Discussion
The results of the current study demonstrated that the medical history,
clinical presentations, and imaging and laboratory findings of patients
with H1N1 influenza could predict the outcomes of the disease. In our
study, Chronic diseases were influential in the outcomes. Moreover,
corticosteroids effectively decreased systemic inflammation, oseltamivir
improved the prognosis, and clinical presentations did not affect the
disease outcome. Vital signs were also important in the disease’s
prognosis, and oxygen saturation had a relationship with the outcome.
There is strong evidence that age is predictive of the outcomes of the
disease. Most cases of the severe disease caused by the virus occur
among children and middle-aged adults, and almost 90% of deaths are
reported in individuals under 65 years of age.[4] Therefore,
although the attack rate in the elderly is low and older adults are at a
lower risk for contracting the disease, they are at a higher risk of
death if they contract the disease.[13] In our study, 59.4% of the
patients were less than 60 years old, and the mortality rate was 9.4%.
It is documented that most patients with the severe and fatal diseases
have coexisting chronic illnesses, and chronic illness can increase the
risk of death.[14] It should be mentioned, however, that almost
one-quarter to one-half of patients with H1N1 virus infection who are
hospitalized or die have no concurrent chronic diseases.[15] Several
risk factors for severe influenza have been documented, such as
pregnancy, diabetes, cardiovascular disease, and several pulmonary
diseases such as obstructive sleep apnea and hypoventilation
syndrome.[16] In our study, most patients (over 81%) had at least
one chronic disease after admission, and the most common ones were
hypertension (17.8%), heart diseases (13.7%), and diabetes mellitus
(11%). Moreover, 35.8% of patients had risk factors for chronic lung
disorders (including asthma), cardiovascular, kidney, liver, blood, or
metabolic diseases (including diabetes).
During the 2009 H1N1 pandemic, there was a heated debate over
corticosteroid administration in severe cases.[17] Some studies have
suggested a positive role for corticosteroids in severe H1N1 influenza,
most animal studies or case series without a control group.[18]
Nonetheless, according to the results of a systematic review,
corticosteroids have no beneficial effect in patients with severe H1N1
influenza and even may increase the risk of death. In our study, 26
patients had a history of corticosteroid use, but it was not possible to
demonstrate or refute any relationship between corticosteroid use and
mortality considering the small sample size.
Although the H1N1 influenza virus is resistant to many conventional
antiviral medications such as amantadine and rimantadine, it is
susceptible to the neuraminidase inhibitor such as oseltamivir (Tamiflu)
and zanamivir (Relenza).[6] Early initiation of oseltamivir therapy
in the infected persons can significantly reduce the hospitalization
duration and prevent severe disease requiring ICU admission or
death.[12] Administration of neuraminidase inhibitors can be vital
in patients with severe or progressive clinical illness or underlying
risk factors such as pregnancy, cardiovascular disease, and
diabetes.[4] In our study, the initial treatment medications were
oseltamivir, vancomycin, and levofloxacin, and 51 patients (80%)
received oseltamivir.
Clinical presentations of the H1N1 virus can vary from mild respiratory
illness to fulminant viral pneumonia. Eight to 32% of the inflicted
individuals have only mild disease, and most have a flu-like disease
with fever, cough, sore throat, and rhinorrhea. [19]
Gastrointestinal presentations such as nausea, vomiting, and diarrhea
can develop in adults with severe disease.[20] The present study’s
most common clinical manifestations were cough, fever, myalgia, sputum,
chills, and shortness of breath, respectively. Our records demonstrated
gastrointestinal presentations were more common in deceased patients.
One of the most important predictors of severe H1N1, hospitalization,
and death is diffuse viral pneumonitis, which initially presents with
severe hypoxemia.[21] Several studies have concluded that in
patients with H1N1, at the initial stages, the Sp02 value may be
considered a reliable predictor of fulminant disease.[22]
Consistently, our findings demonstrated that there was a significant
relationship between the outcome of the disease and the pulse rate
(P=0.012) and breathing rate (P<0.0001) in the patients.
Amongst deceased patients, a significant decrease in oxygen saturation
(ODDs Ratio = 0.821), and increased pulse rate (ODDs Ratio = 1.03) and
respiratory rate (ODDs Ratio = 1.30) were noted.
In patients with severe disease, laboratory investigations at the
initial stages usually demonstrate slightly decreased WBC counts with
lymphocytopenia and a rise in serum aminotransferase levels, lactate
dehydrogenase, creatine kinase, and creatinine.[21] It is documented
that the levels of the alanine aminotransferase (ALT), aspartate
aminotransferase (AST), alkaline phosphatase (ALP), and
gamma-glutamyltransferase (GGT) can reflect the potential liver damages
at the initial stages of the disease.[23] In our study, there were
no significant differences in WBC, Hb, Plat, ESR, CRP and AST between
the deceased patients and those who survived. However, there was an
increase in ALP (ODDs Ratio = 1.01) and ALT (ODDs Ratio = 1.12) levels
in deceased patients. It should be noted that the patients had no
history of preexisting liver diseases.
In patients with H1N1 influenza, CT scan imaging at the early stages
usually demonstrates bilateral multifocal asymmetric GGOs and
consolidations, which are predominantly in the subpleural and
peri-bronchovascular regions of the lungs.[24] In the present study,
in more than 53% of the patients, all lung lobes were symmetrically and
homogenously involved. Moreover, we observed that the most common lesion
pattern was GGO with and without consolidation, which was observed in
over 23% of patients. The centrilobular nodule was also reported in
19.1% of patients. The location of involvement was central, peripheral
(27%), and posterior (22%); in 94%, the margin was ill-defined. None
of the CT scan imaging patterns were related to the ultimate outcome of
the disease.