key: cord-0812015-33dwigo7
authors: Shaban, Ramon Z.; Li, Cecilia; O'Sullivan, Matthew V.N.; Gerrard, John; Stuart, Rhonda; Teh, Joanne; Gilroy, Nicole; Sorrell, Tania C.; White, Elizabeth; Bag, Shopna; Hackett, Kate; Chen, Sharon C.A.; Kok, Jen; Dwyer, Dominic E.; Iredell, Jonathan R.; Maddocks, Susan; Ferguson, Patricia; Varshney, Kavita; Carter, Ian; Barratt, Ruth; Robertson, Mark; Baskar, Sai Rupa; Friend, Caren; Robosa, Roselle S.; Sotomayor‐Castillo, Cristina; Nahidi, Shizar; Macbeth, Deborough A.; Alcorn, Kylie A.D.; Wattiaux, Andre; Moore, Frederick; McMahon, Jamie; Naughton, William; Korman, Tony; Catton, Mike; Kanapathipillai, Rupa; Romanes, Finn; Rowe, Emily; Catford, Jennifer; Kennedy, Brendan; Qiao, Ming; Shaw, David
title: COVID‐19 in Australia: Our national response to the first cases of SARS‐CoV‐2 infection during the early biocontainment phase
date: 2020-11-16
journal: Intern Med J
DOI: 10.1111/imj.15105
sha: 6023ed4fd3c18a61b66aab42f6b735708b0d98d9
doc_id: 812015
cord_uid: 33dwigo7

BACKGROUND: On 31 December 2019, the World Health Organization recognised clusters of pneumonia‐like cases due to a novel coronavirus disease (COVID‐19). COVID‐19 became a pandemic 71 days later. AIM: To report the clinical and epidemiological features, laboratory data and outcomes of the first group of 11 returned travellers with COVID‐19 in Australia. METHODS: This is a retrospective, multi‐centre case series. All patients with confirmed COVID‐19 infection were admitted to tertiary referral hospitals in New South Wales, Queensland, Victoria and South Australia. RESULTS: The median age of our patient cohort was 42 years (IQR, 24–53 years) with six men and five women. Eight patients (72.7%) had returned from Wuhan, one from Shenzhen, one from Japan, and one from Europe. Possible human‐to‐human transmission from close family contacts in gatherings overseas occurred in two cases. Symptoms on admission were fever, cough and sore throat (n = 9, 81.8%). Co‐morbidities included hypertension (n = 3, 27.3%) and hypercholesterolaemia (n = 2, 18.2%). No patients developed severe acute respiratory distress nor required intensive care unit admission or mechanical ventilation. After a median hospital stay of 14.5 days (IQR, 6.75–21), all patients were discharged. CONCLUSIONS: This is a historical record of the first COVID‐19 cases in Australia during the early biocontainment phase of the national response. These findings were invaluable for establishing early inpatient and outpatient COVID‐19 models of care and informing the management of COVID‐19 overtime as the outbreak evolved. Future research should extend this Australian case series to examine global epidemiological variation of this novel infection. This article is protected by copyright. All rights reserved.

A novel coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spread rapidly worldwide since it was first reported to the World Health Organization (WHO) on 31 st December 2019. 1 A COVID-19 pandemic was declared 71 days later. 2, 3 Symptoms of COVID-19 infection include fever, cough, sore throat, myalgia and dyspnoea, with risk factors for moderate to severe disease including age, hypertension, diabetes mellitus and other acute or chronic respiratory infections. 4, 5 Transmission from asymptomatic carriers has been reported [6] [7] [8] and has likely contributed to sustained community transmission. Global efforts to reduce the spread of COVID-19 have included international and national travel restrictions, mandatory quarantine of travellers, close contacts and affected patients, extensive contact tracing, and widespread physical distancing measures. As of 11 th August 2020, there have been 20,092,855 confirmed cases and 736,254 deaths globally. 9 The first confirmed case of COVID-19 in Australia was reported on the 25 th January 2020. 10, 11 As of 11 th August 2020, there have been 21,397 confirmed COVID-19 cases and 313 deaths in Australia. 12 Following the peak of COVID-19 cases in Australia in late March 2020, it was reported that approximately 63% of all confirmed cases were acquired overseas 13 .

However, recent developments in Victoria (VIC) and New South Wales (NSW) have seen increasing numbers of locally acquired infections, with 50.2% of cases across Australia now linked to a confirmed case. 12 In this paper, we report the clinical features, epidemiological characteristics, laboratory data and outcomes of the first group of 11 patients with laboratory-confirmed COVID-19 associated with recent international travel that presented in NSW, VIC, Queensland (QLD) and South Australia (SA). Patients were treated and managed during the early biocontainment phase of the national response, where patients were mostly managed in hospital and under quarantine following advice from state public health units. These findings form part of an important historical record of the COVID-19 pandemic in Australia.

This clinical case series includes 11 patients with laboratory-confirmed COVID-19 who were admitted to four tertiary referral hospitals in four Australian states: NSW, QLD, VIC and SA.

Retrospective, multi-centre case series. 

Site leads obtained and gathered clinical and laboratory data from all patients using their respective Laboratory and Hospital-based Patient Information Systems.

Descriptive statistical analyses, including median and interquartile range (IQR), were undertaken on continuous variables. Categorical variables were described as percentages and frequency rates. All analyses were performed using IBM SPSS Statistics 26.

Four patients were admitted in NSW, three were treated in VIC, two were admitted in QLD, and two were managed in SA. The nine patients in NSW, VIC and QLD were admitted to hospital between 23 rd January -1 st February, and were amongst the first COVID-19 cases in each respective state. The authors were unable to obtain consent from the first two patients with confirmed COVID-19 in SA. The patients included in this study were the third and fourth COVID-19 cases in SA and were admitted in late February -early March. The median age of the patients was 42 years (IQR, 24 -53; range, 21 -66), with male and female patients making up 54.5% and 45.5% of the cohort, respectively (Table 1) .

Eight patients (72.7%) had travelled to Wuhan, Hubei Province but had no direct contact with hospitals, the Huanan Seafood Wholesale Market, or cases of COVID-19. SA-11 had travelled Europe and developed infection upon return but had no known contact with a confirmed case. Human-to-human transmission via close contact was presumed to have occurred for two of the patients while overseas. NSW-2 patient had dined with relatives in Shenzhen, Guangdong province, and later tested positive for SARS-CoV-2. His relatives had recently travelled to Wuhan prior to the family gathering. SA-10 was repatriated to Adelaide from Yokohama, Japan after being diagnosed with COVID-19. Her partner had confirmed COVID-19 infection one week prior and was hospitalised in Japan for three weeks. Both were passengers from the Diamond Princess cruise ship, an international cruise ship which was linked to one of the first COVID-19 outbreaks reported outside of China 14 .

All patients were admitted and managed using standard, contact and droplet precautions.

Airborne precautions were utilised for aerosol-generating procedures. Although not required by jurisdictional public health guidelines, negative pressure rooms were used. In NSW, patients with confirmed COVID-19 were cared for in an intensive care quarantine class (Class Q) negative pressure single room with a dedicated ensuite and separate anteroom.

While undergoing investigation, suspected cases or patients with COVID-19 infection of mild severity were housed in a specially requisitioned ward with 11 standard class (Class S) rooms. In QLD, patients were admitted to a 24-bed isolation unit in a negative pressure (Class N) isolation room. In SA, patients were admitted to a 16-bed isolation unit and cared for in Class Q and Class N negative pressure rooms. In VIC, patients were admitted to a single N-class room. VIC-7 was clinically stable and hospital admission was not required.

Human Services.

Nasopharyngeal swabs, combined nose and throat swabs and/or sputum samples were Apart from a temperature of 37.8°C, other investigations were unremarkable. The patient was discharged to home isolation, with community monitoring by the Department of Health and Human Services Victoria. The other ten patients were all admitted to hospital. On admission, the three most common symptoms were fever (n=9; 81.8%), cough (n=9; 81.8%) and sore throat (n=9; 81.8%), followed by fatigue (n=8; 72.7%), diarrhea or loose stools (n=7; 63.6%), and myalgia (n=6; 54.5%). Headache, nasal congestion, dyspnea and coryza were uncommon (see Table 1 ). The median duration from symptom onset to hospital admission was 4.5 days (IQR, 1.0 -6.5; range, 0 -10).

Five patients had underlying comorbidities. Three patients had hypertension (27.3%) and two had hypercholesterolemia (18.2%). Other chronic medical conditions included type two diabetes mellitus, gout, fatty liver, hypothyroidism and anxiety. One patient was a former smoker. Admission laboratory testing results are shown in Table 3 and azithromycin given to two, oral amoxicillin and clavulanic acid to one, and piperacillintazobactam to another. QLD-8 was commenced on oral lopinavir-ritonavir on day 7 of illness following a persistent fever (on admission: 38.8°C; peak at day 7: 39.4°C) which resolved after four days. His initial symptom was diarrhoea but also developed rhinorrhea, mild hypoxia, cough and chest discomfort during hospitalisation.

The discharge criteria for the patients in this series were developed de novo and evolved over time to reflect those later set out in the COVID-19 Series of National Guidelines 18 .

Initially this comprised of resolution of all acute symptoms for the previous 24 hours and two consecutive negative SARS-CoV-2 PCR of results from combined nasopharyngeal and throat swabs taken at least 24 hours apart. The median duration from onset of symptoms to discharge was 14.5 days (IQR, 6.25 -21; range, 5 -25). At the time of writing, all 11 patients were discharged and/or released from isolation and were well at post-discharge reviews. The impact of widespread international travel has been reflected in the rapid international spread of COVID-19. The first recorded case outside of China was reported on 13 th January 2020 in Thailand from an individual who had travelled from Wuhan 19 . The nine patients who were admitted between 23 rd January -1 st February 2020 to NSW, VIC and QLD were the first cases of COVID-19 in each respective state. These patients were amongst the first ten cases of COVID-19 in Australia. Eight of these patients had recently travelled to Australia from Wuhan, the initial epicenter of infection. The other patient had travelled from Shenzhen, China. None had attended or had direct epidemiological links to The Huanan Seafood Wholesale Market, which was directly linked to the majority of the earliest described cases of COVID-19 20, 21 . The two SA patients in this study were admitted in late February to early March. SA-10 was diagnosed in Japan and was repatriated to Adelaide.

There was presumed human-to-human transmission as her partner was diagnosed in Japan one week earlier. Both were passengers on the Diamond Princess cruise ship in Yokohama that was linked to an outbreak of 700 cases of COVID-19 [22] [23] [24] . Thus, it is possible that SA-10 was exposed to other COVID-19 contacts onboard. The recent overseas travel history for SA-11 included London, Rome, Paris and Amsterdam. France reported three cases of COVID-19 from returned travelled from Wuhan on 24 th January, marking the first confirmed cases in Europe 25 .

The median age of our patient cohort was 42 years. Data published by the Australian COVID-19 National Incident Room Surveillance Team indicate that prior to April 2020, the median age of confirmed cases in Australia was 47 years (IQR, 29 -62) 26 . Similar to our cohort, cases of COVID-19 across male and female groups are relatively equal. The clinical characteristics and laboratory findings in this report correlate with other published international COVID-19 case series 21, [27] [28] [29] [30] [31] . The most reported symptoms were fever, cough and sore throat. None of the patients in this study required intensive care unit (ICU) admission and/or mechanical ventilation. Critically ill patients requiring ICU admission and mechanical ventilation had a higher median age of 60 -65 years 28, 30, 32 and had several comorbidities, which may account for more the severe clinical outcomes seen with advanced age. Hypertension and type two diabetes mellitus are the top two most reported co-morbidities in COVID-19 patients 33 .

Current clinical management in Australia consists of supportive care and appropriate infection prevention and control measures 18, 34 . QLD-8 presented with ongoing high-grade fever on day 7 of his illness and was treated with lopinavir-ritonavir (antiviral therapy) and intravenous piperacillin/tazobactam. His fever finally resolved on day 11 of illness. Current Australian guidelines do not recommend the use of lopinavir-ritonavir outside of randomised trials with appropriate ethics approval 34 . International randomised trials have currently concluded that there is no clinical benefit in using lopinavir-ritonavir in hospitalised COVID-19 patients 35-37 . 29, 383539 Diagnostic testing for SARS-CoV-2 RNA by RT-PCR is primarily performed on nasopharyngeal swabs, combined nose and throat swabs, and sputum samples. Our findings reported the median duration from onset of symptoms to the first SARS-CoV-2 positive respiratory sample was two days. Median documented clearance of SARS-CoV-2 from respiratory samples was 12 days from symptom onset. Studies from Singapore and China have observed viral clearance by day 10 -12 post-onset, with mild cases having an early viral clearance 29, 40 . Two patients in this case series had blood samples collected and none had SARS-CoV-2 RNA detected by RT-PCR. This correlates with the fact that neither patient developed severe acute respiratory distress, required ICU admission or mechanical ventilation. This is also consistent with published studies correlating blood viral load (RNAaemia) with disease severity 41, 42 . Studies have also reported the presence of SARS-CoV-2 in faecal samples 43 . 

In this paper we report the first clinical case series of COVID-19 in Australia during the early biocontainment phase of the national response. The authors acknowledge that one of limitations of this study is our small case size of 11 patients. However, this clinical and laboratory data was collected from four independent states in Australia, providing a historical record of the first cases of COVID-19 prior to the Australian peak at the end of March 2020. As the COVID-19 pandemic evolves on a rapid scale, these findings from the Australian perspective are critical to the global reporting of this disease. This article is protected by copyright. All rights reserved. Table 3 . Laboratory findings of patients on admission. 

World Health Organization, 2020. 2. WHO Timeline -COVID-19

COVID-19: Lessons to be learnt from a once-in-a-century global pandemic

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission

The incidence of the novel coronavirus SARS-CoV-2 among asymptomatic patients: a systematic review

Clinical characteristics of asymptomatic and symptomatic patients with mild COVID-19

First confirmed case of novel coronavirus in Australia

Isolation and rapid sharing of the 2019 novel coronavirus (SARS-CoV-2) from the first patient diagnosed with COVID-19 in Australia

Descriptive study of COVID-19 outbreak among passengers and crew on Diamond Princess cruise ship

Communicable Diseases Network Australia

CDNA National Guidelines for Public Health Units In: Department of Health

2020;44. 17. The World Health Organization. Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected

CDNA National Guidelines for Public Health Units

Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Initial Investigation of Transmission of COVID-19 Among Crew Members During Quarantine of a Cruise Ship -Yokohama

Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship

Chronology of COVID-19 Cases on the Diamond Princess Cruise Ship and Ethical Considerations: A Report From Japan

World Health Organization. 2019-nCoV outbreak: first cases confirmed in Europe

Fortnightly reporting period ending

Sixty-eight consecutive patients assessed for COVID-19 infection: Experience from a UK Regional infectious diseases Unit. Influenza Other Respir Viruses

Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region

Clinical Course and Outcomes of Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Preliminary Report of the First 28 Patients from the Korean Cohort Study on COVID-19

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis

Australian National COVID-19 Clinical Evidence Taskforce. Australian guidelines for the clinical care of people with COVID-19 2020

No clinical benefit from use of lopinavir-ritonavir in hospitalised COVID-19 patients studied in RECOVERY

A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus-A possible reference for coronavirus disease-19 treatment option

Clinical trials for the prevention and treatment of coronavirus disease 2019 (COVID-19): The current state of play

Viral dynamics in mild and severe cases of COVID-19

Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity

Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients

Prolonged presence of SARS-CoV-2 viral RNA in faecal samples

Fecal specimen diagnosis 2019 novel coronavirus-infected pneumonia

Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection

Clinical Characteristics of Coronavirus Disease 2019 in China

Case Management Team KCfDC, Prevention. Early Epidemiological and Clinical Characteristics of 28 Cases of Coronavirus Disease in South Korea

Revealing COVID-19 transmission in Australia by SARS-CoV-2 genome sequencing and agent-based modeling

An emergent clade of SARS-CoV-2 linked to returned travellers from Iran

2020. 51. Department of Health. Australian Health Sector Emergency Response Plan for Novel Coronavirus (COVID-19) Short Form Australian Government; 2020. p. 10. 52. Department of Health. COVID-19, Australia: Epidemiology Report 20. Fortnightly reporting period ending 5

Newmarch House took six days to accept government-funded coronavirus medical staff. The Guardian. 2020 26/05/2020. 54. ABC News. Coronavirus cluster at Melbourne abattoir Cedar Meats grows to 98

Criminal investigation launched into Ruby Princess cruise ship coronavirus disaster. The Guardian

Crossroads Hotel COVID-19 cluster linked to Melbourne outbreak. The Sydney Morning Herald

Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) realtime RT-PCR ORF1ab 2020 (Wuhan-ORF1ab; 2019-nCoV-related test). protocolsio

Avian coronavirus in wild aquatic birds

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RdRp nested RT-PCR. protocolsio

Virome analysis for identification of novel mammalian viruses in bats from Southeast China

Complete Coding Sequence of a Case of Chikungunya Virus Imported into Australia

Pandemic clinical case definitions are non-specific: multiple respiratory viruses circulating in the early phases of the 2009 influenza pandemic in New South Wales