factors may still be insufficient if an 157 extended amount of time is spent in the same room, especially if the room is small and the 158 ventilation low. Increasing ventilation can help to some extent but is not sufficient in a room 159 of the size of a typical office or medical exam room. Note also that ventilation design for 160 hospitals is complex and not always functioning as intended 23 . 161 What are the implications for the normal life and the workplace? 162 • The risk of infection is real when being near an infected person in a room for more 163 than a few minutes and this even when keeping distance to that person. 164 • Sharing a workplace in a small room with a non-symptomatic case seems not 165 advised. This implies that workplaces should not be shared as long as there are no 166 rapid tests to differentiate between healthy and non-symptomatic cases. 167 • Medical staff is advised to wear the best possible respiratory protection whenever in 168 the same room as a patient, especially when this person is coughing. 169 • In addition, every patient, also non-symptomatic ones, should wear a well-fitting 170 surgical face mask to reduce emissions, which will increase the overall protection for 171 the medical staff. 172 Our assessment has a number of limitations. Namely: 173 • The estimated virus levels strongly depend on the number of virus copies produced 174 by a COVID-19 case. We used sputum data from a well described peer-reviewed 175 study 9 assuming that it is a reasonable approximation for the virus load in the 176 respiratory bronchioles, the space where most respiratory aerosols are formed. Our 177 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020 . . https://doi.org/10.1101 high-emitter estimates would be 100-fold higher if the most extreme 178 correspondence data was used 10 . 179 • We used information about virus copies but compare the results with TCID50 infective 180 dose. Research on other virus types suggests that the number of virus copies and 181 TCID50 are comparable 24 . However, it would be important to confirm this 182 relationship for the case of SARS-CoV-2. 183 • For breath aerosols release, we used data reported for normal breathing young 184 healthy subjects. However, aerosol formation is influenced by surface tension of the 185 lung lining liquid 25 . It is likely that aerosol formation will be altered in COVID-19 186 positive cases but it is not clear in which direction. 187 • Aerosol droplet will shrink in dry air 26 , resulting in a shift to smaller particle sizes. 188 This will not directly change the number of copies in the PM10 range but simply 189 upconcentrate the viral load per aerosol. While we addressed passivation of viruses . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. . https://doi.org/10. 1101 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. Average emitter 4,010,000 1,800,000 615,000 317,000 High emitter 2.02e+09 9.06e+08 3.10e+08 1.60e+08 283 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 3, 2020. 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