In this large multicentre cohort, 64 (10.2%) of 625 patients were severe or critically ill. This proportion is lower than the 17.7% reported among the 44 672 cases from Wuhan but similar to the 7.0% reported for areas outside Hubei province,3 which are lower than reported from several case series from Wuhan including 13 (32%) ICU admission among 41 cases with 6 (15%) deaths;5 11 (11%) deaths among 99 cases;6 and 36 (26.1%) ICU admissions among 138 patients, with 6 deaths (4.3%).7 Our lower proportion is likely due to several factors, including more adequate medical resources, better disease recognition and testing capacity, earlier identification of asymptomatic and mild cases and a more informed supportive care in COVID-19-designated hospitals.
Despite this being a hospital-based study, some patients had no symptoms. This is likely due to testing of contacts after the identification of an index case and the policy of hospitalization of all infected individuals at the initial stages of the epidemic, independently of the presence of symptoms. Fever, cough, and sputum were very common among patients and more frequent in patients with severely or critically illness. Fever and cough are the most common symptoms in SARS and MERS cases.8,9 Fever is a primary symptom for cytokine storms, with the production of high concentrations of cytokines stimulating abnormally excessive immune responses and inflammation. Vital signs showed severe or critically ill patients had higher body temperature and respiratory rate, and lower SpO2 on admission. SpO2 < 90% has been used as a marker for the use of glucocorticoids during the outbreak,10 and the oxygenation saturation index is associated with ARDS severity and increased mortality.11,12
Sex seems does not have an impact on severe COVID-19. Although early reports from Wuhan indicated more men than women had severe COVID-19,5,6,13 following studies reported similar proportions of men and women admitted to ICUs, suggesting sex differences disappeared with higher incidence. Earlier reports may have included more males due to a higher occupational infection risk for males in the markets and congregation places.7
Our study found that age was independently associated with severe or critically ill presentation. Age is a well well-established factor for severe/critically ill COVID-19 for individuals > 60, and especially over 80 years old.14,15 Similarly, previous reports have indicated patients in ICUs are older than non-ICU patients,7 and that CFRs are higher among older individuals.5,6,13 Older patients also have faster disease progression than younger patients,16 which is similar to the MERS and SARS presentations, in which, older age (> 60 or 45) is associated with disease severity (MERS),17,18 and mortality.19,20 Older age reflects a greater likelihood of underlying medical conditions such as hypertension, coronary heart disease, and diabetes, which predisposes to immunological vulnerabilities. Also, age-related immunosenescence may also contribute to the severe disease.21
The mean incubation period for severe or critically ill cases in Jiangsu (7 days) was longer than the 5 days (95% CI, 4.1-7.0) reported for the first 425 Wuhan patients with confirmed COVID-19.22 The mean incubation period was slightly longer for less severe than for severe or critically ill patients. Although this was not statistically significant, larger series should explore this finding, as shorter incubation periods may reflect the higher infecting doses often observed at the start of epidemics, as reported for the Middle East Respiratory Syndrome (MERS).23
In our cohort, patients with local and known exposures to confirmed COVID-19 cases were less likely to have severe/critically ill infections than patients who had been or had visitors from Wuhan and those who had no identifiable exposure. As patients with known local exposure were more likely second or third generation SARS-CoV2 transmissions and the virulence of the virus may have changed, as seen for other infections. These patients may have also been aware of the infection risk and taken protective measures which could have reduced the infection dose.
In Wuhan, many asymptomatic patients had abnormal lung CT findings on admission, which then progressed to diffuse ground-glass opacities and consolidation.24 In Jiangsu, several asymptomatic cases also had radiological changes presented as low quadrant scores and pulmonary opacity scores on admission and severe/critically-ill cases had higher CT quadrant and pulmonary opacity scores than moderate cases. Our study also identified pulmonary opacity as an independent predictor of severe/critical illness. This is consistent with the previous study reporting that the CT visual quantitative evaluation of acute lung inflammatory lesions involving each lobe in severe or critical cases was significantly higher than less severe cases.25
We found severe or critically ill patients had more obvious damage of white blood cells and immune cells such as lymphocytes with lymphocytes identified as an independent predictor of more severe disease. COVID-19 may cause the reduced T lymphocytes, especially CD4 + T and CD8 + T cells, leading to reduced IFN-γ production, which may be related to the severity of disease.26 In addition, severe or critically ill patients showed more serious organ dysfunction like reduce albumin on admission which may be a sign of reduced liver production and increased gastrointestinal or renal loss, and increased fibrinogen on admission responding to systemic inflammation and tissue damage, and more fierce inflammatory response presented as much higher level of inflammatory markers, such as C-reactive protein.
This study has several strengths. Firstly, this is one of the largest studies describing the clinical characteristics of patients with COVID-19 and risk factors for severe/critically ill infection outside the Wuhan epicentre. Secondly, the cohort includes almost all COVID-19 cases in the province, which may have reduced selection bias. Thirdly, Jiangsu province, which is far from Hubei, provides an opportunity to assess the epidemiological, laboratory and clinical features of cases imported from other provinces and local cases. Fourthly, asymptomatic and mild cases were included, which provides a more comprehensive description of the characteristics of COVID-19 cases with a broad spectrum of disease severity.
There are also limitations that need mentioning. Firstly, laboratory and radiological data had a large amount of missing data preventing their integration in the analysis. Secondly, the predictive factors identified may be subject to uncontrolled confounders by unknown/unmeasured factors such as occupation and pregnancy. Medical staff and pregnant women may have different severity profiles. Thirdly, this is a retrospective observational study and data is susceptible to measurement and information bias.
In conclusion, this study demonstrates that patients with COVID-19 in Jiangsu had a low rate of severe or critically ill presentation, with no deaths recorded. The COVID-19 severity is associated with epidemiological and clinical characteristics, laboratory tests, and radiological findings. Age, lymphocyte count, and pulmonary opacity in CT on admission were independently associated with risk of severe or critically ill COVID-19 presentation.