Discussion
The main results of the present study indicated a high prevalence of
death in individuals with SARS due to COVID‑19 who required IMV. The
mortality rate was higher in individuals aged >60 years who
received azithromycin during SARS-CoV‑2 infection.
The prevalence of death (46.1%) in individuals hospitalized with SARS
due to COVID‑19 was similar to that reported in other
studies2,8. Notably, the patients included in the
present study were critically ill and treated with IMV on admission to
the ICU. These data are concerning and underscore that the high
mortality due to COVID-19 in critically ill patients may be because of
the continuous need for respiratory support and long stays in the
ICU2.
The findings of the present study confirm that the survival of
critically ill patients with COVID-19 is particularly low in elderly
men. Moreover, age of >60 years was associated with
in-hospital death. A systematic review also stated that advanced age has
been recognized as an important risk factor for COVID‑19
mortality11. One explanation is that aging leads to
impaired functioning of multiple body systems, including the immune
system, which is a factor involved in the increased mortality due to
COVID-19 in the elderly11.
Although mortality was higher in men, no statistical significance was
observed in the present study. Grasselli et al. found a
relationship between the male sex and increased mortality in patients
with COVID‑19 admitted to ICUs2. In addition to higher
mortality, another large study involving 3.1 millions of patients with
COVID-19 reported that the male sex was associated with a higher ICU
admission rate12. This phenomenon is attributed to the
fact that women have a higher number of CD4+ T cells, a more robust
cytotoxic activity of CD8+ T cells, and greater production of
immunoglobulin by B cells than men, enabling them to produce a more
efficient cellular and humoral response12.
The use of azithromycin was also associated with in-hospital death.
Azithromycin is an antibiotic with anti-inflammatory and antiviral
properties, and it was thought to have activity against
SARS-CoV‑213. However, based on different studies, a
systematic review reported that azithromycin, along with other
medications, including angiotensin-converting enzyme inhibitors,
aspirin, colchicine, hydroxychloroquine, inhaled corticosteroids,
intranasal corticosteroids, interferon beta, ivermectin,
lopinavir-ritonavir, and vitamin C, has no important benefit on any
important outcome for patients with COVID‑1914. Based
on the present study design, this association between azithromycin and
death does not indicate causality.
Dexamethasone may be beneficial in patients with COVID‑19, mainly in
more severe forms with exacerbated inflammatory activity, because of its
potential anti-inflammatory effect, which confers it the ability to
decrease gene transcription of several proinflammatory cytokines,
chemokines, and adhesion molecules by inhibiting the generation and
release of these mediators. However, dexamethasone may also prevent
B‑cell-mediated antibody production and reduce T‑cell immune function,
which may result in a higher plasma viral load and an increased risk of
secondary infections15. Although the present study did
not report an association of dexamethasone use with mortality, a
randomized clinical trial in patients hospitalized with COVID‑19 in the
United Kingdom comparing the use of 6 mg dexamethasone once daily for 10
days to placebo reported reduced 28-day mortality rate in patients with
COVID-19 receiving either IMV or oxygen therapy without IMV, with no
impact on mild cases without respiratory support16.
Based on the current evidence, low-dose systemic steroids may be
considered for specific patients with COVID-19 who are critically ill or
require supplemental oxygen. However, routine use of corticosteroids
should be avoided, particularly in patients with mild symptoms or in the
early stages of the disease unless indicated for another reason, such as
those related to an individual’s condition17,18. The
retrospective nature of this study and lack of standardization of dose
and duration of therapy may have contributed to the absence of any
association of corticosteroid use with mortality in the present study.
This is because any use of dexamethasone, whether during the ICU stay or
earlier, was considered in this study.
The prone position contributes positively to the ventilation-perfusion
ratio and to the recruitment of dependent lung segments, culminating in
the opening of collapsed dependent alveoli and thereby providing better
gas exchange and oxygenation. Among mechanically ventilated non-COVID-19
patients with severe acute respiratory distress syndrome, those who were
ventilated in the prone position had a lower mortality
rate.19 The prone position can reduce the relative
fraction of the pulmonary shunt by 30% compared with the supine group
in patients with injured lungs20. A recent
meta-analysis demonstrated that the prone position improved the
PaO₂/FiO₂ ratio, with better SpO₂ than the supine position, in patients
with COVID‑1921. Despite the aforementioned beneficial
effects, the present study found an association between pronation and
death, which may actually reflect the greater severity in patients who
were pronated to improve ventilation and gas exchange. However, after
the multiple regression analysis, pronation was not confirmed as an
independent factor associated with mortality.
The limitations of this study include the observational cross-sectional
design, which made it impossible to establish a causal relationship
between the variables. In addition, the data collection considered a
sample from a medium-sized city in the State of Goiás; therefore,
generalization of the results to the rest of the Brazilian population
must be done with caution. Variables that included previous lung disease
had a low prevalence; therefore, it was impossible to establish an
association with the outcome variable or to associate the use of drugs,
such as chloroquine and hydroxychloroquine, with mortality. In addition,
variables, such as the length of hospital stay, ventilation parameters,
and laboratory tests, were not examined. The authors recommend examining
these variables in future studies.