Up to 14 February 2020, there remain to be nearly 10,000 critical ill patients with COVID-19 in China, and the management of this group of patients becomes the heart of the matter. We hope to provide valuable reference for other colleagues by describing their epidemiological characteristics and treatment status.
We described the epidemiological features of COVID-19 among critical ill patients. Half the patients were men over 60 years old, which were similar to that found in Wuhan and Zhejiang province, including mild and critical patients [4, 7]. According to our results, no patients in Hebei province had been exposed to the Huanan seafood market, however, familial clusters were present in nearly half of the critical ill patients, which was different with Wuhan but similar with Zhejiang. Critical group and severe group showed similar sex, age distributions as well as history of exposure, but those with underlying diseases were more likely to develop to critical type, this is similar to Chen’s study [8]. As compared with critical ill patients in Wuhan, critical ill patients in Hebei province had a higher rate of chronic medicine disease, which may predict a worse prognosis [5]. Moreover, the length of the interval between symptom onset and diagnosis was longer (༞10 days) in the critical group. The underlying diseases and the prolonged confirmation time maybe associated with the severity of the disease.
The cardinal clinical feature was fever, followed by cough, expectoration and dyspnea. Other symptoms include fatigue, myalgia, diarrhea and headache were not frequent. Cough and dyspnea were more common in patients with critical type. Chest CT changes are noticeable, most patients presented with bilateral ground-glass opacities, reticular pattern and consolidation. Lung damage was more severe in critical type than in severe type, which is also in line with the previous reports [9, 10]. Pan et al [9] found that in the early stage, one or two lobes were involved, the lung function remained normal. The consolidation area of the lung began to absorb and became a ground glass opacity or fiber cord focus as the disease progression. The ventilation function will be limited and contributed to disability.
All vital signs we recorded showed that patients in critical group had severe dyspnea and hypotension, and required stronger respiratory support or more vasoactive agents. Early studies have shown leucopenia and lymphopenia were common in general patients with COVID-19 [7, 8]. However, Huang et al [8] reported that white blood cell count and levels of inflammatory cytokines were higher in ICU patients than non-ICU patients, indicating that the cytokine storm was related to the severity of the illness. A study of autopsy [11]found that a marked reduction of the counts of peripheral CD4 and CD8 in the critical patient with COVID-19. Our data from laboratory findings gave similar results, critical type patients had higher levels of WBC, NEUT, ESR, CRP and PCT than severe type patients, but LYMPH, T cell subsets and oxygenation index were lower, suggesting stronger inflammatory responses, and severe lung injury. As a result, most patients in critical group had complications and received more broad-spectrum antibiotic or antifungal therapy. Additionally, patients with critical type had mild elevation of creatine kinase. The biomarkers of coagulation, liver and kidney function, electrolytes were within normal range, but the patients in critical group received more immunizing agents, albumin and blood products. Patients with critical type also had higher APACHE II, SOFA scores and complications, specifically of heart and kidney, which was in keeping with the results of previous studies [7, 8].
Antiviral agents, including interferon, lopinavir/ritonavir and arbidol, were given to all patients, with a few of them also received oseltamivir. The lopinavir/ritonavir is recommended in the Guidelines for Diagnosis and Treatment of Pneumonia Caused by 2019-nCoV (version 5), and arbidol is used as antiviral treatment in Russia and China for influenza infection [12]. Previous clinical studies evaluated the effect of interferon in severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), but benefits from interferon and antiviral drugs are still in discussing [13, 14].Traditional Chinese drugs had been widely used, and received good results in mild patients [15]. However, its value in critically ill patients has not been well understood. Fifteen (100%) critical type patients and 22 (90.90%) severe type patients received low-dose methylprednisolone, which was also a challenging medication. World Health Organization (WHO) recommends against the routine use of corticosteroids for treatment of ARDS or shock induced by COVID-19 pneumonia, because no clinical evidence to supports the benefits from corticosteroids in the treatment of SARS, MERS or influenza [16]. In China, combinations of low-dose and short-course methylprednisolone with immunosuppressive drugs are recommended to critical ill patients infected by COVID-19, further investigation needs to be performed in this area.
The pathogenesis of COVID-19 pneumonia is not well established. Like SARS and MERS, severe ARDS is the result of pathophysiologic processes underlying severe viral pneumonia [5, 17–20]. The severity of ARDS also varied among critical ill patients with COVID-19 pneumonia in Hebei province. Most critical type patients were in the stage of severe ARDS, and majority severe type patients were in the period of mild ARDS. Unfortunately, despite studied for decades, the treatment of severe ARDS remains supportive with lung-protective mechanical ventilation, such as low tidal-volume mechanical ventilation, prone position and extracorporeal membrane oxygenation (ECMO) [21, 22]. In our study, just 60% in critical type patients were treated with invasive mechanical ventilation, less than half of these patients received prone position, no patient received ECMO. We did not find detailed ventilator parameters in the electronic medical records. Blood gases analysis revealed a lower level of plasma PCO2, implying an unsatisfactory results of ventilator settings, sedation or analgesia. Fluid management is also a key point in ARDS. Compared with liberal fluid management, conservative fluid management could significantly decrease the degree of lung edema, the length of ventilator days, the length of ICU stay, and mortality for patients with ARDS [23, 24]. Our results showed that critical group received more fluid and more diuretics, suggesting the physicians may be aware of these guidelines but unable to follow the rules because of the severity of the illness. Some problems remain uninvestigated because the majority of patients were still receiving treatment. Further research is needed to investigate the risk factors associated with the prognosis.
There are several potential weaknesses of our retrospective analysis. First, the number of patients in this study was small, higher missing data rates are present in parameters. Second, these cases in Hebei province represented a rather small part of the critical ill patients with COVID-19 pneumonia, needing to be further evaluation in other regions. Third, at the time of data collection, most patients were still on treatment, we were unable to evaluate their prognosis.