Guan et al, 2020 – Clinical Characteristics of Coronavirus Disease 2019 in China | INTENSIVE Review

Guan WJ, Ni ZY, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China [published online ahead of print, 2020 Feb 28]. N Engl J Med. 2020;10.1056/NEJMoa2002032.

Since it was first reported in Wuhan, China, COronaVIrus Disease 2019 (COVID-19) has spread throughout mainland China and globally. Small early studies, describing cohorts of affected patients near the disease epicentre reported high mortality rates of 4-11%.

In this study, retrospective data was obtained from 552 hospitals across China from a period between 11 December 2019 and 29 January 2020. Of 7739 patients admitted to these hospitals with laboratory confirmed SARS-CoV-2 infection, clinical data was obtained for 1099 patients (the study cohort). Patients were then classified as having either ‘severe’ or ‘non-severe’ disease based on American Thoracic Society criteria for severe community acquired pneumonia.

In this cohort, 173 admissions (15.7%) met ATS criteria for severe disease. A primary composite outcome of ICU admission, mechanical ventilation or death occurred in 67 patients (6% of total cohort) and 43/173 (24.9%) of patients with severe disease.

5% of all patients admitted to hospital required ICU admission and the overall mortality rate was 1.5%, which is lower than that reported in the above early studies. Mortality was higher among patients with severe disease (8.1%). At the data cut-off date, few patients (5%) had been discharged home, with most remaining hospitalised (93% of all patients). Of patients with severe disease, 39% required some form of mechanical ventilation (14.5% invasive), 19% were admitted to an ICU, 5% received continuous renal-replacement therapy and 5 patients (2.9%) received extra-corporeal membrane oxygenation.

This study also provided insight to clinical features of disease, with a median incubation period (where known) of 4 days, and a large proportion of patients (44%) afebrile at time of admission. Most had lymphopenia (83% of all patients, 96% of severe cases) and CT abnormalities (85% of all patients, and 95% of patients with severe disease) which may assist screening and risk stratification prior to results of viral PCR being available.

CRP was elevated in 81% of severe cases, but only half of non-severe cases, and procalcitonin was abnormal in only 3 to 14% of patients, suggesting procalcitonin may be more useful than CRP in detecting bacterial co-infection in patients with COVID-19 (although further study is required).

The rate of mortality in this study is similar to that recently reported from China CDC data, with a case-fatality rate of approximately 1% in mildy affected areas. Few patients from Hubei province were included (only 308 of >11,000 cases at time of the study), which is reflected in this study’s low mortality rate, versus a rate as high as 12% in epicentres and other crisis zones (e.g. Italy, with a recently reported mortality rate of 6.6%).

Limitations of this study include uncertainty as to how the 1066 patients were chosen for inclusion among the 7739 SARS-CoV-2 positive patients at the study hospitals, and raises the potential for selection bias and skewed outcomes compared with the greater cohort. The applicability of this data for hospitals outside China, or within crisis zones is unknown. Finally, with most patients remaining in hospital at the data cut-off date, the ultimate outcome of most patients is unknown.

This study is notable as, at the time of writing it remains the largest cohort analysis of clinical data from patients with COVID-19, other than basic epidemiological data from organisations such as China CDC. It provides a useful snapshot of the spectrum of disease outside crisis zones and identifies potential patterns which may be used to aid diagnosis and risk stratification. In addition, the primary outcome is relevant for system planning as rates of infection rise and resources become stretched. Similar studies from other regions would add to the understanding of this disease as a global phenomenon.

Further reading:

• Zhu N, Zhang D, Wang W et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. New Engl. J Med. 2020 Jan 24: 382:727-33. https://doi.org/10.1056/NEJMoa2001017

• Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA Feb 7 2020 https://doi.org/10.1001/jama.2020.1585

• Chen N, Zhou M, Dong X et al. Epidemiological and clinical characteristics of 99 Cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395:507-13. https://doi.org/10.1016/S0140-6736(20)30211-7

• Metlay J, Waterer G, Long A et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia: An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med 2019; 200(7):e45-e67. https://doi.org/10.1164/rccm.201908-1581ST

• Mizumoto K, Chowell G. Estimating risk for death from 2019 novel coronavirus disease, China, January–February 2020. Emerg Infect Dis. 2020 March 13. DOI: https://doi.org/10.3201/eid2606.200233

• Remuzzi A & Remuzzi G. COVID-19 and Italy: what next? Lancet 2020; March 12; https://doi.org/10.1016/S0140-6736(20)30627-9

Tabulated summary

Category	Epidemiology
Study question	What are the clinical characteristics of early COVID-19 patients in China?
Background	Previous studies have examined small early cohorts of patients affected by COVID-19 near the disease epicentre in China [1-3]. This study explores a larger cohort, from hospitals throughout China to better understand the clinical characteristics and severity of disease.
Design	Multicentre retrospective cohort analysis
Population	7739 patients with laboratory confirmed COVID-19 from 552 hospitals in China Clinical data obtained for 1099 (study cohort) 11 December 2019 to 29 January 2020 Patients categorised as ‘severe’ or ‘non-severe’ based on American Thoracic Society guidelines for community acquired pneumonia [4]
[Intervention]	NA
[Control]	NA
Outcome(s)	Composite end-point of ICU admission, mechanical ventilation or death
Key findings	173 (15.7%) met ATS criteria for severe community-acquired pneumonia (“severe” cohort).   Primary composite outcome occurred in 67 (6%) of all patients and 43 (24.9%) of patients in the “severe” cohort. Death occurred in 15 (1.5%) patients, of which all but one were had severe disease (14/173 patients, 8.1%).   Approximately a quarter (23.7%) of hospitalised patients had co-existing illness. A higher proportion of patients with severe disease had co-existing illness (39%)   Presenting features Median incubation period 4 days (IQR 2 to 7 days)Less than half of patients were febrile at hospital admission (44%)11% did not develop fever at any time during hospitalisation   Laboratory findings 83% had lymphocytopenia (96% of severe cases)CRP elevated in 81% of severe cases but only half of non-severe casesProcalcitonin abnormal in only 3% to 14% of casesLDH, AST &  d-dimer elevated in 50-70% of patients meeting composite end-point86% had abnormal CT84% of patients with non-severe disease95% of patients with severe disease   Complications 5% of patients were admitted to an intensive care unit (20% of severe cases)   Of the 67 patients meeting primary composite end-point of ICU admission, mechanical ventilation or death (6% of total cohort) 40% met ARDS criteria60% required mechanical ventilation7.5% required ECMO (representing 3% of severe patients)12% required renal replacement therapy   Therapies: Antibiotics used in 80% of severe casesSteroids in 45% of severe casesIntravenous immunoglobulin in 33% of severe patients and 40% of patients meeting composite outcome
Strengths	+ Largest dataset to date, both with regard to hospital and patient numbers + Highly descriptive + No loss to follow up + Clinically relevant classification scheme (severe vs. non-severe CAP) and end-points
Weaknesses	– Remains a small proportion of total cases in China during the study time period and particularly near the epicentre (only 308 of >11,000 cases in Hubei province). Characteristics and outcomes may be different in regions where resources are overwhelmed, and thus unable to devote resources to research activities. – Uncertain validity outside China (e.g. Italy reporting higher mortality rates of 6.6% [5] – Most patients remain admitted, with ultimate outcome unknown
Summary	This article is, at the time of writing, the largest cohort analysis of clinical data from patients with COVID-19, other than basic epidemiological data (e.g. China CDC). It provides a useful snapshot of the spectrum of disease and identifies potential patterns which may be used to aid diagnosis and risk stratification. In addition, the primary outcome is relevant for systems planning as rates of infection rise.

References:

[1] Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA Feb 7 2020 doi:10.1001/jama.2020.1585

[2] Chen N, Zhou M, Dong X et al. Epidemiological and clinical characteristics of 99 Cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395:507-13. Doi: 10.1016/S0140-6736(20)30211-7

[3] Zhou F, Ting Y, Ronghui et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; March 9. https://doi.org/10.1016/ S0140-6736(20)30566-3

[4] Metlay J, Waterer G, Long A et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia: An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med 2019; 200(7):e45-e67. https://doi.org/10.1164/rccm.201908-1581ST

[5] Remuzzi A & Remuzzi G. COVID-19 and Italy: what next? Lancet 2020; March 12; https://doi.org/10.1016/S0140-6736(20)30627-9