key: cord-0043650-nux0uy7b authors: Ma, Chunxiang; Zhang, Hu title: COVID-19, a far cry from the influenza date: 2020-05-15 journal: Precis Clin Med DOI: 10.1093/pcmedi/pbaa015 sha: c35a8be2ae883edc5c817f962f84492df811c495 doc_id: 43650 cord_uid: nux0uy7b nan The outbreak of COVID-19 caused by SARS-COV-2 was declared to reach the global pandemic level by WHO on March 11, 2020. As of April 26, 2020, more than 2,900,000 COVID-19 infection cases have been confirmed in more than 200 countries with at least 200,000 reported deaths 1 . Global reinforcement comprehensive interventions have been implemented to stop the pandemic. Unfortunately, since COVID-19 developed in December, 2019, many people including the public and some professionals, have underestimated this destructive outbreak as a wave of influenza. Now that the nations have suffered great losses in lives, living and economy, it is high time that such mistaken ideology be corrected and all people and countries treat COVID-19 seriously as a strongly contagious disease rather than the flu, if the humans wish to win this battle against the pandemic. In many ways COVID-19 does look like the flu to laymen and even physicians. Firstly, it broke out in the flu season, with similar main symptoms related to the respiratory tract. Both COVID-19 and influenza are characterized by typical chest CT presentation of ground-glass opacity and consolidation, and pathological features of diffuse alveolar damage (DAD). Moreover, more than 80% of COVID-19 cases are mild or even asymptomatic 2 . As we all know, other types of human coronavirus can also lead to influenza-like illness. All these may have given people a false impression that this emerging disease is just one new subtype of influenza caused by SARS-COV-2. Secondly, lack of comprehensive knowledge about the emerging COVID-19 has made it difficult to precisely assess its infectivity, particularly in the early stage. The extraordinarily stringent measures taken in China at the early stage of epidemic, including city lockdown, successfully controlled the infection and mortality, making it sound like influenza to some extent. For example, even at its peak stage in China, the daily increase of new cases confirmed by nucleic test was at the most 4,000-5,000, still less than in the current data in some developed countries. The number of deaths was always very low with a mortality less than 0.5% in most provinces other than Hubei Province in China. Even in the worst-hit city, Wuhan, the capital of Hubei Province in China, the mortality of COVID-19 gradually increased from 2% early in February to 4% early in April, far less than that in Italy early in April. To those who regarded COVID-19 as just a wave of influenza, the later higher mortality in Hubei Province was explained as a result of public health service being overwhelmed. The low mortality in China outside Hubei Province added to this misconception. However, such low mortality may be biased due to the following reasons: 1) The other Chinese provinces adopted prompt and strict measures to contain the spread of COVID-19 in the very early stage, including denying entry for travelers from Hubei Province, not limited to Wuhan, and testing SARS-COV-2in suspected patients. The early diagnosis and treatment also substantially reduced the mortality. 2) Most patients were young adults with strong immunity, thus lower mortality. 3) Due to the small number of patients identified outside Hubei Province, the medical resources were enough for their treatment. 4) The social distancing regulations including compulsory face mask wearing in public places contributed to effective control of the morbidity and mortality in provinces outside Hubei in China. In addition, in the countries that have implemented very strict and effective measures, the infectivity and mortality are both very low too (0.6 % in South Korea 3 and zero reported for Singapore 4 ), tending to mislead the public into an understanding that COVID-19 is nothing more serious than the influenza. In terms of pathogenic mechanisms and pathological changes, SARS-CoV-2, the virus causing COVID-19, belongs to β coronaviruses, whose invading receptors are angiotensin-converting enzyme 2 (ACE2), the same as SARS-CoV and MERS-CoV. ACE2 is widely distributed in various human organs, which leads to the DAD with cellular fibrinous exudates in COVID-19 5 . In contrast, influenza is an acute respiratory disease caused by influenza viruses, with the pathogenicity being based on the surface viral antigens, hemagglutinin (HA) and neuraminidase (NA), whose entry points are the sialic acid receptors on the host cell surface 6 . HIN1 could attach to both α-2,3-sialic acid (SA) in the lower respiratory tract and α-2,6-SA in the upper respiratory tract, so its pathological manifestations of respiratory system include the DAD, extensive hemorrhage and necrotizing bronchiolitis of small airways and the necrosis, epithelial hyperplasia and squamous metaplasia of large airways 7 . In contrast, H5N1 attaches only to α-2,3-SA, so it mainly attacks alveolar and bronchioles, and the dominating pathological findings in H5N1 are the apoptosis of alveolar epithelial cells, DAD and extensive hemorrhage in the lung [8] [9] [10] [11] . It's worth noting that though DAD is the common manifestation in chest imaging for COVID-19, H1N1 and H5N1, COVID-19 is unique in the diffused bilateral ground-glass opacities 12 , while the typical presentations for H1N1 and H5N1 are consolidation in the disease area 13, 14 . Despite of the similarities between the two diseases, their differences in pathogenic mechanism and pathological changes should help to differentiate COVID-19 from influenza. In clinical manifestations, COVID-19 could cause systemic inflammation reaction and multiple organ dysfunction syndrome because its receptors are widely distributed in multiple human organs 15 . It involves not only the respiratory system but also the digestive, cardiovascular, nervous systems, therefore often manifested as symptoms in these systems [16] [17] [18] [19] . Among them gastrointestinal (GI) symptoms show a high incidence. In a retrospective study, 74 of 651 (11.4%) COVID-19 patients presented with GI symptoms at admission, including anorexia, nausea or diarrhea 20 . According to a Chinese report, symptoms accounted in even up to 79.1% COVID-19 patients 21 . Furthermore, GI symptoms are associated with the severity of COVID-19, with a higher incidence of diarrhea, nausea or vomiting in severe cases 22 , and in patients admitted into the intensive care unit (ICU) 23 . The GI damages in COVID-19 infection have been proven by GI endoscopy and histological examination, besides viral nucleocapsid proteins detected in the damage sites 24 . Moreover, the detection of virus in stool provides liable evidence for the fecal-oral route of COVID-19 24 . The potential mechanisms of GI damages in COVID-19 could be attributed to the high expression of ACE2 in GI, particularly in the colon 25 . In transmissibility and severity, the basic reproductive number (R0) of COVID-19 was estimated to be 2.2-3.79 26, 27 , as compared with the R0 of 1.3-1.7 for the H1N1 outbreak in Mexico in 2009 26 , and that of 1.14 in H5N1 28 , indicating a much higher transmissibility of COVID-19 than influenza. Moreover, COVID-19 has a mean incubation period of 5.2 days, as compared to H1N1 (2 days) and H5N1 (5 days) 26, 28 . Notably, asymptomatic transmissions have been confirmed in COVID-19 patients, with a communicable period up to three weeks 29 . These data show that COVID-19 transmission is substantially stronger than influenza. As disease severity is concerned, COVID-19 has shown an unprecedentedly high fatality rate (7% for global and 13.5% for Italy up to April 26, 2020) 1 , far greater than others, even the1918 influenza (2%) 30 . In addition, the reported rates of severe cases and the fatality rate of severe cases are 15.6% and 8.1% in COVID-19 31 but 5% and 7% respectively in H1N1 26 . Considering the advance of health care level, the contrasts in these indices could further signify that COVID-19 is actually more devastating than influenza (Table 1) . When a new respiratory epidemic emerges, we should treat it with caution and should not take for granted that it is just another wave of influenza. It is very clear that it takes time for us to understand the disease as it spreads, and that wrong preconceptions may obstacle our endeavor to curb outbreak and save lives. It is imperative to be cautious about possible pending epidemic of the emerging infectious disease and be prepared in terms of resources including personal protection equipment (PPE) and medical services to contain the potential outbreak in its early stage. Moreover, diagnostic technologies should be applied to any suspected cases as early as possible. Recently, Kang Zhang and colleagues found that artificial intelligence (AI) technologies could distinguish the chest CT of COVID-19, common pneumonia and normal controls with very high accuracy, sensitivity and specificity 32 The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. 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