Clinical features of 95 sequential hospitalised patients with novel coronavirus 2019 disease (COVID-19), the first UK cohort

Abstract

Sir, Wang and colleagues recently reported in this journal the characteristics and prognostic factors of novel coronavirus 2019 (COVID-19) disease in 339 patients over 60 years of age presenting to Renmin Hospital of Wuhan University in Wuhan, China. 1 This highlighted the higher case fatality rate in this patient group with 19.2% dying within 30 days and frequent comorbidities including hypertension, diabetes and cardiovascular disease. Numerous other case series of hospitalised patients in China have provided valuable insight into the clinical features of disease, risk factors for severity and case fatality rate. These have informed diagnostic criteria, treatment strategies and public health policy worldwide. In the largest of these, patients over 65 years of age represented 27% of patients with severe disease and 49.2% of patients admitted to the intensive care unit. 2 To date there has been limited clinical data published outside of China and none from the epidemic in the UK which is estimated to be now nearing its peak (14th April, 2020). It is anticipated that age and the frequency of co-existing comorbidities in the UK population are likely to be strong drivers of outcome of and mortality in patients hospitalised with COVID-19 disease. Here, we describe a retrospective single-centre study of all patients hospitalised with SARS-COV-2 infection from March 10th to March 30th within North Bristol NHS Trust, a large, regional teaching hospital in the UK. During this period, 95 cases were admitted to the trust and by the final day of follow up on April 6th, 21 patients (21%) had died, 44 patients (43%) had been discharged, and 30 (29%) were still inpatients. Of the 21 patients that died, 20 died within 14 days suggesting that most mortality occurs within two weeks. 7 patients were admitted to the intensive care unit, of whom 4 had died by the 6th of April, and 3 remained in intensive care. Length of stay for patients who were discharged from hospital was a median of 4 days (IQR 1-16), for those that died 8 days (IQR 6-9) and for those that remained inpatients 9 days (IQR 3-23). Longer length of stay was influenced by the timing of a positive test, which for 23 patients (24%) was more than 7 days after admission. Fifteen patients (16%) had a negative test preceding the positive result indicating some delay in diagnosis due to false negative results. The demographics, symptoms, radiology, laboratory findings and comorbidities of our patient group are presented in Tables 1 and 2 . The median age of patients was similar in both patients alive at 14 days and those that had died, at 74 and 77 respectively. No differences by gender were observed, but there were more men in the study overall (63%). Cardiovascular and cerebrovascular disease was significantly more common in those that had died by 14 days (90% vs 48%) and of these; congestive cardiac failure was the most notably associated with non-survival (35% vs 11%). Diabetes was also significantly more common in those that had died at 14 days (65% vs 32%) whilst respiratory disease was equally distributed between the two groups (30% vs 33%).The most common symptoms were fever (72%) cough (74%) and shortness of breath (43%), followed by confusion (20%). Two patients presented with anosmia. This has recently been recognised as an early clinical feature in European patients 4 and may be underrepresented in our cohort due to the frequency of advanced disease and confusion. Shortness of breath was the only symptom that was significantly more common in patients that died within 14 days (p= 0.013). Table 1 Patient demographics, comorbidities and symptoms. Table 1 Characteristic N = 951 Alive N = 751 Dead N = 201 p-value2 Age 75 (59, 82) 74 (56, 82) 77 (72, 85) 0.062 Gender >0.9  F 35 (37%) 27 (36%) 8 (40%)  M 60 (63%) 48 (64%) 12 (60%) Comorbidities All Cardiovascular disease 54 (57%) 36 (48%) 18 (90%) 0.002  Hypertension 35 (37%) 24 (32%) 11 (55%) 0.10  Ischaemic heart disease 21 (22%) 14 (19%) 7 (35%) 0.14  Cardiac failure 15 (16%) 8 (11%) 7 (35%) 0.014  Arrhythmia 13 (14%) 10 (13%) 3 (15%) >0.9  Valve disease 6 (6.3%) 6 (8.0%) 0 (0%) 0.3  Cerebrovascular 8 (8.4%) 6 (8.0%) 2 (10%) 0.7 All Respiratory disease 31 (33%) 25 (33%) 6 (30%) >0.9  Asthma 21 (22%) 17 (23%) 4 (20%) >0.9  COPD 10 (11%) 6 (8.0%) 4 (20%) 0.2  Bronchiectasis 1 (1.1%) 1 (1.3%) 0 (0%) >0.9  Obstructive Sleep Apnoea 8 (8.4%) 6 (8.0%) 2 (10%) 0.7 Gastrointestinal disease 11 (12%) 8 (11%) 3 (15%) 0.7 Endocrine disease 6 (6.3%) 4 (5.3%) 2 (10%) 0.6 Diabetes 37 (39%) 24 (32%) 13 (65%) 0.015 Malignancy 20 (21%) 17 (23%) 3 (15%) 0.6 Neurological disease 14 (15%) 11 (15%) 3 (15%) >0.9 Renal disease 22 (23%) 16 (21%) 6 (30%) 0.6 Immunocompromised 1 (1.1%) 1 (1.3%) 0 (0%) >0.9 Symptoms Fever 68 (72%) 56 (75%) 12 (60%) 0.3 Cough 70 (74%) 56 (75%) 14 (70%) 0.9 Shortness of breath 41 (43%) 27 (36%) 14 (70%) 0.013 Myalgia 13 (14%) 12 (16%) 1 (5.0%) 0.3 Confusion 20 (21%) 16 (21%) 4 (20%) >0.9 Seizure 1 (1.1%) 1 (1.3%) 0 (0%) >0.9 Headache 9 (9.5%) 9 (12%) 0 (0%) 0.2 Sore throat 6 (6.3%) 6 (8.0%) 0 (0%) 0.3 Chest pain 7 (7.4%) 6 (8.0%) 1 (5.0%) >0.9 Diarrhoea 11 (12%) 7 (9.3%) 4 (20%) 0.2 Nausea and vomiting 13 (14%) 9 (12%) 4 (20%) 0.5 Abdominal pain 5 (5.3%) 4 (5.3%) 1 (5.0%) >0.9 Constipation 4 (4.2%) 4 (5.3%) 0 (0%) 0.6 Anosmia 3 (3.2%) 3 (4.0%) 0 (0%) >0.9 1 Statistics presented: median (IQR); n (%) 2 Statistical tests performed: Wilcoxon rank-sum test; chi-square test of independence; Fisher's exact test Table 2 Patient laboratory, imaging findings and respiratory support. Table 2 Characteristic Normal Range N = 951 Alive N = 751 Dead N = 201 p-value2 C-reactive protein (mg/L) <6 42 (18, 86) 36 (14, 67) 77 (53, 124) 0.001  Not measured 3 3 0 Lymphocytes (x109/L) 1-4 0.79 (0.54, 1.23) 0.81 (0.52, 1.22) 0.73 (0.55, 1.26) 0.9  Not measured 3 3 0 Neutrophil:Lymphocyte Ratio 6 (3, 11) 6 (3, 11) 7 (4, 11) 0.6  Not measured 3 3 0 Ferritin (ug/L) 33-490 557 (235, 974) 493 (184, 948) 816 (592, 1706) 0.4  Not measured 68 54 14 Alanine aminotransferase (U/L) 10-60 26 (19, 37) 26 (19, 38) 28 (17, 37) 0.7  Not measured 17 17 0 Albumin (g/L) 35-50 31 (26, 34) 32 (27, 36) 30 (24, 32) 0.024  Not measured 16 16 0 Troponin T (ng/L) <14 25 (15, 65) 23 (15, 61) 31 (19, 66) 0.5  Not measured 60 50 10 Creatinine (umol/L) 45-84 98 (69, 138) 87 (66, 120) 117 (102, 151) 0.014  Not measured 3 3 0 Chest-X Ray Findings 0.008  Bilateral Consolidation 24 (27%) 14 (20%) 10 (50%)  Unilateral Consolidation 25 (28%) 18 (26%) 7 (35%)  No Consolidation 31 (34%) 28 (40%) 3 (15%)  Not Performed 10 (11%) 10 (14%) 0 (0%) CURB65+ Score 0.001  0 11 (14%) 11 (18%) 0 (0%)  1 16 (21%) 16 (27%) 0 (0%)  2 29 (38%) 22 (37%) 7 (41%)  3 15 (19%) 7 (12%) 8 (47%)  4 5 (6.5%) 3 (5.0%) 2 (12%)  5 1 (1.3%) 1 (1.7%) 0 (0%)  Not calculable 18 15 3 Respiratory support: <0.001  Non-invasive ventilation 10 (10.5%) 4 (5.5%) 6 (30%)  Invasive ventilation 6 (6.3%) 3 (4.1%) 3 (15%)  Oxygen 38 (40%) 27 (37%) 11 (55%)  None 39 (41%) 39 (53%) 0 (0%) 1 Statistics presented: median (IQR); n (%) 2 Statistical tests performed: Wilcoxon rank-sum test; Fisher's exact test We found significantly higher CRP and creatinine in those that died in keeping with progressive inflammation and end organ damage. Median lymphocyte count was low in both groups, ALT was raised in 5 patients and Ferritin was > 2000 in 6 patients but was performed infrequently and showed no significant difference between survivors and non-survivors. We found little evidence of viral or bacterial co-infection with rhinovirus and human metapneumovirus in 2 of the 88 patients tested and one significant respiratory isolate (K. oxytoca). However, sputum culture and testing for Legionella and Pneumococcal antigens was performed infrequently. There were 3 positive blood cultures (D. hominis, S. aureus and E. faecium) none of which were felt to be respiratory in origin. 55 patients received antibiotic therapy, including 20 of the 21 patients that died and 2 patients received antivirals (Aciclovir for suspected meningoencephalitis). Consistent with evidence supporting the use of CURB65 as a predictor of mortality secondary to community acquired pneumonia 5 we found a significantly higher median score in non-survivors versus survivors (2.5 versus 1 respectively). Patients who did not survive were more likely to have chest X-ray findings, and in particular, were more likely to have bilateral consolidation than unilateral.  40% of survivors did not have any radiological evidence of consolidation. Only 6 patients had a CT chest performed which may be useful in detecting early disease in patients that test negative by rtRT-PCR. 6 To our knowledge, this is the first description of a UK cohort of patients with SARS-COV-2 infection and the largest descriptive study of the infection outside of China. We found a much higher median age and case fatality rate than that reported by other studies of all hospitalised patients with COVID-19. All the patients that died were over the age of 60 and only 4 were admitted to intensive care. Given the current availability of beds and ventilatory equipment in the hospital during this study this does not represent deficiencies of medical care. Rather it suggests that there was an anticipated deterioration in these patients in the context of poor premorbid state, and planned decision making around intensive care unit admission. NICE guidance published during this period endorsed the use of a Clinical Frailty Scale (CFS) Score in the assessment for critical care admission which has been shown to perform better than evaluation of cognitive function or comorbidity in estimating risk of death and has been validated in intensive care outcomes. 7 ,8 Further assessment of its application to the COVID-19 pandemic is required and may be instrumental in guiding further public health policy, particularly in areas with a low prevalence where the suspension of health care services such as cancer services may be detrimental to other preventable health outcomes. In summary, despite limited stress on our health care service, around 20% of our hospitalised population died, with the majority dying outside intensive care with significant comorbidities. Further work is needed to characterise other UK cohorts. Uncited References: [3]