Our analysis of critically ill patients with COVID–19 revealed that this disease affected older patients with comorbidities. These patients had severe hypoxia/ ARDS, and the majority of them required mechanical ventilation. Some of these patients needed prone ventilation and ECMO to maintain their gas exchange.The survivors had lower IL–6 and higher Cstat than non-survivors on the first day of ICU admission. The dynamic assessment of variables indicated that the persistent elevation in PaCO2, LIS, HR, and neutrophil counts occurred more often in non-survivors. Also, non-survivors persistently required higher PEEP, more neuromuscular blockers and vasopressor support. Lower Cstat and higher neutrophil counts were risk factors for mortality.
To our knowledge, this is the first report to summarize the clinical features and dynamic pulmonary parameters among critically ill patients with COVID–19.
The high median age and high rate of comorbidities between this cohort of critically ill patients were similar to SARS and MERS [17,18]. The high prevalence of comorbid conditions may be explained in part by the rising prevalence of hypertension and diabetes in the Chinese population. However, it also strongly suggests that patients with such comorbid conditions are susceptible hosts for more severe complications of infection with SARS-CoV–2. Notably, cardiovascular disease was more common in non-survivors than in survivors. Future studies should validate the relationship between cardiovascular diseases and other comorbidities with the poor outcomes in critically ill patients with COVID–19. The timeline between the illness onset to ICU admission was about 10 days, which was similar to previous reports [11,13]. This time point may represent the peak viral shedding period.
At ICU admission, we noted some abnormal laboratory findings in critically ill patients with COVID–19, which included neutrophilia, lymphopenia, prolonged prothrombin time, and hypoxemia. An elevated level of lactate dehydrogenase and aspartate aminotransferase was also common. The above abnormal values indicated the presence of MODS in this systemic viral infection. In the early stage of MODS induced by SARS-CoV–2 infection, the common manifestations included ARDS, coagulation dysfunction, and acute liver injury. Furthermore, the level of white blood cell count, neutrophil count, and IL–6 were higher in non-survivors than those in survivors. Neutrophilia was also a risk factor for death in our cohort. It indicated that systemic inflammatory response syndrome (SIRS) was more obvious in non-survivors. systemic inflammation may be one of the mechanisms of MODS and death related to COVID–19 infection.
During ICU stay, ARDS and refractory hypoxemia were found to be the main presentation of the enrolled patients in our study. The Cstat and PaO2 were lower, particularly in non-survivors. In non-survivors, the PaO2/FiO2 ratio ranged 100–150 mmHg, despite being on average PEEP level of 10cmH2O. To facilitate mechanical ventilation in patients with severe hypoxemia, neuromuscular blockade, and prone ventilation were used frequently in our study, especially for the non-survivors. Low tidal volume ventilation was used in these patients, and as a result of permissive hypercapnia, hypercapnic respiratory acidosis was observed. This was even more obvious among non-survivors from day 3 to day 10. Severe and persistent hypercapnia was probably related to decreased Cstat. Thus, ECMO had to be used for improving gas exchange [19,20]. In the 50 enrolled patients, 15 underwent prone positioning, and 17 were initiated on ECMO. Up to February 15, 6 patients were weaned off ECMO successfully, and the other 7 were still on ECMO, excluding 4 patients who died on ECMO. ECMO was used during the SARS and H1N1 influenza epidemics and has been considered as a useful management measure to salvage the severe ARDS patients.
There is currently no treatment recommended for coronavirus infections except for supportive care as needed [21]. Several antivirals and other agents have been used during the severe acute respiratory syndrome coronavirus (SARS-CoV) outbreak. Herein, most patients were given antiviral and glucocorticoid therapy prior to ICU admission, but the efficacy of these drugs should be assessed in the future. Secondary infection was common in the late stages of the illness and at least partly due to the prolonged ICU length of stay. Thus, controlling the secondary infection is also critical to reduce hospital mortality.
Diffuse alveolar damage with varying degrees of the organization is seen on pathologic examination in patients with SARS who have acute lung injury [22]. For our patents, severe disease with lung injury is believed to reflect an excessive host response with the production of large quantities of proinflammatory cytokines (“cytokine storm”). Angiotensin-converting enzyme 2 (ACE2) and lymphopenia may also be associated with organ injury in SARS-CoV–2 infection, as they were found in other similar viral infection outbreaks [23,24]. Other possible mechanisms include direct viral invasion; the virus was recovered from lung and stool in one report [25]. Additionally, the post-mortem examination may be needed to discover the pathogenesis of the COVID–19. We also identified the Cstat of ICU admission as a clinical risk factor for death by univariate logistic regression analysis. Additionally, increased dead space has been shown in the previous reports. Furthermore, positive pressure ventilation tends to increase alveolar dead space by increasing ventilation in alveoli that do not have a corresponding increase in perfusion, thereby worsening V/Q mismatch and hypercapnia. In fact, hypercapnia was obvious in ICU-non-survivors of our patients.
This study has several limitations. Only 36 patients were discharged (including alive and dead) were used to compare between survivors and non-survivors in this study. Due to the limited number of patients, the differences between survivors and non- survivors should be interpreted carefully. The median of ICU length of stay was 10 days, and we tracked some important data during this timeline. Future studies are needed to track temporal changes for longer periods of time to describe the whole clinical progress among critically ill patients with COVID–19. Although we collected cases from two ICU located in Wuhan, multicenter studies are needed to thoroughly describe the comorbidities and clinical features of this illness.
In conclusion, we have demonstrated that SARS-CoV–2 infection-related critical illness predominantly affects older patients with comorbidities and is associated with severe hypoxemic respiratory failure, often requiring prolonged mechanical ventilation. The low Cstat at ICU admission and continuous elevated PaCO2 indicated poor outcomes.