key: cord-0896312-mkvo5hpn authors: MARTINS, Cesariana P.V.; Xavier, Carolina S.F.; Cobrado, Luís title: Disinfection methods against SARS-CoV-2: a systematic review date: 2021-10-18 journal: J Hosp Infect DOI: 10.1016/j.jhin.2021.07.014 sha: 3a5cedf1a61d477cb1d5f941bfeb926534cee036 doc_id: 896312 cord_uid: mkvo5hpn BACKGROUND: The novel SARS-CoV-2, responsible for the most recent pandemic faced by humanity, has become a global crisis causing millions of deaths. The virus is transmitted by inhalation of infectious particles suspended in the air, direct deposition on mucous membranes and indirect contact via contaminated surfaces. Therefore, disinfection methods that can halt such transmission are important in this pandemic and in future viral infections. AIM: Highlight the efficacy of several disinfection methods against SARS-CoV-2, based on up-to-date evidence found in literature. METHODS: A research was conducted through two databases to assess the disinfection methods used against SARS-CoV-2. From a total of 1229 studies found, 60 were included. Quality assessment was evaluated by the OHAT risk of bias tool. FINDINGS: Disinfection methods on environmental surfaces were approached by 28 studies; 16 articles addressed disinfection methods used on biological surfaces; 4 articles presented disinfection methods for airborne coronavirus and 16 studies demonstrated methods used to recondition PPEs. CONCLUSIONS: Several household and hospital disinfection agents and UV-C irradiation were effective in inactivating SARS-CoV-2 on environmental surfaces. Formulations containing povidone-iodine can provide virucidal action on the skin and mucous membranes. In the case of hand hygiene, typical soap bars and alcohols can inactivate SARS-CoV-2. Air filtration systems incorporated with materials that possess catalytic properties, UV-C devices and heating systems can effectively reduce airborne viral particles. The decontamination of PPEs can be conducted safely by heat and ozone treatment. The COVID-19 pandemic has become an ongoing global health crisis responsible for causing millions of deaths and has devastated the world's economy [1, 2] . The accountable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel betacoronavirus, is known to be transmitted through the exposure to infectious particles in respiratory droplets of infected individuals [3] . This can take place by inhalation of viral particles suspended in the air, deposition of exhaled infectious droplets directly on mucous membranes or indirect contact with contaminated secondary surfaces, such as hands or fomites [4] . It is believed that airborne transmission can be the dominant form of transmission that better justifies the occurrence of superspreading events, the higher risk of transmission in indoor settings and the fact that more than half of the transmission is observed in asymptomatic or pre-symptomatic patients [5] [6] [7] [8] . Particles emitted from infected individuals can be deposited on environmental surfaces and can J o u r n a l P r e -p r o o f Interventions Trials that compare the virucidal effects of disinfection methods that have the potential to halt the transmission of SARS-CoV-2 on environmental surfaces, biological surfaces, air and personal protective equipment were assessed. A search was conducted by 2 reviewers in 2 separate databases from the January to June of 2021. PubMed and Web of Science were searched using the following terms: ("SARS-CoV-2" OR "Coronavirus" OR "COVID-19") AND ("Disinfection Methods" OR" Surface Disinfection" OR "Hand Disinfection" OR "Air disinfection" OR "Environmental disinfection" OR "Inactivation"). 13 articles were identified from other sources and included in the screening process. Two reviewers screened (by title and abstract) the initial 1229 articles found and the information collected was registered on a shared EndNote Vx9 (Clarivate Analytics, PA, USA) library and a shared online Microsoft Excel V16.42/2020 (Microsoft Corporation, USA) document. Eligibility assessment was performed independently in an unblinded standardized manner by 2 reviewers and disagreement between reviewers were solved by consensus. The total of 60 articles were found to respect the criteria outlined before and were included in this systematic review. To determine the risk of bias in the individual studies selected, the Office of Health Assessment and Translation (OHAT) Risk of Bias Rating Tool for Human and Animal Studies was used. This tool consists of a questionnaire aimed to study risk of bias in several domains; temperatures of 4°C and relative humidity of 20%, viruses can persist for up to 28 days [25] . SARS-CoV-2 can be deactivated at different rates when exposed to distinct heating procedures as seen in one study, where conditions that block evaporation can substantially speed up virus inactivation rates [26] . Amongst all the reviewed and included studies, 28 articles were categorised in disinfection methods with potential activity on environmental surfaces [12, reduction of transmissible gastroenteritis virus (TGEV) after 1 minute of exposure [29] . Hygiene wipes containing water and ethanol (0.6 g/wipe) destined to decontaminate plastic food packaging can reduce alphacoronavirus 1 to undetectable levels after 72 hours of refrigeration (4°C) compared to wipes containing 99% water. However, this study showed evidence that hygiene wipes can potentially transfer viral particles to secondary surfaces [38] . Only 2 studies showed virucidal efficacy with at least 20% of ethanol against SARS-CoV-2 in suspension [12, 47] . In the case of Sodium Hypochlorite (SH), one study showed that 0.525% and 0.1% of SH was sufficient to produce a 4 log10 reduction of HCoV after 15 seconds of exposure on porcelain and ceramic surfaces [40] . 0.06% of SH caused less than 1 log10 reduction of MHV and TGEV after 1 minute of exposure on stainless steel. This indicates that either a higher concentration of SH is needed to cause a more significant reduction in viral titres in 1 minute of exposure or longer exposure time should be considered if 0.06% of SH is used [29] . When it comes to SARS-CoV-2, 0.14% of SH has been shown to significantly reduce its viral titres after 30 seconds of exposure [12] . With reference to aldehydes, one study showed that glutaraldehyde can reduce >4 log10 of HCoV with contact times as low as 15 seconds on porcelain and ceramic surfaces [40] . 4% glutaraldehyde and ethylenedioxy dimethanol tested at different concentrations was also capable of causing more than 3.5 log10 reduction in viral titres of SARS-CoV after 15 minutes in a suspension test [28] . 0.55% Ortho-phthalaldehyde (OPA) showed less than 2.5 log10 reduction of MHV and TGEV after 1 minute of exposure indicating that OPA may need more exposure time to reach its total inactivation capacity [29] . Quaternary ammonium compounds (QAC) are common disinfection agents with a wide range of microbicidal action. Disinfectant wipes containing 0.75% didecyl-dimethyl-ammonium chloride associated with 0.5% hydrogen peroxide can reduce viral titres of alphacoronavirus 1 by 3.8 log10 on plastic carriers and can prevent transmission to secondary surfaces [38] . Combined surface disinfection solutions containing 0.5% benzalkonium chloride with laurylamine can reduce viral titres of SARS-CoV by 6.13 log10 after 30 minutes of exposure while 0.5% benzalkonium chloride associated with glutaraldehyde and didecyldimonium chloride showed a 3.75 log10 reduction of SARS-CoV titres also in 30 minutes [28] . However, in a study conducted in 1997 on suspended HCoV revealed that 1% of benzalkonium chloride and a combination of 5% cetrimide and chlorhexidine gluconate were both ineffective in reducing viral titres after 1 J o u r n a l P r e -p r o o f minute of exposure [27] . Moreover, QAC was shown to be active against SARS-CoV-2, vaccinia virus Elstree and modified vaccinia virus Ankara in contact times of 5 minutes or less [12, 47] . Phenols are another group of disinfectants active against variety of microorganisms. Cleaners that consist of 9.09% of O-phenylphenol and 7.66% of P-tertiary amylphenol also showed a moderate reduction of infectivity for MHV and TGEV revealing approximately 0.8 to 3.17 log10 reduction on stainless steel surfaces [29] . 5% of Chloroxylenol was ineffective in reducing viral titres of human coronavirus (HCoV) but a study conducted in 2020 demonstrated that lesser concentrations can efficiently inactivate a number of coronaviruses including SARS-CoV-2 deposited on glass and in suspension after 1 minute of exposure [12, 27] . Ozonated water could be an alternative for environmental disinfection as it can reduce by 2.0 log10 to 5.0 log10 of SARS-CoV-2 viral titres after only 1 minute of exposure [39, 45] . Other chemical agents, such as magnesium monoperoxyphthalate were shown to reduce ≥4.5 log10 of SARS-CoV titres after 15 minutes of exposure [28] . Surface disinfectants based on citric acid, hydrochloride acid or lactic acid were also shown to efficiently reduce viral titres of coronaviruses (including SARS-CoV-2) [12] . Virusend (TX-10), a detergent-based disinfectant, was able to reduce by at least 4.0log10 PFU/mL of infectious SARS-CoV-2 with high titre inoculum and a reduction of at least 2.3log10 PFU/mL with low titre inoculum on both hard surfaces, such as stainless steel, and in solution [31] . On glass surfaces, UV-C radiation can reduce MHV viral titres by an average of 2.71 log10 and 6.11 log10 in exposure times of 5 and 10 minutes, respectively. It is also able to reduce MERS-CoV titres by 5.9 log10 after 5 minutes of exposure [30] . Findings in 2 studies indicated that at least 3 minutes of exposure to UV-C irradiation is capable of completely inactivating SARS-CoV-2 in suspension [35, 46] . Spherical objects such as footballs, volleyballs and basketballs were completely decontaminated from SARS-CoV-2 after 1 minute of exposure to a UVC-LED device J o u r n a l P r e -p r o o f (275nm) [48] . UV-A, characterised by longer wavelengths (315-400 nm) is less efficient in viral inactivation, revealing only 1 log10 reduction after 9 minutes of exposure to radiation [35] . It is suggested that peak emission of approximately 286 nm can be effective in inactivating coronaviruses [34] . An in vitro study provided evidence that UVB (280-315 nm) levels similar to natural sunlight can significantly reduce SARS-CoV-2 titres by 2.5 log10 on stainless steel surfaces after 20 minutes of exposure [42] . UV-C irradiation exposed for 15 minutes to glass, plastic, gauze samples infected with SARS-CoV-2 obtained 99.99% reduction of viral titres while 90-95% reduction was obtained in fleece and wool samples. No reduction of viral titres was quantified on wood samples with this method [43] . In this same study, two hours of exposure to ozone with the concentration of 0.2 ppm was able to completely disinfect (99.99% reduction) the fleece sample, to achieve a 96.8% reduction on gauze, 93.3% on wood, 90% on glass and 82.2% on plastic. Exposure of the same materials to higher concentrations of ozone was effective in reducing viral titres in a shorter period. Uppal et al demonstrated that ozone gas of at least 25ppm can optimally eliminate ≥99% of HCoV deposited on glass in 15 minutes while 80ppm of ozone and 90% relative humidity from another study obtained significant viral inactivation after 60 minutes [44, 49] . Complete inactivation of HCoV is seen on TNP-coated glass coverslip exposed to UVC for 30 seconds and 1 minute. Authors demonstrated that viral inactivation was enhanced and accelerated with TNP coating making viral titres undetectable under shorter time exposures to UVC irradiation [36] . SARS-CoV-2 can be completely eliminated after only one-second of exposure to a high-powered deep UV light. The UV light source is an aluminium gallium nitride (AlGaN) based device and can achieve an output power as high as 2 W at a current of 1.3 A allowing the ultra-rapid inactivation of SARS-CoV-2 [37] . Coating surfaces with cuprous oxide/polyurethane (Cu2O/PU) or conjugated electrolytes such as cationic phenylene ethynylene polymers and oligomers were shown to have virucidal activity against SARS-CoV-2 being able to significantly reduce viral titres after 1 hour of exposure on glass, stainless steel and in suspension [32, 41] . Films made from an accessible household dishwashing detergent containing 8% of surfactant can provide longer virucidal activity on inanimate surfaces reducing avian coronavirus to undetectable levels after 10 minutes of exposure. The activity of this last film can persist up to 7 days [33] . Sixteen articles addressed disinfection methods that can be used on biological surfaces (table III) with application on skin, hands and mucous membranes such as the oral cavity and upper respiratory tract [12, 13, 28, 47, [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] . Alcohols were mostly evaluated via suspension tests showing optimal virucidal activity (including SARS-CoV-2) at concentrations of more than 65% and with exposure times of 15 to 60 seconds specifically for the application on hands and oral cavity [12, 13, 28, 47, 54, 55, 57, 58, 61] . One study evaluated the efficacy of ethanol and propanol directly on human skin against SARS-CoV-2 demonstrating that concentrations of 40% of these alcohols can cause more than 4 log10 reduction in viral titres after just 5 second of exposure [59] . Interestingly, the World Health Organization hand rub formulations containing 80% ethanol or propanol showed inferior efficacy compared to modified formulations (with 75% ethanol or propanol and half of the concentration of glycerol from the original formulation) when tested with SARS-CoV-2 [13] . Soap bars evaluated in two studies were shown to be capable of significantly reducing the quantity of SARS-CoV-2 with optimal result at 20 seconds to 1 minute of contact time [12, 58] . QAC, specifically benzalkonium chloride at 0.2 %, can produce maximum virucidal activity at 60 seconds of exposure, verified in suspension tests and on human skin [12, 59] . Liquids containing J o u r n a l P r e -p r o o f chloroxylenol, citric acid, lactic acid or salicylic acid were also effective in reducing coronavirus titres including SARS-CoV-2 [12] . Oral rinses containing concentrations of 1-3% povidone-iodine (PVP-I) are able to reduce > 4.33 log10 of SARS-CoV-2, MERS-CoV and Modified vaccinia virus Ankara titres in 15 to 30 seconds of contact time [50] [51] [52] 57] . The action of hydrogen peroxide (H2O2) oral rinses, on the other hand, is inferior to PVP-I [51] . Chlorhexidine gluconate (oral and skin formulations) seems to provide suboptimal virucidal activity compared to other agents in in vitro suspension test experiments. However, a prospective cohort study on patients who were initially admitted at a hospital with a positive SARS-CoV-2 test indicate that the application of chlorhexidine gluconate mouthwash and nasopharyngeal spray of the same agent can accelerate the clearance of SARS-CoV-2 in these areas resulting in a negative rRT-PCR test after 4 days [60] . Other antiseptic oral rinses containing chloride and benzalkonium or ethanol have also been demonstrated to deactivate SARS-CoV-2 [54, 57] . PVP-I can also be applied topically on eyes, as an additional pre-procedure disinfection as concentrations of 0.9% can significantly reduce SARS-CoV-2 titres after 30 seconds of exposure [56] . On the other hand, a toxicity study carried out on rabbits revealed that groups exposed to 0.6% and 1.0% of ocular PVP-I every day for a period of 7 days showed signs of mild and transient ocular irritation [56] . Nasal cavity formulations consisting of 0.54 to 5% of PVP-I are able to cause more than 3 log10 reduction in SARS-CoV-2 titres in 15 seconds of exposure [62] . In regard to disinfection methods against airborne coronaviruses, 4 articles were encountered (table IV) [63] [64] [65] [66] . Wafers containing silver and copper combined with aluminium oxide (Ag/Al 2 O 3 and Cu/Al 2 O 3) display catalytic properties and can be incorporated in air conditioning systems to trap and kill viruses. These wafers are active against coronavirus and can cause complete viral inactivation after 5 minutes of exposure [63] . J o u r n a l P r e -p r o o f 13 UV-C can efficiently inactivate up to 99.9% of aerosolised coronaviruses [64] . Ventilation systems fitted with an UV-C light source that can control its flow rate, indirectly control the exposure time of air passage, as lower flow rates translate in longer exposures times which results in superior viral removal efficacy [65] . As all human coronaviruses have similar genomic size, a key determinant of radiation sensitivity, it is likely that UV-C irradiation will show comparable inactivation efficiency against other human coronaviruses, including SARS-CoV-2 [64] . Methods with potential use to decontaminate and recondition personal protective equipment were approached by 16 papers (table V) [49, [67] [68] [69] [70] [71] [72] [73] [74] [75] [76] [77] [78] [79] [80] [81] . Most of the studies were directed towards filtering face respirators especially model 3M of N95 masks. Heat (70ºC -95ºC) combined with different levels of relative humidity is capable of inactivating enveloped viruses, including SARS-CoV-2, inoculated on N95 level melt-blown polypropylene fabric after at least 20 minutes of exposure [68, 74, 79] . Filtration efficacy was maintained after several cycles. However, cycles should be limited to not compromise the masks' function. A limit of 20 disinfection cycles is suggested for treatments under high relative humidity (100%) and temperatures of ≤ 85°C. Treatment should also be limited to 5 cycles under high relative humidity (100%) and temperatures of ≤95°C [68] [69] [70] 73] . Caution must be taken when a dry oven is utilised to generate dry heat (0% RH) since samples placed on parchment paper prior to heating can result in lower efficacy of viral inactivation [77] . Other than heat treatment, face masks made with cloth fabric, disposable gowns, PAPR (powered air purifying respirator) hoods can all be successfully decontaminated with doses of at least 20 ppm of ozone [67] . N95 respirators inoculated with HCoV were also adequately [71] . It is worth noting that cotton and PA66 can strongly trap viruses as only 56% of SARS-CoV-2 can be recovered from cotton samples and 92% from PA66 after viral inoculation. This information is relevant since cotton and PA66 based masks can trap high amounts of SARS-CoV-2, making cross contamination more probable when masks are posteriorly reutilised without decontamination [71] . Copper iodine complex has the potential to be used on non-critical PPE as it has been shown to completely deactivate SARS-CoV-2 in suspension after 30 minutes of exposure [75] . An innovative formulation that consists of silver and antimicrobial substances (ethanol and QAC) has also shown to possess antiviral activity when impregnated in the matrix of surgical masks [81] . Hydrogen peroxide vapor can also inactivate SARS-CoV-2 deposited on N95 masks and FFR's. This last process can be conducted in a STERRAD 100NX sterilisation system (ASP) or a V-PRO Max Steriliser providing exposure cycles of 47 minutes or less [72, 73] . UV irradiation was shown to be able to inactivate coronaviruses deposited on surgical masks and FFR's [73, 76, 78] . Exposure times needed to completely decontaminate these materials ranged from 60 seconds to 4 minutes while models tested were in the family of N95 grade FFRs. It is worth noting that the efficacy of UV-C irradiation is model-dependent and straps that contain hydrophilic properties seem to cause a lower reduction in viral titres [76] . Exposure to 20 minutes of simulated sunlight, characterised by UV irradiation with wavelengths ranging between 300-400nm, can significantly reduce viral titres of SARS-CoV-2 on specific models of N95 masks [80] . Selection bias was not able to be evaluated in all but two studies due to the majority of experiments taking place in in-vitro settings. Blinding of personnel was effectuated in only 1 study meaning that the rest could possibly contain performance bias. 13 studies were considered to have a probable risk of attrition or exclusion bias, 8 studies had probable risk of detection bias, J o u r n a l P r e -p r o o f 2 studies with probable risk of selective reporting bias and 3 studies showed probable risk of potential threat to internal validity. A summary of the evaluation is provided in table VI. Under ambient conditions (temperatures of 21-23°C and relative humidity of 40%) SARS-CoV-2 can remain viable on surfaces from hours to days [7, 40] . The findings in this review support the evidence that coronaviruses are less viable when exposed to higher temperatures and higher relative humidity. It is not always possible to change the room temperature or humidity in indoor settings. However, rooms with the possibility to set these parameters between a determined range, such as intensive care units, operating rooms or hospital wards, can benefit much as the survival of viruses is remarkably reduced in warmer and higher humidity conditions. Although most chemical agents have demonstrated virucidal activity against the coronavirus family, alcohols with concentrations of at least 60% showed a more constant and significant reduction in viral titres, promoting viral inactivation with shorter time exposures. This suggests that alcohols may be a better option when it comes to choosing a fast-acting and effective agent. Sodium hypochlorite, if preferred, should consist of a 0.1% solution, at least. If using QAC, the minimum exposure time of 30 minutes is recommended. As the household dishwashing detergent is more accessible compared to the other coatings discussed, it can be an effective alternative in providing a long lasting virucidal protection on surfaces in household settings or in countries that have difficulty in accessing other products, like alcohols. However, further investigation is still needed to determine the efficacy and practicality of these coatings. Ozone has virucidal activity targeting proteins on the viral envelope, inhibiting its entry to host cells. Higher concentrations of ozone must be used with caution due to the potential toxicity to humans therefore we suggest that ozone concentration of 20ppm and exposure times of 15 minutes is sufficient for optimal disinfection of surfaces [43, 82, 83] . For surface disinfection, UV-C irradiation seems to be the better alternative, as it is widely available and exceptionally convenient. It may be preferred over ozone as it is safer and less toxic to humans. However, when used with the purpose of whole room disinfection, other methods, such as surface antimicrobial agents, could complement the strategy, as not all surfaces may be fully decontaminated due to shadowing or to the composition of absorbable materials, like fleece and wood. Adequate disinfection of hands is an important way to prevent indirect transmission of respiratory infections, especially during the era of SARS-CoV-2. Based on our findings and evidence in literature, the original formulations of WHO-recommended hand rubs seem to be less active against SARS-CoV-2 compared to modified formulations [13, 84] . This is significant since many companies seek standard recommendations from WHO to produce disinfectants with the adequate proportion of ethanol/isopropanol and glycerol. These formulations could be updated to ensure optimal disinfection efficacy of formulations against SARS-CoV-2. Commercially available personal care products such as soap bars, liquid cleansers (containing surfactant) and alcohol-based hand sanitisers (at least 30% of ethanol or propanol) were all able to reduce SARS-CoV-2 titres after 10 to 20 seconds exposure [13, 55, 58, 85] . This suggests that the current procedure for hand washing is effective against SARS-CoV-2, at the established concentrations and duration. No methods are put in practice, at this moment, regarding eye or respiratory tract disinfection in order to stop the transmission of SARS-CoV-2 and such fact deserves further investigation due to potential toxicity. However, there are viable options in specific settings, for example, during ophthalmologic procedures or interventions where aerosols may be generated. While very low concentrations of PVP-I showed in-vitro viral inactivation, in-vivo conditions must be taken into account due to the fact that biological debris such as physiological buffers in nasal secretions can lower the effective concentration of PVP-I. Therefore, at least 1.25% of PVP-I formulation is recommended in in-vivo application [53] . In summary, for oral rinses and skin cleansers, products containing PVP-I should be preferred, as its action is rapid and efficient. Soap bars, surfactant and alcohol-based hand sanitisers are all excellent alternatives for hand hygiene. Recent evidence points to airborne as the main route of transmission of SARS-CoV-2, being more evident in indoor spaces with poor ventilation. Considering that coronaviruses cannot tolerate high temperatures, filtration or ventilation systems coupled with heatable metal filters, may be an effective option. It is also evident that SARS-CoV-2 is susceptible to UVC irradiation. As this last option is the only one commercially available at the moment, the installation of an upper room germicidal UV-C irradiation device, for example, in health care facilities, indoor spaces that accommodate a large number of people, or even in household settings can be beneficial. Other than UV irradiation, the remaining methods in this section provide preliminary evidence of effective ways to decontaminate the air, bringing light to the future of more sophisticated and efficient air conditioning systems. The COVID-19 pandemic had a significant impact on the environment and mass production of PPEs to meet the world's rapid and urgent demand, creating major challenges in waste management on a global scale [86] [87] [88] . Surgical masks, for instance, are composed of plastic that is not biodegradable and may end up in waterbeds, causing harm to the environment and the fauna of these areas. Methods that aim to decontaminate and recondition PPEs for reutilisation can be beneficial not only for the environment but also in cases of shortages of these materials, as experienced by many countries during this COVID-19 pandemic. Based on these studies, there is still not enough evidence to support the virucidal efficacy of metal-embedded fabrics. Moreover, since it is important to preserve the PPEs functionality after the process of decontamination, the only methods that provided evidence of effective sterilisation without compromising the integrity of PPEs (with a limited number of cycles) was heat and ozone treatment, making these method, for the moment, better and safer options. Three of the studies included in this review addressed how different deposition solutions can change the viral inactivation rate. It was found that viral load from SARS-CoV-2 and bacteriophages MS2 and Phi6 deposited in DMEM-A (cell culture medium formulations) showed, under different temperature and humidity exposures, a more significant reduction in viral titres compared to viral load deposited in phosphate-buffered saline (PBS) [40] . Interestingly, viral load deposited in freshly collected human saliva demonstrated a log10 reduction trend more similar to PBS compared to DMEM-A. Bovine serum albumin (BSA) containing higher concentrations of protein can be utilised to mimic body fluids, particularly sputum [31, 42] . This may suggest that laboratory-made solutions may not fully represent the behaviour of biological fluids. One major limitation to this systematic review is that all the studies included are based on in-vitro findings, with some extensive experiments trying to mimic in-vivo conditions. However, the real efficacy in in-vivo settings needs further investigation. Nineteen of the studies included utilised surrogate viruses to mimic the behaviour of SARS-CoV-2. Surrogate viruses were included due to the biosafety level of SARS-CoV-2 that may hinder the use of this virus in some experiments. It may have also been unavailable in some laboratories specially in the beginning of the pandemic when little was known about SARS-CoV-2. To evaluate the efficacy of disinfectants, vaccinia virus in particular, is a reference virus used in Europe as a surrogate for enveloped viruses (EN 14476) [89] . Since SARS-CoV-2 is an enveloped virus easily susceptible to disinfection, as verified in our findings, methods that can effectively target more resilient surrogate enveloped viruses translate in efficacy against SARS-CoV-2. The results demonstrate that several household and hospital disinfection agents, UV-C This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors declare no competing interests. First and foremost, I would like to thank my supervisor, Dr. Luís Cobrado, for his expertise and guidance through the whole extent of this work. I would also like to thank my colleague, Carolina Xavier, for the support, effort, and assistance regarding the writing and language of this work. 5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number. -Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale Page 3, 4 th paragraph Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched. Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated. Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis). A -PRISMA checklist for systematic reviews J o u r n a l P r e -p r o o f 43 Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators. Page 4, 3 rd paragraph/ Figure 1 Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made. Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis. 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