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Coronavirus: Dexamethasone proves first life-saving drug
By Michelle Roberts

Health editor, BBC News online

A cheap and widely available drug can help save the lives of patients seriously ill with coronavirus.
The low-dose steroid treatment dexamethasone is a major breakthrough in the fight against the deadly virus, UK experts say.
The drug is part of the world's biggest trial testing existing treatments to see if they also work for coronavirus.
It cut the risk of death by a third for patients on ventilators. For those on oxygen, it cut deaths by a fifth.
Had the drug had been used to treat patients in the UK from the start of the pandemic, up to 5,000 lives could have been saved, researchers say.
And it could be of huge benefit in poorer countries with high numbers of Covid-19 patients.
Latest coronavirus updates
About 19 out of 20 patients with coronavirus recover without being admitted to hospital.
Of those who are admitted, most also recover but some may need oxygen or mechanical ventilation.
And these are the high-risk patients dexamethasone appears to help.
The drug is already used to reduce inflammation in a range of other conditions.
And it appears to help stop some of the damage that can happen when the body's immune system goes into overdrive as it tries to fight off coronavirus.
This over-reaction, a cytokine storm, can be deadly.
Chart showing effect on patients on ventilators and requiring oxygen
Presentational white space
In the trial, led by a team from Oxford University, about 2,000 hospital patients were given dexamethasone and compared with more than 4,000 who were not.
For patients on ventilators, it cut the risk of death from 40% to 28%.
For patients needing oxygen, it cut the risk of death from 25% to 20%.
Chief investigator Prof Peter Horby said: "This is the only drug so far that has been shown to reduce mortality - and it reduces it significantly. It's a major breakthrough."
Lead researcher Prof Martin Landray said the findings suggested one life could be saved for:
every eight patients on a ventilator
every 20-25 treated with oxygen
"There is a clear, clear benefit," he said.
"The treatment is up to 10 days of dexamethasone and it costs about £5 per patient.
"So essentially it costs £35 to save a life.
"This is a drug that is globally available."
When appropriate, hospital patients should now be given it without delay, Prof Landray said.
But people should not go out and buy it to take at home.
Dexamethasone does not appear to help people with milder symptoms of coronavirus who do not need help with their breathing.
The Recovery Trial, running since March, also looked at the malaria drug hydroxychloroquine, which has subsequently been ditched amid concerns it increases fatalities and heart problems.
The antiviral drug remdesivir, meanwhile, which appears to shorten recovery time for people with coronavirus, is already being made available on the NHS.
Analysis box by Fergus Walsh, health correspondent
The first drug proven to cut deaths from Covid-19 is not some new, expensive medicine but an old, cheap-as-chips steroid.
That is something to celebrate because it means patients across the world could benefit immediately.
And that is why the top-line results of this trial have been rushed out - because the implications are so huge globally.
Dexamethasone has been used since the early 1960s to treat a wide range of conditions, such as rheumatoid arthritis and asthma.
Half of all Covid patients who require a ventilator do not survive, so cutting that risk by a third would have a huge impact.
The drug is given intravenously in intensive care and in tablet form for less seriously ill patients.
So far, the only other drug proven to benefit Covid patients is remdesivir, which has been used for Ebola.
That has been shown to reduce the duration of coronavirus symptoms from 15 days to 11.
But the evidence was not strong enough to show whether it reduced mortality.
Unlike dexamethasone, remdesivir is a new drug with limited supplies and a price has yet to be announced.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-.
Features, Evaluation and Treatment Coronavirus (COVID-19)
Authors
Marco Cascella1; Michael Rajnik2; Arturo Cuomo3; Scott C. Dulebohn; Raffaela Di Napoli4. Affiliations
1 Istituto Nazionale Tumori - IRCCS - Fondazione Pascale, Via Mariano Semmola 80100, Napoli. Italy 2 Uniformed Services Un of the Health Sc
3 Istituto Nazionale Tumori - IRCCS - Fondazione Pascale. Napoli, Italy
4 Institut Jules Bordet
Last Update: March 20, 2020.
Introduction
According to the World Health Organization (WHO), viral diseases continue to emerge and represent a serious issue to public health. In the last twenty years, several viral epidemics such as the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 to 2003, and H1N1 influenza in 2009, have been recorded. Most recently, the Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia in 2012.
In a timeline that reaches the present day, an epidemic of cases with unexplained low respiratory infections detected in Wuhan, the largest metropolitan area in China's Hubei province, was first reported to the WHO Country Office in China, on December 31, 2019. Published literature can trace the beginning of symptomatic individuals back to the beginning of December 2019. As they were unable to identify the causative agent, these first cases were classified as "pneumonia of unknown etiology." The Chinese Center for Disease Control and Prevention (CDC) and local CDCs organized an intensive outbreak investigation program. The etiology of this illness is now attributed to a novel virus belonging to the coronavirus (CoV) family.
On February 11, 2020, the WHO Director-General, Dr. Tedros Adhanom Ghebreyesus, announced that the disease caused by this new CoV was a "COVID-19," which is the acronym of "coronavirus disease 2019". In the past twenty years, two additional coronavirus epidemics have occurred. SARS-CoV provoked a large-scale epidemic beginning in China and involving two dozen countries with approximately 8000 cases and 800 deaths, and the MERS-CoV that began in Saudi Arabia and has approximately 2,500 cases and 800 deaths and still causes as sporadic cases.
This new virus seems to be very contagious and has quickly spread globally. In a meeting on January 30, 2020, per the International Health Regulations (IHR, 2005), the outbreak was declared by the WHO a Public Health Emergency of International Concern (PHEIC) as it had spread to 18 countries with four countries reporting human-to-human transmission. An additional landmark occurred on February 26, 2020, as the first case of the disease, not imported from China, was recorded in the United States.
Initially, the new virus was called 2019-nCoV. Subsequently, the task of experts of the International Committee on Taxonomy of Viruses (ICTV) termed it the SARS-CoV-2 virus as it is very similar to the one that caused the SARS outbreak (SARS-CoVs).
The CoVs have become the major pathogens of emerging respiratory disease outbreaks. They are a large family of single-stranded RNA viruses (+ssRNA) that can be isolated in different animal species.[1] For reasons yet to be explained, these viruses can cross species barriers and can cause, in humans, illness ranging from the common cold to more severe diseases such as MERS and SARS. Interestingly, these latter viruses have probably originated from bats and then moving into other mammalian hosts — the Himalayan palm civet for SARS-CoV, and the dromedary camel for MERS-CoV — before jumping to humans. The dynamics of SARS-Cov-2 are currently unknown, but there is speculation that it also has an animal origin.
The potential for these viruses to grow to become a pandemic worldwide seems to be a serious public health risk. Concerning COVID-19,
the WHO raised the threat to the CoV epidemic to the "very high" level, on February 28, 2020. Probably, the effects of the epidemic caused by the new CoV has yet to emerge as the situation is quickly evolving. On March 11, as the number of COVID-19 cases outside China has increased 13 times and the number of countries involved has tripled with more than 118,000 cases in 114 countries and over 4,000 deaths, WHO declared the COVID-19 a pandemic.
World governments are at work to establish countermeasures to stem possible devastating effects. Health organizations coordinate information flows and issues directives and guidelines to best mitigate the impact of the threat. At the same time, scientists around the world work tirelessly, and information about the transmission mechanisms, the clinical spectrum of disease, new diagnostics, and prevention and therapeutic strategies are rapidly developing. Many uncertainties remain with regard to both the virus-host interaction and the evolution of the epidemic, with specific reference to the times when the epidemic will reach its peak.
At the moment, the therapeutic strategies to deal with the infection are only supportive, and prevention aimed at reducing transmission in the community is our best weapon. Aggressive isolation measures in China have led to a progressive reduction of cases in the last few days. In Italy, in geographic regions of the north, initially, and subsequently throughout the peninsula, political and health authorities are making incredible efforts to contain a shock wave that is severely testing the health system.
In the midst of the crisis, the authors have chosen to use the "Statpearls" platform because, within the PubMed scenario, it represents a unique tool that may allow them to make updates in real-time. The aim, therefore, is to collect information and scientific evidence and to provide an overview of the topic that will be continuously updated.
Etiology
CoVs are positive-stranded RNA viruses with a crown-like appearance under an electron microscope (coronam is the Latin term for crown) due to the presence of spike glycoproteins on the envelope. The subfamily Orthocoronavirinae of the Coronaviridae family (order Nidovirales) classifies into four genera of CoVs: Alphacoronavirus (alphaCoV), Betacoronavirus (betaCoV), Deltacoronavirus (deltaCoV), and Gammacoronavirus (gammaCoV). Furthermore, the betaCoV genus divides into five sub-genera or lineages.[2] Genomic characterization has shown that probably bats and rodents are the gene sources of alphaCoVs and betaCoVs. On the contrary, avian species seem to represent the gene sources of deltaCoVs and gammaCoVs.
Members of this large family of viruses can cause respiratory, enteric, hepatic, and neurological diseases in different animal species, including camels, cattle, cats, and bats. To date, seven human CoVs (HCoVs) — capable of infecting humans — have been identified. Some of HCoVs were identified in the mid-1960s, while others were only detected in the new millennium.
In general, estimates suggest that 2% of the population are healthy carriers of a CoV and that these viruses are responsible for about 5% to 10% of acute respiratory infections.[3]
Common human CoVs: HCoV-OC43, and HCoV-HKU1 (betaCoVs of the A lineage); HCoV-229E, and HCoV-NL63 (alphaCoVs). They can cause common colds and self-limiting upper respiratory infections in immunocompetent individuals. In immunocompromised subjects and the elderly, lower respiratory tract infections can occur.
Other human CoVs: SARS-CoV, SARS-CoV-2, and MERS-CoV (betaCoVs of the B and C lineage, respectively). These cause epidemics with variable clinical severity featuring respiratory and extra-respiratory manifestations. Concerning SARS-CoV, MERS-CoV, the mortality rates are up to 10% and 35%, respectively.
Thus, SARS-CoV-2 belongs to the betaCoVs category. It has round or elliptic and often pleomorphic form, and a diameter of approximately 60– 140 nm. Like other CoVs, it is sensitive to ultraviolet rays and heat. Furthermore, these viruses can be effectively inactivated by lipid solvents including ether (75%), ethanol, chlorine-containing disinfectant, peroxyacetic acid and chloroform except for chlorhexidine.
In genetic terms, Chan et al. have proven that the genome of the new HCoV, isolated from a cluster-patient with atypical pneumonia after visiting Wuhan, had 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV[4]. For this reason, the new virus was called SARS-CoV-2. Its single-stranded RNA genome contains 29891 nucleotides, encoding for 9860 amino acids. Although its origins are not entirely understood, these genomic analyses suggest that SARS-CoV-2 probably evolved from a strain found in bats. The potential amplifying mammalian host, intermediate between bats and humans, is, however, not known. Since the mutation in the original strain could have directly triggered virulence towards humans, it is not certain that this intermediary exists.
Transmission
Because the first cases of the CoVID-19 disease were linked to direct exposure to the Huanan Seafood Wholesale Market of Wuhan, the animal- to-human transmission was presumed as the main mechanism. Nevertheless, subsequent cases were not associated with this exposure mechanism. Therefore, it was concluded that the virus could also be transmitted from human-to-human, and symptomatic people are the most frequent
source of COVID-19 spread. The possibility of transmission before symptoms develop seems to be infrequent, although it cannot be excluded. Moreover, there are suggestions that individuals who remain asymptomatic could transmit the virus. This data suggests that the use of isolation is the best way to contain this epidemic.
As with other respiratory pathogens, including flu and rhinovirus, the transmission is believed to occur through respiratory droplets from coughing and sneezing. Aerosol transmission is also possible in case of protracted exposure to elevated aerosol concentrations in closed spaces. Analysis of data related to the spread of SARS-CoV-2 in China seems to indicate that close contact between individuals is necessary. The spread, in fact, is primarily limited to family members, healthcare professionals, and other close contacts.
Based on data from the first cases in Wuhan and investigations conducted by the China CDC and local CDCs, the incubation time
could be generally within 3 to 7 days and up to 2 weeks as the longest time from infection to symptoms was 12.5 days (95% CI, 9.2 to 18).
[5] This data also showed that this novel epidemic doubled about every seven days, whereas the basic reproduction number (R0 - R naught) is 2.2. In other words, on average, each patient transmits the infection to an additional 2.2 individuals. Of note, estimations of the R0 of the SARS- CoV epidemic in 2002-2003 were approximately 3.[6]
It must be emphasized that this information is the result of the first reports. Thus, further studies are needed to understand the mechanisms of transmission, the incubation times and the clinical course, and the duration of infectivity.
Epidemiology
Data provided by the WHO Health Emergency Dashboard (March 14, 06.00 am CET) report 142.320 confirmed cases worldwide since the beginning of the epidemic. 5.388 (3.78%) cases have been fatal.
In china, 81.021 (57%) cases confirmed clinically and in the laboratory, and 3.173 deaths are reported. In addition to China, there are 61.299 confirmed cases in 129 other countries. The countries with most cases are Italy (17.660) and the Islamic Republic of Iran (11.364). The epidemiological scenario, therefore, has drastically changed, as on March 3 about 92% (79.968) of the confirmed cases were recorded in China, where almost all the deaths were also recorded (2,873, 96.5%). Of note, the "confirmed" cases reported between February 13, 2020, and February 19, 2020, include both laboratory-confirmed and clinically diagnosed patients from the Hubei province.
The most up-to-date source for the epidemiology of this emerging pandemic can be found at the following sources:
The WHO Novel Coronavirus (COVID-19) Situation Board
The Johns Hopkins Center for Systems Science and Engineering site for Coronavirus Global Cases COVID-19, which uses openly public sources to track the spread of the epidemic.
Pathophysiology
CoVs are enveloped, positive-stranded RNA viruses with nucleocapsid. For addressing pathogenetic mechanisms of SARS-CoV-2, its viral structure, and genome must be considerations. In CoVs, the genomic structure is organized in a +ssRNA of approximately 30 kb in length — the largest known RNA viruses — and with a 5′-cap structure and 3′-poly-A tail. Starting from the viral RNA, the synthesis of polyprotein 1a/1ab (pp1a/pp1ab) in the host is realized. The transcription works through the replication-transcription complex (RCT) organized in double-membrane vesicles and via the synthesis of subgenomic RNAs (sgRNAs) sequences. Of note, transcription termination occurs at transcription regulatory sequences, located between the so-called open reading frames (ORFs) that work as templates for the production of subgenomic mRNAs. In the atypical CoV genome, at least six ORFs can be present. Among these, a frameshift between ORF1a and ORF1b guides the production of both pp1a and pp1ab polypeptides that are processed by virally encoded chymotrypsin-like protease (3CLpro) or main protease (Mpro), as well as one or two papain-like proteases for producing 16 non-structural proteins (nsps). Apart from ORF1a and ORF1b, other ORFs encode for structural proteins, including spike, membrane, envelope, and nucleocapsid proteins.[1] and accessory proteic chains. Different CoVs present special structural and accessory proteins translated by dedicated sgRNAs.
Pathophysiology and virulence mechanisms of CoVs, and therefore also of SARS-CoV-2 have links to the function of the nsps and structural proteins. For instance, research underlined that nsp is able to block the host innate immune response.[7] Among functions of structural proteins, the envelope has a crucial role in virus pathogenicity as it promotes viral assembly and release. However, many of these features (e.g., those of nsp 2, and 11) have not yet been described.
Among the structural elements of CoVs, there are the spike glycoproteins composed of two subunits (S1 and S2). Homotrimers of S
proteins compose the spikes on the viral surface, guiding the link to host receptors.[8] Of note, in SARS-CoV-2, the S2 subunit — containing a fusion peptide, a transmembrane domain, and cytoplasmic domain — is highly conserved. Thus, it could be a target for antiviral (anti-S2) compounds. On the contrary, the spike receptor-binding domain presents only a 40% amino acid identity with other SARS-CoVs. Other structural elements on which research must necessarily focus are the ORF3b that has no homology with that of SARS-CoVs and a secreted protein (encoded by ORF8), which is structurally different from those of SARS-CoV.
In international gene banks such as GenBank, researchers have published several Sars-CoV-2 gene sequences. This gene mapping is of fundamental importance allowing researchers to trace the phylogenetic tree of the virus and, above all, the recognition of strains that differ according to the mutations. According to recent research, a spike mutation, which probably occurred in late November 2019, triggered jumping to humans. In particular, Angeletti et al. compared the Sars-Cov-2 gene sequence with that of Sars-CoV. They analyzed the transmembrane helical segments in the ORF1ab encoded 2 (nsp2) and nsp3 and found that position 723 presents a serine instead of a glycine residue, while the position 1010 is occupied by proline instead of isoleucine.[9] The matter of viral mutations is key for explaining potential disease relapses.
Research will be needed to determine the structural characteristics of SARS-COV-2 that underlie the pathogenetic mechanisms. Compared to SARS, for example, initial clinical data show less extra respiratory involvement, although due to the lack of extensive data, it is not possible to draw definitive clinical information.
The pathogenic mechanism that produces pneumonia seems to be particularly complex. Clinical and preclinical research will have to explain many aspects that underlie the particular clinical presentations of the disease. The data so far available seem to indicate that the viral infection is capable of producing an excessive immune reaction in the host. In some cases, a reaction takes place which as a whole is labeled a 'cytokine storm'. The effect is extensive tissue damage. The protagonist of this storm is interleukin 6 (IL-6). IL-6 is produced by activated leukocytes and acts on a large number of cells and tissues. It is able to promote the differentiation of B lymphocytes, promotes the growth of some categories of cells, and inhibits the growth of others. It also stimulates the production of acute phase proteins and plays an important role in thermoregulation, in bone maintenance and in the functionality of the central nervous system. Although the main role played by IL-6 is pro-inflammatory, it can also have anti-inflammatory effects. In turn, IL-6 increases during inflammatory diseases, infections, autoimmune disorders, cardiovascular diseases and some types of cancer. It is also implicated into the pathogenesis of the cytokine release syndrome (CRS) that is an acute systemic inflammatory syndrome characterized by fever and multiple organ dysfunction.
Histopathology
Tian et al.[10] and others reported histopathological data obtained on the lungs of two patients who underwent lung lobectomies for adenocarcinoma and retrospectively found to have had the infection at the time of surgery. Apart from the tumors, the lungs of both 'accidental' cases showed edema and important proteinaceous exudates as large protein globules. The authors also reported vascular congestion combined with inflammatory clusters of fibrinoid material and multinucleated giant cells and hyperplasia of pneumocytes.
History and Physical
The clinical spectrum of COVID-19 varies from asymptomatic or paucisymptomatic forms to clinical conditions characterized by respiratory failure that necessitates mechanical ventilation and support in an intensive care unit (ICU), to multiorgan and systemic manifestations in terms of sepsis, septic shock, and multiple organ dysfunction syndromes (MODS). In one of the first reports on the disease, Huang et al. illustrated that patients (n. 41) suffered from fever, malaise, dry cough, and dyspnea. Chest computerized tomography (CT) scans showed pneumonia with abnormal findings in all cases. About a third of those (13, 32%) required ICU care, and there were 6 (15%) fatal cases.[11]
The case studies of Li et al. published in the New England Journal of Medicine (NEJM) on January 29, 2020, encapsulates the first 425 cases recorded in Wuhan.[5] Data indicate that the patients' median age was 59 years, with a range of 15 to 89 years. Thus, they reported no clinical cases in children below 15 years of age. There were no significant gender differences (56% male). Clinical and epidemiological data from the Chinese CDC and regarding 72,314 case records (confirmed, suspected, diagnosed, and asymptomatic cases) were shared in the Journal of the American Medical Association (JAMA) (February 24, 2020), providing an important illustration of the epidemiologic curve of the Chinese outbreak.[12] There were 62% confirmed cases, including 1% of cases that were asymptomatic, but were laboratory-positive (viral nucleic acid test). Furthermore, the overall case-fatality rate (on confirmed cases) was 2.3%. Of note, the fatal cases were primarily elderly patients, in particular those aged ≥ 80 years (about 15%), and 70 to 79 years (8.0%). Approximately half (49.0%) of the critical patients and affected by preexisting comorbidities such as cardiovascular disease, diabetes, chronic respiratory disease, and oncological diseases, died. While 1% of patients were aged 9 years or younger, no fatal cases occurred in this group.
The authors of the Chinese CDC report divided the clinical manifestations of the disease by there severity:
Mild disease: non-pneumonia and mild pneumonia; this occurred in 81% of cases.
Severe disease: dyspnea, respiratory frequency ≥ 30/min, blood oxygen saturation (SpO2) ≤ 93%, PaO2/FiO2 ratio or P/F [the ratio between the blood pressure of the oxygen (partial pressure of oxygen, PaO2) and the percentage of oxygen supplied (fraction of inspired oxygen, FiO2)] < 300, and/or lung infiltrates > 50% within 24 to 48 hours; this occurred in 14% of cases.
Critical disease: respiratory failure, septic shock, and/or multiple organ dysfunction (MOD) or failure (M*F); this occurred in 5% of cases. [12]
Data obtainable from reports and directives provided by health policy agencies, allow dividing the clinical manifestations of the disease according to the severity of the clinical pictures. The COVID-19 may present with mild, moderate, or severe illness. Among the severe clinical manifestations, there are severe pneumonia, ARDS, sepsis, and septic shock. The clinical course of the disease seems to predict a favorable trend in the majority of patients. In a percentage still to be defined of cases, after about a week there is a sudden worsening of clinical conditions with rapidly worsening respiratory failure and MOD/M*F. As a reference, the criteria of the severity of respiratory insufficiency and the diagnostic criteria of sepsis and septic shock can be used.[13]
Uncomplicated (mild) Illness
These patients usually present with symptoms of an upper respiratory tract viral infection, including mild fever, cough (dry), sore throat, nasal congestion, malaise, headache, muscle pain, or malaise. Signs and symptoms of a more serious disease, such as dyspnea, are not
present. Compared to previous HCoV infections, non-respiratory symptoms such as diarrhea are challenging to find.
Moderate Pneumonia
Respiratory symptoms such as cough and shortness of breath (or tachypnea in children) are present without signs of severe pneumonia.
Severe Pneumonia
Fever is associated with severe dyspnea, respiratory distress, tachypnea (> 30 breaths/min), and hypoxia (SpO2 < 90% on room air). However, the fever symptom must be interpreted carefully as even in severe forms of the disease, it can be moderate or even absent. Cyanosis can occur in children. In this definition, the diagnosis is clinical, and radiologic imaging is used for excluding complications.
Acute Respiratory Distress Syndrome (ARDS)
The diagnosis requires clinical and ventilatory criteria. This syndrome is suggestive of a serious new-onset respiratory failure or for worsening of an already identified respiratory picture. Different forms of ARDS are distinguished based on the degree of hypoxia. The reference parameter is the PaO2/FiO2:
Mild ARDS: 200 mmHg < PaO2/FiO2 ≤ 300 mmHg. In not-ventilated patients or in those managed through non-invasive ventilation (NIV) by using positive end-expiratorypressure (PEEP) or a continuous positive airway pressure (CPAP) ≥ 5 cmH2O.
Moderate ARDS: 100 mmHg < PaO2/FiO2 ≤ 200 mmHg. Severe ARDS: PaO2/FiO2 ≤ 100 mmHg.
When PaO2 is not available, a ratio SpO2/FiO2 ≤ 315 is suggestive of ARDS.
Chest imaging utilized includes chest radiograph, CT scan, or lung ultrasound demonstrating bilateral opacities (lung infiltrates > 50%), not fully explained by effusions, lobar, or lung collapse. Although in some cases, the clinical scenario and ventilator data could be suggestive
for pulmonary edema, the primary respiratory origin of the edema is proven after the exclusion of cardiac failure or other causes such as fluid overload. Echocardiography can be helpful for this purpose.
Sepsis
According to the International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), sepsis represents a life-threatening organ dysfunction caused by a dysregulated host response to suspected or proven infection, with organ dysfunction.[14] The clinical pictures of patients with COVID-19 and with sepsis are particularly serious, characterized by a wide range of signs and symptoms of multiorgan involvement. These signs and symptoms include respiratory manifestations such as severe dyspnea and hypoxemia, renal impairment with reduced urine output, tachycardia, altered mental status, and functional alterations of organs expressed as laboratory data of hyperbilirubinemia, acidosis, high lactate, coagulopathy, and thrombocytopenia. The reference for the evaluation of multiorgan damage and the related prognostic significance is the Sequential Organ Failure Assessment (SOFA) score, which predicts ICU mortality based on lab results and clinical data.[15] A pediatric version of the score has also received validation.[16]Septic Shock
In this scenario, which is associated with increased mortality, circulatory, and cellular/metabolic abnormalities such as serum lactate level greater than 2 mmol/L (18 mg/dL) are present. Because patients usually suffer from persisting hypotension despite volume resuscitation, the administration of vasopressors is required to maintain a mean arterial pressure (MAP) ≥ 65 mmHg.
THE PECULIAR HISTORY OF THIS NEW DISEASEIn some patients, the clinical history of this disease occurs with particular characteristics. It foresees that the patient manifests above all fever, which is not very responsive to antipyretics, and a state of malaise. A dry cough is often associated. After 5-7 days, older patients with already impaired lung function begin to experience shortness of breath and increased respiratory rate. In more fragile patients, however, dyspnea may already appear at the onset of symptoms. On the other hand, in younger subjects and in those who do not have basic respiratory impairments or other comorbidities, dyspnea may appear later. In these patients experiencing worsening inflammatory-induced lung injury, there is a decrease in oxygen saturation (

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