Task1 - What is known about transmission, incubation, and environmental stability?

Range of incubation periods for the disease in humans

Incubation period ( the time from infection to the onset of symptoms ) for the new pathogen varies from 2 to 14 days in human to human transmission ( 13 ) . Furthermore , median incubation period was reported as 5 - 6 days ( ranged from 0 - 14 days ) in WHO report ( 14 ) . Studies that were conducted on those who had traveled to Wuhan and Guangdong mean incubation period of 4 . 8 ( ±2 . 6 ) days was reported . In some other studies the mean incubation period was reported to be 6 . 4 days ( 15 , 16 ) , while another study in China reported longer incubation times up to 24 days ( 13 ) .

The mean incubation period of SARS - CoV - 2 is estimated to be 3 - 7 days ( range , 2 - 14 days ) [ 46 , 47 ] , indicating a long transmission period of SARS - CoV - 2 . It is estimated that SARS - CoV - 2 latency is consistent with those of other known human CoVs , including non - SARS human CoVs ( mean 3 days , range 2 - 5 days ) [ 48 ] , SARS - CoV ( mean 5 days , range 2 - 14 days ) [ 49 ] and MERS - CoV ( mean 5 . 7 days , range 2 - 14 days ) [ 50 ] . Moreover , it has been reported that asymptomatic COVID - 19 patients during their incubation periods can effectively transmit SARS - CoV - 2 [ 51 , 52 ] , which is different from SARS - CoV because most SARS - CoV cases are infected by ' superspreaders ' and SARS - CoV cases cannot infect susceptible persons during the incubation period [ 53 ] . Taken together , these data fully support the current period of active monitoring recommended by the WHO of 14 days .

The incubation period is essential in the control of infectious diseases . To halt a pandemic , a suitable quarantine period should be set by investigating incubation periods . Thus , understanding the characteristics of the incubation period is crucial to design public health efforts . In this cohort , the full range of incubation periods of the Covid - 19 cases ranged from 0 to 33 days among 2015 cases . Both male and female adults had their median incubation periods of 7 - day , which is 1 . 8 - day longer than those in other reports 3 , 4 ( see discussion ) . However , a similar result was released in the recent news from the Chinese Medical Association that the median incubation periods were 5 - 7 days 5 . The median incubation period ( 9 - day ) of children were significantly longer than those of adults ( t - test P = 0 . 02 ) . For adults , the incubation periods for the majority ( 66 . 5 % ) of the cases were 1 - 9 days : most of them ( 57 . 6 % and 52 . 0 % for males and females , respectively ) had 1 - 5 days incubation . Importantly , we found that the incubation periods of 11 . 5 % ( n = 233 , 123 and 105 were male and female , respectively ) of the cases were longer than 14 days , the current WHO - set 14 - day quarantine period . These results agree with a recent study which also reported 12 . 7 % ( n = 13 ) of the cases whose incubation periods were longer than 14 days 4 . These data suggested that the official 14 - day quarantine period only captured 88 . 5 % of the population developing Covid - 19 .

The virus is related to the SARS coronavirus and MERS coronavirus , but is distinct from each of those viruses [ 2 ] , such that the epidemiological key parameters have to be identified for this new virus from incoming case reports as the epidemic continues . Chief among these key parameters is the incubation period distribution . The range of the values for the incubation period is essential to epidemiological case definitions , and is required to determine the appropriate duration of quarantine . Moreover , knowledge of the incubation period helps to assess the effectiveness of entry screening and contact tracing . The distribution of the incubation period is also used in estimating the size of the epidemic [ 3 - 5 ] and the transmission potential [ 6 , 7 ] . In absence of data on the 2019 - nCoV incubation period , the WHO has worked with a broad range of 0 to 14 days , the CDC has taken a range of 2 to 14 days , and several studies have assumed incubation periods of SARS or MERS coronaviruses .

Background The outbreak of a new coronavirus ( SARS - CoV - 2 ) disease ( Covid - 19 ) has become pandemic . To be more effectively controlling the disease , it is critical to set up an optimal quarantine period so that about 95 % of the cases developing symptoms will be retained for isolation . At the moment , the WHO - established quarantine period is 14 days based on previous reports which had studied small sizes of hospitalized cases ( 10 and ~ 100 , respectively ) , however , over 80 % of adult - and 95 % of child - cases were not necessary to stay in hospitals , and therefore , had not been hospitalized . Therefore , we are questioning if the current - inferred median incubation time is representative for the whole Covid - 19 population , and if the current quarantine period is optimal . Methods We compiled and analyzed the patient - level information of 2015 laboratory - confirmed Covid - 19 cases including 99 children in 28 Chinese provinces . This cohort represents a wide - range spectrum of Covid - 19 disease with both hospitalized and non - hospitalized cases . Results The full range of incubation periods of the Covid - 19 cases ranged from 0 to 33 days among 2015 cases . There were 6 ( 0 . 13 % ) symptom - free cases including 4 females with a median age of 25 . 5 years and 2 males with a median age of 36 years . The median incubation period of both male and female adults was similar ( 7 - day ) but significantly shorter than that ( 9 - day ) of child cases ( P = 0 . 02 ) . This cohort contained 4 transmission generations , and incubation periods of the cases between generations were not significantly different , suggesting that the virus has not been rapidly adapted to human beings . Interestingly , incubation periods of 233 cases ( 11 . 6 % ) were longer than the WHO - established quarantine period ( 14 days ) . Data modeling suggested that if adults take an extra 4 - day or 7 - day of isolation ( i . e . , a quarantine period of 18 or 21 days ) , 96 . 2 % or 98 . 3 % , respectively , of the people who are developing symptoms will be more effectively quarantined . Patients transmitted via lunch / dinner parties ( i . e . , gastrointestinal tract infection through oral transmission ) had a significantly longer incubation period ( 9 - day ) than other adults transmitted via respiratory droplets or contaminated surfaces and objects ( P < 0 . 004 ) . Conclusions The whole Covid - 19 population including both hospitalized and non - hospitalized cases had a median incubation period of 7 - day for adults , which is 1 . 8 - day longer than the hospitalized cases reported previously . An extension of the adult quarantine period to 18 days or 21 days could be more effective in preventing virus - spreading and controlling the disease . The cases transmitted by lunch / dinner parties could be infected first in the gastrointestinal tract through oral transmission and then infected in the respiratory system so that they had a longer incubation period .

Range of incubation periods for the disease in humans depending on age

From WHO records , the period from the symptoms onset and to death of COVID - 19 ranged from 6 - 41 days with a median of 14 days . This period depends on the age and the status of immune system . It has been shorter with age under 70 years [ 11 ] .

Incubation period ( the time from infection to the onset of symptoms ) for the new pathogen varies from 2 to 14 days in human to human transmission ( 13 ) . Furthermore , median incubation period was reported as 5 - 6 days ( ranged from 0 - 14 days ) in WHO report ( 14 ) . Studies that were conducted on those who had traveled to Wuhan and Guangdong mean incubation period of 4 . 8 ( ±2 . 6 ) days was reported . In some other studies the mean incubation period was reported to be 6 . 4 days ( 15 , 16 ) , while another study in China reported longer incubation times up to 24 days ( 13 ) .

Background The outbreak of a new coronavirus ( SARS - CoV - 2 ) disease ( Covid - 19 ) has become pandemic . To be more effectively controlling the disease , it is critical to set up an optimal quarantine period so that about 95 % of the cases developing symptoms will be retained for isolation . At the moment , the WHO - established quarantine period is 14 days based on previous reports which had studied small sizes of hospitalized cases ( 10 and ~ 100 , respectively ) , however , over 80 % of adult - and 95 % of child - cases were not necessary to stay in hospitals , and therefore , had not been hospitalized . Therefore , we are questioning if the current - inferred median incubation time is representative for the whole Covid - 19 population , and if the current quarantine period is optimal . Methods We compiled and analyzed the patient - level information of 2015 laboratory - confirmed Covid - 19 cases including 99 children in 28 Chinese provinces . This cohort represents a wide - range spectrum of Covid - 19 disease with both hospitalized and non - hospitalized cases . Results The full range of incubation periods of the Covid - 19 cases ranged from 0 to 33 days among 2015 cases . There were 6 ( 0 . 13 % ) symptom - free cases including 4 females with a median age of 25 . 5 years and 2 males with a median age of 36 years . The median incubation period of both male and female adults was similar ( 7 - day ) but significantly shorter than that ( 9 - day ) of child cases ( P = 0 . 02 ) . This cohort contained 4 transmission generations , and incubation periods of the cases between generations were not significantly different , suggesting that the virus has not been rapidly adapted to human beings . Interestingly , incubation periods of 233 cases ( 11 . 6 % ) were longer than the WHO - established quarantine period ( 14 days ) . Data modeling suggested that if adults take an extra 4 - day or 7 - day of isolation ( i . e . , a quarantine period of 18 or 21 days ) , 96 . 2 % or 98 . 3 % , respectively , of the people who are developing symptoms will be more effectively quarantined . Patients transmitted via lunch / dinner parties ( i . e . , gastrointestinal tract infection through oral transmission ) had a significantly longer incubation period ( 9 - day ) than other adults transmitted via respiratory droplets or contaminated surfaces and objects ( P < 0 . 004 ) . Conclusions The whole Covid - 19 population including both hospitalized and non - hospitalized cases had a median incubation period of 7 - day for adults , which is 1 . 8 - day longer than the hospitalized cases reported previously . An extension of the adult quarantine period to 18 days or 21 days could be more effective in preventing virus - spreading and controlling the disease . The cases transmitted by lunch / dinner parties could be infected first in the gastrointestinal tract through oral transmission and then infected in the respiratory system so that they had a longer incubation period .

The median incubation period was 4 days ( interquartile range , 2 to 7 ) . The median age of the patients was 47 years ( interquartile range , 35 to 58 ) ; 0 . 9 % of the patients were younger than 15 years of age . A total of 41 . 9 % were female . Fever was present in 43 . 8 % of the patients on admission but developed in 88 . 7 % during hospitalization . The second most common symptom was cough ( 67 . 8 % ) ; nausea or vomiting ( 5 . 0 % ) and diarrhea ( 3 . 8 % ) were uncommon . Among the overall population , 23 . 7 % had at least one coexisting illness ( e . g . , hypertension and chronic obstructive pulmonary disease ) .

As shown in Table 1 , the median incubation period was 3 . 0 ( IQR , 2 - 7 ; ranged from 1 to 14 or longer ) days and from illness onset to hospital admission was 2 ( IQR , 1 - 4 ; ranged from 1 to 6 ) days . The median age was 33 ( IQR , 26 to 42 ; ranged from 20 to 52 ) , and 70 % were females and none was pregnant . None of them was health worker .

Range of incubation periods for the disease in humans depending on health status

The incubation period is essential in the control of infectious diseases . To halt a pandemic , a suitable quarantine period should be set by investigating incubation periods . Thus , understanding the characteristics of the incubation period is crucial to design public health efforts . In this cohort , the full range of incubation periods of the Covid - 19 cases ranged from 0 to 33 days among 2015 cases . Both male and female adults had their median incubation periods of 7 - day , which is 1 . 8 - day longer than those in other reports 3 , 4 ( see discussion ) . However , a similar result was released in the recent news from the Chinese Medical Association that the median incubation periods were 5 - 7 days 5 . The median incubation period ( 9 - day ) of children were significantly longer than those of adults ( t - test P = 0 . 02 ) . For adults , the incubation periods for the majority ( 66 . 5 % ) of the cases were 1 - 9 days : most of them ( 57 . 6 % and 52 . 0 % for males and females , respectively ) had 1 - 5 days incubation . Importantly , we found that the incubation periods of 11 . 5 % ( n = 233 , 123 and 105 were male and female , respectively ) of the cases were longer than 14 days , the current WHO - set 14 - day quarantine period . These results agree with a recent study which also reported 12 . 7 % ( n = 13 ) of the cases whose incubation periods were longer than 14 days 4 . These data suggested that the official 14 - day quarantine period only captured 88 . 5 % of the population developing Covid - 19 .

The current outbreak of coronavirus disease 2019 in at least 156 countries has been classified by the World Health Organization as a global pandemic [ 1 ] . The long incubation period and low disease severity in the early stage contributed to rapid increase in case numbers . The infection ranges from mild to severe respiratory illness , potentially progressing to acute respiratory distress syndrome in 17 % to 29 % of patients [ 2 ] . Disease severity resulted in global public health efforts to contain person - to - person viral spread by early detection .

Since the first report of COVID - 19 in Wuhan province in the month of December , the virus has spread across the globe through foreign travelers at rapid pace . The SARS - CoV2 is transmitted human to human among close contacts ( within about 6 feet ) [ 1 ] and has mean incubation period of 6 . 4 days with range of 2 . 1 to 11 . 1 days [ 2 ] . Asymptotic spread has made detection of virus very difficult . Reverse transcription PCR is widely used for detecting COVID - 19 virus which may take few hours and days to obtain results . Observing threat to public health , World Health Organization ( WHO ) has declared novel coronavirus ( 2019 - nCoV ) outbreak to be " public health emergency of international concern " on Jan . 30 , 2020 [ 3 ] and on the 11th of March the disease was declared a global pandemic [ 4 ] .

As shown in Table 1 , the median incubation period was 3 . 0 ( IQR , 2 - 7 ; ranged from 1 to 14 or longer ) days and from illness onset to hospital admission was 2 ( IQR , 1 - 4 ; ranged from 1 to 6 ) days . The median age was 33 ( IQR , 26 to 42 ; ranged from 20 to 52 ) , and 70 % were females and none was pregnant . None of them was health worker .

Background The outbreak of a new coronavirus ( SARS - CoV - 2 ) disease ( Covid - 19 ) has become pandemic . To be more effectively controlling the disease , it is critical to set up an optimal quarantine period so that about 95 % of the cases developing symptoms will be retained for isolation . At the moment , the WHO - established quarantine period is 14 days based on previous reports which had studied small sizes of hospitalized cases ( 10 and ~ 100 , respectively ) , however , over 80 % of adult - and 95 % of child - cases were not necessary to stay in hospitals , and therefore , had not been hospitalized . Therefore , we are questioning if the current - inferred median incubation time is representative for the whole Covid - 19 population , and if the current quarantine period is optimal . Methods We compiled and analyzed the patient - level information of 2015 laboratory - confirmed Covid - 19 cases including 99 children in 28 Chinese provinces . This cohort represents a wide - range spectrum of Covid - 19 disease with both hospitalized and non - hospitalized cases . Results The full range of incubation periods of the Covid - 19 cases ranged from 0 to 33 days among 2015 cases . There were 6 ( 0 . 13 % ) symptom - free cases including 4 females with a median age of 25 . 5 years and 2 males with a median age of 36 years . The median incubation period of both male and female adults was similar ( 7 - day ) but significantly shorter than that ( 9 - day ) of child cases ( P = 0 . 02 ) . This cohort contained 4 transmission generations , and incubation periods of the cases between generations were not significantly different , suggesting that the virus has not been rapidly adapted to human beings . Interestingly , incubation periods of 233 cases ( 11 . 6 % ) were longer than the WHO - established quarantine period ( 14 days ) . Data modeling suggested that if adults take an extra 4 - day or 7 - day of isolation ( i . e . , a quarantine period of 18 or 21 days ) , 96 . 2 % or 98 . 3 % , respectively , of the people who are developing symptoms will be more effectively quarantined . Patients transmitted via lunch / dinner parties ( i . e . , gastrointestinal tract infection through oral transmission ) had a significantly longer incubation period ( 9 - day ) than other adults transmitted via respiratory droplets or contaminated surfaces and objects ( P < 0 . 004 ) . Conclusions The whole Covid - 19 population including both hospitalized and non - hospitalized cases had a median incubation period of 7 - day for adults , which is 1 . 8 - day longer than the hospitalized cases reported previously . An extension of the adult quarantine period to 18 days or 21 days could be more effective in preventing virus - spreading and controlling the disease . The cases transmitted by lunch / dinner parties could be infected first in the gastrointestinal tract through oral transmission and then infected in the respiratory system so that they had a longer incubation period .

How long individuals are contagious?

Prevalence of asymptomatic shedding and transmission

Asymptomatic carriers of other HCoVs including 229E , OC43 , NL63 , and HKU1 have been well documented . Importantly , the detection rate of the virus in this group was lower and viral loads were much lower compared to patients with upper respiratory tract symptoms [ 55 ] . This is generally consistent with the notion that asymptomatic or presymptomatic shedding of SARS - CoV - 2 might be less common than some estimates such as half to half . In this regard , epidemiological studies to determine the percentages of asymptomatic carriers and in selected large cohorts of subjects in Wuhan should help clarify the role of asymptomatic virus shedding in SARS - CoV - 2 transmission . This analysis will also rule in or rule out our prediction that asymptomatic virus shedding exists but is uncommon . Since patients with non - specific and mild symptoms as well as asymptomatic carriers can go undetected easily , the chance that SARS - CoV - 2 will be established in humans is increased . It will likely become either endemic in some regions or pandemic .

An asymptomatic carrier of SARS - CoV - 2 was reported in the first study of a family cluster [ 51 ] . Transmission of SARS - CoV - 2 from an asymptomatic carrier to close contacts was later suggested , but this has subsequently been challenged . However , even if family members and close contacts could be infected by the index patient in the presymptomatic window period as claimed , it is still worthy of a significant concern . Presumed transmission of SARS - CoV - 2 from an asymptomatic carrier to family members has recently been documented [ 54 ] . The existence of many asymptomatic carriers , presymptomatic patients , and patients with very mild symptoms posts a huge challenge to infection control , as the transmission of SARS - CoV - 2 from these people to susceptible groups would be difficult to prevent . The number of people infected with SARS - CoV - 2 could be underestimated . However , existing evidence suggests that the risk might probably be lower than expected . First , asymptomatic carriers are not common . In the first family cluster that was carefully studied , only one of the six family members was found to be asymptomatic or present with non - specific and mild symptoms with the typical ground - glass opacities in only one but not both lungs [ 51 ] . Second , the transmission of SARS - CoV - 2 from asymptomatic carriers and presymptomatic patients could be even less common , if their viral loads are low and virus shedding is not substantial . The key questions concern how often asymptomatic and presymptomatic virus shedding might occur as well as whether their viral loads could be high .

In the hitherto largest pediatric COVID - 19 study that analyzed 2143 children with laboratory - 3 confirmed or suspected cases most pediatric patients ( 94 . 1 % ) were diagnosed as asymptomatic , or with mild or moderate disease [ 10 ] . In fact , 13 % of laboratory - confirmed cases were asymptomatic which is notable as this is certainly an underestimation of the true rate of asymptomatic infection , since many children without symptoms are unlikely to be tested for obvious reasons . Recent virologic data demonstrated that such asymptomatic or oligosymptomatic individuals carry potentially infectious SARS - CoV - 2 particles in their nasopharyngeal secretions thereby very likely contributing to early transmission to close contacts [ 11 , 12 ] . In addition , the evidence of fecal shedding of SARS - CoV - 2 in the stool of an asymptomatic child for a prolonged period raises the concern that infants and children who are not toilet - trained could facilitate fecal - oral transmission of the virus [ 13 ] . The potentially prolonged shedding of the virus in nasal secretions and stool of children and infants has substantial implications for spread of the virus in daycare centers , schools , and in the home .

Influenza viral shedding appears to vary by subtype , but the patterns of shedding were similar in both children and adults [ 63 , 64 ] , and between the seasonal and p ( H1N1 ) outbreaks [ 64 ] [ 65 ] [ 66 ] , although the reproductive number appears different [ 65 ] . We allowed for some of the infections to be asymptomatic [ 59 , 63 ] , which in our model increases the rates of return to the community and transmission , while also reducing the effectiveness of control policies . Meta - analysis of influenza studies [ 14 ] was used to determine shedding and symptom rates by disease state ( see Table A

In conclusion , seasonal respiratory pathogens are more prevalent than SARS - CoV - 2 in the non - endemic patients suspected with COVID - 19 . All the patients shared similar clinical features and laboratory data . The scope of quarantine and active surveillance of suspected patients should be expanded . The application of rapid detection tools , such as FilmArrayä Respiratory Panel , is highly recommended for the determination of causative pathogens . The long duration of SARS - CoV - 2 shedding and the transmission in patients asymptomatic or with mild illness drastically increase the pandemic potential of COVID - 19 . Owing to the early wave of SARS - CoV - 2 transmission in Taiwan , our study was limited by the small number of cases for screening and included 2 COVID - 19 patients with mild illness . Further studies of SARS - CoV - 2 pathogenesis are warranted to illuminate the full spectrum of COVID - 19 and the treatment strategy .

Prevalence of asymptomatic shedding and transmission in children

In the hitherto largest pediatric COVID - 19 study that analyzed 2143 children with laboratory - 3 confirmed or suspected cases most pediatric patients ( 94 . 1 % ) were diagnosed as asymptomatic , or with mild or moderate disease [ 10 ] . In fact , 13 % of laboratory - confirmed cases were asymptomatic which is notable as this is certainly an underestimation of the true rate of asymptomatic infection , since many children without symptoms are unlikely to be tested for obvious reasons . Recent virologic data demonstrated that such asymptomatic or oligosymptomatic individuals carry potentially infectious SARS - CoV - 2 particles in their nasopharyngeal secretions thereby very likely contributing to early transmission to close contacts [ 11 , 12 ] . In addition , the evidence of fecal shedding of SARS - CoV - 2 in the stool of an asymptomatic child for a prolonged period raises the concern that infants and children who are not toilet - trained could facilitate fecal - oral transmission of the virus [ 13 ] . The potentially prolonged shedding of the virus in nasal secretions and stool of children and infants has substantial implications for spread of the virus in daycare centers , schools , and in the home .

Influenza viral shedding appears to vary by subtype , but the patterns of shedding were similar in both children and adults [ 63 , 64 ] , and between the seasonal and p ( H1N1 ) outbreaks [ 64 ] [ 65 ] [ 66 ] , although the reproductive number appears different [ 65 ] . We allowed for some of the infections to be asymptomatic [ 59 , 63 ] , which in our model increases the rates of return to the community and transmission , while also reducing the effectiveness of control policies . Meta - analysis of influenza studies [ 14 ] was used to determine shedding and symptom rates by disease state ( see Table A

It is likely that immunosuppressed patients may be prone to acquiring the virus at higher risk because of its high efficiency in transmission . The virus shedding has been noted not only in respiratory specimens but also in serum and stool . Viral shedding can occur for days or weeks furtively in asymptomatic carrier individuals , especially children , 3 , 9 , 10 and fecal shedding has been noted in patients without diarrhea . 10 Significant environmental contamination has been noted , including wash basin , toilet bowl , and air outlet fan surfaces , in hospitalized patients . 11 Thus , it is prudent to advise transplant recipients to ardently practice mitigation strategies such as social distancing , sanitization , hand hygiene , and avoidance of areas known to harbor potentially infected individuals . These recommendations extend to their care providers as well .

In our study , we described the main clinical , laboratorial and radiological characteristics of children infected with SARS - CoV - 2 reported in the literature . It was observed that only a small proportion of infected children became severely or critically ill . About half of the children with COVID - 19 were asymptomatic or mild cases , and several were classified as moderate due to radiological abnormalities in spite of their mild clinical manifestations . The prognosis seems to be very good , with recovery described in the vast majority of reported cases . Only one death was reported in the included studies , a 10 - month - old child with intussusception . 3 Since COVID - 19 has a favorable clinical course in children , the importance of pediatric cases is mainly due to epidemiological issues . Despite being mild or asymptomatic cases , prolonged viral shedding in stool and nasal secretions made children facilitators of viral transmission . 5 , 42 In the study of Xu et al . , eight of ten children with SARS - CoV02 had persistently positive rectal swabs even after their nasopharyngeal tests . CC - BY - NC - ND 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 .

This report describes a spectrum of illness from SARS - CoV - 2 infection in children . In contrast with infected adults , most infected children appear to have a milder clinical course . Asymptomatic infections were not uncommon . 2 Determination of the transmission potential of these asymptomatic patients is important for guiding the development of measures to control the ongoing pandemic .

Seasonality of transmission

We investigated the impact of a seasonally affected transmission rate , to capture potential decreased transmission during the summer months . We captured seasonal transmission by replacing the constant transmission rate with a time - varying transmission rate given by :

The duration of social distancing measures needed to maintain control of the SARS - CoV - 2 epidemic in the context of seasonally varying transmission remains unclear , as does the impact of increasing critical care capacity on the overall trajectory of the outbreak . To address these unknowns , here we assessed the transmission of SARS - Cov - 2 through 2021 using a mathematical model with seasonal transmission forcing .

The intensity ( peak size ) of outbreaks depends strongly on the degree of seasonal forcing of transmission ( 4 ) . The transmission of many respiratory pathogens , including the human coronaviruses that cause mild common cold - like syndromes , is seasonal in temperate regions , peaking in the winter months ( 4 ) . This variation in transmission strength may be driven by a variety of factors , including increased indoor crowding in the winter , the onset of the school term in the autumn , and climate factors ( 5 ) . If SARS - Cov - 2 transmission is similarly subject to seasonal forcing , summer outbreaks would naturally have lower peaks than winter outbreaks . This aligns with observations from influenza pandemics , where relatively small spring and summer outbreaks are frequently followed by larger autumn / winter outbreaks ( 6 ) . Due to seasonal variation in transmission strength , it may be more difficult to flatten epidemic curves in the winter than in the summer . Moreover , a winter peak for COVID - 19 will coincide with peak influenza ( 5 ) , further straining health care systems .

Per incidence proxy unit , the effect of the cross - immunizing strain was always less than the effect of the strain itself ( Table S1 ) , but the overall impact of cross - immunity could still be substantial if the cross - immunizing strain had a large outbreak ( e . g . HCoV - OC43 in 2014 - 15 and 2016 - 17 ) . Seasonal forcing appears to drive the rise in transmissibility at the start of the season ( late October through early December ) , while depletion of susceptibles plays a comparatively larger role in the decline in transmissibility towards the end of the season . The strain - season coefficients were fairly consistent across seasons for each strain and lacked a clear correlation with incidence in prior seasons , consistent with experimental results showing substantial waning of immunity within a year ( 14 ) .

If the rate of import of seasonal CoV infections is higher , imports dampen the resonance and much stronger seasonality , with values between ε = 0 . 3 and 0 . 7 , is required to fit the observations ( Fig . 2 , top - right - and - center ridge ) . In this regime , seasonal variation in transmissibility modulates the size of micro - outbreaks triggered by imported cases in a mostly immune population .

Charge distribution

The copyright holder for this preprint ( which was not peer - reviewed ) is the . https : / / doi . org / 10 . 1101 / 2020 . 03 . 06 . 977876 doi : bioRxiv preprint The copyright holder for this preprint ( which was not peer - reviewed ) is the . https : / / doi . org / 10 . 1101 / 2020 . 03 . 06 . 977876 doi : bioRxiv preprint binding pocket on HCoV - OC43 N - NTD . In electrostatic surface potential panels , blue denotes 317 positive charge potential , while red indicates negative charge potential . The potential 318 distribution was calculated by Pymol . The values range from - 5 kT ( red ) to 0 ( white ) and to + 5 319 kT , where k is the Boltzmann constant and T is the temperature . 320 author / funder . All rights reserved . No reuse allowed without permission .

Head nurses of wards took charge of requisition , storage and distribution of consumables , and communicated with the Nursing Department and the Materials Department every day for timely 10 supplies . Lists of detailed requirements and standards for various protection equipment formulated by the Infection Control Department were delivered to head nurses of every ward , which were used to ensure that the donated equipment satisfied protection standards .

The copyright holder for this preprint ( which was not peer - reviewed ) is the . https : / / doi . org / 10 . 1101 / 2020 . 03 . 06 . 977876 doi : bioRxiv preprint The copyright holder for this preprint ( which was not peer - reviewed ) is the . https : / / doi . org / 10 . 1101 / 2020 . 03 . 06 . 977876 doi : bioRxiv preprint to b7 , the 310 helix is labeled with h1 ; C . Topological style illustration of SARS - CoV - 2 N - NTD 288 structure ; D . Electrostatic surface of the SARS - CoV - 2 N - NTD . Blue denotes positive charge 289 potential , while red indicates negative charge potential . The potential distribution was calculated 290 by Pymol . The values range from - 5 kT ( red ) to 0 ( white ) and to + 5 kT , where k is the Boltzmann 291 constant and T is the temperature . 292 author / funder . All rights reserved . No reuse allowed without permission .

To examine the influence of a charged lipid on the wt - E channel properties , current recordings in a negatively charged DPhPS membrane were performed . The histograms of the wt - E peptide channel conductance in pure DPhPS membranes point to a single channel conductance of 0 . 1570 . 01 nS in 1 M KCl ( Fig . 5 ) . The comparison with Fig . 3A indicates that the host lipid not only determines the width of the conductance histograms but also the single channel conductance . Thus , the distribution of current jump amplitudes for the wt - E peptide in DPhPS charged membranes was much narrower than in neutral DPhPC membranes , suggesting that simultaneous multi - channel insertions were rare events when the peptide was reconstituted in DPhPS . But more important is the fact that the wt - E peptide channel conductance in a negatively charged lipid is less than half the value in a neutral membrane . This cannot be explained exclusively by the electrostatic interactions arising from the surface charge of the lipid membrane . The accumulation of ions near the pore entrance due to the membrane surface charge should give just the opposite effect , i . e . , greater channel conductance in DPhPS , as occurs in alamethicin ( Aguilella et al . , 2011 ) . Our results suggest that lipids are much more than inert scaffolds but they are functionally involved in the channel formation so that the observed dependence of wt - E channel conductance on the lipid type could be associated to the existence of different conformations in such a way that the aqueous pore in DPhPS membranes is narrower than in DPhPC membranes . Therefore , we can reasonably hypothesize that wt - E peptides induce permeabilization changes in membranes via the formation of protein - lipid pores , and lipid polar heads line totally or partially the pore wall together with several peptide monomers .

To examine the influence of a charged lipid on the wt - E channel properties , current recordings in a negatively charged DPhPS membrane were performed . The histograms of the wt - E peptide channel conductance in pure DPhPS membranes point to a single channel conductance of 0 . 15 ± 0 . 01 nS in 1 M KCl ( Fig . 5 ) . The comparison with Fig . 3A indicates that the host lipid not only determines the width of the conductance histograms but also the single channel conductance . Thus , the distribution of current jump amplitudes for the wt - E peptide in DPhPS charged membranes was much narrower than in neutral DPhPC membranes , suggesting that simultaneous multi - channel insertions were rare events when the peptide was reconstituted in DPhPS . But more important is the fact that the wt - E peptide channel conductance in a negatively charged lipid is less than half the value in a neutral membrane . This cannot be explained exclusively by the electrostatic interactions arising from the surface charge of the lipid membrane . The accumulation of ions near the pore entrance due the membrane surface charge should give just the opposite effect , i . e . greater channel conductance in DPhPS , as occurs in alamethicin ( Aguilella et al . , 2011 ) . Our results suggest that lipids are much more than inert scaffolds but they are functionally involved in the channel formation so that the observed dependence of wt - E channel conductance on the lipid type could be associated to the existence of different conformations in such a way that the aqueous pore in DPhPS membranes is narrower than in DPhPC membranes . Therefore , we can reasonably hypothesize that wt - E peptides induce permeabilization changes in membranes via the formation of protein - lipid pores , and lipid polar heads line totally or partially the pore wall together with several peptide monomers .

Adhesion to hydrophilic/phobic surfaces

Environmental survival to inform decontamination efforts for affected areas

Viral shedding

The dynamic pattern of viral shedding showed that most patients had intermittent virus shedding . Intriguingly , two patients had significant clinical improvement , but their viral nucleic - acid tests remained positive for a few days . As of March 17 , 2020 , the median duration of viral shedding was 31 days ( IQR , 27 - 34 days ) after symptom onset , and the longest duration of viral shedding was 57 days ( Figure 1A ) . The interval between first and last positive PCR assay results ( 4 to 22 days ) was extensively prolonged in patients with poor recovery .

The kinetics of SARS - CoV - 2 viral load have not yet been well characterised in large numbers of patients . Prolonged nasopharyngeal viral shedding was reported in a series of 18 patients from Singapore , with a median of 12 days between first and last positive samples and an initial large decline in viral load followed by a slower decay of residual low - level virus ( 8 ) . Similar kinetics were observed in 17 patients from China , where results were stratified by site tested ( nose / throat ) suggesting quantitatively greater and more prolonged shedding from the nose ( 9 ) . The kinetics of shedding in this case match this pattern , with more prolonged nasal shedding ( Figure ) .

For survivors , the median duration of viral shedding was 20 · 0 days ( IQR 17 · 0 - 24 · 0 ) from illness onset , but the virus was continuously detectable until death in nonsurvivors ( table 2 ; figure 1 ) . The shortest observed duration of viral shedding among survivors was 8 days , whereas the longest was 37 days . Among 29 patients who received lopinavir / ritonavir and were discharged , the median time from illness onset to initiation of antiviral treatment was 14 · 0 days ( IQR 10 · 0 - 17 · 0 ) and the median duration of viral shedding was 22 · 0 days ( 18 · 0 - 24 · 0 ) . The median duration of viral shedding was 19 · 0 days ( 17 · 0 - 22 · 0 ) in patients with severe disease status and 24 · 0 days ( 22 · 0 - 30 · 0 ) in patients with critical disease status .

Viral shedding in feces of pediatric patients 3

Whether these rigorous measures will result in the same victory as for SARS depends on the following questions that currently remain unanswered : ( i ) what is the proportion of subclinical disease ( asymptomatic or mildly symptomatic ) that would be missed by the case definition , hence not be identified and immediately isolated , and therefore contribute to community transmission ? ( ii ) On what day of illness is peak viral shedding , and how much viral shedding occurs before onset of symptoms ? ( iii ) Does viral shedding occur also beyond respiratory droplets , e . g . via fomites ? ( iv ) What is the true case fatality rate if the denominator also takes milder cases into account ?

Persistence and stability on nasal discharge

In a later study , Chan et al . ( 11 ) reported that viral RNA was detected in ≈5 % of stool samples submitted after week 7 of illness . The last positive sample was detected at week 11 of illness ; in that study , the respiratory samples ( tracheal aspirates , nasopharyngeal aspirates , throat swabs , throat washings , nasal swabs , and pooled throat and nasal swabs ) were detected at week 8 of illness . All those who shed virus for a prolonged period ( arbitrarily defined as > 6 weeks after onset of symptoms ) had samples collected while still critically ill . This study had a different cohort of patients compared to ours . Our patients had been discharged and had comparatively shorter and milder illnesses . Determining whether positive carriage persisted in these critically ill patients from the Chan et al . study after discharg would be beneficial .

Each camel showed minor clinical signs of disease , consisting of rhinorrhea ( Figure 1 , panel A ) and a mild elevation in body temperature at 2 dpi and 5 – 6 dpi ( Figure 1 , panel B ) ; no other clinical signs were observed . Rhinorrhea developed in all 3 camels beginning at 2 ( camels 1 and 3 ) and 5 ( camel 2 ) dpi , and persisted < 2 weeks . The nasal discharge drained from both nares and varied in character from serous to purulent ; minor hemorrhage was observed on some occasions , but may have been caused by trauma that occurred during collection of samples .

The initially described coronavirus strain 229E has been previously identified as the second most frequent cause of common cold after rhinoviruses in healthy adults . Predominant symptoms were acute rhinorrhea , nasal congestion , and / or sore throat [ 9 , 10 ] . Nasal discharge was the hallmark of all symptoms after inoculation of HuCoV - 229E to healthy volunteers , and further observed symptoms were malaise , headache , chills , and cough [ 6 ] .

All patients were treated in isolation and interferon atomization therapy . Most were given antibiotic or antiviral treatment . 6 ( 6 . 10 % ) children received nasal catheter oxygen therapy . Only 8 was transferred to ICU and given intensive care . 3 had serious complications . Till Feb . 20 , 60 ( 73 . 17 % ) patients had been discharged whereas others still in hospital . Two discharged . The mean hospital stay was 11 . 2 day .

Data are n ( % ) or mean ( SD ) , unless otherwise specified . SARS - CoV - 2 = severe acute respiratory syndrome coronavirus 2 . * Patients who have confirmed SARS - CoV - 2 infection or are highly suspected of being infected . Of the 20 patients who survived , eight patients were discharged . Three patients were still on invasive ventilation at 28 days , including one patient who was also on ECMO . One patient was on non - invasive ventilation , two were using high - flow nasal cannula , and six were using common nasal cannula .

Persistence and stability on sputum

It has been postulated that coronaviruses can be transmitted from contaminated dry surfaces including selfinoculation of mucous membranes of the nose , eyes or mouth [ 4 , 5 ] . One ml of sputum has been described to contain approximately 10 8 viral copies [ 6 ] . In a recent review all E - mail address : guenter . kampf @ uni - greifswald . de . available data on the persistence of coronaviruses on inanimate surfaces were summarized [ 7 ] . Most data were described with the endemic human coronavirus ( HCoV ) strain 229E which can remain infectious for 2 h - 9 d on different types of materials . A higher temperature such as 30 C or 40 C is associated with a shorter persistence of highly pathogenic Middle East Respiratory Syndrome ( MERS ) coronavirus . Few comparative data obtained with SARS - CoV indicate that persistence was longer with higher inocula . In addition it was shown at room temperature that HCoV - 229E persists better at 50 % relative humidity compared to 30 % [ 8 ] .

It has been postulated that coronaviruses can be transmitted from contaminated dry surfaces including selfinoculation of mucous membranes of the nose , eyes or mouth [ 4 , 5 ] . One ml of sputum has been described to contain approximately 10 8 viral copies [ 6 ] . In a recent review all E - mail address : guenter . kampf @ uni - greifswald . de . available data on the persistence of coronaviruses on inanimate surfaces were summarized [ 7 ] . Most data were described with the endemic human coronavirus ( HCoV ) strain 229E which can remain infectious for 2 h - 9 d on different types of materials . A higher temperature such as 30 C or 40 C is associated with a shorter persistence of highly pathogenic Middle East Respiratory Syndrome ( MERS ) coronavirus . Few comparative data obtained with SARS - CoV indicate that persistence was longer with higher inocula . In addition it was shown at room temperature that HCoV - 229E persists better at 50 % relative humidity compared to 30 % [ 8 ] .

Given the patient ' s recurrent fevers , other laboratory testing was performed , but results revealed no abnormalities , including RT - PCR testing for influenza A RNA , blood cultures , sputum cultures , sputum smear for acid fast bacillus , tumor markers ( CEA , AFP , PSA , CA125 , CA199 ) , blood biochemistry ( hepatic function , renal function , myocardial enzyme spectrum , thyroid function , glucose , fat , electrolyte ) , coagulation function , D - D dimer , routine urine and stool test , erythrocyte sedimentation rate , specific antibody of syphilis , human immunodeficiency virus , hepatitis B virus , hepatitis C virus and rheumatism . Chest CT images on day 2 showed evidence of pneumonia in the bilateral lower lobes . Given high temperature of 38 . 5°C persisted , methylprednisolone ( 40 mg qd , ivgtt ) was administrated on day 4 , and the patient was afebrile afterwards . After discontinuation of 3 days of methylprednisolone course , the patient was febrile again , the highest temperature was up to 38 . 9°C .

The first symptom of COVID - 19 patient A was sore throat , which developed on the day ( 28th January , illness day 1 ; Fig . 1A ) next to his contact with Taiwan No . 19 case patient . Productive cough and rhinorrhea appeared on illness day 3 . Fever up to 39 . 1 C and dyspnea developed on illness day 9 and 19 , respectively . On 16th February ( illness day 20 ) , this patient was admitted to CMUH and diagnosed of COVID - 19 , as confirmed by positive rRT - PCR tests of nasopharyngeal swab and sputum . Despite of relatively mild symptoms , this patient developed a prolonged and insidious disease course and had gastrointestinal symptoms , presented as upper abdominal dull pain and diarrhea during hospitalization . COVID - 19 patient B who also contacted with Taiwan No . 19 case patient on 27th January developed fever up to 38 C on 6 days later ( 3rd February , illness day 1 ; Fig . 1A ) and had dry cough as the primary manifestation that persisted until illness day 19 . During the third sampling on 24th February , the loads of SARS - CoV - 2 in the naso - oropharyngeal specimens from COVID - 19 patients A and B were both at an undetectable level . However , their sputum was still tested positive for SARS - CoV - 2 . Patient A ' s sputum remained positive rRT - PCR on illness day 28 , and then turned negative on illness day 35 . The oropharyngeal specimens rRT - PCR of patient B altered to detectable again on illness day 29 and 33 , and sputum rRT - PCR also remained positive at least until illness day 33 .

In the first instance , ascertain whether the patient is productive of sputum and able to clear sputum independently . If so , physiotherapy is not required for a sputum sample .

Persistence and stability on urine

On 7 February , off - label oral treatment with lopinavir / ritonavir ( 400 / 100 mg every 12 h ) was started after obtaining written informed consent [ 7 ] . SARS - CoV - 2 RNA in stools , nasopharyngeal and oropharyngeal swabs resulted positive at different time points , whereas urine , spermatic fluid , saliva , blood and conjunctival swabs were persistently negative ( Table ) .

As hypokalemia has an adverse effect on myocardial functions , in - time treatment is required for achieving good outcomes . However , the mechanism of hypokalemia in the present study hinted that it was challenging to achieve normokalemia in the presence of continuous renal loss of K + . This worry was proved by the elevated amount of urine K + measured in umol / gram of creatinine ( Figure 1 ) . The continual K + supplements had very little effect on the return of normokalemia when the urine loss of K + persisted in the severe cases . Interestingly , we found a noteworthy phenomenon in most patients who were cured of COVID - 19 . As shown in Figure 1 , when patients were inclined to recovery , they responded well to K + supplement treatment and steadily returned to normokalemia . This phenomenon indicated the end of urine loss of K + due to disordered RAS balance ; in other words , the ACE2 function began to return . This exciting finding suggested that return of normokalemia might be a reliable biomarker for monitoring ACE2 function .

There are a number of important questions still to be answered about the transmission dynamics . These include information about the infectivity during the incubation period ; the length of time and virus load during incubation and during the symptomatic period of virus shedding ; the incidence and infectiousness of asymptomatic cases , the risk of vertical transmission from mother to fetus35 , and other modes of transmission , such as from faeces , saliva and urine . There is some evidence that virus can be isolated from saliva36 and while the initial family cluster found no evidence of virus in stools or urine8 , it has since been detected in faeces by PCR in other patients30 , 37 , 38 and cultured in one patient , but there has been no evidence of virus in urine . The number of mild or asymptomatic cases has not been determined and relatively few cases have been recorded , but it is probable that current figures only see the tip of the iceberg , and many cases remain undiagnosed19 . They pose the greatest threat for increased virus spread27 . Information is also needed on the stability of the virus in the environment to better determine transmission risks , and especially the survival of the virus in aerosols and on hard surfaces under different conditions of temperature and humidity .

We tested samples collected from nine patients diagnosed with coronavirus disease 2019 ( COVID - 19 ) . The virus was found in urine , blood , anal swabs and oropharyngeal swabs . It is the first time for SARS - CoV - 2 found in urine , though no urinary irritation was found .

The pathogenic mechanism of SARS - CoV - 2 infection is still unclear . Current evidences indicate that it can invade multiple organ systems , including the respiratory system , digestive system and hematological system ( 3 ) ( 4 ) ( 5 ) . But whether it can invade the urinary system has not been reported . In our study , urine , blood , anal swab and oropharyngeal swab from 9 patients were retested by qRT - PCR . It is the first time for the SARS - CoV - 2 found in urine , though no urinary irritation was found . In addition , the quantity of the virus in the anal swab was closer to that of the oropharyngeal test , and those in the blood and urine were less than that of the oropharyngeal test , indicating that the " clearing effect " of the digestive tract on the virus is not obvious .

Persistence and stability on fecal matter

Persistence and stability on blood

During the development of mild disease into severe condition , the proportion of lymphocytes in the blood gradually decreased and maintained at a low level . By the time the disease began to improve , LYM % in the blood gradually rose to normal or nearly normal levels . Patients with persistently low levels of blood lymphocytes , especially less than 5 % , often had a poor prognosis .

We report the kinetics of the immune response in relation to clinical and virological features of a patient with mild - to - moderate coronavirus disease - 19 ( COVID - 19 ) requiring hospitalisation . Increased antibody - secreting cells , follicular T - helper cells , activated CD4 + and CD8 + T - cells and IgM / IgG SARS - CoV - 2 - binding antibodies were detected in blood , prior to symptomatic recovery . These immunological changes persisted for at least 7 days following full resolution of symptoms , indicating substantial anti - viral immunity in this non - severe COVID - 19 .

. CC - BY - NC - ND 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 . Fig . S1 . Noteworthily , the levels of blood lymphocytes , interleukin - 6 and procalcitonin have been recognized as indicators for disease severity and prognosis of COVID - 19 patients by us and others 5 , 9 . These three indexes were all normal and stable in this patient ( Fig . 2A - C ) , while the viral load persisted in a high level as the severe or critical ill patients did ( Fig . 2D ) .

Our knowledge of critically ill COVID - 19 in the late phase was quite limited . These cases highlight the presence of cytokine storm or pathogenic antibodies after three weeks of COVID - 19 onset ( Fig . 1 ) , which correlated with the disease severities . Monitoring inflammation and antibodies are important especially in patients infected by virus with persistent fever or abnormal coagulopathy . Expeditious control of the cytokine storm in early phase might be beneficial to selective patients , and blood purification therapy is effective in our limited experiences . The therapies are tolerable to most patients if performed with the assistance of nephrology specialists , in order to minimize risks of infection and bleeding . Although randomized trial data is lacking , we propose that multi - disciplinary efforts should be made to maximize the availability of blood purification therapy to proper patients .

The second pattern , observed in the patient classified as having critical disease and who died ( patient 3 ) , consists of a persistent and high viral excretion in the upper respiratory tract samples combined with positive virus detection by rtRT - PCR in other body fluids , including blood . By contrast with the previous pattern , this persistent high viral load suggests the ability of the SARS - CoV - 2 to evade the immune response . Indeed , we can speculate that , as shown during Middle East respiratory syndrome ( MERS ) and SARS coronavirus infections , 21 , 22 SARS - CoV - 2 might be able to inhibit the interferon signalling pathways , resulting in higher respiratory virus load , positive viraemia , and eventually poor prognosis , as for MERS - CoV . 23 , 24 Indeed , the 80 - year - old patient , unlike the other cases , had evidence of high viral replication in the respiratory tract and evidence for systemic virus dissemination beyond the respiratory tract , with virus detection in plasma and pleural effusion fluid . The impaired immune response might have facilitated the bacterial and fungal superinfections . Patients with similar , severe patterns ( sustained viral RNA in the respiratory tract and detection of SARS - CoV - 2 in the blood ) have also been reported in China . 6 As reported in previous studies , 12 , 25 severely ill patients are often older patient with comorbidities . Patient 3 was aged 80 years and might have had an impaired interferon pathway .

Persistence of virus on surfaces of different materials

A Medline search has been done on January 28 , 2020 . The following terms were used , always in combination with " coronavirus " , " TGEV " , " MHV " or " CCV " : survival surface ( 88 / 10 / 25 / 0 hits ) , persistence surface ( 47 / 1 / 32 / 0 hits ) , persistence hand ( 8 / 0 / 3 / 0 hits ) , survival hand ( 22 / 0 / 3 / 1 hits ) , survival skin ( 8 / 0 / 0 / 1 hits ) , persistence skin ( 1 / 0 / 0 / 1 hit ) , virucidal ( 23 / 3 / 3 / 1 hits ) , chemical inactivation ( 33 / 0 / 6 / 1 ) , suspension test ( 18 / 0 / 0 / 0 hits ) and carrier test ( 17 / 4 / 0 / 0 hits ) . Publications were included and results were extracted given they provided original data on coronaviruses on persistence ( surfaces , materials ) and inactivation by biocidal agents used for disinfection ( suspension tests , carrier tests , fumigation studies ) . Data with commercial products based on various different types of biocidal agents were excluded . Reviews were not included , but screened for any information within the scope of this review .

It has been postulated that coronaviruses can be transmitted from contaminated dry surfaces including selfinoculation of mucous membranes of the nose , eyes or mouth [ 4 , 5 ] . One ml of sputum has been described to contain approximately 10 8 viral copies [ 6 ] . In a recent review all E - mail address : guenter . kampf @ uni - greifswald . de . available data on the persistence of coronaviruses on inanimate surfaces were summarized [ 7 ] . Most data were described with the endemic human coronavirus ( HCoV ) strain 229E which can remain infectious for 2 h - 9 d on different types of materials . A higher temperature such as 30 C or 40 C is associated with a shorter persistence of highly pathogenic Middle East Respiratory Syndrome ( MERS ) coronavirus . Few comparative data obtained with SARS - CoV indicate that persistence was longer with higher inocula . In addition it was shown at room temperature that HCoV - 229E persists better at 50 % relative humidity compared to 30 % [ 8 ] .

It has been postulated that coronaviruses can be transmitted from contaminated dry surfaces including selfinoculation of mucous membranes of the nose , eyes or mouth [ 4 , 5 ] . One ml of sputum has been described to contain approximately 10 8 viral copies [ 6 ] . In a recent review all E - mail address : guenter . kampf @ uni - greifswald . de . available data on the persistence of coronaviruses on inanimate surfaces were summarized [ 7 ] . Most data were described with the endemic human coronavirus ( HCoV ) strain 229E which can remain infectious for 2 h - 9 d on different types of materials . A higher temperature such as 30 C or 40 C is associated with a shorter persistence of highly pathogenic Middle East Respiratory Syndrome ( MERS ) coronavirus . Few comparative data obtained with SARS - CoV indicate that persistence was longer with higher inocula . In addition it was shown at room temperature that HCoV - 229E persists better at 50 % relative humidity compared to 30 % [ 8 ] .

To date , no studies have addressed this issue specifically for the virus that causes COVID - 19 . A recent paper [ 66 ] has been cited as suggesting that silicone hydrogels are more likely to bind SARS - CoV - 2 than hydrogels [ 61 ] . However , this paper did not examine contact lens materials . The inanimate surfaces described in the paper [ 66 ] which most closely resemble contact lens materials were " plastic " and silicon rubber [ 64 , 81 , 82 ] . Neither of these materials appropriately represents the complex bulk and surface chemistry of contemporary contact lens materials [ 83 ] [ 84 ] [ 85 ] and cannot be used to reflect the likely binding of any pathogenic organism to modern day contact lenses . Soft lens material surfaces are far more hydrophilic than the plastic and silicon rubber surfaces examined in this manuscript and the binding of virus particles to substrates is complex , depending upon the charges and topographic characteristics of the virus and the characteristics of the surface in question [ 86 ] . The factors governing the binding of SARS - CoV - 2 to inanimate surfaces are so far unknown , but for a variety of waterborne viruses the major driving factors were electrostatic interactions ( charge driven ) , followed by hydrophobic interactions , with only minor impact from van der Waals interactions [ 86 ] .

As influenza viruses can be spread by hands , frequent hand cleansing is important . Alcohol based hand rubs are the gold standard for hand hygiene practice in healthcare settings . However , if hands are visibly soiled or had direct contact with body fluids they should be washed with liquid soap and running water then dried thoroughly with disposable paper towel ( refer to Appendices 1 . 1 - 1 . 4 , and Hand Hygiene Australia ( HHA ) ( http : / / www . hha . org . au / home / ) ) . Influenza viruses can persist on hard surfaces and remain viable for up to 24 hours on hard , non - porous surfaces . Infectious influenza virus can be transferred to hands from these surfaces for at least 2 - 8 hours after contamination of the surface . Virus transfer from porous materials to hands is less efficient due to rapid drying of the virus . 23 Increased environmental cleaning can help interrupt virus transmission . Hands should be cleaned with an alcohol - based hand rub or water and liquid soap solution before and after caring for a resident . • All staff must perform hand hygiene after every contact with an ill resident . • Even when hands are visibly clean . • After being in contact with contaminated surfaces . • Whether or not gloves are worn .

Persistence of virus on copper

• Only one study found 10 . Virus undetectable after 4 days on plastic and stainless steel , with shorter survival on cardboard and copper 10 ( 2 days and 4 hours , respectively ) ( Table 1 ) .

SARS - CoV - 2 was more stable on plastic and stainless steel than on copper and cardboard , and viable virus was detected up to 72 hours after application to these surfaces ( Figure 1A ) , although the virus titer was greatly reduced ( from 103 . 7 to 100 . 6 TCID50 per milliliter of medium after 72 hours on plastic and from 103 . 7 to 100 . 6 TCID50 per milliliter after 48 hours on stainless steel ) . The stability kinetics of SARS - CoV - 1 were similar ( from 103 . 4 to 100 . 7 TCID50 per milliliter after 72 hours on plastic and from 103 . 6 to 100 . 6 TCID50 per milliliter after 48 hours on stainless steel ) . On copper , no viable SARS - CoV - 2 was measured after 4 hours and no viable SARS - CoV - 1 was measured after 8 hours . On cardboard , no viable SARS - CoV - 2 was measured after 24 hours and no viable SARS - CoV - 1 was measured after 8 hours ( Figure 1A ) .

Vero E6 cells were infected with the new virus at a multiplicity of infection ( MOI ) of 0 . 5 and collected 48 h after infection . Cells were fixed with 2 . 5 % ( w / v ) glutaraldehyde and 1 % osmium tetroxide , dehydrated through a graded series of ethanol concentrations ( from 30 to 100 % ) and embedded with epoxy resin . Ultrathin sections ( 80 nm ) of embedded cells were prepared , deposited onto Formvar - coated copper grids ( 200 mesh ) , stained with uranyl acetate and lead citrate , and analysed using a 200 - kV Tecnai G2 electron microscope .

Monolayers of Vero E6 cells in 6 - well plates were incubated with SARS - CoV - 2 at a MOI of 0 . 001 for 2h at 37°C . The virus inoculum was then removed and replaced with DMEM medium supplemented with 2 % FBS containing LH ( 600 μg / mL ) or remdesivir ( 5 μM ) . At 48 h p . i . , the cells were fixed , dehydrated and embedded as described previously [ 18 ] . Ultrathin sections ( 70 nm ) of embedded cells were prepared , deposited onto Formvar - coated copper grids ( 200 mesh ) , stained with uranyl acetate and lead citrate , and then observed under JEM - 1400 PLUS transmission electron microscopy ( Japan Electron Optics Laboratory Co . , Ltd . , JEM - 1400 PLUS ) .

HCoV - 19 was most stable on plastic and stainless steel and viable virus could be detected up to 33 72 hours post application ( Figure 1A ) , though the virus titer was greatly reduced ( plastic from 10 3 . 7 to 34 10 0 . 6 TCID 50 / mL after 72 hours , stainless steel from 10 3 . 7 to 10 0 . 6 TCID 50 / mL after 48 hours ) . SARS - CoV - 35 1 had similar stability kinetics ( polypropylene from 10 3 . 4 to 10 0 . 7 TCID 50 / mL after 72 hours , stainless steel 36 from 10 3 . 6 to 10 0 . 6 TCID 50 / mL after 48 hours ) . No viable virus could be measured after 4 hours on copper 37 for HCoV - 19 and 8 hours for SARS - CoV - 1 , or after 24 hours on cardboard for HCoV - 19 and 8 hours for 38 SARS - CoV - 1 ( Figure 1A ) . This article is a US Government work . It is not subject to copyright under 17 USC 105 and is also made available author / funder , who has granted medRxiv a license to display the preprint in perpetuity .

Persistence of virus on stainless steel

• Only one study found 10 . Virus undetectable after 4 days on plastic and stainless steel , with shorter survival on cardboard and copper 10 ( 2 days and 4 hours , respectively ) ( Table 1 ) .

SARS - CoV - 2 was more stable on plastic and stainless steel than on copper and cardboard , and viable virus was detected up to 72 hours after application to these surfaces ( Figure 1A ) , although the virus titer was greatly reduced ( from 103 . 7 to 100 . 6 TCID50 per milliliter of medium after 72 hours on plastic and from 103 . 7 to 100 . 6 TCID50 per milliliter after 48 hours on stainless steel ) . The stability kinetics of SARS - CoV - 1 were similar ( from 103 . 4 to 100 . 7 TCID50 per milliliter after 72 hours on plastic and from 103 . 6 to 100 . 6 TCID50 per milliliter after 48 hours on stainless steel ) . On copper , no viable SARS - CoV - 2 was measured after 4 hours and no viable SARS - CoV - 1 was measured after 8 hours . On cardboard , no viable SARS - CoV - 2 was measured after 24 hours and no viable SARS - CoV - 1 was measured after 8 hours ( Figure 1A ) .

HCoV - 19 was most stable on plastic and stainless steel and viable virus could be detected up to 33 72 hours post application ( Figure 1A ) , though the virus titer was greatly reduced ( plastic from 10 3 . 7 to 34 10 0 . 6 TCID 50 / mL after 72 hours , stainless steel from 10 3 . 7 to 10 0 . 6 TCID 50 / mL after 48 hours ) . SARS - CoV - 35 1 had similar stability kinetics ( polypropylene from 10 3 . 4 to 10 0 . 7 TCID 50 / mL after 72 hours , stainless steel 36 from 10 3 . 6 to 10 0 . 6 TCID 50 / mL after 48 hours ) . No viable virus could be measured after 4 hours on copper 37 for HCoV - 19 and 8 hours for SARS - CoV - 1 , or after 24 hours on cardboard for HCoV - 19 and 8 hours for 38 SARS - CoV - 1 ( Figure 1A ) . This article is a US Government work . It is not subject to copyright under 17 USC 105 and is also made available author / funder , who has granted medRxiv a license to display the preprint in perpetuity .

The pathogen behind the current pandemic COVID - 19 derives its uniqueness from its molecular structure , discussed above . Even casual contact such as handshakes is sufficient to spread this deadly virus , and its epidemiology makes it hard to detect this infection at an early stage . Scientists have found that the pathogen remains on surfaces for a long time ranging from 3 hours in aerosols , 24 hours on cardboard and up to 3 days on plastic and stainless steel . Worse still , a large number of affected patients don ' t show symptoms for five or more days after exposure .

Both viruses had an exponential decay in virus titer across all experimental conditions , as indicated by a linear decrease in the log10TCID50 per liter of air or milliliter of medium over time ( Figure 1B ) . The half - lives of SARS - CoV - 2 and SARS - CoV - 1 were similar in aerosols , with median estimates of approximately 1 . 1 to 1 . 2 hours and 95 % credible intervals of 0 . 64 to 2 . 64 for SARS - CoV - 2 and 0 . 78 to 2 . 43 for SARS - CoV - 1 ( Figure 1C , and Table S1 in the Supplementary Appendix ) . The half - lives of the two viruses were also similar on copper . On cardboard , the half - life of SARS - CoV - 2 was longer than that of SARS - CoV - 1 . The longest viability of both viruses was on stainless steel and plastic ; the estimated median half - life of SARS - CoV - 2 was approximately 5 . 6 hours on stainless steel and 6 . 8 hours on plastic ( Figure 1C ) . Estimated differences in the half - lives of the two viruses were small except for those on cardboard ( Figure 1C ) . Individual replicate data were noticeably “ noisier ” ( i . e . , there was more variation in the experiment , resulting in a larger standard error ) for cardboard than for other surfaces ( Fig . S1 through S5 ) , so we advise caution in interpreting this result .

Persistence of virus on plastic

• Only one study found 10 . Virus undetectable after 4 days on plastic and stainless steel , with shorter survival on cardboard and copper 10 ( 2 days and 4 hours , respectively ) ( Table 1 ) .

The European Association of Urology guidelines contain no formal recommendations for fresh - frozen sections [ 3 ] . If a fresh - frozen specimen is absolutely necessary , the same protections for technical and medical staff must be applied . The main problem is persistence of SARS - CoV - 2 on inanimate surfaces such as cryostats ; the virus can survive temperatures of 20 C , the temperature used for cutting of fresh - frozen sections [ 4 ] . The virus remains on surfaces such as glass , metal , and plastic for up to 9 d , but can be inactivated by surface disinfection with ethanol ( 62 - 70 % ) , hydrogen peroxide 0 . 5 % , or sodium hypochlorite 0 . 1 % within 1 min . Other procedures are less efficient [ 5 ] . Therefore , it is extremely important to reduce fresh - frozen sections to a strict necessity basis , as cryostat disinfection takes a long time and many laboratories have only one cryostat available for fresh - frozen sections . Formalin significantly decreases the infectivity of the virus on day 1 , and a temperature of 56 C for 90 min , 67 C for 60 min , or 75 C for 30 min seem to render the virus noninfectious [ 3 ] . Paraffin for inclusion is mostly used at a temperature of 60 - 65 C for 120 min , so fixed and embedded tissue sections are most likely not infectious .

SARS - CoV - 2 was more stable on plastic and stainless steel than on copper and cardboard , and viable virus was detected up to 72 hours after application to these surfaces ( Figure 1A ) , although the virus titer was greatly reduced ( from 103 . 7 to 100 . 6 TCID50 per milliliter of medium after 72 hours on plastic and from 103 . 7 to 100 . 6 TCID50 per milliliter after 48 hours on stainless steel ) . The stability kinetics of SARS - CoV - 1 were similar ( from 103 . 4 to 100 . 7 TCID50 per milliliter after 72 hours on plastic and from 103 . 6 to 100 . 6 TCID50 per milliliter after 48 hours on stainless steel ) . On copper , no viable SARS - CoV - 2 was measured after 4 hours and no viable SARS - CoV - 1 was measured after 8 hours . On cardboard , no viable SARS - CoV - 2 was measured after 24 hours and no viable SARS - CoV - 1 was measured after 8 hours ( Figure 1A ) .

Infectious MERS - CoV is presumed to be found in droplets [ 59 ] but modelling has also suggested the possibility of airborne spread [ 45 ] . Virus remains viable for at least 48 h on plastic and steel surfaces , presumably underpinning the extensive contamination of air and surfaces in hospitals housing patients with MERS [ 66 , 67 , 68 , 69 , 70 , 71 ] . The virus appears sensitive to standard heat and chemical inactivation measures [ 72 , 73 ] .

The high mortality of Ebola coupled with the low inoculated dose required to initiate infection has led to a massive public health response in the United States , including screening by public health personnel of persons returned from epidemic countries in West Africa , development of specialized Ebola treatment centers , and training of thousands of HCP in the use of specialized PPE to minimize the risk of Ebola acquisition during patient care . Detailed recommendations on screening for Ebola among potentially infected returned travelers and management of patients with EVD are available on the CDC Web pages and in published articles . [ 65 ] [ 66 ] [ 67 ] Given the high volume of diarrhea and vomiting and the potential for fomite transmission , environmental control is a critical issue in the care of an Ebola - infected patient . Ebola virus may persist on steel and plastic surfaces for > 7 days . 68 , 69 It may also persist in liquid media for prolonged periods . Sodium hypochlorite ( 0 . 5 % and 1 % ) sterilized surfaces within 5 minutes , and 67 % ethanol sterilized carriers at 5 minutes . 68 A > 4 log10 reduction of an Ebola strain was achieved in 15 seconds using the following povidone iodine solutions : 4 % , 7 . 5 % , 10 % , and 3 . 2 % iodine with 78 % alcohol . 70 Consistent use of appropriate PPE with strict adherence to donning and doffing protocols is crucial to preventing acquisition of EVD during patient care . [ 65 ] [ 66 ] [ 67 ] A key component of reducing HCP risk is proper training in PPE donning and doffing with ongoing training to maintain competency .

Natural history of the virus

It is important to know the natural history of the disease as well as viral shedding in different stages of clinical illness . Viral shedding can vary from acute to convalescent to post - recovery phase as well . Host factors such as young children and immunocompromised population may also matter . Host infection following transmission of the virus is dependent on local mucosal immunity to natural immunity or crossprotection or vaccine induced immunity . Virus stability in community or hospital environment may vary and determines a high or low risk of transmission depending upon the significant exposure of the host . Animal models may also help in studying the pathogenesis of COVID - 19 .

Once the highly infectious and virulent nature of SARS became apparent , a process was rapidly implemented for identifying suspected patients . This process centered on the clinical findings of fever , cough , respiratory difficulties , and radiographic changes , including consolidation or findings of adult respiratory distress syndrome . It was also important to determine any history of close contact with someone infected by SARS or travel to SARS - affected regions ( appendix 1 ) . At the time , the nature of the virus was still unconfirmed , and no diagnostic tests were yet available .

If well tracked , early introductions of an emerging pathogen provide a unique opportunity to characterize its transmission , natural history , and the effectiveness of screening . The careful monitoring of cases and low probability of infection from the general community enables inferences , critical to modeling the course of the outbreak , that are difficult to make during a widely disseminated epidemic . In particular , we are able to make assumptions about when and where cases were likely infected that are impossible when the pathogen is widespread . Furthermore , during these early phases , uninfected and asymptomatic contacts are often closely tracked , providing critical information on transmission and natural history . Combined , this data on early introductions can be used to give insights into disease natural history 9 , transmission characteristics 10 , and the unseen burden of infection 11 .

Since there are too many parameters in our model , several limitations exist in this study . Firstly , we did not use the detailed data of the SARS - CoV - 2 to perform the estimation instead of using the data from literatures [ 3 ] . We simulated the natural history of the infection that the proportion of asymptomatic infection was 50 % , and the transmissibility of asymptomatic infection was half of that of symptomatic infection , which were different to those of MERS and SARS . It is known that the proportion of asymptomatic infection of MERS and SARS was lower than 10 % . Secondly , the parameters of population mobility were not from an accurate dataset . Thirdly , since there was no data of the initial prevalence of the virus in the seafood market , we assumed the initial value of 1 / 100 000 . This assumption might lead to the simulation been under - or over - estimated . In addition , since we did not consider the changing rate of the individual ' s activity ( such as wearing masks , increasing social distance , and not to travel to Wuhan City ) , the estimation of importation of the virus might not be correct . All these limitations will lead to the uncertainty of our results . Therefore , the accuracy and the validity of the estimation would be better if the models fit the first - hand data on the population mobility and the data on the natural history , the epidemiological characteristics , and the transmission mechanism of the virus .

The infection from the COVID - 19 virus produces flu symptoms in most cases , with an asymptomatic but potentially infecting phase . [ 5 ] . Regardless of that , the natural history of this disease can be modeled in principle as to SIR or SIRS compartmental models . For the present times , in which the pandemic is just starting , and before there is evidence supporting the possibility of reinfection , we assume a SIR model to describe the dynamics of the local spreading for every country . Then , at the early stages , it can be approximated by the linear differential equation :

Shedding the virus from an infected person

In this effort to evacuate 126 people from Wuhan to Frankfurt , a symptom - based screening process was ineffective in detecting SARS - CoV - 2 infection in 2 persons who later were found to have evidence of SARS - CoV - 2 in a throat swab . We discovered that shedding of potentially infectious virus may occur in persons who have no fever and no signs or only minor signs of infection .

The significance of mass gatherings to disease transmission is directly linked to the efficiency of transmission expressed in epidemiologic terms as the basic reproduction number or R 0 . The most recent analysis of 425 cases at the epicenter of COVID - 19 crisis in Wuhan indicate an R 0 of 2 . 2 . This indirectly means that the number affected will double within the incubation period . Subsumed in the calculation of R 0 are both the incubation period of the illness and the viral shedding that enables excretion of the virus from the infected to non - infected . Such high rates of transmission are made possible by high titers of virus in the oropharynx early in the course of the disease at a time of minimal symptoms [ 8 ] . As with other coronoviruses , asymptomatic infected persons may also transmit the infection [ 9 , 10 ] .

In an analysis of the first 425 confirmed cases of infection , 73 % of cases with illness onset between 12 and 22 January reported no exposure to either a wet market or another person with symptoms of a respiratory illness [ 2 ] . The lack of reported exposure to another ill person could be attributed to lack of awareness or recall bias , but China ’ s health minister publicly warned that pre - symptomatic transmission could be occurring [ 6 ] . Determining the extent to which asymptomatic or pre - symptomatic transmission might be occurring is an urgent priority , because it has direct implications for public health and hospital infection control . Data on viral shedding dynamics could help in assessing duration of infectiousness . For severe acute respiratory syndrome - related coronavirus ( SARS - CoV ) , infectivity peaked at around 10 days after illness onset [ 7 ] , consistent with the peak in viral load at around that time [ 8 ] . This allowed control of the SARS epidemic through prompt detection of cases and strict isolation . For influenza virus infections , virus shedding is highest on the day of illness onset and relatively higher from shortly before symptom onset until a few days after onset [ 9 ] . To date , transmission patterns of 2019 - nCoV appear more similar to influenza , with contagiousness occurring around the time of symptom onset , rather than SARS .

From studies of viral shedding in patients with mild and more severe infections , shedding seems to be greatest during the early phase of disease ( Myoung - don Oh and Gabriel Leung , WHO Collaborating Centre for Infectious Disease Epidemiology and Control , School of Public Health , LKS Faculty of Medicine , The University of Hong Kong , Hong Kong , Special Administrative Region , China , personal communication ) . 8 , 9 The role , if any , of asymptomatic carriers in transmitting infection is not yet completely understood . 4 Presymptomatic infec tiousness is a concern ( Myoung - don Oh and Gabriel Leung , personal communication ) 8 , 9 and many countries are now using 1 - 2 days of symptom onset as the start day for contact identification .

‘ Isolation ’ is the separation of ill persons with contagious diseases from non - infected persons to protect non - infected persons , and usually occurs in hospital settings . An isolation room could also be equipped with negative pressure to reduce transmission via aerosols , but for large droplets like for SARS CoV , control was achieved without negative pressure rooms . Isolation of patients is particularly effective in interrupting transmission if early detection is possible before overt viral shedding . Given that influenza patients can already transmit before clinical symptoms set it , isolation is often too late to be sufficiently effective to halt transmission and control an influenza pandemic . However , for SARS CoV the incubation time is longer than for influenza ( about 5 versus 2 days ) , 3 and viral shedding was highest once the patient is truly sick . A longer incubation time allows for more time to identify cases and put them into isolation . The incubation time of the 2019 - nCoV also has a median of 5 days , 4 however , at this stage , it remains unknown when viral shedding and transmissibility peaks and how frequently pre - symptomatic cases result in secondary cases .

Implementation of diagnostics to improve clinical processes

Once the highly infectious and virulent nature of SARS became apparent , a process was rapidly implemented for identifying suspected patients . This process centered on the clinical findings of fever , cough , respiratory difficulties , and radiographic changes , including consolidation or findings of adult respiratory distress syndrome . It was also important to determine any history of close contact with someone infected by SARS or travel to SARS - affected regions ( appendix 1 ) . At the time , the nature of the virus was still unconfirmed , and no diagnostic tests were yet available .

Being able to reliably identify SARS - CoV - 2 and distinguish it from other similar pathogens is important to contain its spread . The time of processing samples and the availability of reliable diagnostic tests is a challenge during an outbreak . Developing innovative diagnostic tools that target the genome to improve the identification of pathogens , can help reduce health costs and 330 time to identify the infection , instead of using unsuitable treatments or testing .

Consequently , the 2019 - nCoV outbreak has led to implementation of extraordinary public health measures to reduce further spread of the virus within China and elsewhere . Although WHO has not recommended any international travelling restrictions so far , 15 the local government in Wuhan announced on Jan 23 , 2020 , the suspension of public transportation , with closure of airports , railway stations , and highways in the city , to prevent further disease transmission . 16 Further efforts in travel restriction might follow . Active surveillance for new cases and close monitoring of their contacts are being implemented . To improve detection efficiency , front - line clinics , apart from local centres for disease control and prevention , should be armed with validated point - of - care diagnostic kits .

is the ( which was not peer - reviewed ) The copyright holder for this preprint . https : / / doi . org / 10 . 1101 / 2020 . 03 . 16 . 20037036 doi : medRxiv preprint diagnostic tests in order to improve the accuracy and speed of clinical diagnosis and enhance reporting rates .

In response to the epidemic , to identify suspected cases from common fever patients and reduce the hospital acquired infection , the Nursing Department and the Information Department improved the information pre - screening triage process . Patients attending the clinic scanned the two - dimensional code with their mobile phones for online pre - screening and triage , and filled in personal information , epidemiological history , and fever - related symptoms . After submission , the system would automatically prompt patients to enter fever clinic area A ( for common fever ) or fever clinic area B ( for suspected cases ) for treatment . This process improvement is simple and convenient to operate , and is conducive to reducing the occurrence of cross infection in the hospital .

Implementation of products to improve clinical processes

In response to the epidemic , to identify suspected cases from common fever patients and reduce the hospital acquired infection , the Nursing Department and the Information Department improved the information pre - screening triage process . Patients attending the clinic scanned the two - dimensional code with their mobile phones for online pre - screening and triage , and filled in personal information , epidemiological history , and fever - related symptoms . After submission , the system would automatically prompt patients to enter fever clinic area A ( for common fever ) or fever clinic area B ( for suspected cases ) for treatment . This process improvement is simple and convenient to operate , and is conducive to reducing the occurrence of cross infection in the hospital .

During the outbreak and epidemic of novel coronavirus pneumonia , anesthesiologists are not only the high - risk group of secondary infection , but also undertake tasks to initiate clinical research so that the regular pattern of disease could be summarized , which will product clinical evidences for clinical decision - making and optimization of anesthesia therapy as soon as possible . The clinical research evidences of anaesthesia are of great importance for improving the prevention and control strategy of infectious diseases and implementing relevant measures effectively . The recommendations from the epidemiological perspective are provided on how to conduct clinical research on anesthesiology during epidemic of the novel coronavirus pneumonia in the present paper : ( 1 ) The case report and case series research should be initiated promptly once the infectious cases treated in anesthesia department are diagnosed ; ( 2 ) To focus on need of evidence of decision - making of diagnosis and treatment , to summarize general rules timely and to promote the rapidly production of evidence ; ( 3 ) To establish a special cohort of novel coronavirus pneumonia so that more prognosis studies could be carried out ; ( 4 ) To explore the risk factors which result in hospital infection among medical staffs so that hospital infection could be controlled . The purpose of this study is to provide clinicians with methodological suggestions on how to carry out high - quality clinical research in the epidemic period of infectious diseases , and to close the gap between clinical and public health .

Another solution would be to improve on current vaccine production technologies ( egg - derived vaccines ) . Several pharmaceutical companies have embarked on projects for the development of cell - culture vaccines , as this could help overcome current vaccine production bottlenecks , limited availability of specific pathogen - free egg supply and time constraints . Furthermore , it would improve possibilities of up - scaling vaccine production capacities in face of a pandemic . Influenza virus can be adapted to grow on a variety of mammalian cell lines , including Vero , PER . C - 6 , and Madin - Darby canine kidney ( MDCK ) cell lines . Crucell ( Holland ) is partnering with Sanofi - Pasteur ( France ) to develop largescale cell - culture methods using human PER . C - 6 cells for both a pandemic vaccine and the annual influenza vaccine . Clinical trials are expected to start in the summer of 2005 .

In this study , the clinical manifestations , epidemiology , laboratory test results , and chest CT findings of 131 confirmed COVID - 19 patients were summarized and investigated , to improve the understanding of the disease , thereby achieving effective control of the epidemic through early diagnosis , prompt treatment , and quarantine , beneficial to the timely implementation of measures for monitoring public health .

During prevention and control of the epidemic , the Nursing Department , as one of the main functional departments of the hospital , has broken the conventional operation mode and implemented contingency management strategies based on clinical practice , ensuring timely , orderly , safe , and efficient centralized rescue . After several tests of SARS , H1N1 , H7N9 , Ebola in West Africa , and COVID - 19 , a set of perfect emergency system should be established to deal with public health emergencies based on contingency management strategies in the future . Prospective training and exercises , establishing a talent echelon for all kinds of public events based on the current comprehensive emergency echelon mainly composed of head nurses , and standardizing processes in new hospital areas and new wards should be considered . Contingency plans should be regularly rehearsed and continuously improved .

Disease models, including animal models for infection, disease and transmission

Establishing an animal model of infection and disease pathogenesis is imperative for understanding several essential elements of viral disease in the infected host , including host tropism , immune responses , and modes of transmission , as well as for the progression of therapeutic development . Having an animal model that can recapitulate human disease is essential for vaccine and therapeutic development as well as testing . For a potential animal model to be susceptible to infection , the virus must be able to 1 . ) gain entry into host cells ; 2 . ) overcome the host ' s antiviral responses ; and 3 . ) disseminate virus following infection to allow infection of other neighbouring cells and tissues . It is also of importance for the model to be able to recapitulate human disease and viral transmission modes . When evaluating the ability of an animal to be infected by a virus and serve as a model , viral shedding , clinical disease , and seroconversion should be determined . The past animal models for SARS - CoV and MERS - CoV were not universal due to the expression of the virus - specific cellular receptors for entry [ 63 ] . As SARS - CoV and MERS - CoV do not share a cellular receptor , they do not share the same host range and susceptibility , which includes research animal models [ 64 ] . Cynomolgus macaques , ferrets , and cats were some of the first animals to be determined susceptible to SARS - CoV [ 65 , 66 ] . The advantage of ferrets is that they are a smaller animal compared to non - human primates and also are able to recapitulate some of the clinical symptoms and transmission kinetics of human respiratory viruses including coughing , sneezing , fever , and weight loss [ 67 ] . Although mice can be infected with SARS - CoV , as shown by recovery of vRNA and the elicitation of neutralizing antibodies , infection does not cause severe disease [ 68 ] . However , SARS - CoV could be passaged in mice ( 15 times ) for the establishment of a model with clinical features [ 69 ] . After the identification of MERS - CoV , it was quickly determined that typical research animal models were not susceptible to the virus including mice , Syrian hamsters , and ferrets . Larger non - human primate models , such as Rhesus macaques and common marmoset were determined susceptible . To make use of small animal models , transgenic mice have been engineered for MERS - CoV susceptibility through expression of the human DPP4 receptor [ 70 ] . Other attempts at other mouse model developments were not successful , including an immunocompromised 129 / SATA1 - / - 1 mouse [ 63 ] . Having an understanding of the animal models and model development previously utilized for the other coronaviruses of interest will aid in the development of a model for 2019 - nCoV . As is necessary , elucidation of the receptor will help guide in development , and creating a clinical picture of the acute symptoms in humans will be essential for vaccine and antiviral evaluation .

Animal models of infectious diseases serve two key purposes : 1 ) to characterize viral pathogenesis , and 2 ) to evaluate anti - viral agents and vaccines . In the context of infectious diseases for which it is not feasible or ethical to perform clinical trials , animal studies play an additional role . Under the FDA ' s Animal Efficacy Rule ( " Animal Rule " ) therapeutics against rare , emerging , or virulent agents can achieve regulatory approval provided efficacy is demonstrated in two animal models ( one of which must be a non - rodent species ) that display clinical illness representative of human disease ( 46 ) . The ideal animal model is permissive to infection and reproduces the clinical course and pathology observed in humans . An algorithm for the development of animal models is presented in Figure 1 . Small animal models offer several advantages over NHP ' s including availability of animals and species specific reagents , ease of handling , reduced cost , and the ability to use sufficient numbers for statistical analysis . Especially with coronaviruses , rodents vary in susceptibility and may be semi - permissive to infection and refractory to clinical disease ( 47 ) , even so , they can be used to screen countermeasures ( 48 ) ( 49 ) ( 50 ) ( 51 ) . Thus , to generate a rodent model that displays clinical disease it may be necessary to adapt the virus to enhance virulence for the rodent host or generate transgenic animals . Pathogenesis in these models should be fully characterized because the disease mechanism of an adapted virus or in a transgenic animal may be different from that in the natural host ( Figure 1 ) .

Establishment of effective animal models is important for evaluating the efficacy of candidate vaccines against MERS - CoV . Unlike SARS - CoV , which can infect a variety of animals , including non - human primates , and small animal models such as ferrets , hamsters and mice [ 76 , 78 , 116 – 118 ] , the animal species that could be infected by MERS - CoV are very limited . It has been shown that MERS - CoV is unable to replicate in hamsters , ferrets and mice [ 119 – 122 ] , significantly restricting the efficacy evaluation of MERS vaccines in small animal models . Although rhesus macaques can be infected by MERS - CoV , with the infected animals showing clinical signs of disease and virus replication [ 123 , 124 ] , the high cost of non - human primate models would prevent the majority of researchers from using this animal model . Therefore , the development of effective small animal models for MERS - CoV infection is urgently needed [ 125 ] . It was recently reported that mice transduced with adenoviral vectors expressing MERS - CoV ’ s receptor DPP4 were susceptible to MERS - CoV infection , with the infected mice developing pneumonia and clinical disease accompanied by histopathological changes [ 126 ] . Nevertheless , a better transgenic mouse model with the gene encoding human DPP4 integrated into its genome has been developed by several laboratories [ 127 ] .

Animal models of infectious diseases serve two key purposes : 1 ) to characterize viral pathogenesis , and 2 ) to evaluate anti - viral agents and vaccines . In the context of infectious diseases for which it is not feasible or ethical to perform clinical trials , animal studies play an additional role . Under the FDA ' s Animal Efficacy Rule ( " Animal Rule " ) therapeutics against rare , emerging , or virulent agents can achieve regulatory approval provided efficacy is demonstrated in two animal models ( one of which must be a non - rodent species ) that display clinical illness representative of human disease ( FDA , 2014 ) . The ideal animal model is permissive to infection and reproduces the clinical course and pathology observed in humans . An algorithm for the development of animal models is presented in Fig . 1 . Small animal models offer several advantages over NHPs including availability of animals and species specific reagents , ease of handling , reduced cost , and the ability to use sufficient numbers for statistical analysis . Especially with coronaviruses , rodents vary in susceptibility and may be semi - permissive to infection and refractory to clinical disease , even so , they can be used to screen countermeasures Bisht et al . , 2004 ; Buchholz et al . , 2004 ; . Thus , to generate a rodent model that displays clinical disease it may be necessary to adapt the virus to enhance virulence for the rodent host or generate transgenic animals . Pathogenesis in these models should be fully characterized because the disease mechanism of an adapted virus or in a transgenic animal may be different from that in the natural host ( Fig . 1 ) .

The continuing emergence of virulent human coronaviruses emphasizes the need for animal models for studying viral replication , pathogenesis and transmission . Thus far , this work has largely focused on SARS - CoV infection . SARS - CoV replication has been reported in mice , hamsters , cats , civets and primates , and the most severe disease symptoms have been observed in aged animals . MERS - CoV has a broad host range in vitro55 , which provides some promise for the development of a small animal model for human disease in the near future . However , a functional small animal model for MERS - CoV replication or pathogenesis has not yet been characterized or reported ; the possibility of ongoing selection in the receptor - binding sequence in the spike protein or other sequences that are important for host specificity might contribute to this limitation . Inoculation of rhesus macaques with 7 × 106 half - maximal tissue culture infectious doses ( TCID50 ) of a MERS - CoV isolate results in transient mild - to - moderate clinical disease , which includes localized or widespread pneumonia56 ; however , the lack of a small animal model is clearly a major obstacle to furthering our understanding of viral pathogenesis and to testing vaccines and therapeutics .

Tools to monitor phenotypic change and potential adaptation of the virus

Changes in genome sequence may herald alterations to virus transmissibility , replication , persistence , lethality or response to future drugs . If we have prior knowledge of the impact of genetic changes because of thorough characterization studies , we can closely monitor the genomic regions and better understand any changes in transmission or disease patterns as they occur . Genetic mutations noted during the largest of human outbreaks , Jeddah - 2014 , did not impart any major replicative or immunomodulatory changes when compared to earlier viral variants in vitro [ 156 , 176 ] . However , we understand very little of the phenotypic outcomes that result from subtle genetic change in MERS - CoV genomes . To date no clinical relevance or obvious in vivo changes to viral replication , shedding or transmission has been reported or attributed to mutations or to new recombinant viruses [ 156 ] . But vigilance and larger , more contemporary and in vivo studies are needed .

As an alternative to evaluating multiple animal species , another strategy to generate an animal model with clinical disease is to adapt the virus to the new host by serial passage ( Figure 1 ) . To generate a mouse model with associated mortality , the SARS - CoV Urbani strain was serially passaged in the lungs of young BALB / c mice ( 41 ) . After 15 passages , a single virus clone was isolated that caused 100 % mortality in young ( 6 - 8 week old ) , 4 week old , and aged BALB / c mice . This virus was designated MA15 . Severe disease was the result of an overwhelming viral infection with significantly higher titers and prolonged replication in the lungs accompanied by extensive damage to bronchiolar and alveolar epithelial cells ( 41 ) . MA15 was also capable of extrapulmonary spread as evident by viremia , and recovery of virus from spleen , liver , and brain tissues . Sequence analysis and reverse genetics studies identified 6 amino acid mutations associated with the lethal phenotype . These mutations included 3 changes in ORF1a , and single changes in ORF1b , the M protein , and the S protein .

During production of the recSARS - CoV P1 stock , it was apparent that the plaque phenotype of recSARS - CoV and SARS - CoV HKU - 39849 is different compared to SARS - CoV Frankfurt - 1 . This is illustrated in Figure 2C , which shows the plaque phenotype of recSARS - CoV , SARS - CoV Frankfurt - 1 , SARS - CoV HKU - 39849 obtained from J . S . Peiris and SARS - CoV HKU - 39849 that was recovered from the RNA used to produce the recSARS - CoV cDNAs . Clearly , the HKU - 39849 lineage has a smaller plaque phenotype and replicates to lower titres compared to the SARS - CoV Frankfurt - 1 virus . As shown in Table 1 , there are a number of nucleotide changes between the genomes of recSARS - CoV and SARS - CoV Frankfurt - 1 . In addition , it is known that the SARS - CoV Frankfurt - 1 virus propagated in the laboratory contains a 45 nucleotide in - frame deletion ( 27670 – 27714 ) in ORF7b [ 8 ] , [ 19 ] . These changes may explain the different plaque sizes between the two viruses and further studies are needed to investigate this issue .

On the other hand , it is known that host tRNA pools undergo reprogramming upon viral infection of HIV - 1 , vaccinia virus , and influenza A virus 17 , 52 . In this context , differences in codon usage between early and late viral genes have been previously reported , but the directionality of such changes remained unclear 10 , 53 . Based on our concept of tissue - specific adaptation , we therefore validate that early replication - related proteins are better adapted to the tissue of infection . Upon infection , we then unveil that changes in tRNA abundance switch the adaptation towards the expression of late structural proteins , confirming a general trend that had previously only been observed in HIV - 1 17 .

2019 - nCoV is an emerging infectious disease with rapidly evolving features , the full scope of which will be defined over time . Prior outbreaks of coronaviruses can help inform needed actions in the short term to assist with both treatment of individual patients and prevention of global disease spread . This adaptation of the Identify - Isolate - Inform Tool serves as a resource for healthcare workers who need to make clear , rapid assessments when confronted with potential patients . The concise nature of the 2019 - nCoV 3I Tool allows for the rapid and effective management of a novel disease by healthcare providers .

Studies to monitor phenotypic change and potential adaptation of the virus

Changes in genome sequence may herald alterations to virus transmissibility , replication , persistence , lethality or response to future drugs . If we have prior knowledge of the impact of genetic changes because of thorough characterization studies , we can closely monitor the genomic regions and better understand any changes in transmission or disease patterns as they occur . Genetic mutations noted during the largest of human outbreaks , Jeddah - 2014 , did not impart any major replicative or immunomodulatory changes when compared to earlier viral variants in vitro [ 156 , 176 ] . However , we understand very little of the phenotypic outcomes that result from subtle genetic change in MERS - CoV genomes . To date no clinical relevance or obvious in vivo changes to viral replication , shedding or transmission has been reported or attributed to mutations or to new recombinant viruses [ 156 ] . But vigilance and larger , more contemporary and in vivo studies are needed .

As an alternative to evaluating multiple animal species , another strategy to generate an animal model with clinical disease is to adapt the virus to the new host by serial passage ( Figure 1 ) . To generate a mouse model with associated mortality , the SARS - CoV Urbani strain was serially passaged in the lungs of young BALB / c mice ( 41 ) . After 15 passages , a single virus clone was isolated that caused 100 % mortality in young ( 6 - 8 week old ) , 4 week old , and aged BALB / c mice . This virus was designated MA15 . Severe disease was the result of an overwhelming viral infection with significantly higher titers and prolonged replication in the lungs accompanied by extensive damage to bronchiolar and alveolar epithelial cells ( 41 ) . MA15 was also capable of extrapulmonary spread as evident by viremia , and recovery of virus from spleen , liver , and brain tissues . Sequence analysis and reverse genetics studies identified 6 amino acid mutations associated with the lethal phenotype . These mutations included 3 changes in ORF1a , and single changes in ORF1b , the M protein , and the S protein .

During production of the recSARS - CoV P1 stock , it was apparent that the plaque phenotype of recSARS - CoV and SARS - CoV HKU - 39849 is different compared to SARS - CoV Frankfurt - 1 . This is illustrated in Figure 2C , which shows the plaque phenotype of recSARS - CoV , SARS - CoV Frankfurt - 1 , SARS - CoV HKU - 39849 obtained from J . S . Peiris and SARS - CoV HKU - 39849 that was recovered from the RNA used to produce the recSARS - CoV cDNAs . Clearly , the HKU - 39849 lineage has a smaller plaque phenotype and replicates to lower titres compared to the SARS - CoV Frankfurt - 1 virus . As shown in Table 1 , there are a number of nucleotide changes between the genomes of recSARS - CoV and SARS - CoV Frankfurt - 1 . In addition , it is known that the SARS - CoV Frankfurt - 1 virus propagated in the laboratory contains a 45 nucleotide in - frame deletion ( 27670 – 27714 ) in ORF7b [ 8 ] , [ 19 ] . These changes may explain the different plaque sizes between the two viruses and further studies are needed to investigate this issue .

Like most other members of the coronavirus family , Betacoronavirus exhibit high species specificity , but subtle genetic changes can significantly alter their tissue tropism , host range , and pathogenicity . A striking example of the adaptability of these viruses is the emergence of deadly zoonotic diseases in human history caused by SARS - CoV [ 37 ] and MERS - CoV [ 38 ] . In both viruses , bats served as the natural reservoir and humans were the terminal host , with the palm civet and dromedary camel the intermediary host for SARS - CoV and MERS - CoV , respectively [ 39 , 40 ] . Intermediate hosts clearly play a critical role in cross species transmission as they can facilitate increased contact between a virus and a new host and enable further adaptation necessary for an effective replication in the new host [ 41 ] . Because of the pandemic potential of SARS - CoV - 2 , careful surveillance is immensely important to monitor its future host adaptation , viral evolution , infectivity , transmissibility , and pathogenicity .

The blood specimens used in this study were collected for a larger study where residents of a college resident community in an Eastern university were monitored prospectively to identify acute respiratory infection ( ARI ) cases using questionnaires and RT - qPCR , so as to characterize contagious phenotypes including social connections , built environment , and immunologic phenotypes 8 . From among de - identified blood specimens for which future research use authorization was obtained , five specimens that showed high IgG reactivity against human coronaviruses in the larger study were chosen for validation of the coronavirus antigen microarray .

Immune response and immunity

Kidney transplant patients , due to immunosuppression , the immune response have been altered and particularly the T - cell immune response .

The exact reason for why children are less severely affected is still unclear . One possible explanation is related to children ' s immature immune system . Their adaptive immunity is less developed to mount an inflammatory response during immune dysregulation phase induced by viral infection . 23 Relatively stronger humoral responses in children may also contribute to this phenomenon . Innate immunity is able to react more rapidly in response to pathogen invasion than adaptive immunity . author / funder , who has granted medRxiv a license to display the preprint in perpetuity .

Potential anti - coronavirus therapies can be divided into two categories depending on the target , one is acting on the human immune system or human cells , and the other is on coronavirus itself . In terms of the human immune system , the innate immune system response plays an important role in controlling the replication and infection of coronavirus , and interferon is expected to enhance the immune response 11 .

Potential anti - coronavirus therapies can be divided into two categories depending on the target , one is acting on the human immune system or human cells , and the other is on coronavirus itself . In terms of the human immune system , the innate immune system response plays an important role in controlling the replication and infection of coronavirus , and interferon is expected to enhance the immune response 11 .

The copyright holder for this preprint . https : / / doi . org / 10 . 1101 / 2020 . 02 . 03 . 20020206 doi : medRxiv preprint production of acute respiratory distress syndrome - associated cytokines ( 7 ) . ACE2 is also related to adaptive immune responses ( 8 ) . In this current study , the GSEA analysis showed that the high expression of ACE2 was related to innate immune response , acquired immune response , B cell regulatory immunity and cytokine secretion , and enhanced the inflammatory response induced by IL - 1 , IL - 10 , IL - 6 , IL - 8 cytokines . We speculated that the immune system dysfunction involved in the high expression of . CC - BY - NC - ND 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 .

Effectiveness of movement control strategies to prevent secondary transmission in health care and community settings

For COVID - 19 , Infection Control committee should supervise on daily basis and identify the gaps and provide necessary resources and directions to minimize the transmission . Starting from entry in hospital premises , the movement control strategy must be defined to prevent secondary transmission in healthcare as well as in community settings . Optimum and effective use of PPE in designated areas will play a crucial role in reducing the risk of transmission in health care workers . 8 Behavioural and cultural factors must also be taken into an account as they influence the compliance . Quarantine facilities should be welldesigned and away from habitation . Isolation facilities with separate rooms and negative air pressure in case of suspected and confirmed COVID - 19 positive cases will substantially be useful for containment as well as protection of health workers . Personnel may be trained for DOs and DON ' Ts in quarantine facility .

Public health measures and precautions in health care settings are critical in controlling 2019 - nCoV . The present study may help prevent cross - infection in the operating room by means of implementing anesthesia and infection control management procedures for emergency procedures in patients with confirmed or suspected COVID 19 . Implementation of similar measures might be important and , it is hoped , successful in reducing the nosocomial transmission of 2019 - nCoV in the perioperative setting .

PHAC , 2010 ; Country : Canada Sponsor : Public Health Agency of Canada Scope : infection prevention and control guidance to healthcare workers in the management of patients with suspected or confirmed seasonal influenza Source Control , achieved through administrative and engineering measures , is the most effective way to prevent the transmission of infectious agents in all healthcare settings . The most effective way to prevent and control seasonal influenza is through immunization of both healthcare workers and patients .

Background Middle East respiratory syndrome coronavirus ( MERS - CoV ) is a novel coronavirus that causes a severe respiratory disease with high case fatality rate . Starting in March 2014 , a dramatic increase of cases has occurred in the Arabian Peninsula , many of which were acquired in health care settings . As of May 9 , 2014 , 536 laboratory - confirmed cases and 145 deaths have been reported globally . Methods Review of publicly available data about MERS - CoV health care – associated transmission . Results We identified 11 events of possible or confirmed health care – associated transmission with high morbidity and mortality , mainly among patients with comorbidities . Health care workers are also frequently affected ; however , they tend to have milder symptoms and better prognosis . Gaps in infection control were noted in all events . Currently , health care – associated outbreaks are playing a pivotal role in the evolution of the MERS - CoV epidemic in countries in the Arabian Peninsula . Conclusion There is a need to increase infection control capacity in affected areas and areas at increased risk of being affected to prevent transmission in health care settings . Vaccines and antiviral agents are urgently needed . Overall , our knowledge about the epidemiologic characteristics of MERS - CoV that impact health care transmission is very limited . As the MERS - CoV epidemic continues to evolve , issues concerning best infection control measures will arise , and studies to better define their effectiveness in real life are needed .

As the international community responds to SARS - CoV - 2 , public health authorities in humanitarian crises begin at a disadvantage to enact appropriate infection control to prevent transmission in healthcare settings , identify infectious cases , administer supportive care and novel treatments for the seriously ill , and trace contacts . These standard public health measures are particularly difficult to perform in humanitarian settings . For example , limited public health , laboratory , and primary care services represent a barrier to testing . Providing the limited healthcare worker cadre with appropriate training and personal protective equipment , and ensuring a continuous supply chain for such , is a challenge in all settings , exacerbated in complex humanitarian crises . Frequent displacement and limited contact information may prevent effective contact tracing . Finally , intractable structural challenges such as overcrowding limit the implementation of both quarantine of those exposed and isolation of those who are ill . Given these increased vulnerabilities , humanitarian crises should be viewed as a priority for national and international bodies that seek to combat this unfolding pandemic . Resources must be identified to protect healthcare workers , develop and deploy rapid testing , improve surveillance , and enact quarantine and isolation of contacts and cases .

Effectiveness of personal protective equipment (PPE) and its usefulness to reduce risk of transmission in health care and community settings

Hand rubs that are based on alcohol alone should not be used owing to their rapid evaporation and lack of residual effect . Consequently , hand rubs must be laced with agents such as chlorhexidine , octenidine or triclosan to achieve the needed effect . 41 After using an alcohol - based hand rub , the clinician must dry his or her hands thoroughly before putting on gloves , because any residual alcohol may increase the risk of glove perforation . 42 Personal protective equipment . Personal protective equipment , or PPE , is designed to protect the skin and mucous membranes of the eyes , nose and mouth from exposure to potentially infectious material . Recent experience with the SARS coronavirus has shown that vast numbers of health care workers acquired the infection in hospital settings , either as a result of inadequate barrier protection methods or the improper use of these methods . 29 This barrier protection equipment consists of protective eyewear , masks , gloves , face shields and protective overwear . We should note that general work clothes such as uniforms do not protect against a hazard and should not be considered PPE . We describe below the relevant aspects of PPE that pertain to protection against airborne hazards .

is the ( which was not peer - reviewed ) The copyright holder for this preprint . https : / / doi . org / 10 . 1101 / 2020 . 04 . 01 . 20050005 doi : medRxiv preprint Introduction : 47 The early medical response to the COVID - 19 pandemic in the United States has been highlighted health care workers has been described extensively 6 , 7 . The use of personal protective equipment 57 ( PPE ) by health care workers obtaining testing samples is critical to reduce transmission , but 58 there are shortages of such equipment in many hospitals 8 .

For COVID - 19 , Infection Control committee should supervise on daily basis and identify the gaps and provide necessary resources and directions to minimize the transmission . Starting from entry in hospital premises , the movement control strategy must be defined to prevent secondary transmission in healthcare as well as in community settings . Optimum and effective use of PPE in designated areas will play a crucial role in reducing the risk of transmission in health care workers . 8 Behavioural and cultural factors must also be taken into an account as they influence the compliance . Quarantine facilities should be welldesigned and away from habitation . Isolation facilities with separate rooms and negative air pressure in case of suspected and confirmed COVID - 19 positive cases will substantially be useful for containment as well as protection of health workers . Personnel may be trained for DOs and DON ' Ts in quarantine facility .

Risk Assessment 6 was conducted in a situation where the number of imported cases and local transmission were identified . At this stage , the public health measures aimed to contain , if applicable , or mitigate transmission . This strategy will help to gain time for development and supply of personal protective equipment ( PPE ) and antivirals . It helps to reduce the burden of national health systems , and to increase the number of laboratory testing kits and increase capacity in the healthcare system . Communication of risk at this stage informs the stakeholders of public health measures , including case isolation , contact tracing , and PPE use . ECDC evaluations of the likelihood of importation to Europe were escalated from “ low ” to “ moderate , ” and likelihood of importation to neighboring Asian countries as “ high . ” Infection contracted in hospital was considered a “ low ” risk when appropriate infection prevention and control measures were in place [ 9 ] . The WHO evaluates risk in China as “ very high ” and the Asia region ’ s risk as “ high . ” The WHO proposed that super - spread events may occur with human - to - human transmission among family members , and healthcare workers [ 10 ] .

Host susceptibility level ( and the resulting community transmission rate ) could be reduced by additional preventive means , e . g . personal protective equipment ( PPE ) and washing hands . PPE shortages have been described in the most affected facilities . Hence , in a non - typicalCOVID - 19 ward , there is high probability HCW staff has insufficient protective gear ( e . g . masks ) , or they may lack awareness .

Role of the environment in transmission

Commissioned by the Minister of the Ministry of Health , Labour , and Welfare of Japan , we collected secondary transmission data with the aim of identifying high risk transmission settings . We show that closed environments contribute to secondary transmission of COVID - 19 and promote superspreading events . Closed environments are consistent with large - scale COVID - 19 transmission events such as that of the ski chalet - associated cluster in France and the church - and hospital - associated clusters in South Korea . Our findings are also consistent with the declining incidence of COVID - 19 cases in China , as gathering in closed environments was prohibited in the wake of the rapid spread of the disease . Reduction of unnecessary close contact in closed environments may help prevent large case clusters and superspreading events .

A novel coronavirus ( COVID - 19 ) was identified in Wuhan , Hubei Province , China , in December 2019 and has caused over 40 , 000 cases worldwide to date . Previous studies have supported an epidemiological hypothesis that cold and dry ( low absolute humidity ) environments facilitate the survival and spread of droplet - mediated viral diseases , and warm and humid ( high absolute humidity ) environments see attenuated viral transmission ( i . e . , influenza ) . However , the role of absolute humidity in transmission of COVID - 19 has not yet been established . Here , we examine province - level variability of the basic reproductive numbers of COVID - 19 across China and find that changes in weather alone ( i . e . , increase of temperature and humidity as spring and summer months arrive in the North Hemisphere ) will not necessarily lead to declines in COVID - 19 case counts without the implementation of extensive public health interventions .

Finally , as strategies for controlling this outbreak continue to evolve , it is critical to keep in mind that almost everything that we appreciate about urban environments , including their economic prowess , their ability to innovate , and their role in their inhabitants social and mental health , is predicated on network effects mediated by socioeconomic interactions . The ability to succeed against a fast emerging epidemic like COVID - 19 depends on preserving as much person - to - person connectivity ( e . g . , through technology ) , while stopping disease transmission .

Third , we cannot exclude the possible effects of some mixed factors , such as population flow and air pollution , which may affect the number of diseases and further deviate our results . In addition , we did not consider host factors , such as immunity or vulnerability , which play a role in disease transmission . A large number of studies have shown that viral activity that causes respiratory infectious diseases is sensitive to climate . Climatic factors may affect the survival and transmission of the virus in the environment , host susceptibility and exposure possibility . We found that 2019 - nCoV showed significant role in meteorological factors during the outbreak of the COVID - 19 in Hubei province , but we are also very clear , as scholars have agreed , meteorological parameters can only explain no more than 30 % changes in influenza activity ( Monamele et al . , 2017 ) , there are still many problems about 2019 - nCoV to be confirmed .

SARS has been convincingly demonstrated to be caused by a coronavirus [ 26 ] . Certain other characteristics have been ascertained from the previously known coronaviruses , 229E and OC43 , including their ability to survive after drying on inanimate surfaces in the hospital environment as well as differences in the viability of the virus at different conditions of temperature and humidity [ 27 , 28 ] . While the SARS coronavirus has a certain amount of homology with the other pathogenic human coronaviruses [ 10 ] , too little is known about its behavior under different environmental and atmospheric conditions to make a definitive statement about the role of the environment in nosocomial transmission . There have been reports of the SARS coronavirus persisting for prolonged periods of up to 2 days on environmental surfaces [ 29 ] . Survival in stool is reported to be even longer at up to 4 days in alkaline diarrheal stools . This would certainly help explain such circumstances as the Hotel M outbreak .