2020 Cascella The protagonist of this [cytokine] storm is interleukin 6 (IL-6). Features, Evaluation and Treatment Coronavirus (COVID-19) 2020 Chen Covid-10 lowers potassium levels BACKGROUND: SARS-CoV-2 has caused a series of COVID-19 globally. SARS-CoV-2 binds angiotensin I converting enzyme 2 (ACE2) of renin-angiotensin system (RAS) and causes prevalent hypokalemia METHODS: The patients with COVID-19 were classified into severe hypokalemia, hypokalemia, and normokalemia group. The study aimed to determine the relationship between hypokalemia and clinical features, the underlying causes and clinical implications of hypokalemia. RESULTS: By Feb 15, 2020, 175 patients with COVID-19 (92 women and 83 men; median age, 46 [IQR, 34-54] years) were admitted to hospital in Wenzhou, China, consisting 39 severe hypokalemia-, 69 hypokalemia-, and 67 normokalemia patients. Gastrointestinal symptoms were not associated with hypokalemia among 108 hypokalemia patients (P>0.05). Body temperature, CK, CK-MB, LDH, and CRP were significantly associated with the severity of hypokalemia (P<0.01). 93% of severe and critically ill patients had hypokalemia which was most common among elevated CK, CK-MB, LDH, and CRP. Urine K+ loss was the primary cause of hypokalemia. severe hypokalemia patients was given 3 g/day, adding up to an average of 34 (SD=4) g potassium during hospital stay. The exciting finding was that patients responded well to K+ supplements when they were inclined to recovery. CONCLUSIONS: Hypokalemia is prevailing in patients with COVID-19. The correction of hypokalemia is challenging because of continuous renal K+ loss resulting from the degradation of ACE2. The end of urine K+ loss indicates a good prognosis and may be a reliable, in-time, and sensitive biomarker directly reflecting the end of adverse effect on RAS system. 2020 Colson Plenty of coronaviruses but no SARS-CoV-2 separator In our reference institute for infectious diseases, we have been implementing since the end of January 2020 PCR detection of SARS-CoV-2 RNA using several systems, including those released at the European level [4]. In total, we have tested to date (as at 19 February 2020) 4,084 respiratory samples by PCR and all the tests have been negative for SARS-CoV-2. These tests were carried out on the samples of 32 suspected SARS-CoV-2 cases, 337 people repatriated at the beginning of February 2020 from China tested twice, 164 patients who died in public hospitals in Marseille between 2014 and 2019 of whom at least one respiratory sample had been sent to our laboratory, and they also included 3,214 respiratory samples sent since January 2020 to our laboratory to search for a viral aetiology. In striking contrast, we have tested 5,080 respiratory samples for various suspected respiratory viral infections since 1 January 2020 and identified in 3,380 cases respiratory viruses. In decreasing order of frequency, they were: influenza A virus (n = 794), influenza B virus (n = 588), rhinovirus (n = 567), respiratory syncytial virus (n = 361), adenovirus (n = 226), metapneumovirus (n = 192), enterovirus (n = 171), bocavirus (n = 83), parainfluenza virus (n = 24), and parechovirus (n = 8). Among the diagnosed viruses, there were also 373 common human coronaviruses (HCoV), including 205 HCoV-HKU1, 94 HCoV-NL63, 46 HCoV-OC43, and 28 HCoV-229E [5]. Furthermore, analysis of the mortality associated with these viruses has been able to show that since 1 January 2020, one patient died after being diagnosed with HCoV-HKU1, and respiratory viruses were found in 13 other patients who died, which included influenza A virus (3 cases), respiratory syncytial virus (3 cases), rhinovirus (5 cases), adenovirus (1 case) and metapneumovirus (1 case). Retrospectively, analysis of deaths in patients who have had a respiratory sample has shown that at least nine patients have died between 2017 and 2019 after being diagnosed with one of the four coronaviruses commonly circulating in humans [6]. 2020 Cryanoski Profile of a killer: the complex biology powering the coronavirus pandemic Coronaviruses are also one of the few RNA viruses with a genomic proofreading mechanism — which keeps the virus from accumulating mutations that could weaken it. That ability might be why common antivirals such as ribavirin, which can thwart viruses such as hepatitis C, have failed to subdue SARS-CoV-2. The drugs weaken viruses by inducing mutations. But in the coronaviruses, the proofreader can weed out those changes. Mutations can have their advantages for viruses. Influenza mutates up to three times more often than coronaviruses do, a pace that enables it to evolve quickly and sidestep vaccines. But coronaviruses have a special trick that gives them a deadly dynamism: they frequently recombine, swapping chunks of their RNA with other coronaviruses. Typically, this is a meaningless trading of like parts between like viruses. But when two distant coronavirus relatives end up in the same cell, recombination can lead to formidable versions that infect new cell types and jump to other species, says Rambaut The origin of SARS-CoV-2 is still an open question (see ‘Family of killers’). The virus shares 96% of its genetic material with a virus found in a bat in a cave in Yunnan, China4 — a convincing argument that it came from bats, say researchers. But there’s a crucial difference. The spike proteins of coronaviruses have a unit called a receptor-binding domain, which is central to their success in entering human cells. The SARS-CoV-2 binding domain is particularly efficient, and it differs in important ways from that of the Yunnan bat virus, which seems not to infect people5. Although the known human coronaviruses can infect many cell types, they all mainly cause respiratory infections. The difference is that the four that cause common colds easily attack the upper respiratory tract, whereas MERS-CoV and SARS-CoV have more difficulty gaining a hold there, but are more successful at infecting cells in the lungs. SARS-CoV-2, unfortunately, can do both very efficiently. That gives it two places to get a foothold, says Shu-Yuan Xiao, a pathologist at the University of Chicago, Illinois. A neighbour’s cough that sends ten viral particles your way might be enough to start an infection in your throat, but the hair-like cilia found there are likely to do their job and clear the invaders. If the neighbour is closer and coughs 100 particles towards you, the virus might be able get all the way down to the lungs, says Xiao. These varying capacities might explain why people with COVID-19 have such different experiences. The virus can start in the throat or nose, producing a cough and disrupting taste and smell, and then end there. Or it might work its way down to the lungs and debilitate that organ. How it gets down there, whether it moves cell by cell or somehow gets washed down, is not known, says Stanley Perlman, an immunologist at the University of Iowa in Iowa City who studies coronaviruses. Clemens-Martin Wendtner, an infectious-disease physician at the Munich Clinic Schwabing in Germany, says it could be a problem with the immune system that lets the virus sneak down into the lungs. Most infected people create neutralizing antibodies that are tailored by the immune system to bind with the virus and block it from entering a cell. But some people seem unable to make them, says Wendtner. That might be why some recover after a week of mild symptoms, whereas others get hit with late-onset lung disease. But the virus can also bypass the throat cells and go straight down into the lungs. Then patients might get pneumonia without the usual mild symptoms such as a cough or low-grade fever that would otherwise come first, says Wendtner. Having these two infection points means that SARS-CoV-2 can mix the transmissibility of the common cold coronaviruses with the lethality of MERS-CoV and SARS-CoV. “It is an unfortunate and dangerous combination of this coronavirus strain,” he says. The virus’s ability to infect and actively reproduce in the upper respiratory tract was something of a surprise, given that its close genetic relative, SARS-CoV, lacks that ability. Last month, Wendtner published results8 of experiments in which his team was able to culture virus from the throats of nine people with COVID-19, showing that the virus is actively reproducing and infectious there. That explains a crucial difference between the close relatives. SARS-CoV-2 can shed viral particles from the throat into saliva even before symptoms start, and these can then pass easily from person to person. SARS-CoV was much less effective at making that jump, passing only when symptoms were full-blown, making it easier to contain. These differences have led to some confusion about the lethality of SARS-CoV-2. Some experts and media reports describe it as less deadly than SARS-CoV because it kills about 1% of the people it infects, whereas SARS-CoV killed at roughly ten times that rate. But Perlman says that’s the wrong way to look at it. SARS-CoV-2 is much better at infecting people, but many of the infections don’t progress to the lungs. “Once it gets down in the lungs, it’s probably just as deadly,” he says. Many scientists are reserving judgement on whether the tamer coronaviruses were once as virulent as SARS-CoV-2. People like to think that “the other coronaviruses were terrible and became mild”, says Perlman. “That’s an optimistic way to think about what’s going on now, but we don’t have evidence.” 2020 Fan ACE2 Expression in Kidney and Testis May Cause Kidney and Testis Damage After 2019-nCoV Infection In December 2019 and January 2020, novel coronavirus (2019-nCoV) - infected pneumonia (NCIP) occurred in Wuhan, and has already posed a serious threat to public health. ACE2 (Angiotensin Converting Enzyme 2) has been shown to be one of the major receptors that mediate the entry of 2019-nCoV into human cells, which also happens in severe acute respiratory syndrome coronavirus (SARS). Several researches have indicated that some patients have abnormal renal function or even kidney damage in addition to injury in respiratory system, and the related mechanism is unknown. This arouses our interest in whether coronavirus infection will affect the urinary and male reproductive systems. Here in this study, we used the online datasets to analyze ACE2 expression in different human organs. The results indicate that ACE2 highly expresses in renal tubular cells, Leydig cells and cells in seminiferous ducts in testis. Therefore, virus might directly bind to such ACE2 positive cells and damage the kidney and testicular tissue of patients. Our results indicate that renal function evaluation and special care should be performed in 2019-nCoV patients during clinical work, because of the kidney damage caused by virus and antiviral drugs with certain renal toxicity. In addition, due to the potential pathogenicity of the virus to testicular tissues, clinicians should pay attention to the risk of testicular lesions in patients during hospitalization and later clinical follow-up, especially the assessment and appropriate intervention in young patients' fertility. 2020 Gupta Extrapulmonary manifestations of COVID-19 Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.

2020 Lui-Lu COVID-19: Attacks the1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism The novel coronavirus pneumonia (COVID-19) is an infectious acute respiratory infection caused by the novel coronavirus. The virus is a positive-strand RNA virus with high homology to bat coronavirus. In this study, conserved domain analysis, homology modeling, and molecular docking were used to compare the biological roles of certain proteins of the novel coronavirus. The results showed the ORF8 and surface glycoprotein could bind to the porphyrin, respectively. At the same time, orf1ab, ORF10, and ORF3a proteins could coordinate attack the heme on the 1-beta chain of hemoglobin to dissociate the iron to form the porphyrin. The attack will cause less and less hemoglobin that can carry oxygen and carbon dioxide. The lung cells have extremely intense poisoning and inflammatory due to the inability to exchange carbon dioxide and oxygen frequently, which eventually results in ground-glass-like lung images. The mechanism also interfered with the normal heme anabolic pathway of the human body, is expected to result in human disease. According to the validation analysis of these finds, chloroquine could prevent orf1ab, ORF3a, and ORF10 to attack the heme to form the porphyrin, and inhibit the binding of ORF8 and surface glycoproteins to porphyrins to a certain extent, effectively relieve the symptoms of respiratory distress. Favipiravir could inhibit the envelope protein and ORF7a protein bind to porphyrin, prevent the virus from entering host cells, and catching free porphyrins. Because the novel coronavirus is dependent on porphyrins, it may originate from an ancient virus. Therefore, this research is of high value to contemporary biological experiments, disease prevention, and clinical treatment. 2020 Matyasek Mutation patterns of human SARS-COV-2 and bat RaTG13 coronaviruses genomes are strongly biased towards C>U indicating rapid evolution in their hosts Background: The world pandemy caused by SARS-CoV-2 spreading has raised considerable interest about its evolutionary origin and genome structure. Here we analysed mutation patterns in 13 human SARS-COV-2 isolates and a closely related RaTG13 isolated from Rhinolophus affinis bat. We also evaluated the CpG dinucleotide contents in SARS-COV-2 and other human and animal coronavirus genomes. Results: Out of 1107 single nucleotide differences (c. 4% divergence) between human SARS-COV-2 and bat RaTG13, 672 (61%) can be attributed to C>U and U>T substitutions significantly (P<0.001) exceeding other types of SNPs. A similar trend was observed among the 13 sequenced SARS-COV-2 genomes. Accumulation of C>U mutations was also observed in a highly variable subregion encoding the ACE2 receptor contact domain. Contrast to most other coronaviruses both SARS-COV-2 and RaTG13 exhibited CpG depletion in their genomes. Conclusion: The data support that the C-to-U conversion played a significant role in the evolution of pathogenic RNA coronaviruses including SARS-COV-2. These mutations apparently also influenced amino acid composition of the SARS-Cov-2 spike protein domain receptor implicated in virus pathogenicity. We propose that SARS-COV-2 was evolving relatively long in humans following the transfer from animals before spreading world-wide. 2020 Moutal A ‘silencing’ of pain - SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia lobal spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues unabated. Binding of SARS-CoV-2’s Spike protein to host angiotensin converting enzyme 2 triggers viral entry, but other proteins may participate, including neuropilin-1 receptor (NRP-1). As both Spike protein and vascular endothelial growth factor-A (VEGF-A) – a pro-nociceptive and angiogenic factor, bind NRP-1, we tested if Spike could block VEGF-A/NRP-1 signaling. VEGF-A–triggered sensory neuronal firing was blocked by Spike protein and NRP-1 inhibitor EG00229. Pro-nociceptive behaviors of VEGF-A were similarly blocked via suppression of spontaneous spinal synaptic activity and reduction of electrogenic currents in sensory neurons. Remarkably, preventing VEGF-A/NRP-1 signaling was antiallodynic in a neuropathic pain model. A ‘silencing’ of pain via subversion of VEGF-A/NRP-1 signaling may underlie increased disease transmission in asymptomatic individuals. 2020 Puntman Cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 heme leak Heme; ignore the chloroquine nonsense "That little iron ion, along with millions of its friends released from other hemes, are now floating through your blood freely. As I mentioned before, this type of iron ion is highly reactive and causes oxidative damage. It turns out that this happens to a limited extent naturally in our bodies and we have cleanup & defense mechanisms to keep the balance. The lungs, in particular, have 3 primary defenses to maintain “iron homeostasis”, 2 of which are in the alveoli, those little sacs in your lungs we talked about earlier. The first of the two are little macrophages that roam around and scavenge up any free radicals like this oxidative iron. The second is a lining on the walls (called the epithelial surface) which has a thin layer of fluid packed with high levels of antioxidant molecules.. things like abscorbic [SIC] acid (AKA Vitamin C) among others. Well, this is usually good enough for naturally occurring rogue iron ions but with COVID-19 running rampant your body is now basically like a progressive state letting out all the prisoners out of the prisons… it’s just too much iron and it begins to overwhelm your lungs’ countermeasures, and thus begins the process of pulmonary oxidative stress. This leads to damage and inflammation, which leads to all that nasty stuff and damage you see in CT scans of COVID-19 patient lungs. Ever noticed how it’s always bilateral? (both lungs at the same time) Pneumonia rarely ever does that, but COVID-19 does… EVERY. SINGLE. TIME."