key: cord-0944401-bbae1qyx authors: Liu, Bin title: Free DNA, a reason for severe COVID-19 infection? date: 2020-05-05 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109812 sha: fc2bd31784a6b46e75fdf2adbc2f7a0247f93dca doc_id: 944401 cord_uid: bbae1qyx Abstract The fast-growing outbreak of 2019 novel coronaviruses (SARS-CoV-2) reached all continents except the Antarctica in merely three months. Severe SARS-CoV-2 infection (COVID-19) has a bad clinical outcome, and some reports emphasized the role of cytokine storm and dysfunctions of multiple organs. However, the etiology of severe COVID-19 has been largely unknown. Similar as SARS-CoV and MERS-CoV, SARS-CoV-2 is also thought derived from bat coronaviruses. However, it is not pathogenic for bat at all, because free DNA in cytoplasm or blood cannot bring up violent immune response in bat; but it can produce severe inflammations in human. I hypothesized that the damage induced by free DNA is a reason for severe COVID-19, which can explain many symptoms of this disease, such as cytokine storm, ARDS and muscus plug, acute injuries of heart, liver and kidney, and some special symptoms of COVID-19. My hypothesis will be helpful for better understand the etiology of severe COVID-19. MERS-CoV, SARS-CoV-2 is also thought derived from bat coronaviruses. However, 20 it is not pathogenic for bat at all, because free DNA in cytoplasm or blood cannot 21 bring up violent immune response in bat; but it can produce severe inflammations in 22 human. I hypothesized that the damage induced by free DNA is a reason for severe 23 COVID-19, which can explain many symptoms of this disease, such as cytokine 24 storm, ARDS and muscus plug, acute injuries of heart, liver and kidney, and some 25 special symptoms of COVID-19. My hypothesis will be helpful for better understand 26 the etiology of severe COVID-19. cytokines, 5,6 thus risk for "cytokine storm". In addition to these cytokines, free DNA 56 can also destroy vascular endothelial cells directly: 7 in vitro study showed it can harm 57 human umbilical vein endothelial cells. The damage of endothelial cells will boost the 58 dysfunctions of multiple organs by cytokine storm, as described as follow. 59 Meanwhile, cytokine storm will also promote the permeability of blood vessels. Level 60 of lymphocytes is thought as the early identification of risk factors for severe 61 COVID-19, [1] [2] [3] 8 while I hypothesized that it was related to free DNA-related cytokine 62 storm and blood vessel damage, which can explain many symptoms of this disease, 63 including some "special" symptoms in COVID-19, as shown in Figure 1 . have no fever at admission to hospital, but most of them will develop a fever during 143 hospital. 2 I thought that the "delayed fever" was partly due to an increasing level of 144 free DNA, in addition to the amplification of the virus. Third, many clinicians found 145 that some severe COVID-19 patients have experienced two or more "attack" even 146 after viral load was reduced. I thought that some attack was due to direct invasion by No research support for this manuscript. 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