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.