Key results
Our findings reinforce the consensus that COVID-19 is an acute, life threatening disease that is associated with considerable mortality. The study highlights the importance of clinical, laboratory and radiological parameters in assessing disease severity. At admission, the most common abnormalities identified among our cohort were elevated levels of C-reactive protein, ferritin, D-dimer, abnormal chest imaging, a NEWS Score (Modified) of ≥3 and tachycardia.
Correlation with other centres’ experiences
To date, most data on COVID-19 disease has been reported from China although in recent weeks literature has started to emerge from Europe and the United States (Table 4). The baseline clinical characteristics of our population show striking similarities to those reported in studies from China, with regards in particular to male predominance, high prevalence of cough and fever, blood test abnormalities (including lymphopenia and elevated CRP, ferritin and D-dimer levels) and high frequency of abnormalities on chest imaging10 22-25. Cohorts reported from outside of China (e.g. Korea, Europe and United States) also identified these findings 26-30.
Table 4. Summary of studies reporting cohorts of patients requiring in-patient hospital treatment (search conducted 15th April 2020)
Study
|
Population
|
Comorbidities
|
Presentation
|
Transmission
|
Labs
|
Treatment
|
Imaging
|
Severity/Outcome
|
China (Wuhan)
|
|
|
|
|
|
|
|
|
Zhou et al9
Jin Yin-tan Hospital and Wuhan Pulmonary Hospital (Wuhan, China)
Retrospective multicentre cohort study
January 2020
|
N=191
Median age 56 (IQR 46-67)
Female 72(38%)
Male 119(62%)
|
91 (48%)
HTN (30%)
DM (19%)
CAD (8%)
Smoker 11(6%)
COPD 6(3%)
|
Median 11 days (8-14) until hospital presentation
Fever 180(94%)
Cough 151(79%)
Sputum 44(23%)
Fatigue 44(23%)
Myalgia 29(15%)
Diarrhoea 9(5%)
Nausea 7(4%)
|
No data
|
Lymphopenia (40%)
Anaemia 29 (15%)
Platelets <100 13 (7%)
ALT >40 U/L 59 (31%)
Troponin >28 pg/ml 24 (17%)
D-dimer
>0.5 to ≤1 45 (26%)
>1 72 (42%)
Ferritin >300 µ/L 102 (80%)
|
Antibiotics 181(95%)
Antiviral treatment (LPV/r) 41(21%)
Corticosteroids 57(30%)
IVIG 46(24%)
HFNC 41(21%)
NIV 26(14%)
IMV32(17%)
ECMO 3(2%)
|
Consolidation 112 (59%)
Ground-glass opacity 136 (71%)
Bilateral pulmonary infiltration 143 (75%)
|
In-patient deaths n= 54
Discharged n=137
(No active in-patients included)
General 72 (38%)
Severe 66 (35%)
Critical 53 (28%)
Sepsis 112(59%)
Respiratory failure 103(54%)
ARDS 59(31%)
ICU 50(26%)
|
Wang et al21
Zhongnan Hospital of Wuhan University
(Wuhan, China)
Retrospective single centre case series
January 2020
|
N=138
Median age 56 (IQR 42-68)
Female 63(45.7%)
Male 75 (54.3%)
|
64 (46.4%)
HTN 43(31.2%)
CV disease 20(14.5%)
DM 14(10.1%)
Malignancy 10(7.2%)
COPD 4(2.9%)
|
Median 7 days (4-8) until hospitalisation, 10 days (IQR 6-12) to ICU
Fever 136(99%)
Fatigue 96(70%)
Dry cough 82(60%)
Anorexia 55(40%)
Myalgia 48(35%)
Dyspnoea 43(31%)
Sputum 37(27%)
Pharyngitis 24(17%)
Diarrhoea 14(10%)
Nausea 14(10.1%)
|
Hospital acquired 57(41.3%)
HCW 40(29%)
Hospitalised patients 17(12.3%)
Community acquired 81(58.7%)
|
Lymphopenia 97(70.3%)
Prolonged PT 80(58%)
Raised LDH 55(40%)
|
Antibiotics
-moxifloxacin 89(64%)
-ceftriaxone 34(24.6%)
-azithromycin 25(18.1%)
Antiviral treatment (oseltamivir) 124(90%)
Corticosteroids 62 (44.9%)
OT 106(76.8%)
NIV 15(10.9%)
IMV 17(12.3%)
ECMO 4(2.9%)
|
Bilateral patchy shadows or ground glass opacity on CT imaging in all patients n=138
|
In-patient deaths n=6(4.3%)
Discharged n=47(34%)
Active in-patients n=85
acute cardiac injury 10(7.2%)
Shock 11(30.6%)
Arrythmia 16(44.4%)
ARDS 22(61%)
ICU 36(26%)
|
Guan et al22
Multi-site, 552 hospitals
Retrospective cohort study of hospitalised and OPD patients
|
N=1099
Median age 47 (35-58)
Female 459(41.9%)
|
261 (21.3%)
HTN 165(15%)
DM 81(7.4%)
CAD 27(2.5%)
HepB 23(2.1%)
COPD 12(1.1%)
Cancer 10(0.9%)
Smoker 137(12.6%)
|
Median incubation 4 days (IQR 2-7)
Fever 975(88.7%)
Cough 745(67.8%)
Fatigue 419(38.1%)
Sputum 370(33.7%)
SOB 205(18.7%)
Myalgia/arthralgia 164(14.9%)
Headache 150(13.6%)
Chills 126(11.5%)
|
Living in wuhan 483(43.9%)
Contact with Wuhan resident 442(72.3%)
|
Lymphopenia (83.2%)
Thrombocytopenia (36.2%)
Leukopenia (33.7%)
CRP >10mg/L 481/793(60.7%)
Raised LDH 277/675(41%)
Raised ALT 158/741(21.3%)
Raised d-dimer 260/560(46.4%)
Raised CK 90/657(13.7%)
|
Antibiotics 637(58%)
Antiviral (oseltamivir) 393(35.8%)
Corticosteroids 204(18.6%)
IVIG 144(13.1%)
OT 41.3%
NIV 56(5.1%)
IMV 25(2.3%)
ECMO 5(0.5%)
|
CT in n=975
Abnormality (86.2%)
Ground-glass change (56.4%)
Bilateral infiltrates (51.8%)
(Abnormalities detected on Xray in 59%)
|
Death n=15(1.4%)
Discharged 55(5%)
Active in-patients1029(93.6%)
Non-severe 926
Severe 173
Septic shock 12(1.1%)
Pneumonia 972/1067(91.1%)
ARDS 37(3.4%)
ICU 55(5%)
|
China (Outside Wuhan)
|
|
|
|
|
|
|
|
|
Yang et al23
3 hospitals in Wenzhou, Zhejiang, China
Retrospective multicentre cohort study
Jan-Feb 2020
|
N=149
Mean age 45.11 ± 13.35
Female 68
Male 81(54.4%)
|
52(34.9%)
Cardio-cerebrovascular disease 28(18.8%)
Malignancy 2(1.34%)
Endocrine disease 9(6.04%)
Respiratory disease 1(0.67%)
|
Median 6.8 days until hospitalisation
Fever 114(76.5%)
Cough 87(58.4%)
Sputum 48(32.2%)
Sore throat 21(14%)
Chills 21(14%)
Chest tightness 16(10.74%)
Headache 13(8.7%)
Diarrhoea 11(7.38%)
|
Hubei travel/residency 85
Contact with those from Hubei 49(32.9%)
No relation with Hubei 15(10%)
|
Lymphopenia 53(35.6%)
Leukopenia 22(24.2%)
Raised CRP 82(55%)
Thrombocytopenia 20(13.42%)
Increased PT 17(11.41%)
Raised d-dimer 21(14.1%)
Raised ALT 18(12.1%)
Raised LDH 45(30.2%)
|
Antibiotics 34(22.8%)
Antiviral 140(94%)
Interferon 144(96.6%)
Corticosteroids 5(3.36%)
IVIG 19(12.75%)
OT 134(89.9%)
NIV 2(1.34%)
IMV 0(0%)
|
CT abnormal in 137/149(91.9%)
|
Deaths 0(0%)
Discharged 73(49%)
Active in-patients 76(51%)
Septic shock 0(0%)
ARDS 0(0%)
ICU 0(0%)
|
Tian et al24
Multicentre cohort study
(Beijing)
Jan-Feb 2020
|
N=262
Median age 47.5
Male 127(48.5%)
|
No data
|
Days of illness onset to hospitalisation 4.5 ±3.7
Fever 215(82.1%)
Cough 120(45.8%)
Fatigue 69(26.3%)
Dyspnoea 18(6.9%)
Headache 17(6.5%)
|
Residents of Beijing 192(73.3%),50(26%) of whom travelled to Wuhan. Residents of Wuhan 53(20.2%)
Residents elsewhere 17(6.5%). Close contact with confirmed cases 116(60.4%)
No contact with confirmed cases 21(10.9%)
|
No data
|
No data
|
No data
|
Deaths 3(0.9%)
Discharges 45(17.2%)
Active in-patients 214(81.7%)
Severe 46(17.6%)
Non-severe 216(82.4%)
|
Korea
|
|
|
|
|
|
|
|
|
COVID-19 National Emergency Response Centre25
|
N=28
Mean age 42.6 years (range 20-73)
Female 13(46.4%)
Male 15(53.6%)
|
N=10(35.7%)
HTN, DM, Asthma, chronic rhinitis, dyspilidaemia, hypothyroidism
|
Fever 9(32.1%)
Sore throat 9(32.1%)
Cough/sputum 5(17.9%)
Chills 5(17.9%)
Myalgia 4(14.3%)
Weakness 3(10.7%)
Headache 3(10.7%)
|
Imported cases:
Wuhan 11(68%)
Zhuhai 1(6.3%)
Japan 1(6.3%)
Singapore 2(12.5%)
Thailand 1(6.3%)
Local transmission 10
|
No data
|
No data
|
No data
|
No data
|
Europe
|
|
|
|
|
|
|
|
|
Spiteri et al26
WHO, ECDC surveillance report
|
N=38 (35 hospitalised)
Median age 42(range 2-81 years)
Male 25
|
Cardiac disease 1
Obesity 1
|
Median days symptomatic before hospitalisation 3.7 (range 0-10)
Of 31 patients:
Fever 20
Cough 14
Weakness 8
headache 6
sore throat 2
rhinorrhoea 2
SOB 2
|
14 infected in China
21 infected in Europe
|
No data
|
IMV 3
|
No data
|
Death 1
Discharged 20
4 active in-patients
ICU 3
|
Grasselli et al27
Multi centre retrospective analysis in ICU patients
(Lombardy, Italy)
|
N= 1591
Median age 63 (IQR 56-70)
Male 1304(82%)
|
N=709/1043(68%)
HTN 509(49%)
CV disease 223(21%)
DM 180(17%)
Malignancy 81(8%)
COPD 42(4%)
CKD 36(3%)
CLD 28(3%)
|
No data
|
No data
|
No data
|
NIV 137(11%)
IMV 1150(88%)
|
No data
|
Deaths 405(26%)
Discharged from ICU 256(16%)
Active patients 920(58%)
|
Caruso et al28
Single centre prospective cohort study
(Rome, Italy)
|
N=158
Mean age 57±17
Female 75(47%)
Male 83(52%)
|
No data
|
Fever 97(61%)
Cough 88(56%)
Dyspnoea 52(33%)
|
No data
|
Lymphopenia 95(60%)
Raised CRP 139(88%)
Raised LDH 128(81%)
|
No data
|
CT findings n=58
Ground glass opacification 58(100%)
Consolidation 42(72%)
|
No data
|
US
|
|
|
|
|
|
|
|
|
Arentz et al29
Single centre retrospective cohort study
(Washington)
|
N=21
(Critically ill patients in ICU)
Mean age 70 (range 42-90)
Male 52%
|
N=18(86%)
CKD 10(47.6%)
CCF 9(42.9%)
COPD 7(33.3%)
DM 7(33.3%)
OSA 6(28.6%)
Immunosuppression 3(14.3%)
|
Mean days of symptoms pre hospitalisation 3.5
(81% admitted to ICU within 24h of admission)
SOB 17(76.2%)
Fever 11(52.4%)
Cough 11(47.6%)
|
No data
|
Lymphopenia 14(67%)
Deranged LBTs 8(38%)
|
Vasopressors 14(67%)
IMV 15(71%)
|
XR chest abnormal in 95% on admission
Bilat. Reticulonodular opacities 11(52%)
Ground glass opacities 10(48%)
|
Deaths 67%
Discharged from ICU 9.5%
Active cases 24%
Cardiomyopathy 7(33%)
ARDS 100% of IMV patients
|
HTN -hypertension, DM – diabetes mellitus, CAD – coronary artery disease, COPD - chronic obstructive pulmonary disease, CKD – chronic kidney disease, CLD – chronic liver disease, CCF – congestive cardiac failure, OSA – obstructive sleep apnoea, HepB – hepatitis B, SOB- shortness of breath, ALT – alanine aminotransferase. IVIG – intravenous immunoglobulin, HFNC - high flow nasal canulae, NIV- non-invasive ventilation, IMV – invasive mechanical ventilation, ECMO – extra corporeal membrane oxygenation, OT – oxygen therapy, ARDS – acute respiratory distress syndrome, ICU – intensive care unit, CT computer tomography, PT – prothrombin time, CRP – C-reactive protein, LDH – lactate dehydrogenase, LBT- liver blood tests.
There is little consensus in the published literature to date regarding optimum therapeutic strategies. For example, the use of antibiotics has ranged from 23-95% 10 22-24. Antiviral choice and use is also variable, with one study reporting use of lopinavir/ritonavir (LPV/r) in 21%10, two studies describing oseltamivir in 90% and 35% of patients, respectively 22 23, and one study reporting ‘antiviral’ administration in 94% without specifying which drugs were used 24. The reported rates of systemic corticosteroids has ranged from 3%24 to 45%22 and the reported rates of use of intravenous immunoglobulin (IVIG) has ranged from 1324-24%10. The reported rates requiring supplemental oxygenation for COVID-19 infection has ranged from 21%10 to 90%24 with reported rates of ventilation ranging from 0%24 to 17%10.
Spiteri et al describe the first 38 cases in Europe with comparable prevalence of IMV at 9% of hospitalized patients. Since the studies from the United States and Italy (see Table 4) primarily describe patients in an Intensive Care Unit (ICU) setting, the proportion of patients requiring ventilation is higher at 71-88% 28 30. The median length of stay in studies from China has ranged from 10-12 days where such data was available 4 10 23. This is comparable to our cohort who spent a median of nine days in hospital. Furthermore, the rate of complications including requirement for ICU admission, development of ARDS and death also appear comparable to that reported previously.
To date, the largest cohorts have been reported by Guan et al 23, who reported 1099 patients across multiple sites in China and Grasselli et al28, who reported on 1591 patients admitted to ICUs in Lombardy, Italy. In terms of size, setting and population, the studies which report on a setting most similar to ours are Wang et al22 (retrospective study of 138 patients attending Zhongnan Hospital of Wuhan University, China), Yang et al24 (retrospective study of 149 patients attending three hospitals in Wenzhou, Zhejiang, China) and Caruso et al29 (single centre prospective cohort study of 158 patients hospitalised in Rome, Italy). Our findings are comparable with these other centres with regard to male gender, age, symptoms at presentation, treatment requirements and laboratory abnormalities. Of our cohort, 75% have been discharged and this is higher than that reported by Wang et al22 and Yang et al24. However, our observed mortality rate of 4% died is the same as that reported by Wang et al22. Finally, our cohort characteristics are consistent with those reported in Ireland overall, in terms of age and those most at risk of severe illness being those with an underlying health condition 3.
Our findings differ from that reported in other cohorts in that more people had a pre-existing chronic illness. While respiratory symptoms and fever were common among our sample, we also observed less specific symptoms such as myalgia, fatigue and gastrointestinal symptoms (e.g. nausea, diarrhoea) more commonly than has been previously reported.
In our sample, the application (albeit post hoc) of standard ‘early warning scores’ 16 17 would have resulted in less than half of people who required admission actually being admitted (45% using NEWS and 48% using NEWS2 parameter, respectively). We therefore recommend against relying on these measures alone when assessing requirement for patient admission, since these scoring systems were developed to aid in decision making for patients with bacterial sepsis as opposed to viral pneumonitis due to COVID-19.
Methodological considerations
This paper reports on real world data from a University teaching hospital in Dublin with a high incidence of COVID-19 disease. As the disease has unfolded it has become apparent that communities living in our local catchment area are especially at risk of the infection and its deleterious consequences 31 and this finding has been reported in other large cities 32. The data was collected as our understanding of the natural history of this disease was unfolding. In that regard, while we endeavoured to ensure that the dataset is as complete as possible, this was not always possible and some data points were therefore missing. Nonetheless, we strove to minimise the bias resulting from this by reviewing clinical and administrative records and treating such missing data in accordance with ‘STROBE Guidance’19.
We acknowledge a number of limitations in our study. Firstly, there may have been a low threshold to admit patients for hospital treatment due to an initial containment strategy and relative absence of capacity constraints at the outbreak’s onset. This may continue to change as both hospital bed capacity and our understanding of the factors associated with worse outcomes evolves in the months ahead. The sample size, while small, is nonetheless, at the time of writing, one of the ten largest cohorts reported to date and to our knowledge the first such from Ireland or the UK.