=====Covid-19==== {{:wiki:infection:coronavirus2.jpeg?300|}}

*Coronaviruses are large, enveloped, single-stranded RNA viruses *SARS-CoV-2 (Covid-19) is the 3rd coronavirus to cause serious outbreak after SARS and MERS *bats thought to be natural host but transmission thought to be via pangolin *Early in infection, SARS-CoV-2 targets cells via the viral structural spike (S) protein that binds to the angiotensin-converting enzyme 2 (ACE2) receptor *The type 2 transmembrane serine protease (TMPRSS2), present in the host cell, promotes viral uptake by cleaving ACE2 and activating the SARS-CoV-2 S protein, which mediates coronavirus entry into host cells. *viral replication accelerates and epithelial-endothelial barrier integrity is compromised and, in the lung, interstitial mononuclear inflammatory infiltrates and oedema develop *In severe COVID-19, fulminant activation of coagulation and consumption of clotting factors occur *Common laboratory abnormalities in hospitalised patients: *lymphopenia (83%) *elevated inflammatory markers (eg, erythrocyte sedimentation rate, C-reactive protein, ferritin, tumour necrosis factor-α, IL-1, IL-6) *abnormal coagulation parameters (eg, prolonged prothrombin time, thrombocytopenia, elevated D-dimer [46% of patients], low fibrinogen). *common CXR findings - ground glass appearance but pulmonary oedema and consolidation also occur * ===Clinical== *Hospitalised patients presentation: *fever ~90% *Loss of taste & smell ~70% *dry cough ~75% *SOB ~70% *fatigue ~40% *nausea/vomiting or diarrhoea ~25% *myalgia ~30% *Patients can also present with non-classical symptoms, such as isolated gastrointestinal symptoms. Anosmia or ageusia may be the sole presenting symptom in approximately 3% of patients **deaths most commonly associated with co-morbidities: ** *patients dying in Italy, 3.6% patients presented with no co-morbidities, 14.4% with a single co-morbidity, 21.1% with two, and 60.9% with three or more co-morbidities. *Among these co-morbidities: *hypertension (69.1%) *ischaemic heart disease (27.5%) *chronic renal failure (21.1%) *atrial fibrillation (22%) *pulmonary diseases (17.1%) *heart failure (16.1%) *other co-morbidities with <15% incidence. *all these pathologies are characterized by a downregulation of ACE2 and a high ACE/ACE2 ratio ===ACE2== Angiotensin-converting enzyme 2 (ACE2) is an amino-peptidase that converts Angiotensin (Ang) II into Ang (1-7). Coronavirus uses ACE2 as a cellular receptor to invade target cells. *Ang II, acting on AT1 receptors, exerts powerful vasoconstrictor, pro-fibrotic, and pro-inflammatory effects. *Ang (1-7), acting on Mas receptors (MasR), is a potent vasodilator, anti-apoptotic, and anti-proliferative agent (Figure 1). *Therefore, ACE2 is a negative regulator of classical ACE in the renin-angiotensin system (RAS). *ACE2 is largely expressed in lungs, liver, intestine, brain, heart, and kidneys, and also in testes. *In almost all the pathological conditions, especially those of the cardiovascular system, there is an increase in the ACE/ACE2 ratio within the organs and systems (5–9). This ACE/ACE2 imbalance is very often due to a downregulation of ACE2 levels. *initial investigations implied that SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for cellular entry. There are other portals for entry also. Covid19 has 10x the affinity for the receptor compared with SARS ===Pneumonia== *Clinically, pneumonias have been subdivided into specific phenotypes: a spectrum from patchy ground-glass opacification to the oedematous lung with atypical acute respiratory distress syndrome features ===Pulmonary embolism=== *d-Dimer values are frequently elevated in Covid-19 patients, with higher levels reflecting higher mortality *whilst the incidence of PE is higher in Covid-19 patients, a higher level of d-Dimer should probably be used as the cut-off before ordering CTPA. In the absence of other VTE risk factors, a d-Dimer of 1200 ng/ml has been suggested as a minimum. *Wells score has been reported as a poor marker for prediction of PE in patients with COVID-19 ===Management=== *O2 therapy - ranging from high flow O2 to mechanical ventilation with debates relating to timing of intervention for CPAP and/or intubation *fluid therapy - varying approaches with concerns by some to avoid fluid overload while others concerned that this approach encourages renal failure *dexamethasone - widely accepted to shorten illness *anti-virals -eg remdesivir (in the UK) is inhibitor of the viral RNA-dependent, RNA polymerase *casirivimab and imdevimab {{ :wiki:infection:guideline_for_the_use_of_casirivimab_and_imdevimab_ronapreve_for_the_management_of_covid-19_infection_adults_or_children_over_12_years_at_chs.pdf |CUH Guideline for use}} *anti-coagulants - debatable - ==References include:== [[https://www.frontiersin.org/articles/10.3389/fmed.2020.00335/full|ACE/ACE2 ratios in Covid]]\\ [[https://www.emjreviews.com/microbiology-infectious-diseases/article/primer-on-the-pathogenesis-of-severe-covid-19-part-one/|Euro Med J - Covid19 pathogenesis]]\\ [[https://jamanetwork.com/journals/jama/fullarticle/2768391|JAMA Covid-19 pathogenesis etc]]\\ [[https://link.springer.com/article/10.1007/s10140-020-01859-1|Emerg Rad. 2020. Higher dDimer to predict PE in Covid]]\\ [[https://pubs.rsna.org/doi/10.1148/ryct.2020200308|Radiology 2020 PE in Thoracic imaging Covid]]\\ [[https://erj.ersjournals.com/content/56/4/2001811|Eur Resp J. Elevated dDimer and anticoag predict PE]]\\ Apollos' Arrow - The Profound and Enduring Impact of Coronavirus on the Way We Live. Book by Prof Nicholas Christakis 2020\\ {{ :wiki:cuh_protocol_for_non_critical_care_management_of_covid_final_nov_2020.pdf |}}\\ [[https://www.degruyter.com/document/doi/10.1515/cclm-2022-0633/html?lang=en|dDimer in Covid]]\\