Early and critical care in severe patients with COVID-19 infection in Jiangsu Province, China: a descriptive study

Background: Patients with coronavirus disease 2019 (COVID-19) infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which originated in Wuhan, China, and spreading over the country including Jiangsu Province. Our study aimed to study the epidemiological, clinical characteristics and therapies of these severe cases in Jiangsu Province. Methods: A multicenter retrospective cohort study was conducted to extract and analyze epidemiological, clinical, laboratory data and treatment of 60 severe cases with COVID-19 infection from 12 large hospitals in Jiangsu Province between Jan 24 and Feb 23, 2020. Cases were identified by real-time reverse transcription polymerase chain reaction (RT-PCR). The improvement and deterioration subgroups were compared to identify predictors of disease progression. Clinical outcomes were followed up until Feb 23, 2020. Results: A total of 631 infected cases with COVID-19 in Jiangsu Province, 60 of which were severe cases. Up until Feb 23, 2020, the mortality rate of these severe patients was 0%. The median age was 57 years (range, 26 to 97), and 58.3% were man. The body mass index (BMI) of these patients was higher, with an average of 25 kg/m². More than 90 percent of the patients had a history of contact with an infected patient or dined together, and two patients were infected while staying in the same train compartment with a confirmed patient. 51.7% of severe cases had at least one underlying disease, and low fever (80.0%) and dry cough (51.7%) were the most common symptoms. Mean acute physiology and chronic health evaluation (APACHE) II score on admission was 14±5. Acute respiratory distress syndrome (ARDS) appeared in 15% of the patients. White blood cell counts decreased in 45.0% of patients, lymphopenia in 63.3%, thrombocytopenia in 13.3%, and procalcitonin levels in 88.3% of the patients were less than 0.5 ng/mL. There were no statistically significant differences in immunoglobulin therapy and glucocorticoids


Conclusions:
The COVID-19 infection had a low mortality rate in Jiangsu Province, China.
The higher levels of troponin T and lower lymphocyte count were predictors of disease progression. Antiviral therapy with interferon was not recommended. The early prone ventilation may be an effective treatment for severe cases.

Background
The coronavirus disease 2019 (COVID-19) was a novel highly contagious disease first reported from Wuhan, Hubei Province, China on Dec 8, 2019, and then rapidly spread globally by human-to-human transmission, of which severe cases could cause difficulty breathing and acute respiratory distress syndrome. [1,2] Increasing confirmed cases and deaths pose huge challenges to public health and governance. [3] Cases have now spread to at least four continents in global. [4,5] As of Feb 23, 2020, there were more than 77,000 cases with laboratory-confirmed COVID-19 infection, and over 2,400 deaths in China.
At present, several publications have described the epidemiological characteristics, clinical manifestations, clinical prognosis, genomics characteristics and antiviral treatment of COVID-19 infection cases. [9,[12][13][14][15][16] The clinical spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia varies in different studies. In some patients, the disease changed rapidly and could quickly develop into progressive pneumonia, respiratory failure, and even death. [17,18] However, the clinical characteristics and systematic review of treatment for COVID-19 infected patients in critical condition have not been reported. Up to Feb 23, 2020, a total of 631 cases were confirmed in Jiangsu Province, among there were 60 severe cases admitted to intensive care unit (ICU). 6 Although the epidemic occurred relatively late in Jiangsu, as an infectious disease, patients with COVID-19 had to come to the hospital as soon as possible and receive early diagnosis and treatment.
Our aim was to study the epidemiological, clinical, laboratory and radiological characteristics, treatment regimens and clinical outcomes of severe patients diagnosed with COVID-19 infection in Jiangsu Province, China. We hope that our findings can provide some reference experience and theoretical basis for the treatment of severe cases of COVID-19 infection in the global community. were defined as obvious respiratory distress (respiratory rate greater than 30 breaths per minute), hypoxemia (oxygen saturation less than 93% or oxygenation index no more than 300 mmHg), and even respiratory failure requiring to be admitted to ICU. In severe patients, oxygen support referred to high flow nasal cannula (HFNC), non-invasive mechanical ventilation, invasive mechanical ventilation or early prone position ventilation.

Study Design and Patients
The oxygenation index was calculated by dividing the partial pressure of arterial oxygen (PaO₂) by the inspiratory oxygen fraction (FiO₂), and the normal value was between 400 and 500 mmHg.

Role of the funding source
This research was not funded. Corresponding authors had access to all the data in the study and are ultimately responsible for the decision to submit for publication.

Results
Demographic, and Baseline Characteristics By Feb 23, 2020, 77,048 symptomatic patients had been confirmed with the COVID-19 infection in China, of which 631 confirmed patients in Jiangsu Province, China. Further study and analysis were conducted on 60 severe cases of 631 confirmed patients from 12 hospitals in Jiangsu Province (Fig. 1).
The demographic and clinical characteristics are shown in Table 1. The 60 confirmed severe cases were positive by real-time RT-PCR test of secretions from throat swabs. 35 (58.3%) were man; the median age of the patients was 57 years (range, 26 to 97); the proportion of patients over the age of 50 was 63.3%, higher than that of patients under the age of 50. The mean BMI of the severe patients was 25 ± 3.3 kg/m². A history of contact with people from Wuhan, contact with a confirmed patient, staying in the same train compartment with the patient, and dining together was documented in 41.7%, 16.7%, 5.0% and 3.3% of patients, respectively. 3.3% were healthcare workers. 30.0% were family cluster. The mean incubation period for these patients was 7.7 ± 3.9 days. Fever (80.0%) and dry cough (51.7%) were the most common symptoms, whereas expectoration (5.0%), vomiting (3.3%) and chest pain (1.7%) were rare. Among the patients with fever, patients with temperature above 38.5 accounted for 6.7%, significantly less than those with temperature below 38.5. Thirty-one patients (51.7%) had at least one preexisting condition (i.e., hypertension, diabetes, autoimmune disease, stroke), including one pregnancy. Mean APACHE II score at admission was 14 ± 5.  All patients had abnormal imaging presentations consistent with pneumonia. The most common pattern of chest CT was bilateral patchy shadows (85.0%). Figure 2 showed the representative radiologic findings of a severe patient at the early and deterioration stages of disease.

Clinical Outcomes
As of Feb 23, 2020, no patients had died, 50 patients had significantly improved, 2 patients had been discharged, and 8 patients were still in serious conditions. The clinical outcomes were shown in the last section of Table 3. Based on the clinical outcome, patients were assigned to improvement group and deterioration group for further analysis.
Univariate analysis revealed significant differences between the patients who had improved and patients with aggravated conditions subgroups. Patients in the latter group were more likely to have lower lymphocyte count, higher levels of troponin T, and antiviral therapy with interferon. Also, this group had lower rates of the application of early prone ventilation and higher rates of non-invasive mechanical ventilation. There were no statistically significant differences between the two groups in BMI, preexisting conditions, APACHE II score, white blood cell count, platelet count, administration of glucocorticoid, immunoglobulin therapy, negative fluid balance, or HFNC (All P > 0.05).

Discussion
The study presented a cohort of 60 severe patients of COVID-19 in Jiangsu Province, China. The overall mortality rate in Jiangsu Province was 0% by Feb 23, 2020. There were 86.7% of severe patients improved or were discharged from hospital, suggesting that the COVID-19 had been effectively controlled and treated in Jiangsu Province.
There was no significant difference between male and female in these severe cases. The median age of the patients was 57 years, and the proportion of patients over the age of 50 was 63.3%. The age distribution was similar to seasonal influenza. Most patients had normal or low white blood cell count, low lymphocyte count, and less than 0.5 ng/mL of procalcitonin level. It also caused elevated levels of liver enzymes and troponin T. Lung imaging in most patients showed bilateral ground-glass lesions. These laboratory and radiologic characteristics were similar to those of some recently published studies. [14,29] At present, the commonly used antiviral drugs are abidor, lopinavir and ritonavir tablets, interferon and so on, among which the most commonly used is abidor in Jiangsu Province,

China. Patients with COVID-19 infection should also be followed up, in accordance with
WHO guidelines about the early initiation of antiviral therapy for patients with influenza.
[33] Due to the long incubation period of the disease, pneumonia patients with suspected COVID-19 infection could be given empirical antiviral treatment until COVID-19 infection was ruled out.
[19] In our study, all severe patients were treated with antiviral therapy. In terms of antibiotics, blind or inappropriate use of antibiotics should be avoided, especially in combination with broad-spectrum antibiotics. In our cohort, we mainly used a single fluoroquinolone to prevent secondary bacterial infections in severe patients.
Early studies have shown that increased serum levels of pro-inflammatory cytokines (e.g., interleukin-1 beta, interferon γ, monocyte chemotactic protein 1 and inducible protein 10) in patients with COVID-19 infection were associated with pulmonary inflammatory responses and extensive lung injury. [15] In consideration of the high amount of cytokines and inflammatory storm induced by COVID-19, glucocorticoids were frequently used to reduce inflammatory lung injury in patients with severe illness. In our study, 34 patients with COVID-19 infection were treated with glucocorticoids. All 4 patients who developed secondary infections were received glucocorticoids, although there were no statistically significant differences between the improvement and deterioration subgroups. In our study, the effect of glucocorticoids was not significant. Furthermore, low lymphocyte count were found in most patients and nearly half of them were treated with intravenous immunoglobulin, but the incidence of secondary infections did not showed significance between the two groups as well. Further larger sample size studies results are pending to provide more efficient evidence. Lung

Conclusions
The mortality rate for severe patients with COVID-19 infection in Jiangsu Province was 0%.
The BMI of these patients was higher, with an average of 25 kg/m². More than half of severe cases had at least one underlying diseases. ARDS appeared in 15% patients.
Antiviral therapy with interferon was not recommended. The higher levels of troponin T and lower lymphocyte count were predictors of disease progression. While non-invasive mechanical ventilation did not improve the prognosis of patients, further analysis showed with early prone ventilation method appeared to be the effective approach to the treatment of COVID-19 pneumonia. Further research will be needed to verify the significance of these results in clinical practice.

Declarations
We acknowledge all the medical workers involved in the diagnosis and treatment of the patients; we thank the National Health Commission of China for coordinating the collection of data for patients with COVID-19 infection.

Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate
The research was approved by the institutional ethics board of the First Affiliated Hospital of Nanjing Medical University. Written informed consent was waived in view of the urgent need to collect clinical data.

Declaration of interests
The authors declare no financial conflicts of interest.

Consent for publication
New England journal of medicine 2020.  The representative radiologic findings of a severe COVID-19 patient A: The early stage; B: The deterioration stage