The COVID-19 pandemic has pushed health care systems globally to the limit with the unprecedented task of managing large volumes of critically ill patients. This pandemic has affected numerous communities, and reports of overburdened hospitals, specifically critical care units, have become commonplace 4,7,8. High quality supportive care remains the foundation for ensuring that people with COVID-19 who are critically ill have the best chance of surviving. Such care in pre-pandemic times relied on sufficient expert staffing, specialized equipment, and appropriate environments of care to reliably implement a myriad of processes that are associated with better outcomes 15,17. Patients with COVID-19 treated in the ICU during periods of high ICU load or demand fared worse than those treated during times of low COVID-19 ICU load or demand. Being elderly and requiring mechanical ventilation had a stronger association with hazard of death, but ICU strain had a clear association with mortality 25.
The spectrum of disease described in our study is similar to those from the Centers for Disease Control and Prevention’s COVID-19–Associated Hospitalization Surveillance Network, the New York City area, and China.21, 24.
We noticed the shorter duration of symptoms during pre-hospitalization was related to worst survival (p < 0.001), as shown on univariate analysis. The shorter the symptoms, the worse the prognosis and faster the progression to severe presentation.
COVID-19 infection, caused by SARS-CoV-2, has led to a global pandemic. The clinical and pathological features of acute infection have been extensively published, with a wide spectrum of disease seen, from asymptomatic infection to mild self-limiting symptoms to acute respiratory failure requiring invasive mechanical ventilation (MV) 26. The most common clinical finding is fever, cough and fatigue with some laboratory findings such as increased serum ferritin, D dimers and C reactive protein (CRP) 27. Some studies reported that risk factors associated with development of acute respiratory distress syndrome and death included older age, neutrophilia, organ dysfunction, coagulopathy, and elevated D-dimer levels 45.
Previous ICU studies found mortality rates of 62% (China) and 67% (USA), but these figures had not accounted for many who were still in the ICU 41,42. However, these numbers may reflect the pandemics beginning, a time when there was not much knowledge about the virus and disease outcome. We found a lower mortality rate (25.4%), maybe related to the better understanding of the infection.
It affects more older adults and there is also a high fatality rate in this subset of patients. Acute respiratory distress syndrome (ARDS) is the primary cause of death in COVID-19 28 and a recent scope review found that for COVID-19, < 5% of patients were reported as experiencing bacterial/fungal coinfection at admission, but development of secondary infections during ICU admission is common 29,30.
As seen in our study, older ages were correlated with increased mortality on univariate (p < 0.001) and multivariate (p = 0.003) analysis as well. We found an 34% (n = 68) mortality rate, although some authors reported mortality as high as 49% in patients with critical illness 35. Regarding gender, our study found 66.3% male and 33.7% patients admitted to ICU, showing on this sample a prevalence of men entering ICU. A systematic review including 18.246 patients concluded there was no significant difference between the number of male (50.5%) and female (49.5%) patients. Individuals of all age groups were included. On the other hand, another study with 4.203 patients, 2.797 were male (66.5%) and 1.406 were female (33.5%).
Early reports have suggested an incubation period of two to 14 days, with clinical presentations ranging from mild infection to severe disease to fatal illness 9,10,11. The most commonly reported symptoms are cough, fever, and dyspnea 12,13,14,15. Myalgia and gastrointestinal symptoms, including diarrhea and nausea or vomiting, are also common.8 In the present study, myalgia was found in 25% of the patients, and was a survival predictor on univariate analysis (p < 0.001).
The need for mechanical ventilation (p = 0.000) and longer ICU stay (p = 0.002), were also correlated to worse prognosis on univariate analysis. According to other authors, 97% of patients on invasive mechanical ventilation died in a multicenter study conducted early in the Wuhan outbreak, mortality is affected by local practices, and larger studies are awaited 43. The same study reported that 53% of deaths were related to respiratory failure43.
Recent reports 12,15,16,17 suggest that approximately 14–29% of hospitalized patients with COVID-19 pneumonia require intensive care, primarily for respiratory support in the setting of hypoxic respiratory failure, with acute respiratory distress syndrome (ARDS) developing in 33% of hospitalized patients at a median time from symptom onset of eight days 9. In these reports 12,13 critically ill patients were older, more likely to be male, and to have underlying comorbidities. The mortality rate ranged from 8.7–21% among those patients admitted with pneumonia 12,14,15,16. Our findings support the observations of earlier studies, which found a high percentage of hospitalized patients of advanced age with preexisting conditions, hypertension being the most common 18,19,20.
COVID-19 rapidly spread throughout the state of São Paulo and has disproportionately affected the population, who have high rates of comorbid conditions and mean BMI of 30. The obese patients had a high incidence of unfavorable outcome, as reported previously by others authors. In the present study, obesity was present in 27.9% in the deceased group. Although it is a considerable number of patients, it was not important on univariate analysis (p = 0.748).
In the initial reports from Wuhan, China, during the early stages of the pandemic, shortness of breath was reported in 54%of patients and was associated with composite end point of admission to an ICU, use of mechanical ventilation, and death 19. A similar prevalence of dyspnea was reported in 21 critically ill patients in Washington State and in the COVID-19–Associated Hospitalization Surveillance Network database 21. In our series, dyspnea at presentation was associated with hospitalization and the need for ICU management - it was the most prevalent symptom, especially for those who were not discharged (n = 55/80.9%).
Some authors found that the prevalence of dyspnea in the ICU group was 67.2%, compared with 10.2% in the non-ICU group 31. Although dyspnea by definition may be indicative of lung involvement and therefore more severe disease, there have been reports of ‘silent hypoxia’, where oxygen saturations can fall and precipitate acute respiratory failure in the absence of dyspnea and other symptoms of respiratory distress 31,32.
However, symptoms of fever (65%), cough (60%) and myalgia (25.6%) at presentation were more common among patients in the ICU on univariable analysis, especially myalgia as predictor of survival (p = 0.001). According to Jail et col, dyspnea was the only symptom significantly associated with both severe disease (pOR 3.70, 95% CI 1.83–7.46) and ICU admission (pOR 6.55, 95% CI 4.28–10.0), being more strongly associated with the latter 31.
A recent systematic review and meta-analysis showed that COPD, CVD and hypertension were the comorbidities significantly predictive for both severe disease and ICU admission. The pORs for severe disease were as follows: COPD (6.42, 95% CI 2.44–16.9), CVD (2.70, 95% CI 1.52–4.80) and hypertension (1.97, 95% CI 1.40–2.77). COPD, CVD and hypertension were more strongly associated with ICU admission, compared with severe disease, with pORs of 17.8 (95% CI 6.56–48.2), 4.44 (95% CI 2.64–7.47), and 3.65 (95% CI 2.22–5.99), respectively 31. Those findings corroborate our data, in which COPD (p = 0.003) and cardiovascular disease (p = 0.002) patients, had higher admission to ICU, and worse prognosis as well. According to Yan et al., COPD was an extremely strong predictor for both severe disease and ICU admission 32. COPD has been identified as an independent risk factor associated with COVID-19 patients with OR of 5.97 (P < 0.001) 36. Patients with CVD and hypertension were 4.4 and 3.7 times more likely to have ICU admission, respectively, compared to patients without these comorbidities31,32.
The cardiovascular system’s complications inducted by SARS-CoV-2 includes: acute myocardial damage, myocarditis, myocardial infarction, heart failure, rhythm disorders, and thromboembolism. Also, in the treatment of COVID-19, interaction with cardiovascular drugs must be considered 34. A study, which included more than 44,000 COVID-19 patients with diseases of the cardiovascular system, showed a five-fold increase in mortality compared to initially healthy patients (10.5% and 2.3%, respectively) 35.
A substantial proportion of our patients presenting with gastrointestinal (GI) symptoms - such as diarrhea (18.5%) - required hospitalization, similar to the data reported in the COVID-19 Associated Hospitalization Surveillance Network 22. A systematic review of GI symptoms in COVID-19 showed an overall prevalence of diarrhea between 5–10%, although rates varied extensively between studies. Larger cohort studies report prevalence rates between 20–30% 37.
Another systematic review including 18.246 patients concluded there was no significant difference between the number of male (50.5%) and female (49.5%) patients. Individuals of all age groups were included 37. The prevalence of GI symptoms was similar among men and women (52.1% and 49.5%, respectively). Diarrhea was the most common GI symptom, affecting 11.5% of the patients, followed by nausea and vomiting (6.3%) and abdominal pain (2.3%). With regard to clinical severity, 17.5% of the patients were classified as severely ill, whereas 9.8% of them were considered to have a non-severe disease 37.
Reports suggest that non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) were used in between one-third and two-thirds of critically ill patients with COVID-19 in China. Minimal data exist to confirm or refute safety concerns regarding the risk of aerossol generation by these devices 38. Epidemiological data suggest that NIV was associated with nosocomial transmission of SARS; however, human laboratory data suggest that NIV does not generate aerosols. Suggestions that HFNC might be safe are questionable: studies that might be taken to support the safety of HFNC were not designed to show whether or not HFNC is aerosol generating and did not examine the spread of viruses 39. Those data were worrying in the beginning of the pandemics. Our data shows that 174 patients used nasal catheter (NC), 14 HFNC and 71 non-rebreathing mask (NRM) when entering ICU. We did not find any relation to survival according to these factors.
Liang et al. developed and validated a clinical risk score and a web-based risk calculator to predict the development of critical illness among hospitalized COVID-19 infected patients 38. The ten variables required for calculation of the risk of developing critical illness are generally readily available at hospital admission. Chest radiography abnormality, age, hemoptysis, dyspnea, unconsciousness, number of comorbidities, cancer history, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, and direct bilirubin were included in the COVID risk score. Previous studies have found several of these variables to be risk factors for severe illness related to COVID-19. Although, potential limitations of this study include a modest sample size for constructing the risk score and a relatively small sample for validation. Besides, the data for score development and validation are entirely from China. According to our laboratory findings, lymphopenia (p = 0.004), elevated D-dimer (p = 0.011) and SAPS3 level, were relevant variables on univariate analysis. The study in 710 patients by Liang et al, showed that radiological abnormalities, number of comorbidities and DHL level, were related to survival im multivariate analysis 45.
The need for vasopressors drugs might be due one or the combination of such factors: muscle blockers, septic shock, myocarditis or others myocardial disfunctions. The scenario with such findings denotes severe ill patients. We found the need for vasopressors had an impact on survival on multivariate analysis (p = 0.000).
Tracheostomy is a common procedure in critically ill patients who require an extended period of time on MV. Use of tracheostomy can facilitate weaning from MV and potentially increase the availability of intensive care unit (ICU) beds. On our analysis, 11% (22/200) of the patients who was discharged from hospital tracheostomy was performed in ICU. On the other hand, 30.9% (21/68) of the deceased group underwent tracheostomy, showing higher incidence of such procedure on the worse patients group. According to our data and previous publications, we could infer that tracheostomy did not impact on the natural history of these patients, although those who underwent the procedure had worse prognosis (p = 0.000). On the multivariate analysis, the patients who had tracheostomy had an impact on survival as well (p = 0.002). Maybe, we performed tracheostomy in patients in worse conditions for the procedure, advanced age, those who had less conditions for MV weaning, or with more comorbidities. As far as we know, there are no guidelines for COVID-19 patients in MV who should undergo or not to tracheostomy.