Volume 212 Issue 10

A lockdown can substantially reduce epidemic size and flatten the curve, ensuring that health system capacity is not exceeded and economic recovery occurs sooner than with a phased approach Exponential epidemic growth has been clearly demonstrated for coronavirus disease 2019 (COVID‐19) in every country it has touched, with ascertained cases growing from 25 at the start of March in Australia to over 6000 cases 6 weeks later. For every ascertained case, there may be anywhere up to nine infections that are not detected.1 This silent component of spread is likely driven by asymptomatic2 or mild infection, especially in younger people. In countries which restrict testing to symptomatic high risk people only, there will be silent growth of undetected infection until the epidemic is large enough to be felt in the health system.3 The epidemic in China was largely localised through January 2020, with small numbers of imported cases in other countries. Following a lockdown on 23 January, it peaked on 5 February4 and has declined since. However, as the cases decreased in China, COVID‐19 began surging in other countries by late February. Asian countries such as South Korea took an aggressive approach to testing and achieved control.5 In contrast, a more relaxed approach saw Europe becoming the new epicentre, followed by the United States,6 which had epidemic growth because of major testing failures. In Italy, Spain and parts of the US, health systems capacity has been exceeded, with resulting shortages of intensive care beds and ventilators. Case fatality rates (CFRs) have varied globally, from 0.85% in South Korea to over 10% in Italy.7 Whether the CFR is 0.85% or 10%, this is orders of magnitude higher than seasonal influenza8 or even the 2009 influenza pandemic.9 Two factors influence CFR — testing and capacity to ventilate. More widespread testing will result in identification of mild and asymptomatic cases, as in South Korea, and a lower apparent CFR. Given respiratory failure is the leading cause of death from COVID‐19, the inability to ventilate patients will drive the CFR up. In Germany, the number of intensive care unit (ICU) beds per head of population is 29.2 per 100 000 compared with 12.5 per 100 000 in Italy,10 so despite having a high number of cases, capacity has not been exceeded. In Italy and Spain, however, ICU capacity was exhausted. In contrast, in China, large hospitals were built in a matter of days to ensure that capacity to ventilate patients was not lost, keeping the CFR lower than in Italy. From this perspective, it is key that Australia flattens the curve to keep health system capacity available to ventilate every patient who needs it. We have 9.4 ICU beds per 100 000 population — less than Italy — although Australian capacity has been expanded as part of COVID‐19 preparedness.11 R0 and flattening the curve Central to flattening the epidemic curve is R0, the basic reproductive number. R0 is the number of secondary cases arising from one index case in a completely susceptible population. The epidemic threshold is defined mathematically as when R0 exceeds 1, which creates conditions for an epidemic, although an epidemic may not always occur. If R0 is less than 1, an epidemic cannot be sustained because one infectious case infects less than one other person on average, and infection will die out. The best estimates of R0 for COVID‐19 lie between 2 and 3.12 Public health disease control strategies such as vaccination, social distancing and travel bans aim to reduce the R value to below 1, thereby stopping the epidemic. The R modified by such measures is manifested as flattening of the curve, which is dampening of the natural trajectory of the epidemic that would otherwise occur. Herd immunity strategy — risks and no benefits Closely related to R0 is the concept of herd immunity. Herd immunity is a concept related largely to vaccination programs. It is the observation that when enough people are immune to an infection, even people who are non‐immune are protected because the number of non‐immune individuals is too small for infection to spread. Immunity can be gained by infection or by vaccination. Unless we can eradicate an infection, vaccination is the only way to control it long term. However, a range of non‐pharmaceutical measures will also control epidemics, and can be used in the short to medium term to reduce the size of the epidemic, manage demand in the health system, and save as many lives as possible. The required proportion of people in a population who need to be immune to induce herd immunity (H) is related to R0 and calculated by the formula H = 1 − (1/R0).13 If we assume R0 is 2.6, we need 61% of the Australian population to be immune to gain herd immunity for the remaining 39% of people. Therefore, any desire to “allow” some transmission (an idea floated by some experts in the United Kingdom and Australia) will only cause more disease and death without any benefit at infection rates < 60%.14 If > 60% of Australians were infected, we would have a worst‐case scenario, endanger our health workers, and rapidly exhaust our health system capacity. Further, allowing transmission of COVID‐19 would not get rid of the disease — it would cause recurrent, cycling epidemics of a mass scale, as seen with measles, mumps, rubella, smallpox and all other epidemic infectious diseases before vaccination. We would also see resulting high morbidity and mortality in older people, as 50% of the population is aged over 40 years. Younger people would also be affected. In the US, 36% of patients admitted to the ICU were aged 45–64 years and 12% were aged 20–44 years. Deaths in the US have been seen in all age groups above 18 years.6 Large studies also show that children can have severe disease or die — 50% had mild disease, 30% moderate disease and 6% critical illness.15 In one study, a child aged 10 months died.16 Young people and children tend to transmit respiratory infections most intensely in society because they have the highest contact rates.17 This means that mild or asymptomatic infection in young people could be a driver of epidemic growth. Many people live in multigenerational arrangements, so young people becoming infected could result in older people or people with chronic diseases becoming ill. The Australian response The Deputy Chief Medical Officer suggested, based on modelling, a worst case scenario of 15 million Australians infected and 150 000 deaths.18 We are a high income country of 26 million people, and it should be noted that in China, with nearly 1.4 billion people, even if true case numbers were 100 times greater than reported, less than 1% of their population was infected and 3298 people had died as of 23 March 2020.7 We may not be able to achieve China‐style lockdowns, but surely we can control the disease enough to spare our health system and minimise morbidity and mortality. Modelling for Australia suggests we could run out of ICU beds if the epidemic trajectory remains unaltered.19 The protection of the health workforce is also key to our response. The other impact of health system overload is the infection of health workers, who are already vulnerable because of the failure to stockpile adequate personal protective equipment (PPE), thus further compromising the ability to respond. Studies have shown that viable severe acute respiratory syndrome coronavirus 2 can be found widely on surfaces and in the air 3 hours after aerosolisation, highlighting the risk of airborne transmission.20 This is supported by the finding of the virus in air outlet fans in the hospital room of an infected patient.21 It is therefore likely that transmission is multimodal, including respiratory and contact. In the US, critical PPE shortages forced health workers to use plastic garbage bags as gowns, with some workers dying. The US Centers for Disease Control and Prevention initially recommended respirators for health workers treating COVID‐19, but as shortages worsened, downgraded this to surgical masks and even bandanas.22 We must flatten the curve to ensure that Australian health workers are not placed at risk by PPE shortages. Further, if hospital beds are full with COVID‐19 patients and a large proportion of health workers are infected, the ability to treat other serious conditions like cardiovascular disease will be reduced. Mass community palliative care Another consequence of health system overload will be the need for community palliative care for patients with COVID‐19 who are unable to access hospital care. While the potential for mass mortality is sometimes considered in major disaster plans, the issue of mass palliation is often neglected. In severe COVID‐19 pneumonia, where respiratory support is not available there is a progressive decline of the patient until ultimate demise associated with severe hypoxaemia, cardiac failure, acute respiratory failure and sepsis. In the days and hours before death, however, the patient will usually suffer from progressive dyspnoea, chest pain and delirium, and will become progressively moribund and immobile.23 Provision of equitable, compassionate, safe and dignified end‐of‐life care to people with COVID‐19 who are unable to be offered life‐saving critical care is fundamental to ensuring the integrity of the Australian social fabric, and the moral and mental welfare of potentially large swathes of the population. Up to 40% of older women and 22% of older men aged 80 years and over live alone (https://aifs.gov.au/publications/nature-living-alone-australia), complicating how to achieve what is necessary and right. Planning around the country for this worst case outcome is currently underway, but requires significant resources, personnel, government support and a national approach. Short, sharp lockdown versus phased approach The impact of interventions is generally seen one to two incubation periods from implementation. The flattening of the curve seen in Australia from 24 March probably reflects the impacts of rolling travel bans implemented from 5–10 March. However, New South Wales is the epicentre of infection in Australia, and the lapses in border control with the Ruby Princess and other cruise ships may have led to an increase in cases by mid‐April. In light of this, a comprehensive lockdown including school closure buys time to scale up testing for when restrictions are lifted. A slow trickle of phased interventions and a “wait and see” strategy will leave us dealing with COVID‐19 in the health system for longer. For doctors, it is no consolation to hear that “we are not like Italy, Spain or the US”. All are high income countries that used a restricted testing strategy, unlike our Asian neighbours. The UK is probably the country whose approach has been most similar to ours. They are facing a strain on the National Health Service and shortages of PPE, despite confident assertions by authorities only weeks ago. The UK, like Australia, used restricted testing and did not test asymptomatic close contacts and other high risk groups.24 To ensure that Australia continues to flatten the curve, social distancing is especially important because of asymptomatic transmitters of infection. Being unable to identify infectious cases makes disease control much harder. Until we have a vaccine, all we have available in the toolkit is social distancing and travel restrictions, along with isolation of sick people and quarantine of contacts and return travellers. The World Health Organization recommends school closure during a serious pandemic, and outlines the evidence showing that comprehensive, simultaneous social distancing measures and early school closure work better than phased or gradual measures.25 China has demonstrated the feasibility of a short lockdown followed by phased lifting of restrictions. The Chinese epidemic curve4 shows the success of the lockdown, implemented in Wuhan on 3 January, while the epidemic was in the exponential growth phase with thousands of new cases a day. Within one incubation period, cases started to fall. China began lifting restrictions on 9 February, just over one incubation period from the lockdown. They have continued to gradually lift restrictions, from a more manageable baseline position of far fewer cases to track and contain, all within 8 weeks. A lockdown is a temporary measure which can result in substantial reduction of epidemic size, more manageable case numbers and a flattening of the curve so that health system capacity is not exceeded and economic recovery can occur sooner. Lockdown can be relaxed safely in a phased manner, but must be accompanied by extensive testing, including of asymptomatic high risk people such as close contacts, evacuees and people in institutional outbreak settings. To ensure all community cases are detected, any doctor should be able to exercise clinical judgement and order a test for COVID‐19. Failure to test asymptomatic at‐risk people and allow wider community testing will result in undetected transmission in the community and a bounce‐back of the epidemic as lockdown restrictions are lifted. The only two countries to achieve sustained flattening of the curve to date are South Korea and China. South Korea has achieved this with more targeted, short lockdowns along with extensive testing.5 The risk of a phased and gradual approach is continued epidemic growth, potential failure of the health system, and a far longer road to recovery. We have examples of countries that have failed and succeeded, which can guide such a response. Epidemic control is time critical, because epidemics rise exponentially. There is no real choice available between jobs and lives — failing to save lives now will result in more net job losses and a longer recession. In addition to expanded testing, key strategies to accompany a lockdown must be a financial aid package that is accessible and leaves no person in need; a mental health and domestic violence package with outreach capability; aged care and disability support; and support for Aboriginal and Torres Strait Islander communities. Much of this is already being addressed by the government. Other needs may also become apparent, such as a communications and social engagement package; a physical fitness package; and identification of other vulnerable groups and required support to ensure the wellbeing of all Australians. The unedited version of this article was published as a preprint on mja.com.au on 1 April 2020.

C Raina MacIntyre · David J Heslop

The maintenance of sustainable low cost physical distancing and enhanced hygiene may decrease the number and severity of cases It is estimated that about two‐thirds of cases of coronavirus disease 2019 (COVID‐19) exported from China between 1 and 13 January 2020 were undetected globally.1 Most of these exported cases were mild and were only detected after several hundred cases had accumulated and severe or fatal cases were recognised 5–8 weeks later, as likely occurred in the COVID‐19 outbreaks in Iran, South Korea, Italy and Seattle, United States.2 The spread of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission globally has been very rapid. The basic reproduction number (R0) is estimated at between 2 and 3.3,4 The mode of transmission is thought to be droplet and contact infection, although opportunistic or close range airborne infection may be involved.4 The transmission dynamics of the early cases of COVID‐19 were significantly different to those during the severe acute respiratory syndrome (SARS) epidemic in 2003. In particular, the proportion of COVID‐19 cases from health care settings was low and the proportion with no known risk exposures was high.4 Another significant factor is that viral loads in nasopharyngeal and respiratory secretions are highest soon after symptom onset in patients with COVID‐195 compared with a peak of around 10 days in patients with SARS,6 making transmission before entering health care facilities and in the pre‐symptomatic phase more likely.7 Even though the understanding of transmission dynamics is at an early stage, they do suggest that the stepwise introduction of stringent measures will be necessary to control this epidemic and highlight the importance of early community control. Australia and other countries have experienced a first wave of disease and managed to effect a decline in cases.8 Quarantine; city lockdowns; complete childcare, school, university and workplace closures; and cancellation of mass gatherings and events have a significant social and economic impact and were not often implemented until significant transmission was confirmed — when they may be less effective. Countries are now challenged with identifying which of these various controls can be relaxed to allow some routine societal and economic activities to return. However, there are low cost, sustainable interventions that may be maintained over what may be many years of continued mitigation9 (Box 1). These low cost enhanced hygiene and physical distancing measures are applicable pre‐emptively before confirmation of local community transmission or where transmission of SARS‐CoV‐2 appears to be under control. The purpose of these interventions is to slow the transmission of disease and limit the impact on health services, particularly on hospitals and intensive care units, to ensure access to high level care when needed. The interventions are based on the following assumptions, which require further exploration: community‐wide SARS‐CoV‐2 transmission may be occurring undetected or may only be recognised after containment is no longer feasible; interventions implemented after community‐wide transmission is detected will be less effective; reduction of the force of infection, particularly early, will delay the epidemic peak, blunt the epidemic peak, spread cases over a longer time, and help limit the potential for critical care services to be overwhelmed, which may be lifesaving;12,13 low cost sustainable interventions will assist in the relaxation of more economically costly interventions, and enhanced hygiene and physical distancing interventions should: ▸decrease the total number of cases per week; and ▸decrease the severity of cases through reducing viral inocula. Box 2 illustrates the concept of limiting the peak in cases so that health services are less likely to be overwhelmed and there is less unmet health service need. Unmet need may include inability to admit patients to a hospital or to provide hospitalised patients in critical condition access to intensive care. Interventions to reduce infection lead to longer but less peaked epidemics. A slower evolution in the epidemic also allows time for health care staff to provide better care, for recovery of infected health care workers, for learning and adapting to the evolving situation by administrators, and for vaccines and treatments to be developed. This principle is validated in simulations for influenza14 and appears to be validated with the reduction in COVID‐19 cases in Australia and the relative lack of overburden on clinical services.8 Measures to decrease the number and severity of cases Pre‐emptive and ongoing maintenance of low cost interventions (such as enhanced hygiene and physical distancing measures) (Box 1) may not only decrease the total number of cases but may also decrease the severity of cases. The R0 is the average number of secondary cases of an infectious disease that arise from cases in a totally susceptible population and reflects the epidemic potential of a pathogen.15R0 is a function of the number of contacts an infectious person has, the risk of transmission per contact, and the duration of infectiousness. Physical distancing mostly acts on the first factor by reducing the number of contacts each person makes. Hygiene measures mostly act on the second factor, as they reduce the risk of transmission if a contact occurs. It is difficult to disentangle the effectiveness of the multiple control measures implemented in pandemic‐affected areas. The World Health Organization–China Joint Mission on COVID‐19 determined that widespread community transmission and outbreaks occurred in Wuhan before the implementation of comprehensive control measures.4 However, in other parts of China, community transmission has been limited and after public gatherings were cancelled and people were restricted to their homes, most transmission occurred in families. For example, among 344 clusters involving 1308 cases (out of a total 1836 cases reported) in Guangdong Province and Sichuan Province, 78–85% have occurred in families.4 Community‐wide interventions may decrease the average viral exposure dose encountered in the community. People exposed to a higher viral dose (inoculum) are more likely to become infected and have more severe disease. Animal models for other coronavirus infections demonstrate that increased viral inocula lead to more severe disease and higher viral loads in the lungs and other organs and fluids.16 The SARS outbreak in Amoy Gardens, Hong Kong, in 2003 provided evidence that patients with presumed higher exposure to the index case had higher nasopharyngeal viral loads and more severe illness.17 SARS‐CoV‐2 cases with more severe disease have been found to have around 60 times higher viral load than those with mild disease.18 Modelling of the 2009 influenza pandemic also supported a hypothesis that severe illness was due to a higher infectious dose of the virus mediated by the number of simultaneous infectious contacts.19 Viral loads in severe patients with Middle East respiratory syndrome (MERS) were higher than those in a mild group, and the patients in the severe group had more prolonged viral shedding in respiratory secretions, beyond 21 days after the onset of symptoms, whereas viral RNA was no longer detected by 21 days in the mild group.20 Therefore, it is proposed that early measures that lower the number of contacts, the likelihood of transmission, and average viral infective dose in an area of transmission may have a multiplier effect leading to fewer cases and fewer severe cases that are less infectious. Maintaining the early reduction of the R0 would result in fewer cases overall and have a significant negative multiplier effect on the overall impact of the epidemic, including the number of deaths (Box 3). The higher case fatality rate in Wuhan, compared with other provinces in China, may partially relate to health care resource availability and shortages in the face of overwhelming community transmission as well as greater severity of disease due to higher infection doses.12,17 These interventions will be particularly important for people over 60 years of age and those with underlying medical conditions. The costs of intervention The suite of low cost interventions, other than a working from home policy, is unlikely to affect work productivity and may provide the community with some reassurance that all is being done to prevent the epidemic and that maintenance of the low cost measures may allow earlier opening of some workplaces. WHO is supportive of pre‐emptive interventions to prevent COVID‐19 in workplaces.21 Some may see it as being overreaching, but thus far, communities seem to voluntarily adopt low cost interventions, and acceptance may be enhanced through consultation and trust building.22,23 Influenza co‐benefits For regions approaching their influenza season, optimal prevention and control of seasonal influenza, such as vaccination, in the face of potential COVID‐19 cocirculation is also crucial to minimise the double burden on health services. The measures discussed here (enhanced hygiene and physical distancing) are also effective against influenza, resulting in potential co‐benefits for both pathogens. Early indications from Flutracking.net (https://info.flutracking.net/reports-2/australia-reports) indicate that physical distancing and hygiene enhancements have markedly decreased influenza‐like illness in Australia. Limitations While physical distancing and enhanced hygiene interventions in Australia appear to be working, the evidence on the effectiveness of individual interventions in preventing COVID‐19 is not yet available. However, there is evidence from observational and simulation studies for the effectiveness of physical distancing measures in controlling seasonal influenza.13 Other measures, such as hand hygiene and cleaning surfaces, have a long history of use in infection prevention and control.24 Despite the lack of robust evidence of effectiveness for these measures, their relative low cost means that there is little harm and much potential benefit in maintaining and optimising them. We have made no recommendations in regard to masks. The use of masks outside of health settings is controversial and it is important that medical grade masks not be diverted from health care supplies. Nevertheless, surgical masks are protective of large droplet spread, have about half the effectiveness of N95 masks for small droplet transmission, and are suggested to be cost‐saving in some modelled pandemic influenza scenarios.25 The use of masks may have a role in the community setting if there are adequate supplies.10 There is evidence suggesting that community use of masks may have reduced the risk of contracting SARS.26 It is clear that masks should be used in households caring for patients with COVID‐19 at home. Policy development and scientific review of the literature on community use of masks is very dynamic at this time. The US Centers for Disease Control and Prevention has made a recent recommendation that cloth masks be used at the community level and many recent reviews have come to divergent conclusions about the usefulness and risks of community mask use.27,28,29,30 Coherent policy development in this space will rely on transparently articulating the scientific evidence on community mask use with a public conversation on the potential risks in implementation. The interventions discussed here should be tailored to individual settings and communities, in partnership with members of those communities. In particular, these interventions should be adapted to the unique circumstances of groups, such as Indigenous communities; vulnerable groups, including homeless populations; and culturally and linguistic diverse communities. Conclusion SARS‐CoV‐2 continues to disseminate globally and there are likely to be recurrent waves of infection into the foreseeable future. We would argue that these low cost interventions, although formulated at an earlier stage of the epidemic, have increasing relevance. They will protect against the emerging concern for pre‐symptomatic transmission and their optimisation will better enable the more restrictive and economically damaging constraints to be relaxed.7 Box 1 – Low cost hygiene and physical distancing interventions Settings Interventions Workplace No handshaking policy Promote cough and sneeze etiquette, but focus is on excluding ill staff Videoconferencing as default for meetings Defer large meetings Signage for all offices/meeting rooms advising of maximum occupancy based on 4 m2 per person and 2 m distancing Enforced sanitisation of hands at entrance Regular hand sanitation schedule reminders via email Avoid gathering in lunch and break rooms Gamifying hygiene rules, for example, to discourage touching face Ill* people should stay at home and ill workers immediately isolated Hold necessary meetings outside in open air if possible Staff with ill household contacts should stay at home† Disinfect high touch surfaces regularly and between users Work from home where possible and consider staggering of staff Consider opening windows and adjusting air conditioning to increase air flow and maintain warmer more humid environments‡ Limit food handling and sharing of food in the workplace Assess staff business travel risks§ Enhance hygiene and screening for illness among food preparation (canteen) staff and their close contacts Analyse the root cause of crowding events on site and prevent through rescheduling, staggering or cancelling Mark floor areas to indicate 2 m distancing points in areas where staff spontaneously gather to prompt distancing Minimise the number of employees in a work vehicle at any one time School Supervised sanitisation of hands at entrance and at regular intervals Defer activities that lead to mixing between classes and years Promote cough and sneeze etiquette, but focus on excluding ill persons Strict stay at home policy if ill Gamifying hygiene rules, for example, to discourage touching face Regular handwashing schedule Disinfect high touch surfaces regularly and between users Outdoor lessons where possible Consider opening windows and adjusting air conditioning Enhance hygiene and screening for illness among food preparation (canteen) staff and their close contacts Review after‐school care arrangements that lead to mixing of children from multiple classes and ages Commercial, entertainment and transport Sanitisation of hands at building entrance encouraged Tap and pay preferred to limit handling of money Disinfect high touch surfaces regularly Avoid crowding through booking and scheduling, online pre‐purchasing, limiting attendance numbers Enhance hygiene and screening for illness among food preparation staff and their close contacts Enhance airflow and adjust air conditioning to increase air flow and maintain warmer more humid environments Public transport workers, taxi and ride share drivers — vehicle windows opened where possible, increased air flow, high touch surfaces disinfected Household All households Enhanced hand sanitisation Gamifying hygiene rules, for example, to discourage touching face Disinfect high touch surfaces regularly “Welcome if you are well” signs on front door Increase ventilation rates in the home by opening windows or adjusting air conditioning Promote cough and sneeze etiquette Households with ill members Measures listed above Confirmed cases of COVID‐19 should be isolated away from susceptible household members if there are not completely separate bedroom, bathroom and kitchen facilities If care must be provided at home, ill household members are given their own room and only one person cares for them The door to the ill person's room is kept closed10 Wearing simple surgical or dust masks by both infected persons and other family members caring for the patient if needing to be in the same room Consider extra protection or alternative accommodation for household members aged over 65 years or with underlying illness COVID‐19 = coronavirus disease 2019. *Ill person refers to someone with symptoms of respiratory illness or fever, who is not yet under investigation for COVID‐19 but could be an unrecognised case. †This could be costly unless used judiciously while awaiting exclusion of COVID‐19 in the suspected case and should be introduced based on likelihood of local transmission. ‡Evidence that low temperature and low humidity in air‐conditioned environments may enhance the survival of coronaviruses such as severe acute respiratory syndrome (SARS).11 §When international travel restrictions are lifted, sites such as the Centers for Disease Control and Prevention travel risk assessment site may be useful (https://www.cdc.gov/coronavirus/2019-ncov/travelers/map-and-travel-notices.html). Box 2 – Intended impact of enhanced hygiene and physical distancing measures on the coronavirus disease 2019 (COVID‐19) pandemic* *Figure adapted from Fong et al.13 Box 3 – Conceptual model of how pre‐emptive interventions with a negative multiplier effect could affect an impending epidemic

Craig B Dalton · Stephen J Corbett · Anthea L Katelaris

Usual care must be rapidly adapted to isolate, assess and test large numbers of patients during the COVID‐19 pandemic Coronavirus disease 2019 (COVID‐19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), emerged in China in late 2019.1 COVID‐19 is an example of a high consequence infectious disease that may present to an Australian hospital. These infections are uncommon in Australia and, in most cases, were imported from overseas. Less frequently, there is onward local transmission, such as during the influenza A(H1N1)pdm09 pandemic in 2009. High consequence infectious diseases present unique challenges to Australian hospitals. Their rarity leads to unfamiliarity and loss of institutional knowledge between events. Many hospitals operate at near maximal capacity between outbreaks and have limited surge capacity.2 Protocols designed to manage single patients require adaptation to situations where larger numbers of patients require isolation, assessment and testing for infection. While every Australian hospital has a mass casualty or disaster protocol, these are developed for all hazards and may not address problems specific to high consequence infectious diseases, including: the need to rapidly identify and isolate potentially infectious patients to prevent nosocomial transmission; the complexity of rapid triage and assessment on frequently evolving epidemiological and clinical grounds; the difficulty of differentiating high consequence infectious diseases from more common but clinically similar conditions;3 the absence of rapid diagnostic tests to aid clinical decision making; and the potential for a prolonged surge for weeks to months during which time the workforce may be affected by both infection and absenteeism. Here we describe the strategic approach of the Royal Melbourne Hospital to triage and screen patients who have presented at risk (or concerned that they are at risk) during the early phases of COVID‐19. Our resources may be of value to other organisations refining their triage and clinical algorithms. The Royal Melbourne Hospital response The Royal Melbourne Hospital is an adult tertiary referral centre and the designated state‐wide provider for quarantinable diseases. The emergency department (ED) treats over 80 000 patients annually. From 6 January 2020, we instituted tools to identify at triage those patients with risk factors for COVID‐19 and rapidly isolate them. Initially, there was capacity to assess patients in one of three existing negative pressure rooms. On 25 January, the first patient with COVID‐19 in Australia, who had arrived in Melbourne on a flight from Guangzhou, was confirmed. The Victorian Department of Health and Human Services informed all passengers on the flight of their possible contact with the patient, leading to a significant surge in presentations to the Royal Melbourne Hospital. Box 1 presents an overview of the challenges in managing high consequence infectious diseases and details of our coordinated approach. Key components that can be used by other services are detailed below. Governance Unlike other major incident responses, which tend to be short‐lived, response to an outbreak requires a sustained response that will inevitably have an impact on other clinical services. A governance process that includes executive sponsors and senior clinical leaders is essential. The Royal Melbourne Hospital COVID‐19 response leveraged an existing code brown (external emergency) pandemic subplan and clinical code yellow (internal infectious disease emergency) plans as a governance framework. A governance group including medical and nursing executives and senior clinicians from the ED, infectious diseases, infection prevention services and microbiology meet regularly. A single standard operating procedure exists on our hospital intranet that provides all clinically relevant information for frontline health care workers (eg, personal protective equipment guidelines, current case definitions, patient assessment algorithms). It is updated frequently given the dynamic situation and, thus, functions as a living document for staff. This document provides 24/7 access to an authoritative source that supports junior and senior staff alike to feel confident in their practices and approach. Infrastructure Establishment of a fever clinic. A particular design feature that may be adopted by other facilities is the rapid establishment of an out‐of‐department fever clinic. In response to the first surge of patients, we rapidly repurposed the nearby hospital transit lounge, which was closed for the weekend, into a fever clinic (Box 2). The clinic received its first patient within 2 hours of notification from the Victorian Department of Health and Human Services of the first local case. In its first 7 days, we assessed 109 patients. We discharged over 90% of patients within 4 hours of arrival. We retain this model as patient numbers continue to increase. In this model of care, patients are physically segregated from the rest of the ED into a dedicated rapid assessment and treatment space from their arrival, limiting exposure to other patients. The main benefit of this approach is that cases yet to be identified can be an important contributor to nosocomial transmission; therefore, early separation and detection are vital.4,5 However, immediate recognition of cases is difficult due to unfamiliarity with the disease, overlap in clinical presentation with more common illnesses, and due to patient wait times. Our fever clinic model of care was based on the success of this model in Toronto and Taiwan during the severe acute respiratory syndrome (SARS) outbreak,6 where no transmission was reported in these facilities despite hospital exposure being implicated in the majority of cases in these regions (eg, it was the presumed source of exposure for 72% of patients in Toronto7,8). It has also been reported as an effective strategy for triaging patients in Wuhan for COVID‐19.9 Similar approaches appear to have been used in other countries, but detailed descriptions are not yet available in the literature. In Australia, segregation of major incident patients was exemplified by the Royal Darwin Hospital, which functioned as the forward receiving hospital for medically evacuated patients during the 2002 Bali bombings.4 The benefits of establishing a fever clinic include: protecting an existing environment for the maintenance of business continuity; facilitating protocolised interventions for spatially clustered groups of patients; providing a physical location to send additional disaster resources without cluttering areas of core business; and enhancing record‐keeping. Limitations of our approach include the additional staffing required, operational impact of loss of transit lounge, staff unfamiliarity with the location of resources (such as resuscitation trolleys), and a slightly further distance from resuscitation bays if patients deteriorate. Moreover, we were also concerned about the risk of stigmatisation of patients who are seen to be segregated from the main ED waiting room cohort. Implementation of electronic self‐registration and self‐screening. A surge related to an emerging infectious disease provided our clerks’ department with a confluence of unique administrative and logistical challenges. These included: a high proportion of patients came from a non‐English speaking background; contact tracing and follow‐up requires accurate registration and an extended suite of contact details, but usual disaster response medical records protocols generate only anonymised patient registrations; non‐clinical staff (ward clerks) unfamiliar with personal protective equipment would be required to extensively interview patients to confirm details at some point; patients came in bursts, producing delays in registration; manual screening paperwork and registration papers provide a potential fomite for disease transmission; and our ED is paper‐free under usual circumstances. We developed a novel solution to this problem, leveraging the fact that over 91% of Australian citizens and over 96% of Chinese citizens own a smartphone5,10 and converted an initial paper‐based bilingual screening tool to an online one. This is hosted using the research electronic data capture (REDCap) tool (www.projectredcap.org).11 Patients are directed to a secure website optimised for use on a smartphone. The registration portal is free to use. They answer questions regarding their epidemiological risk (such as a detailed travel history, or being a health care worker), clinical risk factors (such as being immunocompromised) and symptoms. Results are immediately fed to remote clinical computers where ward clerks can register the patient without direct patient contact and clinicians can see screening information before their clinical encounter. While not yet tested under a pandemic scenario, we anticipate this method of self‐registration may be particularly useful in the event of a significant surge in patient numbers. Triage sieve and sort of patients can be rapidly undertaken by clinicians who are fed real‐time registration data. Compared with usual mass casualty principles, the inclusion of epidemiological data in the electronic tool is valuable for triage in this setting to screen out the relatively high proportion of patients with perceived, but not actual epidemiological risk factors. Our REDCap infrastructure is available in the Supporting Information for adaptation by other health services. Conclusion The importation of emerging infections into Australia is rare, and onward transmission is rarer still. As the Royal Melbourne Hospital received a surge in patients who required screening for COVID‐19 relatively early during the current outbreak, our recent observations may provide opportunities for other hospitals to enhance their preparedness and response plans. We prioritise prevention of nosocomial transmission (using a scalable, separated fever clinic) early planning for worsening surge (adopting scalable solutions) and clear clinical governance (providing malleable and accessible centralised resources). Box 1 – Elements of the Royal Melbourne Hospital clinical response Element of response Challenges Approach used Clinical governance Multiple clinical units involved, with tangible impacts on business as usual activity and frequent changes to the model of care and the expectations Where possible, we operated within existing plans and policies. Daily executive and head of unit level huddles were instituted initially, and then stepped down to weekly as needed, producing hospital agreement on messaging and expectations of all teams and sharing of information between executive, infectious diseases (ID), infection prevention services (IPS) and emergency medicine (EM). COVID‐19 multidisciplinary working groups were formed within the ED and ID clinical units Infrastructure A space was needed to accommodate the extra patients while maintaining infectious isolation among them, and between them and the rest of the ED census A graduated response used with existing ED negative pressure rooms used for small numbers, a cohort subwaiting area was created when several patients were present in the ED at once, and a separate fever clinic was created in the nearby transit lounge used for surge response Infection prevention and control practices Transmission dynamics are incompletely understood and there is a risk of nosocomial amplification (especially during aerosolising procedures) Education sessions, posters, and videos used to reinforce PPE training; nebulisers removed from dedicated treatment space; hand sanitiser stations; PPE stations and infectious waste bins deployed; and a SOP employed for aerosolising procedures (Supporting Information) Clinical care (including triage, assessment and testing) There is rapidly evolving understanding of clinical and epidemiological characteristics of the disease. Staff lack familiarity with the disease and with the roles performed (concierge nurse, fever clinic doctor), while the normal ED and hospital functions need to continue alongside Creation of a SOP including clinical algorithms for triage, assessment and biological sampling as a living document hosted on the hospital intranet, and updated as needed and used as a single source of truth for clinical staff. Gradual transition to algorithm‐driven assessment by junior medical staff to free up senior staff for unwell patients. Action cards with role descriptions were provided in the SOP for all fever clinic staff Communication with patients Initially, most patients were Mandarin‐speaking Bilingual signage (English and Mandarin) deployed in the fever clinic, and bilingual patient resources and screening questionnaire generated. Discharge information sheets specific to different tiers of risk were translated into Mandarin and provided to all patients discharged from the fever clinic Human resources Maintenance of staff competence and confidence essential for safety and prevention of absenteeism Regular education sessions to provide updated clinical information and epidemiology, train in PPE, and answer questions COVID‐19 = coronavirus disease 2019; ED = emergency department; PPE = personal protective equipment; SOP = standard operating procedure. Box 2 – Floor plan of the Royal Melbourne Hospital fever clinic and guiding principles for a fever clinic COVID‐19 = coronavirus disease 2019; PPE = personal protective equipment; SOP = standard operating procedure.

Amanda M Rojek · Martin Dutch · David Camilleri · Emma Gardiner · Emma Smith · Caroline Marshall · Kirsty L Buising · Nicola Walsham · Mark Putland

Investment is urgently needed in repurposed drugs which could ease the burden of the COVID-19 pandemic

Jennifer H Martin · Nikola A Bowden

Gaps in availability of both meningococcal ACWY and B vaccines exist for high risk groups Invasive meningococcal disease (IMD) is a serious disease and an emotive public health issue in Australia. In the early 2000s, IMD case numbers declined nationally by about 80%, from 688 in 2002 to 149 in 2013,1 due to a drop in serogroup C and B disease. The decline in serogroup C disease followed the comprehensive childhood meningococcal C vaccination program — free vaccination was available up to age 19 years — introduced in 2003.2 Simultaneously, but without clear cause in the absence of vaccination, meningococcal B (MenB) disease declined slowly from 1.49 cases per 100 000 population in 2003 to 0.47 in 2015 (293 and 112 cases respectively).3 Overall, the IMD incidence rose again after 2014, driven mainly by the emergence of serogroup W and, to a lesser extent, serogroup Y.1,4 Most serogroup W strains are close variants of the virulent ST‐11 clone initially identified in the United Kingdom and South America in 2009, which was associated with more frequent atypical clinical presentations, greater severity and increased mortality.1 Although the emergence of serogroups W and Y was a game changer, serogroup B still accounted for about half of all IMD cases in Australia between 2016 and 2018.4 Compared with some other vaccine‐preventable diseases, IMD is relatively rare, affecting about one in every 100 000 Australians, equating to an average of 250 cases per year between 2014 and 2018.1,4 However, the case fatality rate is high, and around 10–30% of survivors experience long term sequelae.3,5 Although IMD can occur at any age, it is more common in children aged less than 2 years (especially those aged < 12 months) and older adolescents (Box 1). Aboriginal and Torres Strait Islander (hereafter respectfully referred to as Indigenous) children aged up to 14 years are also disproportionately affected compared with non‐Indigenous children (Box 2). For example, rates of serogroup W IMD in Indigenous children were more than 30‐fold higher compared with non‐Indigenous children of the same age during 2016–2018 (Box 2). People with certain medical conditions also have a high risk of IMD.6 These conditions include asplenia; complement deficiency, which in some types the risk is up to 10 000 times greater than in the general population;7 and use of eculizumab, which is a monoclonal antibody directed against complement and is used for treating paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome. Increased use of quadrivalent meningococcal conjugate vaccines Three brands of quadrivalent meningococcal conjugate (MenACWY) vaccines are available in Australia: Menactra (Sanofi), Menveo (GlaxoSmithKline) and Nimenrix (Pfizer). These quadrivalent vaccines include a capsular polysaccharide from each ACWY serogroup conjugated to a carrier protein, superseding the less immunogenic polysaccharide‐only vaccines previously used. The rapid rise of serogroups W and Y disease prompted all states and territories to fund MenACWY vaccination programs in 2017 and 2018 as an outbreak response.8 These programs varied but predominantly targeted adolescents aged 15–19 years, aiming to both directly prevent disease and to interrupt community transmission of meningococci through reduced acquisition of nasopharyngeal carriage, which is most prevalent in this age group.9,10 Some jurisdictions also implemented time‐limited vaccination programs covering select age groups, from infancy up to older adolescence, to control serogroup W outbreaks. The most notable of these outbreaks began in September 2017 in the Northern Territory and spread to nearby communities in central Australia, including regions in Western Australia, Queensland and South Australia. Indigenous children aged less than 10 years living in remote communities were primarily affected, with 19 cases within a few months.11 Meningococcal B vaccine use in Australia The modes of transmission, pathogenesis and treatment of serogroup B IMD are the same as for IMD caused by other serogroups, although the case fatality rate appears lower for serogroup B (6.9%) than for serogroups W, C and Y (12.8%, 12.0% and 10.8% respectively).12 However, the development of a vaccine against serogroup B disease was problematic for decades because serogroup B capsular polysaccharide is cross‐reactive with human tissues (an autoantigen) and thus poorly immunogenic.13 Two MenB vaccines, developed using novel recombinantly derived protein antigens common to many serogroup B strains, are now available in Australia: Bexsero (GlaxoSmithKline), since 2013, and Trumenba (Pfizer), since 2017. Trumenba is only registered for use from 10 years of age, whereas Bexsero can be used from 6 weeks of age. Both MenB vaccines have a high cost (around $100 per dose) and require multiple doses. Bexsero also causes higher rates of fever in young children than other vaccines included in the National Immunisation Program (NIP), necessitating the use of prophylactic paracetamol around the time of immunisation.6 Data on the benefits of MenB vaccine use are gradually accumulating, predominantly from the UK, which is the only country to have formally evaluated an ongoing funded population‐based program. Infants in the UK have been offered a three‐dose course of Bexsero (scheduled at ages 2, 4 and 12 months) since 2015. New data from the UK over 3 years estimate vaccine effectiveness against serogroup B IMD to be 52.7% (95% CI, −33.5 to 83.2) for a two‐dose primary schedule for infants, and 59.1% (95% CI, −31.1 to 87.2) for a two‐dose primary schedule followed by a booster dose at one year.14 However, Bexsero does not appear to have an impact on nasopharyngeal carriage of serogroup B,9 which implies that herd immunity (indirect protection in unvaccinated individuals) would be limited or absent despite population‐based vaccination.9 In addition, for both vaccines, protection against only around three‐quarters of all circulating MenB strains is predicted, based on in vitro assays.15 To date, the use of MenB vaccines in Australia has been limited in the absence of NIP funding. In October 2018, in the context of higher serogroup B IMD incidence rates compared with other parts of Australia, the South Australian government introduced the only state‐funded MenB vaccination program for young children, expanding to adolescents in February 2019.8 In 2020, a population‐level study of adolescent MenB vaccination in the Northern Territory will commence to explore its impact on gonorrhoea — a high incidence sexually transmitted disease caused by the related organism Neisseria gonorrhoea — as well as on serogroup B IMD (Helen Marshall, Professor in Vaccinology and National Health and Medical Research Council Practitioner Fellow, Robinson Research Institute, University of Adelaide, Australia, personal communication, January 2020). Assessment and introduction of meningococcal vaccines to Australia's National Immunisation Program Both equity and cost‐effectiveness are important considerations when approaching decision making regarding vaccine incorporation into immunisation programs. To be added to the Australian NIP, vaccines require a comprehensive assessment and must be recommended as cost‐effective by the Pharmaceutical Benefits Advisory Committee (PBAC); this is based on economic modelling, typically undertaken by the vaccine manufacturer.16 With a low IMD incidence (one per 100 000), relatively small numbers of deaths, and trends in serogroup incidence being difficult to predict, the accurate assessment of the cost‐effectiveness of both types of meningococcal vaccines (MenACWY and MenB) has been challenging. Low incidence rates have meant reliance on immunologic correlates of protection to predict vaccine impact (randomised placebo‐controlled efficacy studies are not feasible for such rare outcomes) and a limited number of post‐market vaccine effectiveness estimates. Other key uncertainties include the duration of protection and the magnitude of any herd protection effect, particularly for MenB vaccines, for which evidence is showing that there is no effect on nasopharyngeal meningococcal carriage.9 These uncertainties, together with the high cost of the MenB vaccines in particular, provide challenges for the value for money assessment necessary to underpin vaccine introduction into long term programs. In 2018, the MenACWY vaccine Nimenrix replaced the meningococcal serogroup C vaccine on the NIP at 12 months of age, and was also added to the NIP for use in a single birth cohort of adolescents aged 14–16 years from early 2019, replacing jurisdictionally funded programs.8 This is expected to provide direct protection to vaccinated individuals as well as some indirect protection to unvaccinated people over time.17 The potential to fund the MenACWY vaccine for certain high risk groups with underlying medical conditions through the NIP has also been flagged in a recent positive PBAC recommendation,18 which is under active consideration by the Australian Government. The Bexsero MenB vaccine was assessed by the PBAC on three occasions between 2013 and 2015, but was deemed as not being cost‐effective at the manufacturer's proposed price.19 In November 2019, following another manufacturer application, the PBAC recommended the NIP inclusion of Bexsero for Indigenous infants (with a catch‐up to 2 years of age) and for anyone with certain medical conditions (asplenia, complement deficiency, and eculizumab treatment). However, once again, the use of the vaccine in a broader population‐based program for infants and adolescents was not considered cost‐effective.20 The implementation of these recommendations is under active consideration by the Australian Government. Gaps in the prevention of meningococcal disease in Australia The Australian immunisation handbook recommends that any person who wants to protect themselves against invasive meningococcal disease can receive MenACWY and MenB vaccines from as early as 6 weeks of age.6 Box 3 shows groups particularly recommended for vaccination based on their higher risk of disease, compared with current and anticipated funded meningococcal vaccine programs. New proposed and existing funded programs are a substantial achievement and will provide protection to many individuals most at risk from vaccine‐preventable meningococcal strains. However, some equity gaps remain. It will take time to accrue the benefits of reduced MenACWY disease incidence and disease transmission across the population when vaccinating only at ages one and 15 years, especially without including all infants in the NIP‐funded program. It is possible that the disparity in IMD rates between Indigenous and non‐Indigenous children may persist for years, particularly for serogroup B disease, in the absence of herd immunity and of an adolescent program funded by the NIP. Assessing program impact on disease, particularly in jurisdictions where wider populations did, or continue to, receive state‐funded vaccines (against MenACWY or MenB disease), such as Western Australia, Tasmania and South Australia,8 is essential to evaluate evidence of benefit. The remaining access gaps are very challenging to address for high cost vaccines that are not offered at cost‐effective prices by the manufacturer. Other initiatives, such as ensuring that health services fund vaccination of persons living with human immunodeficiency virus and of at‐risk laboratory workers (two groups not included in the NIP), and addressing the social determinants of health that underpin high rates of meningococcal disease (and other vaccine‐preventable diseases), are also important.21 Conclusion Australia has progressively implemented funded vaccination programs for various high risk groups using MenACWY and MenB vaccines over the past 5 years. The anticipated expansion of NIP funding to include medical at‐risk groups for both vaccines and to include young Indigenous children for MenB vaccine, in addition to established MenACWY programs, should be effective over time to protect those most at risk of disease. Close monitoring of emerging data on the duration of vaccine protection from Australia and internationally is needed, particularly for individuals with underlying medical conditions whose risk is enduring. It remains challenging that for one disease, IMD, we must use two vaccines; while at least one pentavalent vaccine (MenABCWY) is under development, it is years away from use, and the assessment of cost‐effectiveness is equally uncertain. This rare but deadly disease will continue to challenge; clinicians should remain aware and discuss vaccination options against both MenB and MenACWY disease with their patients. Box 1 – Invasive meningococcal disease (IMD) notification rates by serogroup and age group (Australia, 2016–2018) The graph shows the rate of cases of IMD notified to the National Notifiable Diseases Surveillance System between 1 January 2016 and 31 December 2018. The total cases include all notified cases of IMD, including serogroups B, C, E, W, Y and unknown serogroup. There were no cases of serogroup A in this period. Box 2 – Average annual notification rates of invasive meningococcal disease (IMD) for Aboriginal and Torres Strait Islander people compared with non‐Indigenous people, by age group and serogroup (Australia, 2016–2018) RR = rate ratio. The graph shows the rate of cases of serogroup B and W IMD notified to the National Notifiable Diseases Surveillance System between 1 January 2016 and 31 December 2018. Box 3 – Australian recommendations for meningococcal vaccination and funded programs*† Recommendations Funded programs for MenB vaccines‡ Funded programs for MenACWY vaccines‡ Overall AIH recommendation Any person who wants to protect themselves against invasive meningococcal disease can receive MenACWY and MenB vaccines from as early as 6 weeks of age No funded programs that cover all age groups No funded programs that cover all age groups Specific AIH recommendations for high risk groups§ All individuals in particular age groups (6 weeks to 4 years and 15–19 years) State/territory: South Australia: 6 weeks to 12 months of age, with catch‐up to 4 years of age8 Northern Territory: to be provided for adolescents from early 2020 as part of an NHMRC‐funded research study¶ NIP: One dose at age 12 months One school‐based cohort (age ~ 15–16 years)8 State/territory: Various current and previous programs — for further detail refer to summary document8 or individual health department websites Aboriginal and Torres Strait Islander people (6 weeks to 19 years of age) NIP: Nil, but anticipated it will likely be included for infants, with catch‐up to 2 years of age20 NIP: One dose at age 12 months One school‐based cohort (age ~ 15–16 years)8 State/territory: South Australia: 6 weeks to 12 months of age, with catch‐up to 4 years of age8 Northern Territory: to be provided for adolescents from early 2020 as part of an NHMRC‐funded research study¶ State/territory: Various current and previous programs — for further detail refer to summary document8 and individual health department websites High risk due to medical condition (asplenia/hyposplenia, complement deficiency, eculizumab use, HIV, post‐HSCT; all people aged ≥ 6 weeks) NIP: Nil, but anticipated it will be included for individuals with asplenia/hyposplenia, complement deficiency, eculizumab use20 NIP: Nil, but anticipated it will be included for individuals with asplenia/hyposplenia, complement deficiency, eculizumab use20 Other: Some individual hospitals or local health services may fund the vaccine for patients with HIV or HSCT Other: Some individual hospitals or local health services may fund the vaccine for patients with HIV or HSCT Other risk factors (young adults aged 20–24 years who smoke or live in close quarters; eg, military barracks or university residential accommodation) Nil (self‐funded) Nil (self‐funded) Laboratory workers at risk Nil (may be employer‐funded) Nil (may be employer‐funded) Travellers to endemic areas Nil (self‐funded) Nil (self‐funded) AIH = Australian immunisation handbook; HIV = human immunodeficiency virus; HSCT = haematopoietic stem cell transplant; NHMRC = National Health and Medical Research Council; MenACWY = serogroups A, C, W and Y meningococci; MenB = serogroup B meningococcus; NIP = National Immunisation Program. * Adapted from the AIH6 and other referenced sources. † Note that the number of doses recommended varies by specific group — refer to the AIH for details. ‡ As of 17 January 2020. § Recommendations are for both MenACWY and MenB vaccines. ¶ Helen Marshall, Professor in Vaccinology and NHMRC Practitioner Fellow, Robinson Research Institute, University of Adelaide, Australia, personal communication, January 2020.

Cyra Patel · Clayton K Chiu · Frank H Beard · Nigel W Crawford · Kristine Macartney