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. The mean BMI of the severe patients was 25 ± 3.3 kg/m², which was overweight. 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. Our study provided further evidence for human-to-human transmission and airborne transmission within a certain area. Recently, several studies have confirmed that SARS-CoV-2 could also be detected in gastrointestinal tract, saliva or urine, and proposed the transmission way of digestive tract. The findings could provide useful evidence for curbing the rapid spread of the disease around the world.
The severe patients with COVID-19 infection usually presented with low fever, dry cough and muscle soreness whereas gastrointestinal symptoms were rare, and more than 50% of the patients had at least one underlying disease, suggesting that the tropism of the virus was different from that of SARS-CoV, MERS-CoV and influenza[30–32]. The APACHE II score on admission was not high, and the illness progressed slowly, and ARDS appeared in 15% of the patients and secondary bacterial or fungal infections occurred in 6.7% of the patients, indicating a low fatality rate of the disease. Based on some published studies with a large sample and national official statistics, the cumulative mortality rate was 3.17% in China out of 77,048 confirmed cases as of Feb 23, 2020, lower than that of SARS-CoV, MERS-CoV and influenza.[6, 11, 29]
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. 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. 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. 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 was an important target organ for COVID-19 viral infection, and severe infection could lead to hypoxemia and respiratory failure, even multiple organ dysfunction syndrome (MODS). The severity of hypoxemia assessed by the PaO2/FiO2 ratio was associated with mortality. Oxygen therapy to correct hypoxemia and avoid hypoxemia damage of vital organs was an important treatment measure. Having a full rest in early stage may decrease oxygen consumption. In this group of cases, through early and active oxygen therapy, including non-invasive mechanical ventilation, high-flow nasal cannula, and prone ventilation were performed early, keeping PaO2 above 60 mmHg, protecting important organs from hypoxemia are the key to effective treatment.
Our univariate analysis and logistic regression analysis demonstrated that early prone ventilation was significantly linked to an improvement of the disease. The mechanism of the improvement while ventilation under prone position reduces might due to the reduction/homogenization of lung stress/strain. However, higher levels of troponin T, lower lymphocyte count and antiviral therapy with interferon were predictors of disease progression. Therefore, the treatment of COVID-19 infection with interferon was not recommended in this study. There were also significantly statistical differences in the application of non-invasive mechanical ventilation between the improvement and deterioration subgroups. It could be explained by the fact that most patients with disease progression received the therapy of non-invasive mechanical ventilation, but non-invasive mechanical ventilation did not improve the prognosis of severe patients. We hope that our findings can provide some reference experience and theoretical basis for the treatment of severe cases of COVID-19 in the global community.
Our study has some limitations. First, as an early report on a novel human infectious disease, this study only collected data of severe patients from 12 hospitals in Jiangsu Province, China, and the sample size was limited. Second, most of the patients still under hospitalization, the comparison between different prognostic subgroups might be biased. Moreover, it was likely that some patients did not received confirmed diagnosis an/or systemic treatment leading to missing data. Finally, this is a retrospective study. We referred to internal and existing international guidelines for the diagnosis and treatment of COVID-19 infections[23, 34]. The data in this study permit a preliminary guidance of optimal management for critical patients with SARS-CoV-2 infection. Further studies are still needed.