The SARS-CoV-2, influenza A H7N9 and H1N1 viruses all belong to the RNA viruses, which spread through the respiratory tract or close contact, and damage multiple organs including the lungs . The RT-PCR is widely used for the diagnose of patients with SARS-CoV-2 infection. However, the quantification of viral genomes cannot be used to evaluate the severity of pneumonia when planning management for patients. Nevertheless, the routine examination of patients with pneumonia through the hematological and radiological methods help clinicians to assess risk and predict prognosis of patients, which show special advantage when treating the patients with uncleared etiology. In this article, the clinical parameters of hematological and radiological examinations were comprehensively compared in between COVID-19 and H7N9/H1N1 pneumonia, which indicate the different clinical characteristics of the three pneumonia.
In this research, we found the higher proportion of male patients in the H7N9 group, which was similar to the data from some previous clinical studies, which can be explained by more involvement of males in poultry breeding and slaughtering [7–9]. By comparison, cough and chest tightness were more common in the influenza groups compared with the COVID-19 group. However, these symptoms belong to the common symptoms of pneumonia, which are unspecific parameters useless for the distinguishing of different viral pneumonia. Therefore, careful inquiries of epidemiological history and clinical manifestations may be helpful. Interestingly, our research showed that those symptoms of COVID-19 patients were milder and had better prognosis compared with the influenza groups. The patients with COVID-19 had less underlying chronic disease and lower APACHE II score (within 24 hours) compared with the influenza groups. For this reason, the patients in the COVID-19 group received less life support treatment, and consequently had lower mortality compared with the influenza group. Similar to our findings, a case-control study found that the preexisting comorbidities (hypertension excluded) were significantly associated with human infection with H7N9 . Moreover, a Spanish study in H1N1 showed that independent factors, including hospital-acquired infection, APACHE II score, underlying hematological diseases, continuous veno-venous hemofiltration, and mechanical ventilation were associated with higher mortality . The COVID-19 group had milder symptoms and better survivals, which can be explained by the early diagnosis of COVID-19 due to the rapid response of medical system facing the urgent event . Another explanation for this is the development of molecular medicine and emergency medicine from the prevalence year of H1N1 pneumonia (2009) to the outbreak of COVID-19 (2020). COVID-19 patients received more advanced testing method of RT-PCR, as well as better intensive care for critically ill patients, which accounts for the much better prognosis of COVID-19 compared to H1N1 or H7N9 patients.
Previous observations showed that severe influenza A H1N1 infections had marked lymphopenia detected by hematological examination [13, 14]. Another case report detected more lymphocyte infiltration in the lung tissue from an autopsy of H1N1 patients . Clinical studies also reported marked lymphopenia in patients with H7N9 infection, among which two death cases showed diffuse alveolar injury with lymphocyte and monocyte infiltration in percutaneous lung biopsies [7–9]. In the case of COVID-19, it was reported that hospitalized patients had some extent of lymphopenia, which was even more obvious in the patients with disease progression [16, 17]. In our study, the lymphopenia was less obvious in the COVID-19 patients compared with the influenza groups, which is in consistent with the observations in other studies. A systematic review suggested that peripheral blood leucocyte ratio was an useful infection parameter for the distinguish of bacterial and viral infection . Given the similar hemogram of patients with viral infections, a higher NLR was detected in the two influenza groups, especially in the influenza groups with patient death. A multi-center retrospective study also reported the NLR was an independent risk factor for patient survivals in H7N9 pneumonia . A retrospective observational study found that the NLR was an easily measurable, available, cost-effective and reliable parameter, which continuous monitoring may be useful for the diagnosis and treatment of COVID-19 . Taken together, these results reveal that the NLR in hematological examination is an important clinical parameter for the prediction of patient prognosis in the pneumonia caused by viral infections, including the influenza and COVID-19.
A single-center retrospective study of 242 COVID-19 cases with 52 patient death, found that the median absolute monocyte count was significantly reduced in the death group, while the NLR was significantly increased in the survival group . In our research, there was no patient death in the COVID-19 group, with the median monocyte count within the normal range. One study conducted multivariate logistic regression analysis demonstrated that age, lymphocyte percentage and monocyte count were non-specific laboratory markers predictive for COVID-19 . As a result, the relevance of monocytes in prediction of severity of COVID-19 demands further research.
Studies had reported that COVID-19 patients had increased D-dimer and fibrin/fibrinogen degradation products, while abnormalities in prothrombin time, partial thromboplastin time, and platelet counts were relatively rare [22, 23]. Three to four-fold increase of D-dimer levels was detected in the early stages of COVID-19 patients, which was associated with poor prognosis of COVID-19 patients . Measuring the level of D-dimer and coagulation parameters from the early stage can also be useful in controlling and managing of COVID-19 disease . Our data also showed that fibrinogen was elevated in the COVID-19 group, which suggested an activation of coagulation in the patients. Due to the lack of D-dimer data in the influenza groups, it was impossible to further compare the levels of D-dimer between the COVID-19 and the influenza groups.
A retrospective study of 1014 patients, which compared the accuracy between chest CT and RT-PCR in the diagnosis of potential COVID-19 patients, reported 59% positivity in RT-PCR and 88% positivity in chest CT, in which the chest CT had 97% accuracy in reference to the results of RT-PCR, which demonstrated the value of chest CT in diagnosis and monitoring the injury of COVID-19 . Studies comparing the different manifestations of CT imaging between different viral pneumonia showed that the COVID-19 had areas of rounded opacity and septal thickening in peripheral regions of lungs, while the influenza A showed diffused distribution of lesions, including multiple nodules and "tree-in-bud" sign . Another study compared the CT feature of H7N9 and H1N1 patients with acute respiratory distress syndrome (ARDS), which showed common manifestations, such as consolidation, GGO, air bronchogram, interlobular septal thickening, and nodular shadow, while pleural effusion was more specific in H7N9 pneumonia . Compared to those studies, our study showed more GGO in the COVID-19 group, while pleural effusion was rare in COVID-19 group, but more common in the H7N9 group. The days from the onset to first CT examination was shorter in the COVID-19 group, due to the active response strategy and screening of patients with fever or respiratory symptoms in COVID-19, which led to the early diagnosis of COVID-19 with milder injury in the lungs.
The limitations of this study are the small number of included cases, the long time span, the lack of comparison of the characteristics in mild cases, and the lack of inflammatory factors and infection markers.