key: cord-0733198-lykzet9e
authors: Li, Dan; Zhao, Mitchie Y; Hsern, Malcolm Tan Turk
title: What makes a foodborne virus: comparison between coronaviruses with human noroviruses
date: 2020-05-04
journal: Curr Opin Food Sci
DOI: 10.1016/j.cofs.2020.04.011
sha: 7222e71872a83be2da2e9d07ca439a31603c245d
doc_id: 733198
cord_uid: lykzet9e

In order to answer the question whether coronaviruses (CoVs) can be transmitted via foods, this review made a comparison between CoVs with the most recognized foodborne virus, human noroviruses (NoVs). As a result, although CoVs indeed have shown the possibilities to remain infectious on foods and/or food packaging materials long enough (from several days to several weeks) to potentially cause transmission, they seem to be less persistent than NoVs towards common disinfection practices with alcohols, chlorine and ultraviolet (UV). More importantly, the chance of foodborne transmission of CoVs is considered low as CoVs mainly spread through the respiratory tract and there is no clear evidence showing CoVs can follow fecal-oral routes like human NoVs and other foodborne viruses.

Human noroviruses (NoVs) are the most frequently linked virus with foodborne outbreaks, and as such are identified as the foodborne virus with the highest priority worldwide. In 2015, the World Health Organization (WHO) listed human NoVs as the "Number 1" cause of foodborne illnesses [1] . Next to NoVs, commonly recognized foodborne viruses also include hepatitis A virus, hepatitis E virus, rotaviruses, astroviruses, etc [2] .

Due to the current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), numerous concerns have been raised over whether SARS-CoVs-2 can be transmitted via foods and/or food packaging materials. Indeed, the possibility of foodborne transmission cannot be ruled out for any virus. However, these possibilities should be understood in-depth as supported by scientific data and analysis so that the virus spread could be controlled in a more focused and efficient way. In this review, we intend to make a comparison between coronaviruses (CoVs) with the most recognized foodborne virus, human NoVs, in order to supply evidence to evaluate the possibilities of foodborne transmission of CoVs. The comparisons were performed from four different perspectives including the epidemiological evidence, their presence in foods, their persistence in food systems, and their relevant clinical manifestations.

In 2015, WHO estimated 684 million diarrheal disease cases caused by human NoVs annually, amongst which 212,000 deaths were caused [2] . The link between many of the illnesses and the human NoVscontaminated-food consumption has been clearly demonstrated (Table 1 ) thanks to the comprehensive investigations among all the components of a food control system. Typically, a successful foodborne outbreak investigation will need collaborative efforts from food law and regulations, food control management, inspection services, epidemiological and food monitoring (laboratory services) and consumers' education of and communication. Verhoef et al. [3] estimated the proportion of foodborne infections caused by human NoVs on a global scale to be as high as ~14%. Meanwhile, it should be well noted that large-scale outbreaks are often the result of a combination of several transmission routes. For example, the virus can first infect a sensitive population by food, water or an asymptomatic shedder, and a more efficient viral spread in a large group of population could be followed by direct person-to-person contact or via a contaminated environment.

In comparison, to the best of our knowledge, despite the long history and wide spread of CoVs in human communities, there is no epidemiological evidence showing that any of the illnesses was due to food consumption.

The discovery of human NoVs from food systems is not rare. Numerous reports have been published for human NoVs screening from food and environmental samples ( Table 2 ). The most common categories of food linked to outbreaks are shellfish, which can bio-accumulate viral particles from a large volume of water and is often consumed uncooked; and fresh produce, especially soft berry fruits and leafy green vegetables, which can be contaminated during the primary production, and are generally consumed without effective treatment to get rid of the contaminated viruses. However, one must realize that any food can be implicated in outbreaks, especially when the contamination is due to infected food handlers [1] .

Again, no record over the presence of CoVs in foods could be found from the literature. One may argue that the CoV presence could have been understudied and in the future, especially with the use of metagenomics technologies, CoVs might be able to be found within the viromes of foods. However, care should be taken when interpreting the results of virus detection from foods with the use of molecular methods. In-depth understanding over the virus quantities in relation to a dose-dependent effect and the virus viability (as the molecular methods detecting the presence of nucleic acids are not able to differentiate between infectious and non-infectious viruses) are of crucial importance in order to determine the relevant public health influence. Figure 1 illustrates the foodborne transmission routes of human NoVs. Since viruses cannot multiply themselves without a host, after being shed to the environment, the viruses must be able to resist the possible environmental stress in the food systems, such as solar irradiation, desiccation, high or low temperature, unfavourable chemicals, etc., and remain infectious for durations long enough until being J o u r n a l P r e -p r o o f ingested again. In fact, human NoVs are known as the "super survivor" in the food systems as shown by numerous studies (Table 3) . Table 3 intends to compare the stability between NoVs and CoVs under different possible conditions in the food systems. Since molecular methods underestimate largely the infectivity decrease of viruses, we only included data generated with the use of cell culture based methods or from human volunteer studies. (Table 3) .

Low temperature is favourable for both NoVs and CoVs to survive both on food-contact surfaces/solid foods and in water/liquid foods as shown consistently in multiple studies as summarized in Table 3 .

However, the influence of relative humidity (RH) is contradictory for different viruses. HAV survived better at higher RH [5] , while MS2 and MERS-CoV survived better at lower RH [5] [6] . Similarly, no consensus could be reached for the influence of organic (food) matters. On one hand, MNV showed 6. 

In addition, different experimental set-ups were used in different studies, including the tested environmental parameters, the virus spike levels, the test durations, the virus recovery methods, and the data interpretation methods (log-reductions vs. durations until the viruses became non-infectious), etc. Therefore, it is not possible to make direct comparisons between NoVs and CoVs over their stabilities on foods (both solid and liquid foods) or possible food-contact surfaces. Nevertheless, it seems that both NoVs and CoVs were able to remain infectious on foods and/or food packaging materials long enough (from several days to several weeks) to potentially cause transmission especially at low temperatures. 19] ), assumptions could be made that the viruses may migrate from the oral ingestion to the respiratory tracts via, for instance, the throat. However, this assumption will need sound experimental and/or clinical supports not only in a qualitative way (to show whether it is possible for the virus to migrate from oral ingestion to the respiratory tract), but also in a quantitative way. Since if large quantities of viruses must be ingested in order to cause the migration, the chance of such occurrence could be very low in reality. The acute gastroenteritis outbreak affected 137 out of 361 people of a nursing home.

Ten of the 28 stool samples were positive for NoVs (two GI, six GII and two GI/GII). Turkey was suggested to be the initial source of the outbreak and was subsequently spreading via person-to-person transmission.

[21]

Mussels 2017, Spain Thirty-nine people were sick after consuming mussels contaminated with NoV First outbreak: 8 faecal samples from symptomatic individuals and coleslaw samples were positive for NoV GII. Nucleotide sequencing of the faecal samples reveals that the outbreak strain belongs to GII.6 genotype. Second outbreak: 3 employees and 2 out of 10 restaurant personnel were positive for NoV GII. The close connection between two outbreaks suggests the possible spread of the same NoV genotype (GII.6), which could be attributed to a mixture of foodborne and person-to-person transmission. [31] SARS-CoV-2 at 21 to 23°C and 40% relative humidity (RH): more stable on plastic (3.1-log reduction after 3 days) and stainless steel (3.1-log reduction on plastic after 2 days) than on copper and cardboard, and viable virus was detected up to 3 days after application to these surfaces.

[32]

On dried stainless steel surfaces for 7 days: MNV and FCV showed ~1-log reduction at 4°C; ~4-log reduction at room temperature after 7 days.

[33] SARS-CoV remained stable on plastic surface at room temperature with 40-50% RH for up to 4 weeks, yet lost its infectivity significantly at 38 ºC with >95% RH during 24 h in air.

[34]

On stainless steel coupons for 30 days at 25°C: MNV showed 6.2-log reduction on residue-free coupons and 1.4-log reduction on coupons with lettuce, cabbage, or ground pork residues

[7] Air-dried SARS-CoV on polystyrene surfaces retained its infectivity for 6 days at 4 ºC.

[35]

Bacteriophage MS2 4°C: <1-log reduction for all produce types by day 7, <2-log reduction in cabbage and carrots by day 87; 8°C: <1-log reduction for all produce types by day 7, ~1-log reduction in tomato, cabbage, carrots and lettuce by day 39; 22°C: 1-log reduction on lettuce and <1-log reduction on tomato and parsley by day 7 [36] MERS-CoV survived on both plastic and steel surfaces surfaces after 48 hours at 20 ºC, 40% RH, while it remained viable only for 8 hours at 30 ºC, 80%RH and 24 hours at 30 ºC, 30% RH. At 20 ºC, MERS-CoV's viability decreased 7% at 40% RH, and 89% at 70% RH respectively.

[6]

Hepatitis A virus (HAV), MS2, MNV on oyster and peppers at 4°C, 15°C, 25°C, and 40°C: viruses survived best at 4°C and were inactivated most at 40°C. On oysters, a 1-log reduction of both HAV and MNV occurred at 4°C, even after 14 days. However, a 5log reduction of MNV occurred on peppers at 4°C. MNV showed the shortest survival duration on peppers at all temperatures compared to the other viruses. Viral survival was better on oysters than on peppers. At a given temperature, HAV survived better at higher RH, while MS2 survived better at lower RH. At 40°C, inactivation of HAV was1 log at 50% RH but only 0.1-log at 70% RH on day-1 postinoculation.

[5] Human coronavirus (HCoV) strain 229E survived on lettuce during 2 days of storage at 4 ºC, yet became non-infectious by day 4 (reduction>1.31-log). No HCoV could be recovered from raspberries or strawberries after spiking. [37] J o u r n a l P r e -p r o o f

World Health Organization: WHO estimates of the global burden of foodborne diseases: foodborne disease burden epidemiology reference group 2007-2015. Edited by World Health Organization

Foodborne viruses: Detection, risk assessment, and control options in food processing

Norovirus genotype profiles associated with foodborne transmission

Emerging Infectious Diseases -(Open Access)

Replication of human noroviruses in stem cell-derived human enteroids

This is the only currently well-accepted human norovirus tissue culture model

Effect of temperature and relative humidity on the survival of foodborne viruses during food storage

Stability of Middle East respiratory syndrome coronavirus (MERS-CoV) under different environmental conditions. Euro surveillance : bulletin

Survival of viruses on fresh produce, using MS2 as a surrogate for norovirus

Survival of Respiratory Viruses on Fresh Produce

Survival of human norovirus surrogates in milk, orange, and pomegranate juice, and juice blends at refrigeration (4 °C)

Stability of Middle East respiratory syndrome coronavirus in milk

Study on the resistance of severe acute respiratory syndrome-associated coronavirus

China Human NoV was detected in 9% (81/900) of frozen and 12.1% (109/900) of fresh domestic retailed berry samples

Fresh seafood (oysters, clams, shrimps and finfish) India NoV GII was detected in 41 out of 104 (41.3%) fresh seafood samples. The incidence of NoV was the highest in bivalves (52.7% -39/74)

Reverse-transcription PCR (RT-PCR), nested PCR, Southern hybridization

Vietnam Human NoV was detected in 81.8% (99/121) of the analyzed samples

China Human NoV was detected in 20.7% (135/652) of the oyster samples. Real-time RT-PCR

Japan NoV GII was detected in 89% (48/54) of the composite oyster samples pooled from 162 individual oysters. Multiple genotypes of GII were identified

This study was supported by a Ministry of Education (MOE) academic research fund (AcRF) TIER 1 project "Study of important foodborne viruses from relevant foods in Singapore" (Jan 2019 to Dec 2021).

MNV showed infectivity reduction rate of 0.16-log PFU/day in surface water and 0.04-log PFU/day in groundwater at 25°C.[8]HCoV survived (with 99.9% decrease of infectivity) for 10 days at 23 ºC, for > 100 days at 4 ºC in tap water, yet for only 2 to 4 days in wastewater.[9]Norwalk virus (NV, prototype of NoVs) remained infectious at least for 61 days in groundwater at room temperature in the dark as tested by human volunteer studies.[38] At 25 ºC, transmissible gastroenteritis (TGEV) survived for 22 days, and mouse hepatitis virus (MHV) survived for 17 days in reagent-grade water, whereas in wastewater, TGEV survived for 9 days and MHV survived for 7 days (with 99% decrease of infectivity). At 4 ºC, both viruses survived longer than four weeks.[10]MNV showed no reduction, FCV showed 3-log PFU/ml reduction, MS2 showed <1-log reduction in milk after 21 days at refrigeration (4°C).[39] MERS-CoV survived in dromedary camel milk at 4 °C for 72 hours (with 37% reduction of infectivity), while it lost infectivity rapidly at 22 °C in dromedary camel milk, goat milk, and cow milk (88%-99% reduction) within 48 hours of storage.[40]

Regardless of concentration or exposure time, alcohols slightly reduced, but did not completely inactivate, human norovirus (3 GII.4 strains tested by the enteroid culture model).[11]No SARS-CoV residual infectivity was detected after fixation with 70% ethanol for 10 min or 100% ethanol for 5 min. Isopropanol 70% and 100% achieved > 3.31-log reduction of SARS-CoV infectivity after 30 s.[35]

Complete inactivation of the 3 GII.4 viruses occurred at concentrations at 50 ppm of chlorine after incubating the solutions for 1 min at room temperature strains tested by the enteroid culture model.[11] SARS-CoV could be completely inactivated with 10 ppm chlorine for 10 min or more, and with 20 ppm chlorine for 1 min or more.[41]

The susceptibility of MHV was 7-10 times that of the MS2.[12]