This retrospective cohort study identified several risk factors for unfavorable outcome (death or requirement of invasive mechanical ventilation at 28 days after ICU admission) in critically ill adults in Toulouse who were hospitalized with Covid-19. In particular, chronic kidney disease on ICU admission, was associated with higher odds of in-hospital unfavorable outcome. Among follow-up data, acute kidney injury and ventilator- associated pneumonia were negatively related to patient’s outcome. It is worth noting that in this cohort, data from repeated and detailed pathophysiological characterization of Covid-19 respiratory failure22 - including respiratory system mechanics - was not associated to 28 days patient’s outcome. Altogether these results, put the spotlight on the major impact of non-respiratory organ failures in this challenging clinical setting.
The case fatality rate of 15.3% in this cohort is lower to that reported among critically ill patients in Chinese7, Italian6 or American5,23 hospitals. This data could reflect a different organization of health care system. In our case, the needed amount of intensive care support has been provided by a regional network of previously existing level 2 ICUs (providing invasive and noninvasive mechanical ventilation, renal replacement therapies). Public and private hospitals participating to this network, early canceled elective operations and speed home patients with less critical illness. Those efforts permitted to rapidly increase the number of ICU free beds available for coronavirus patients (rising from 119 to 235 over February, 2020).
Kidney involvement is frequent in Covid-19; > 40% of cases have abnormal proteinuria at hospital admission19. In line with previous reports18, we have identified that acute kidney injury was observed in approximately one third of critically ill patients from our cohort. An understanding of the pathophysiological and mechanisms that can explain such a high rate of acute kidney injury is emerging. Factors as volume depletion, ventilator-induced hemodynamic effects, cytokine burden and renal tropism of SARS-CoV-2, might be common triggers and worsening factors for AKI. To our knowledge, we demonstrated for the first time that acute kidney injury is a relevant marker of disease severity and a negative prognostic factor in terms of mortality for critically ill Covid-19 patients. This result emphasizes the need for an early recognition of kidney involvement in Covid-19 and pave the way for the use of preventive and therapeutic measures to limit subsequent acute kidney injury or progression to more severe stages as aiming to reduce morbidity and mortality.
Data on the risk of secondary bacterial pneumonia in critically ill Covid-19 patients are limited. Converging evidence suggest that ventilator- associated pneumonia might be a frequent and major complication for these patients. SARS-CoV-2 can cause immune dysregulation due to increased production and circulation of cytokines, leading to hyper-inflammation and defects in lymphoid function21. In addition, it is well known that this virus infects the ciliated cells in the alveoli, and therefore stop carrying out their airway clearance activity. Finally, iatrogenic factors, as immunotherapeutics use, may contribute to increase the incidence of ventilator- associated pneumonia in this setting24. A recent report on 52 critically ill adult patients with SARS-CoV-2 pneumonia described ventilator-associated pneumonia in 11% of cases7. We confirm this result, but we observed greater (60.7%) proportion of ventilator- associated pneumonia from a larger cohort of patients. In addition, we observed that ventilator- associated pneumonia clearly worsens patient’s clinical condition and is significantly associated to unfavorable outcome. Future studies should focus on assessing the impact of preventing, identifying and treating early ventilator-associated associated pneumonia to increase the chances of successful treatment in patients with Covid-19.
We observed a sustained viral detection in throat samples in both favorable and unfavorable outcomes. Interestingly, duration of the viral shedding was significantly longer in patients with unfavorable outcome. In Influenza virus and SARS-CoV-2 infection, prolonged viral shedding was associated with fatal outcome25. We think that this might have implication for both patients’ isolation decision making and guidance about the length of antiviral treatment.
Based on current evidence and experience, chest CT scan is largely used for screening and early diagnosis of Covid-19 in high-risk groups. We have specifically explored the potential association between chest CT imaging findings and patient outcome. A blinded and standardized10–12 image analysis process shown that patients in our cohort have very extensive lung anomalies. However, it should be noted that radiological scores were not associated to patient’s outcome. Further studies are needed to know whether CT is suitable for severity assessment and patient’s prognostication in severe forms of Covid-19.
Our study has several limitations. First, the interpretation of our findings might be limited by the sample size. It is possible that critically ill patients with established goals of care that were not consistent with admission to an ICU were not included in this study. However, by including all adult patients who were admitted for Covid-19 in the 12 ICUs of our network, we believe that our study population is representative of cases diagnosed and treated in Toulouse region. Second, despite the fact that this is a retrospective study, we think that a strength of this study is that it includes a homogenous population of critically ill adults with a lung insult from a well-defined cause. In addition, we have validated the information collected through repeated direct contacts with corresponding physician in each ICU.