key: cord-1046597-az7f7zgr authors: Sagripanti, Jose‐Luis; Lytle, C. David title: Estimated Inactivation of Coronaviruses by Solar Radiation With Special Reference to COVID‐19 date: 2020-06-05 journal: Photochem Photobiol DOI: 10.1111/php.13293 sha: fb6bb02cb4e8298500b6ed22e834d198c227e299 doc_id: 1046597 cord_uid: az7f7zgr Using a model developed for estimating solar inactivation of viruses of biodefense concerns, we calculated the expected inactivation of SARS‐CoV‐2 virus, cause of COVID‐19 pandemic, by artificial UVC and by solar ultraviolet radiation in several cities of the world during different times of the year. The UV sensitivity estimated here for SARS‐CoV‐2 is compared with those reported for other ssRNA viruses, including influenza A virus. The results indicate that SARS‐CoV‐2 aerosolized from infected patients and deposited on surfaces could remain infectious outdoors for considerable time during the winter in many temperate‐zone cities, with continued risk for re‐aerosolization and human infection. Conversely, the presented data indicate that SARS‐CoV‐2 should be inactivated relatively fast (faster than influenza A) during summer in many populous cities of the world, indicating that sunlight should have a role in the occurrence, spread rate, and duration of coronavirus pandemics. The current (2019-2020) COVID-19 world pandemic is caused by a member of the Coronaviridae family [Reviewed in (1) ]. Coronaviruses have a lipid-containing envelope with the genome consisting of a single-stranded, positive-sense RNA genome that is not segmented (2) (3) (4) (5) . Coronaviruses have the largest genomes of all ssRNA viruses which will become of relevance latter This article is protected by copyright. All rights reserved in this work. In the absence of pandemics, coronaviruses cause about 15-20% of all upper respiratory infections in humans (6) . Previous pandemics like Severe Acute Respiratory Syndrome (caused by SARS-CoV during 2002 -2003 , and Middle East Respiratory Syndrome (caused by MERS-CoV during 2012) indicate that pandemics caused by coronaviruses should be expected to occur with frequency (7-8). Additional coronaviruses are known to cause disease in animals closely associated to humans like cat and dog, rat and mouse, cow, swine, chicken and turkey (6) . Although clusters of infected family members and medical workers have confirmed direct, person-to-person transmission (9), the rapid expansion of COVID-19, that progressed unquenched even after quarantine of nearly one third of the world population and major social distancing measures, suggests that an environmental component (with the virus remaining infectious outside the host) plays a role in disease transmission. Of relevance here is the amount of infectious virus present in the aerosolized droplets produced by COVID-19 symptomatic patients or non-symptomatic carriers. This amount is not well established for coronaviruses, but it has been reported that nasal secretions contain up to 10 7 infectious influenza viral particles per ml (10), from which aerosolized droplets generated by coughing, sneezing, and talking can contain several hundred infectious virions (11). These micro droplets can reach distances of 12.5 meters (over 40 feet, [12] ). SARS-CoV has been reported to persist on contaminated surfaces with risk of disease transmission for up to 96 h (13) and other coronaviruses for up to 9 days (14). SARS-CoV-2 persisted viable from 3 hours to 3 days depending on the type of surface on which it was deposited (15). Influenza virus was readily reaerosolized by sweeping floors without much loss in infectivity (16). It must be assumed that SARS-CoV-2 will be re-aerosolized in a similar manner. Three main physical factors generally considered with a potential effect on virus persistence outdoors, include temperature, humidity, and the contribution of sunlight. The survival of influenza virus, a member of the Orthomyxoviridae family, also with ssRNA and a lipid-containing envelope, only varied up to 9% when the relative humidity changed between 50% and 70% (17). Rather extreme changes in relative humidity between 15% and 90% varied survival of influenza 12. 5 This article is protected by copyright. All rights reserved tested, ranging from 23% to 98% (19). In agreement with the relatively small effect of humidity and temperature on influenza virus inactivation, epidemiological studies concluded that the mortality increase in winter was largely independent of temperature and humidity (20-21). If the limited role of relative humidity and temperature (within the range encountered in the environment) reported for influenza A parallels that for SARS-CoV-2 then, the effect of artificial and natural UV radiation on SARS-CoV-2 inactivation should be preeminent. The preeminent effect indoors of germicidal UV (UVC, 254nm) radiation is clearly confirmed by a report whereby inactivation of air-borne virions by UV radiation virtually prevented the spread of influenza among patients in a veterans hospital, during the same time that an epidemic of influenza ravaged similar patients in nearby non-irradiated rooms (22). There are published reports indicating that very high doses of UVC are effective for inactivating SARS-CoV-2 or SARS-CoV that had been added to different blood products or remaining in virus culture medium (23-28) but there is no data on the viral sensitivity to UVC in UVtransparent liquids or in absence of protective substances, as needed to estimate UVC sensitivity. Nor is there information for UVC inactivation of the virus suspended in aerosols or deposited on surfaces as needed for environmental risk assessment. Ultraviolet radiation in sunlight is the primary virucidal agent in the environment (29-31). This notion is supported by the correlation found in Brazil between increased influenza incidence in hospital admission records and solar UV-blocking by smoke during the burning season (32). The reports on influenza A warrant the present study to estimate UV sensitivity of SARS-CoV-2 and its possible role in the COVID-19 pandemic. The purpose of this study was two-fold, i) to estimate the sensitivity of SARS-CoV-2 to inactivation by germicidal UV (UVC) and ii) to predict the inactivation of the virus by the UVB in sunlight for various populous cities of the world at different times of the year. These goals were achieved by utilizing a model developed for biodefense purposes for estimating solar UVB inactivation of dangerous viruses (30). This methodology has been validated with Ebola and Lassa viruses (33). The model has also been used to estimate inactivation of influenza viruses at various times in numerous locations in the U.S. and globally (34). here should be useful in evaluating the persistence of SARS-CoV-2 in environments exposed to solar radiation. We estimated SARS-CoV-2 virus UV (254 nm) sensitivity and inactivation at different U.S. and global locations by an approach originally developed to predict the survival of viruses of interest in biodefense (30) and later employed to estimate persistence of influenza A virus (34) SARS-CO V2 virus UV 254 sensitivity. The UVC sensitivity is reported here as D 37 which corresponds to the UV fluence that produces, on average, one lethal hit to the virus, resulting in 37% survival. D 37 equals the reciprocal of the slope on the semi-logarithmic graph of viral survival versus dose and can be calculated by dividing the fluence that results in 1 Log 10 reduction of virus load by 2.3 (the natural logarithmic base). A lower value of D 37 indicates a higher sensitivity to inactivation by UV radiation. Comparison of a virus of unknown UVC sensitivity to that of other viruses of similar genomic structure allows an estimate to be determined (30). An important part of the method is the fact that UVC sensitivities of viruses depends proportionally on genome size, especially with single-stranded RNA or DNA, i.e., the larger the genome "target", the more sensitive (and lower D 37 ). This results in the product of the genome size and the D 37 , defined as size normalized sensitivity (SnS), being relatively constant for a given type of viral genome (30) and it is used in this study to compare viruses with ssRNA genomes. This approach has been used successfully to estimate the UVC sensitivities of determined that 35% of the total daily UVB occurs in the two-hour period (120 minutes) around solar noon (37). Thus 35% of the total daily UVB fluence divided by 120 minutes yields the noontime UVB flux (in J/m 2 /min) at the locations and times of the year presented in Tables 2 and 3 . It should be noted that the solar UVB flux used in the present study assumed no atmospheric influence, whether by haze, clouds, or air pollution. Also, there was no correction for an increase in the solar virucidal effect due to the elevation of the urban sites (38) . In Table 1 Table 1 , the median value for the SARS-CoV-2 D 37 was 5.0 J/m2. The D 37 value of 3.0 J/m2 was used in the following calculations because it follows from values derived directly from members of the same Coronaviridae family; D 10 (6.9 J/m 2 ) was used as it represents 10% survival (90% inactivation). It may be useful to estimate the solar exposure for 99% virus inactivation (1% survival) or for even lower levels of survival. Because the material in aerosols created by COVID-19 patients and carriers may shield the virus from the UV as has been shown in laboratory experiments with viruses in culture medium, the virus survival curves indicate that the virus apparently becomes less UV sensitive (33, This article is protected by copyright. All rights reserved 36, [40] [41] [42] . This resulted in a change of slope of approximately 4-fold in experiments with Ebola and Lassa viruses and affected several percent of the virus population (33, 42). Therefore, for survival beyond 10%, a UV fluence of 4 times the chosen D 10 (28 J/m 2 ) was assumed. This value was used to estimate the solar exposure needed for 99% inactivation. Assuming that the survival curve maintains that 4-fold greater UV resistance at lower survival levels, 99.9% inactivation (disinfection level) would require 56 J/m 2 ; sterilization level inactivation (10 -6 survival) would require 140 J/m 2 . Table 2 shows reported solar virucidal flux at solar noon together with the estimated minutes of sunlight exposure needed at various populous North American metropolitan areas to inactivate 90% of SARS-CoV-2. The (+) sign in Table 2 indicates that 99% of SARS-CoV-2 may be inactivated within the two hours period around solar noon during summer in most US cities located south of Latitude 43 o N. Also 99% of the virus will be inactivated during two hours midday in several cities south of latitude 35 o N in Fall, but only Miami and Houston will receive enough solar radiation to inactivate 99% of the virus in spring. During winter, most cities will not receive enough solar radiation to produce 90% viral inactivation during 2-hours midday exposure (underlined values in Table 2 ).
Table 3 presents germicidal solar flux values and resulting inactivation of SARS-CoV-2 for populous metropolitan areas on other continents. The values in Tables 2 and 3 clearly illustrate that SARS-CoV-2 in environments exposed to sunlight will be differentially inactivated in different cities and at different times of the year. For example, at winter solstice (December, in the northern hemisphere), just at the beginning of the COVID-19 pandemic, virus exposed to full midday sunlight would be reduced by at least 90% (1 Log 10 ) during 22 minutes in Mexico City, and will be receiving enough germicidal solar flux to inactivate 99% of virus as indicated by (+) in Table 3 This article is protected by copyright. All rights reserved 37% survival)]between 15 and 43 hours for the different viruses studied) (53), and iii) with the rapid inactivation of vaccinia virus exposed to direct sunlight or simulated solar UVB (42) . The solar germicidal flux shown in Tables 2 and 3 Considering that SARS-Co V-2 is three-times more sensitive to UV than influenza A (as presented in Table 1 and discussed in RESULTS) it should be inferred that sunlight should have an effect on coronaviruses transmission at least similar to that previously established for the evolution of influenza epidemics (22,32) If we accept a possible virucidal role of sunlight during coronavirus This article is protected by copyright. All rights reserved pandemics, then forcing people to remain indoors may have increased (or assured) contagion of COVID-19 among same house-hold dwellers and among patients and personnel inside the same hospital or geriatric facilities. In contrast, healthy people outdoors receiving sunlight could have been exposed to lower viral dose with more chances for mounting an efficient immune response. This argument supports considering the results of two opposed containment approaches to deal with the COVID-19 crisis. Almost all countries and territories affected with COVID-19 have closed their borders, mandated the use of masks and promoted social distancing. By 26 March, 2020, 1.7 billion people worldwide were under some form of lock-down, which increased to 3.9 billion people by the first week of April, amounting to more than half of the world's population (56). Schools, universities and colleges have closed either on a nationwide or local basis in 177 countries, affecting approximately 98.6 per cent of the world's student population (57). In addition to these measures, some countries (for example: Italy, Spain, the UK, Peru, Chile, Argentina and Rep South Africa) implemented nation-wide strict quarantine and in-house lock-down measures, often enforced by police, that decreased the time individuals could spent outdoors thus preventing potential exposure to sunlight. Most countries (like USA, Finland, and Brazil) implemented regional less stringent lock-down measures at varying degrees. A third group of countries (for example: Sweden, Belorussia, Nicaragua, Uruguay, Indonesia, South Korea and Namibia) did not mandate lock-downs that prevented healthy individuals to remain outdoors with potential exposure to sunlight (58). These Analyzing the value (if any) of whole-population quarantine or in-house lock-down of healthy individuals is beyond the scope of the present work. However, the freely available epidemiological data (as of May 29, 2020 [55]) demonstrates that lock-down measures preventing healthy individuals from remaining outdoors have not resulted in an obvious and statistically significant difference on infections per million inhabitants when compared to countries where healthy individuals were free to stay outdoors, with potential exposure to sunlight radiation. If lock-down of healthy citizens may not be determinant as these statistics suggest, then the potential role of being outside exposed to direct This article is protected by copyright. All rights reserved or scattered sunlight in COVID-19 pandemic should not be underestimated. The data presented estimates the sensitivity to UVC (254nm) of the SARS-CoV-2 virus with a D 37 of 3.0 J/m 2 , corresponding to 90% inactivation (D 10 ) after a dose of 7 J/m 2 . Inactivation of 99% viral load (D 1 ) was estimated to be 28 J/m 2 (4x D 10 ) due to the biphasic nature of the virus inactivation curve found for other viruses shielded by culture media and other components that accompany virus infections. 90% or more of SARS-CoV-2 virus will be inactivated after being exposed for \11-34 minutes of midday sunlight in most US and world cities during summer. In contrast, the virus will persist infectious for a day or more in winter (December-March), with risk of re-aerosolization and transmission in most of these cities. c UVC fluence that causes one lethal event per virus on average, resulting in 37% survival. d Size-normalized sensitivity defined as the product of the D 37 and the genome size in thousands of bases is relatively constant for a given genome type, but can be vastly different for different genomic types. If the size and genome type is known for an untested virus, the D 37 can be predicted from the SNS. This article is protected by copyright. All rights reserved Tables 2 and 3. 4. The UVB fluence D 10 to inactivate SARS-CoV-2 90% (10% survival) was estimated as 6.9 J/m 2 . 5. Under ideal conditions, solar UV could inactivate SARS-CoV-2 99% (1% survival) during 2-hour period around solar noon. Four times the D 10 was chosen to account for the likely biphasic inactivation due to protective elements surrounding the virus. 6 . Underlined values indicate solar UVB is likely not enough to inactivate SARS-CoV-2 90% (10% survival) during two-hour period around solar noon. This article is protected by copyright. All rights reserved Coronavirus disease 2019 (COVID-19) A literature review The molecular biology of corona viruses A model for inactivation of microbes suspended in the atmosphere by solar ultraviolet radiation Resistance of Berne virus to physical and chemical treatment Principles of selective inactivation of viral genome. I. UV-induced inactivation of Influenza virus Principles of selective inactivation of viral genome. II. Influence of stirring and optical density of the layer to be irradiated upon UV-induced inactivation of viruses Inactivation of Vaccinia virus by natural sunlight and by artificial UVB radiation Comparison of the sensitivity to ultraviolet radiation of reovirus 3 and some viruses of the Kamerovo group Effects of UV-irradiation upon Venezuelean equine encephalomyelitis virus Interferon induction with Newcastle disease virus in FS-4 cells: effect of priming with priming with interferon and of virus inactivating treatments Radiation studies of avian tumor viruses and of Newcastle 1. Maximum solar exposure with no clouds, haze, air pollution or shadows to reduce exposure Obtained using the virus inactivation action spectrum normalized to unity at 254nm (30) Methodology: Maximum daily solar UVB fluence values for the selected locations at specific times of year have been represented in Tables 1 and 2 in the previous article on predicted Influenza inactivation by solar UVB (34). 35% of the total daily UVB fluence divided by 120 minutes yields the noontime UVB flux in J/m 2 /min at the locations and times in Tables The UVB fluence D 10 to inactivate SARS-CoV-2 90% Under ideal conditions, solar UV could inactivate SARS-CoV-2 99% (1% survival) during 2-hour period around solar noon. Four times the D 10 was chosen to account for the likely biphasic inactivation due to protective elements surrounding the virus Underlined values indicate solar UVB is likely not enough to inactivate SARS-CoV-2 90% (10% survival) during two-hour period around solar noon Acknowledgements-The authors appreciate the encouragement to initiate this study received from Ms. Jessica Seigel (journalist, New York University). Accepted Article