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VisualWikitext

Latest revision as of 08:31, 11 November 2021

For COVID-19 frequently asked inpatient questions, click here
For COVID-19 frequently asked outpatient questions, click here
For COVID-19 patient information, click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-in-Chief: Sara Zand, M.D.

Synonyms and keywords: Pulmonary hypertension, PH, COVID-19, SARS-COV-2, ARDS

Overview

Pulmonary hypertension (PH) is determined as an increase in mean pulmonary arterial pressure (mPAP) of 25 mm Hg or greater at rest. It occurs due to pulmonary arterial remodeling and vasoconstriction prompting an increase in pulmonary artery pressure and finally leading to right heart failure. Few cases of Covid-19 with PH were found and it seems due to keeping social distance and quarantine, the number of cases is underestimated. Pulmonary hypertension is a rare disease and studies about PH during SARS-CoV disease in 2003 implied the role of inflammation in this process.

Historical Perspective

In 2003, the association between corona infection and pulmonary hypertension was established during SARS-CoV epidemic.

Classification

Pulmonary hypertension in COVID-19 may be classified into two subtypes:

Pulmonary hypertension due to lung disease or hypoxia.
Microvascular thromboembolic pulmonary hypertension.

Pathophysiology

The SARS-CoV-2 and SARS-CoV virus genomes are highly similar, and patients infected with these viruses have common pathological features.^[1]
The pathogenesis of PH in COVID-19 is characterized by pulmonary vasoconstriction due to lack of ACE2 and pulmonary microthromboembolism due to local endothelial cell dysfunction.
Renin angiotensin system (RAS) is responsible for hemostasis of blood pressure and electrolyte balance and inflammatory response.
Renin is a protease that is generated in the kidney and cleaves angiotensinogen to angiotensin1, Then angiotensin converting enzyme (ACE) cleaves angiotensin 1 to angiotensin 2.
Angiotensin 2 is a key factor of RAS and has two receptors including type 1 and type 2.
Unbalance between ACE/Ang II/AT1R pathway and ACE2/Ang (1-7) receptor pathway in the RAS system will induce multi-system inflammation.^[2]
Angiotensin-converting enzyme 2 (ACE2), and neprilysin hydrolyze angiotensin 2 to anti inflammatory agents including Ang1–7, Ang III, Ang IV, and Ang A.^[3]
Angiotensin-converting enzyme 2 (ACE2) was a receptor of spike protein on SARS corona virus in epithelial cell and after attaching virus the activity of enzyme(ACE2) was decreased and then virus spread quickly.^[4]^[5]
Lack of ACE2 causes elevation in angiotensin 2 level causing vascular permeability and lung edema and neutrophil infiltration and further lung deterioration.
ACE2 has anti inflammation effect and protected the lung from acute lung injury.^[6]
Phosphorilized ACE2 is a much more stable form in which it converts angiotensin 2 to angiotensin 1-7 and increases the bioavailability of endothelial nitric oxide synthase-derived NO.
Lack of phosphorilized ACE2 causes vasoconstriction and pulmonary hypertension.^[7]
Nitric oxide inhalation for SARS-corona patients was correlated with vasodilation and relaxation of pulmonary artery, reduction in pulmonary artery pressure and improvement in arterial oxygenation.^[8]
Endothelin-1 caused downregulated ACE2 expression in lung epithelial cells and reduced pulmonary vasoconstriction.^[9]
On microscopic histopathological analysis, pulmonary wall edema,hyalin thrombosis, inflammatory cell infiltration of pulmonary microvasculature , vessle thrombosis due to diffuse alveolar damage and septal inflammation are characteristic findings of PH in COVID-19.^[10]

Causes

Factors contributing to the microthrombi formation in the pulmonary artery in COVID-19 include:

Hypoxia following diffuse alveolar and interestitial inflammation. Hypoxia may induce endothelial dysfunction and activation of coagulation cascade in small vessles.^[11]
ACE2 receptor expression downregulation after attaching the spike site of COVID-19 to pneumocytes type2.
Activation of the innate coagulation cascade in older age.
Mechanical ventilation may induce immune micro thrombosis in small arteries.^[12]
Bacterial superinfection.

Differentiating COVID-19-associated pulmonary hypertension from other Diseases

Pulmonary intravascular coagulopathy causing pulmonary hypertention in COVID-19 must be differentiated from disseminated intravascular coagulation (DIC) based on clinical features and lab data:^[13]

	Disseminated intravascular coagulopathy	Pulmonary intravascular coagulopathy
Onset	Acute	Subacute
Pulmonary involvement (%)	50%	100%
Thrombosis	Multi-organ clotting	Mainly lung
Bleeding	Generalised	Intrapulmonary microhaemorrhage
Liver function	Decreased fibrinogen and other clotting factors; increased transaminase +++	Preservation of liver synthetic function; +/−
Anemia	+++	−
Thrombocytopenia	+++	Normal or low
cytopenia	++	No.may be lymphopenia is a finding of COVID-19
Creatine kinase	+	+
Troponin T	+	++
Elevated prothrombin time or activated partial thromboplastin time	+++/+++	+ or normal
Fibrinogen levels	Decreased	Normal or slight increase
Fibrin degradation products or D-dimer	Increased	Increased
C-reactive protein	Elevated	Elevated
Ferritin elevation	+++	Elevated
Hypercytokinaemia	+++	++

Epidemiology and Demographics

Data on the incidence of pulmonary hypertension in COVID-19 patients is limited.
There is no racial predilection to pulmonary hypertension in COVID-19.
Male are more commonly affected by COVID-19 than female, therefore, the prevalence of pulmonary hypertension induced by Covid-19 is higher in the male gender.

Risk Factors

Common risk factors in the development of pulmonary hypertention in COVID-19 include the following:^[14]

Screening

There is insufficient evidence to recommend routine screening for pulmonary hypertension in COVID-19.

Natural History, Complications, and Prognosis

Severe COVID-19 infection induces cytokine storm which leads to activation of the coagulation cascade and thrombotic process.
Inflammatory markers including IL-1,IL-6 and tumor necrosis factor and ferritin concentration, cause pulmonary endothelial dysfunction and thromboinflammatory process.^[15]
Hypoxia in COVID-19 pneumonia will cause endothelial dysfunction and expression of active tissue factor on endothelium, macrophage, neutrophils, and finally activation of coagulation cascade and reduction of fibrinolysis and plasminogen activation inhibitor 1.
Thrombosis and hemorrhage occur in small vessels of the lung and thrombin generation and fibrin deposition enhances in the bronchoalveolar system.
These show the severity of inflammation.
D-dimer level correlated with severe COVID-19 and indicates activation fibrinolysis and plasmin generation.^[16]
COVID-19 downregulates ACE2 on pneumocytes type2 which are adjusted pulmonary vascular bed, then vasculopathy and thrombosis happens.
Prognosis is generally poor in older patients and in patients with high level of fibrin degeredated factors, including, D-dimer and cardiac troponin T due to right ventricular failure.^[17]
COVID-19 associated pulmonary hypertension is a chronic progressive disease with a high mortality rate.

Diagnosis

Diagnostic Study of Choice

The diagnosis of pulmonary hypertension is made when at least three of the following diagnostic criteria in right heart catheterization (RHC) are met:
Mean PAP≥25 mmHg,
Pulmonary artery wedge pressure≤15 mmHg.
Pulmonary vascular resistance>3 wood units.

History and Symptoms

The most common symptoms of pulmonary hypertension include:
Less common symptoms include:
- Syncope

Physical Examination

Physical examination in PH may be remarkable for:
- Rales
- Dullness or decreased breath sound due to pulmonary congestion or effusion.
- Central cyanosis due to hypoxia.
- Holosystolic murmur with increased intensity during inspiration due to tricuspid regurgitation (TR).
- Diastolic murmur due to pulmonary regurgitation.
- Hepatojugular reflux.
- Right ventricular S3 due to RV dysfunction.
- Distention of jugular vein s due to RV dysfunction and TR
- Peripheral edema and ascites.
- Low blood Pressure.
- Diminished pulse pressure.
- Cool extremities due to reduced cardiac output and peripheral vasoconstriction.
- Abdominal distention
- Lower extremity edema (seen in advanced disease and right ventricular failure).
- Racing pulse

Laboratory Findings

Laboratory findings consistent with the diagnosis of pulmonary hypertension in COVID-19 include:

Increased D-dimer (due to pulmonary vascular bed thrombosis with fibrinolysis).
Elevated concentration of cardiac enzymes due to right ventricular strain induced by pulmonary hypertension.
Normal fibrinogen and platelet level.

Electrocardiogram

An ECG may be helpful in the diagnosis of pulmonary hypertension. Findings on an ECG suggestive pulmonary hypertension include:

X-ray

Chest x-ray may be helpful in the diagnosis of pulmonary hypertension in COVID-19. Findings on chest x-ray suggestive of pulmonary hypertension include:
- Enlarged main pulmonary artery.
- Prunning or attenuation of the peripheral vasculature.
- Right ventricular enlargement especially in lateral view.
- With other evidence of lung involvement in COVID-19.

Echocardiography or Ultrasound

Echocardiography is the first modality in the diagnosis of pulmonary hypertension. Findings on an echocardiography suggestive of pulmonary hypertension include:
- Right atrial enlargement
- Right ventricular enlargement and dysfunction
- Small left side chambers
- Interventricular setal flattening
- Tricuspid regurgitation

CT scan

Chest CT scan even unenhanced may be helpful in the diagnosis of pulmonary hypertension in COVID-19.. Findings on CT scan suggestive pulmonary hypertension in COVID-19 in comparison with baseline chest CT scan include:^[18]

Pulmonary artery dilation above 27mm in women and 29mm in men.
Increased median Pulmonary Artery/Aorta ratio from 26mm to 31mm after SARS-COVID infection.

In one study, pulmonary artery dilation was correlated with high level of D-dimer and pulmonary artery thrombosis and poor outcome in COVID-19.^[19]

MRI

Cardiac MRI is one of the most accurate method in the diagnosis of pulmonary hypertension. Findings on MRI for evaluation of pulmonary hypertension include :^[20]
- Assessment of the anatomy of the pulmonary arteries.
- Assessment of pulmonary blood flow.
- Assessment of right ventricular size, morphology, and function.

Other Imaging Findings

Perfusion ventilation scan may be helpful in the diagnosis of chronic thromboembolic pulmonary hypertension without the ventilation portion due to difficulty in disinfecting the ventilation system in COVID-19 pandemic.
If lung perfusion image is normal, chronic thromboembolism is ruled out and further invasive catheterization may be avoided.^[21]

Other Diagnostic Studies

There are no other diagnostic studies associated with pulmonary hypertension in COVID-19.

Treatment

Medical Therapy

The mainstay of therapy for pulmonary hypertension in Covid-19 including:^[22]^[23]

Pulmonary vasodilation.Nitric oxide has antiviral and anti inflammatory effect in SARS-CoV .^[24]
Supplement oxygen for correction of hypoxia and prevention of pulmonary vasoconstriction to maintain oxygen saturation above 92%.
Avoidance of inhaled prostacyclin for prevention of spreading COVID-19 and using the parenteral form for the protection of health care providers.
Endothelin receptor antagonist agents.
Anticoagulation therapy if there is evidence of thromboembolic mechanism.^[25]
Correction of hypotension with fluild and inotropic agents in order to avoid decreased RV coronary perfusion and RV ejection fraction.
Correction of acidosis, hypercarbia, hypothermia, hypervolemia.
Intubation is not recommended due to the effect of positive pressure ventilation in increasing RV preload and also vasodilatory effect of sedation agents impending systemic hypotension and hemodynamic collapse.
If intubation is indicated, a vasoactive agent should be given before anesthesia. Etomidate is recommended for general anesthesia due to little effect on cardiac contractility and vascular tone.
Ventilator should be set with low tidal volumes and moderate positive end-expiratory pressure for minimum airway pressure and sufficient oxygenation and ventilation.

Surgery

Surgical intervention is not recommended for the management of pulmonary hypertension in COVID-19.

Primary Prevention

Effective measures for the primary prevention of PH and COVID-19 include keeping social distancing and maintaining the medication used for pulmonary hypertension.

Secondary Prevention

There are no established measures for the secondary prevention of pulmonary hypertension in COVID-19.

References

↑ Zhu, Na; Zhang, Dingyu; Wang, Wenling; Li, Xingwang; Yang, Bo; Song, Jingdong; Zhao, Xiang; Huang, Baoying; Shi, Weifeng; Lu, Roujian; Niu, Peihua; Zhan, Faxian; Ma, Xuejun; Wang, Dayan; Xu, Wenbo; Wu, Guizhen; Gao, George F.; Tan, Wenjie (2020). "A Novel Coronavirus from Patients with Pneumonia in China, 2019". New England Journal of Medicine. 382 (8): 727–733. doi:10.1056/NEJMoa2001017. ISSN 0028-4793.
↑ Konishi H, Kuroda S, Inada Y, Fujisawa Y (March 1994). "Novel subtype of human angiotensin II type 1 receptor: cDNA cloning and expression". Biochem. Biophys. Res. Commun. 199 (2): 467–74. doi:10.1006/bbrc.1994.1252. PMID 8135787.
↑ Chappell MC (October 2012). "Nonclassical renin-angiotensin system and renal function". Compr Physiol. 2 (4): 2733–52. doi:10.1002/cphy.c120002. PMC 4186703. PMID 23720263.
↑ Li, Wenhui; Moore, Michael J.; Vasilieva, Natalya; Sui, Jianhua; Wong, Swee Kee; Berne, Michael A.; Somasundaran, Mohan; Sullivan, John L.; Luzuriaga, Katherine; Greenough, Thomas C.; Choe, Hyeryun; Farzan, Michael (2003). "Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus". Nature. 426 (6965): 450–454. doi:10.1038/nature02145. ISSN 0028-0836.
↑ Glowacka I, Bertram S, Herzog P, Pfefferle S, Steffen I, Muench MO, Simmons G, Hofmann H, Kuri T, Weber F, Eichler J, Drosten C, Pöhlmann S (January 2010). "Differential downregulation of ACE2 by the spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus NL63". J. Virol. 84 (2): 1198–205. doi:10.1128/JVI.01248-09. PMC 2798380. PMID 19864379.
↑ Imai, Yumiko; Kuba, Keiji; Rao, Shuan; Huan, Yi; Guo, Feng; Guan, Bin; Yang, Peng; Sarao, Renu; Wada, Teiji; Leong-Poi, Howard; Crackower, Michael A.; Fukamizu, Akiyoshi; Hui, Chi-Chung; Hein, Lutz; Uhlig, Stefan; Slutsky, Arthur S.; Jiang, Chengyu; Penninger, Josef M. (2005). "Angiotensin-converting enzyme 2 protects from severe acute lung failure". Nature. 436 (7047): 112–116. doi:10.1038/nature03712. ISSN 0028-0836.
↑ Zhang, Jiao; Dong, Jianjie; Martin, Marcy; He, Ming; Gongol, Brendan; Marin, Traci L.; Chen, Lili; Shi, Xinxing; Yin, Yanjun; Shang, Fenqing; Wu, Yan; Huang, Hsi-Yuan; Zhang, Jin; Zhang, Yu; Kang, Jian; Moya, Esteban A.; Huang, Hsien-Da; Powell, Frank L.; Chen, Zhen; Thistlethwaite, Patricia A.; Yuan, Zu-Yi; Shyy, John Y.-J. (2018). "AMP-activated Protein Kinase Phosphorylation of Angiotensin-Converting Enzyme 2 in Endothelium Mitigates Pulmonary Hypertension". American Journal of Respiratory and Critical Care Medicine. 198 (4): 509–520. doi:10.1164/rccm.201712-2570OC. ISSN 1073-449X.
↑ Chen, L.; Liu, P.; Gao, H.; Sun, B.; Chao, D.; Wang, F.; Zhu, Y.; Hedenstierna, G.; Wang, C. G. (2004). "Inhalation of Nitric Oxide in the Treatment of Severe Acute Respiratory Syndrome: A Rescue Trial in Beijing". Clinical Infectious Diseases. 39 (10): 1531–1535. doi:10.1086/425357. ISSN 1058-4838.
↑ Zhang H, Li Y, Zeng Y, Wu R, Ou J (2013). "Endothelin-1 downregulates angiotensin-converting enzyme-2 expression in human bronchial epithelial cells". Pharmacology. 91 (5–6): 297–304. doi:10.1159/000350395. PMID 23751363.
↑ Fox, Sharon E.; Akmatbekov, Aibek; Harbert, Jack L.; Li, Guang; Brown, J. Quincy; Vander Heide, Richard S. (2020). doi:10.1101/2020.04.06.20050575. Missing or empty |title= (help)
↑ Ten, Vadim S.; Pinsky, David J. (2002). "Endothelial response to hypoxia: physiologic adaptation and pathologic dysfunction". Current Opinion in Critical Care. 8 (3): 242–250. doi:10.1097/00075198-200206000-00008. ISSN 1070-5295.
↑ Engelmann B, Massberg S (January 2013). "Thrombosis as an intravascular effector of innate immunity". Nat. Rev. Immunol. 13 (1): 34–45. doi:10.1038/nri3345. PMID 23222502.
↑ McGonagle, Dennis; Sharif, Kassem; O'Regan, Anthony; Bridgewood, Charlie (2020). "The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease". Autoimmunity Reviews. 19 (6): 102537. doi:10.1016/j.autrev.2020.102537. ISSN 1568-9972.
↑ McGonagle, Dennis; O'Donnell, James S; Sharif, Kassem; Emery, Paul; Bridgewood, Charles (2020). "Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia". The Lancet Rheumatology. 2 (7): e437–e445. doi:10.1016/S2665-9913(20)30121-1. ISSN 2665-9913.
↑ Levi M, van der Poll T (January 2017). "Coagulation and sepsis". Thromb. Res. 149: 38–44. doi:10.1016/j.thromres.2016.11.007. PMID 27886531.
↑ Ji HL, Zhao R, Matalon S, Matthay MA (July 2020). "Elevated Plasmin(ogen) as a Common Risk Factor for COVID-19 Susceptibility". Physiol. Rev. 100 (3): 1065–1075. doi:10.1152/physrev.00013.2020. PMC 7191627 Check |pmc= value (help). PMID 32216698 Check |pmid= value (help).
↑ Zhou, Fei; Yu, Ting; Du, Ronghui; Fan, Guohui; Liu, Ying; Liu, Zhibo; Xiang, Jie; Wang, Yeming; Song, Bin; Gu, Xiaoying; Guan, Lulu; Wei, Yuan; Li, Hui; Wu, Xudong; Xu, Jiuyang; Tu, Shengjin; Zhang, Yi; Chen, Hua; Cao, Bin (2020). "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study". The Lancet. 395 (10229): 1054–1062. doi:10.1016/S0140-6736(20)30566-3. ISSN 0140-6736.
↑ Spagnolo, Pietro; Cozzi, Andrea; Foà, Riccardo Alessandro; Spinazzola, Angelo; Monfardini, Lorenzo; Bnà, Claudio; Alì, Marco; Schiaffino, Simone; Sardanelli, Francesco (2020). "CT-derived pulmonary vascular metrics and clinical outcome in COVID-19 patients". Quantitative Imaging in Medicine and Surgery. 10 (6): 1325–1333. doi:10.21037/qims-20-546. ISSN 2223-4292.
↑ Dolhnikoff, Marisa; Duarte‐Neto, Amaro Nunes; Almeida Monteiro, Renata Aparecida; Silva, Luiz Fernando Ferraz; Oliveira, Ellen Pierre; Saldiva, Paulo Hilário Nascimento; Mauad, Thais; Negri, Elnara Marcia (2020). "Pathological evidence of pulmonary thrombotic phenomena in severe COVID‐19". Journal of Thrombosis and Haemostasis. 18 (6): 1517–1519. doi:10.1111/jth.14844. ISSN 1538-7933.
↑ Frazier AA, Burke AP (December 2012). "The imaging of pulmonary hypertension". Semin. Ultrasound CT MR. 33 (6): 535–51. doi:10.1053/j.sult.2012.06.002. PMID 23168063.
↑ Galiè, Nazzareno; Humbert, Marc; Vachiery, Jean-Luc; Gibbs, Simon; Lang, Irene; Torbicki, Adam; Simonneau, Gérald; Peacock, Andrew; Vonk Noordegraaf, Anton; Beghetti, Maurice; Ghofrani, Ardeschir; Gomez Sanchez, Miguel Angel; Hansmann, Georg; Klepetko, Walter; Lancellotti, Patrizio; Matucci, Marco; McDonagh, Theresa; Pierard, Luc A.; Trindade, Pedro T.; Zompatori, Maurizio; Hoeper, Marius (2016). "2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension". European Heart Journal. 37 (1): 67–119. doi:10.1093/eurheartj/ehv317. ISSN 0195-668X.
↑ Gordon, Claire; Collard, Charles D; Pan, Wei (2010). "Intraoperative management of pulmonary hypertension and associated right heart failure". Current Opinion in Anaesthesiology. 23 (1): 49–56. doi:10.1097/ACO.0b013e3283346c51. ISSN 0952-7907.
↑ Pritts, Chad D; Pearl, Ronald G (2010). "Anesthesia for patients with pulmonary hypertension". Current Opinion in Anaesthesiology. 23 (3): 411–416. doi:10.1097/ACO.0b013e32833953fb. ISSN 0952-7907.
↑ Chen L, Liu P, Gao H, Sun B, Chao D, Wang F, Zhu Y, Hedenstierna G, Wang CG (November 2004). "Inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: a rescue trial in Beijing". Clin. Infect. Dis. 39 (10): 1531–5. doi:10.1086/425357. PMC 7107896 Check |pmc= value (help). PMID 15546092.
↑ Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, Baxter-Stoltzfus A, Laurence J (June 2020). "Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases". Transl Res. 220: 1–13. doi:10.1016/j.trsl.2020.04.007. PMC 7158248 Check |pmc= value (help). PMID 32299776 Check |pmid= value (help).

Template:WikiDoc Sources

.

[ZhuZhang2020-1] Zhu, Na; Zhang, Dingyu; Wang, Wenling; Li, Xingwang; Yang, Bo; Song, Jingdong; Zhao, Xiang; Huang, Baoying; Shi, Weifeng; Lu, Roujian; Niu, Peihua; Zhan, Faxian; Ma, Xuejun; Wang, Dayan; Xu, Wenbo; Wu, Guizhen; Gao, George F.; Tan, Wenjie (2020). "A Novel Coronavirus from Patients with Pneumonia in China, 2019". New England Journal of Medicine. 382 (8): 727–733. doi:10.1056/NEJMoa2001017. ISSN 0028-4793.

[pmid8135787-2] Konishi H, Kuroda S, Inada Y, Fujisawa Y (March 1994). "Novel subtype of human angiotensin II type 1 receptor: cDNA cloning and expression". Biochem. Biophys. Res. Commun. 199 (2): 467–74. doi:10.1006/bbrc.1994.1252. PMID 8135787.

[pmid23720263-3] Chappell MC (October 2012). "Nonclassical renin-angiotensin system and renal function". Compr Physiol. 2 (4): 2733–52. doi:10.1002/cphy.c120002. PMC 4186703. PMID 23720263.

[LiMoore2003-4] Li, Wenhui; Moore, Michael J.; Vasilieva, Natalya; Sui, Jianhua; Wong, Swee Kee; Berne, Michael A.; Somasundaran, Mohan; Sullivan, John L.; Luzuriaga, Katherine; Greenough, Thomas C.; Choe, Hyeryun; Farzan, Michael (2003). "Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus". Nature. 426 (6965): 450–454. doi:10.1038/nature02145. ISSN 0028-0836.

[pmid19864379-5] Glowacka I, Bertram S, Herzog P, Pfefferle S, Steffen I, Muench MO, Simmons G, Hofmann H, Kuri T, Weber F, Eichler J, Drosten C, Pöhlmann S (January 2010). "Differential downregulation of ACE2 by the spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus NL63". J. Virol. 84 (2): 1198–205. doi:10.1128/JVI.01248-09. PMC 2798380. PMID 19864379.

[ImaiKuba2005-6] Imai, Yumiko; Kuba, Keiji; Rao, Shuan; Huan, Yi; Guo, Feng; Guan, Bin; Yang, Peng; Sarao, Renu; Wada, Teiji; Leong-Poi, Howard; Crackower, Michael A.; Fukamizu, Akiyoshi; Hui, Chi-Chung; Hein, Lutz; Uhlig, Stefan; Slutsky, Arthur S.; Jiang, Chengyu; Penninger, Josef M. (2005). "Angiotensin-converting enzyme 2 protects from severe acute lung failure". Nature. 436 (7047): 112–116. doi:10.1038/nature03712. ISSN 0028-0836.

[ZhangDong2018-7] Zhang, Jiao; Dong, Jianjie; Martin, Marcy; He, Ming; Gongol, Brendan; Marin, Traci L.; Chen, Lili; Shi, Xinxing; Yin, Yanjun; Shang, Fenqing; Wu, Yan; Huang, Hsi-Yuan; Zhang, Jin; Zhang, Yu; Kang, Jian; Moya, Esteban A.; Huang, Hsien-Da; Powell, Frank L.; Chen, Zhen; Thistlethwaite, Patricia A.; Yuan, Zu-Yi; Shyy, John Y.-J. (2018). "AMP-activated Protein Kinase Phosphorylation of Angiotensin-Converting Enzyme 2 in Endothelium Mitigates Pulmonary Hypertension". American Journal of Respiratory and Critical Care Medicine. 198 (4): 509–520. doi:10.1164/rccm.201712-2570OC. ISSN 1073-449X.

[ChenLiu2004-8] Chen, L.; Liu, P.; Gao, H.; Sun, B.; Chao, D.; Wang, F.; Zhu, Y.; Hedenstierna, G.; Wang, C. G. (2004). "Inhalation of Nitric Oxide in the Treatment of Severe Acute Respiratory Syndrome: A Rescue Trial in Beijing". Clinical Infectious Diseases. 39 (10): 1531–1535. doi:10.1086/425357. ISSN 1058-4838.

[pmid23751363-9] Zhang H, Li Y, Zeng Y, Wu R, Ou J (2013). "Endothelin-1 downregulates angiotensin-converting enzyme-2 expression in human bronchial epithelial cells". Pharmacology. 91 (5–6): 297–304. doi:10.1159/000350395. PMID 23751363.

[FoxAkmatbekov2020-10] Fox, Sharon E.; Akmatbekov, Aibek; Harbert, Jack L.; Li, Guang; Brown, J. Quincy; Vander Heide, Richard S. (2020). doi:10.1101/2020.04.06.20050575. Missing or empty |title= (help)

[TenPinsky2002-11] Ten, Vadim S.; Pinsky, David J. (2002). "Endothelial response to hypoxia: physiologic adaptation and pathologic dysfunction". Current Opinion in Critical Care. 8 (3): 242–250. doi:10.1097/00075198-200206000-00008. ISSN 1070-5295.

[pmid23222502-12] Engelmann B, Massberg S (January 2013). "Thrombosis as an intravascular effector of innate immunity". Nat. Rev. Immunol. 13 (1): 34–45. doi:10.1038/nri3345. PMID 23222502.

[McGonagleSharif2020-13] McGonagle, Dennis; Sharif, Kassem; O'Regan, Anthony; Bridgewood, Charlie (2020). "The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease". Autoimmunity Reviews. 19 (6): 102537. doi:10.1016/j.autrev.2020.102537. ISSN 1568-9972.

[McGonagleO'Donnell2020-14] McGonagle, Dennis; O'Donnell, James S; Sharif, Kassem; Emery, Paul; Bridgewood, Charles (2020). "Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia". The Lancet Rheumatology. 2 (7): e437–e445. doi:10.1016/S2665-9913(20)30121-1. ISSN 2665-9913.

[pmid27886531-15] Levi M, van der Poll T (January 2017). "Coagulation and sepsis". Thromb. Res. 149: 38–44. doi:10.1016/j.thromres.2016.11.007. PMID 27886531.

[pmid32216698-16] Ji HL, Zhao R, Matalon S, Matthay MA (July 2020). "Elevated Plasmin(ogen) as a Common Risk Factor for COVID-19 Susceptibility". Physiol. Rev. 100 (3): 1065–1075. doi:10.1152/physrev.00013.2020. PMC 7191627 Check |pmc= value (help). PMID 32216698 Check |pmid= value (help).

[ZhouYu2020-17] Zhou, Fei; Yu, Ting; Du, Ronghui; Fan, Guohui; Liu, Ying; Liu, Zhibo; Xiang, Jie; Wang, Yeming; Song, Bin; Gu, Xiaoying; Guan, Lulu; Wei, Yuan; Li, Hui; Wu, Xudong; Xu, Jiuyang; Tu, Shengjin; Zhang, Yi; Chen, Hua; Cao, Bin (2020). "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study". The Lancet. 395 (10229): 1054–1062. doi:10.1016/S0140-6736(20)30566-3. ISSN 0140-6736.

[SpagnoloCozzi2020-18] Spagnolo, Pietro; Cozzi, Andrea; Foà, Riccardo Alessandro; Spinazzola, Angelo; Monfardini, Lorenzo; Bnà, Claudio; Alì, Marco; Schiaffino, Simone; Sardanelli, Francesco (2020). "CT-derived pulmonary vascular metrics and clinical outcome in COVID-19 patients". Quantitative Imaging in Medicine and Surgery. 10 (6): 1325–1333. doi:10.21037/qims-20-546. ISSN 2223-4292.

[DolhnikoffDuarte‐Neto2020-19] Dolhnikoff, Marisa; Duarte‐Neto, Amaro Nunes; Almeida Monteiro, Renata Aparecida; Silva, Luiz Fernando Ferraz; Oliveira, Ellen Pierre; Saldiva, Paulo Hilário Nascimento; Mauad, Thais; Negri, Elnara Marcia (2020). "Pathological evidence of pulmonary thrombotic phenomena in severe COVID‐19". Journal of Thrombosis and Haemostasis. 18 (6): 1517–1519. doi:10.1111/jth.14844. ISSN 1538-7933.

[pmid23168063-20] Frazier AA, Burke AP (December 2012). "The imaging of pulmonary hypertension". Semin. Ultrasound CT MR. 33 (6): 535–51. doi:10.1053/j.sult.2012.06.002. PMID 23168063.

[GalièHumbert2016-21] Galiè, Nazzareno; Humbert, Marc; Vachiery, Jean-Luc; Gibbs, Simon; Lang, Irene; Torbicki, Adam; Simonneau, Gérald; Peacock, Andrew; Vonk Noordegraaf, Anton; Beghetti, Maurice; Ghofrani, Ardeschir; Gomez Sanchez, Miguel Angel; Hansmann, Georg; Klepetko, Walter; Lancellotti, Patrizio; Matucci, Marco; McDonagh, Theresa; Pierard, Luc A.; Trindade, Pedro T.; Zompatori, Maurizio; Hoeper, Marius (2016). "2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension". European Heart Journal. 37 (1): 67–119. doi:10.1093/eurheartj/ehv317. ISSN 0195-668X.

[GordonCollard2010-22] Gordon, Claire; Collard, Charles D; Pan, Wei (2010). "Intraoperative management of pulmonary hypertension and associated right heart failure". Current Opinion in Anaesthesiology. 23 (1): 49–56. doi:10.1097/ACO.0b013e3283346c51. ISSN 0952-7907.

[PrittsPearl2010-23] Pritts, Chad D; Pearl, Ronald G (2010). "Anesthesia for patients with pulmonary hypertension". Current Opinion in Anaesthesiology. 23 (3): 411–416. doi:10.1097/ACO.0b013e32833953fb. ISSN 0952-7907.

[pmid15546092-24] Chen L, Liu P, Gao H, Sun B, Chao D, Wang F, Zhu Y, Hedenstierna G, Wang CG (November 2004). "Inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: a rescue trial in Beijing". Clin. Infect. Dis. 39 (10): 1531–5. doi:10.1086/425357. PMC 7107896 Check |pmc= value (help). PMID 15546092.

[pmid32299776-25] Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, Baxter-Stoltzfus A, Laurence J (June 2020). "Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases". Transl Res. 220: 1–13. doi:10.1016/j.trsl.2020.04.007. PMC 7158248 Check |pmc= value (help). PMID 32299776 Check |pmid= value (help).

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 __NOTOC__
+{{Main article|COVID-19}}
 {{SI}}
-{{CMG}}; {{AE}}sara zand,MD
+'''For COVID-19 frequently asked inpatient questions, click [[COVID-19 frequently asked inpatient questions|here]]'''<br>
+'''For COVID-19 frequently asked outpatient questions, click [[COVID-19 frequently asked outpatient questions|here]]'''<br>'''For COVID-19 patient information, click [[COVID-19 (patient information)|here]]'''
-{{SK}}
+{{CMG}}; {{AE}} [[User:Sara Zand|Sara Zand, M.D.]]
+{{SK}} Pulmonary hypertension, PH, COVID-19, SARS-COV-2, ARDS
 ==Overview==
+[[Pulmonary hypertension]] ([[PH]]) is determined as an increase in mean [[pulmonary arterial pressure]] (mPAP) of 25 mm Hg or greater at rest. It occurs due to [[pulmonary arterial remodeling]] and [[vasoconstriction]] prompting an increase in [[pulmonary artery pressure]] and finally leading to [[right heart failure]]. Few cases of [[Covid-19]] with PH were found and it seems due to [[keeping social distance]] and quarantine, the number of cases is underestimated. [[Pulmonary hypertension]] is a rare disease and studies about [[PH]] during [[SARS-CoV]] disease in 2003 implied the role of [[inflammation]] in this process.
-Pulmonary hypertention (PH) is determined as an increase in mean pulmonary arterial pressure(mPAP) of 25 mm Hg or greater at rest.Pulmonary arterial  remodeling and vasoconstriction prompting to increase pulmonary artery pressure and finally right heart failure..Few cases of covid 19 with PH were found and it seems due to keeping social distance and quarantine the number of cases are understimated. PH  is a rare disease and Studies about  PH in SARS -COV implied the role of inflammation in this process.
-<br />
 ==Historical Perspective==
-[Disease name] was first discovered by [name of scientist], a [nationality + occupation], in [year]/during/following [event].
+*In 2003, the association between corona infection and [[pulmonary hypertension]] was established during [[SARS-CoV]] epidemic.
-The association between [important risk factor/cause] and [disease name] was made in/during [year/event].
-In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].
-In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].
-There have been several outbreaks of [disease name], including -----.
-In [year], [diagnostic test/therapy] was developed by [scientist] to treat/diagnose [disease name].
 ==Classification==
-There is no established system for the classification of [disease name].
-OR
-[Disease name] may be classified according to [classification method] into [number] subtypes/groups: [group1], [group2], [group3], and [group4].
-OR
-[Disease name] may be classified into [large number > 6] subtypes based on [classification method 1], [classification method 2], and [classification method 3].
-[Disease name] may be classified into several subtypes based on [classification method 1], [classification method 2], and [classification method 3].
-OR
-Based on the duration of symptoms, [disease name] may be classified as either acute or chronic.
-OR
-If the staging system involves specific and characteristic findings and features:
-According to the [staging system + reference], there are [number] stages of [malignancy name] based on the [finding1], [finding2], and [finding3]. Each stage is assigned a [letter/number1] and a [letter/number2] that designate the [feature1] and [feature2].
-OR
-The staging of [malignancy name] is based on the [staging system].
-OR
-There is no established system for the staging of [malignancy name].
+*[[Pulmonary hypertension]] in [[COVID-19]] may be classified into two subtypes:
+# Pulmonary hypertension due to lung disease or [[hypoxia]].
+#[[Microvascular thromboembolic pulmonary hypertensio]]<nowiki/>n.
 ==Pathophysiology==
-* .The SARS-CoV-2 and SARS-CoV virus genomes are highly similar, and patients infected with these viruses  have common pathological features.(8)
+*The [[SARS-CoV-2]] and [[SARS-CoV]] virus genomes are highly similar, and patients infected with these viruses have common pathological features.<ref name="ZhuZhang2020">{{cite journal|last1=Zhu|first1=Na|last2=Zhang|first2=Dingyu|last3=Wang|first3=Wenling|last4=Li|first4=Xingwang|last5=Yang|first5=Bo|last6=Song|first6=Jingdong|last7=Zhao|first7=Xiang|last8=Huang|first8=Baoying|last9=Shi|first9=Weifeng|last10=Lu|first10=Roujian|last11=Niu|first11=Peihua|last12=Zhan|first12=Faxian|last13=Ma|first13=Xuejun|last14=Wang|first14=Dayan|last15=Xu|first15=Wenbo|last16=Wu|first16=Guizhen|last17=Gao|first17=George F.|last18=Tan|first18=Wenjie|title=A Novel Coronavirus from Patients with Pneumonia in China, 2019|journal=New England Journal of Medicine|volume=382|issue=8|year=2020|pages=727–733|issn=0028-4793|doi=10.1056/NEJMoa2001017}}</ref>
-* The pathogenesis of PH in covid19 is characterized by pulmonary vasoconstriction  due to lack of ACE2 and pulmonary microthromboembolism due to local endothelial cell dysfunction  .(lancet rheumatology ,dennis mc ganagle)
+*The pathogenesis of PH in [[COVID-19]] is characterized by pulmonary vasoconstriction due to lack of ACE2 and pulmonary microthromboembolism due to local endothelial cell dysfunction.
-* Renin angiotensin system (RAS) is responsible for  hemeostasis of  blood pressure and electrolyte balance and inflammatory response. Renin is a protease which is produced in kidney and cleaves angiotensinogen to angiotensin 1.Then angiotensin convertase enzyme(ACE) cleaves angiotensin 1 to angiotensin 2. Angiotensin2 is a key factor of RAS and has two receptors including type1 and type2 [1].
+*[[Renin angiotensin system (RAS)]] is responsible for [[hemostasis]] of [[blood pressure]] and [[electrolyte balance]] and [[inflammatory response]].
-* angiotensin-converting enzyme 2 (ACE2), and neprilysin hydrolyze angiotensin 2 to anti inflammatory agents including  Ang1–7, Ang III, Ang IV, and Ang A .[2]
+*[[Renin]] is a protease that is generated in the kidney and cleaves angiotensinogen to angiotensin1, Then [[angiotensin converting enzyme]] ([[Angiotensin-converting enzyme|ACE]]) cleaves [[angiotensin 1]] to angiotensin 2.
+*[[Angiotensin2|Angiotensin 2]] is a key factor of RAS and has two receptors including type 1 and type 2.
-* Angiotensin-converting enzyme 2 (ACE2) was a receptor of  spike protein on SARS corona virus in epithelial cell and after attaching virus the activity of enzyme(ACE2)  was decreased and then virus spread quickly[3](12)
+*Unbalance between ACE/Ang II/AT1R pathway and ACE2/Ang (1-7) receptor pathway in the RAS system will induce [[multi-system inflammation]].<ref name="pmid8135787">{{cite journal |vauthors=Konishi H, Kuroda S, Inada Y, Fujisawa Y |title=Novel subtype of human angiotensin II type 1 receptor: cDNA cloning and expression |journal=Biochem. Biophys. Res. Commun. |volume=199 |issue=2 |pages=467–74 |date=March 1994 |pmid=8135787 |doi=10.1006/bbrc.1994.1252 |url=}}</ref>
-* Lack of ACE2  causes elevation in angiotensin2 level  causing vascular permeability and lung edema and neutrophil infiltration and further lung deterioration.
+*Angiotensin-converting enzyme 2 (ACE2), and [[neprilysin]] hydrolyze angiotensin 2 to anti inflammatory agents including Ang1–7, Ang III, Ang IV, and Ang A.<ref name="pmid23720263">{{cite journal |vauthors=Chappell MC |title=Nonclassical renin-angiotensin system and renal function |journal=Compr Physiol |volume=2 |issue=4 |pages=2733–52 |date=October 2012 |pmid=23720263 |pmc=4186703 |doi=10.1002/cphy.c120002 |url=}}</ref>
+*Angiotensin-converting enzyme 2 (ACE2) was a receptor of [[spike protein]] on [[SARS corona virus]] in epithelial cell and after attaching virus the activity of enzyme([[ACE2]]) was decreased and then virus spread quickly.<ref name="LiMoore2003">{{cite journal|last1=Li|first1=Wenhui|last2=Moore|first2=Michael J.|last3=Vasilieva|first3=Natalya|last4=Sui|first4=Jianhua|last5=Wong|first5=Swee Kee|last6=Berne|first6=Michael A.|last7=Somasundaran|first7=Mohan|last8=Sullivan|first8=John L.|last9=Luzuriaga|first9=Katherine|last10=Greenough|first10=Thomas C.|last11=Choe|first11=Hyeryun|last12=Farzan|first12=Michael|title=Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus|journal=Nature|volume=426|issue=6965|year=2003|pages=450–454|issn=0028-0836|doi=10.1038/nature02145}}</ref><ref name="pmid19864379">{{cite journal |vauthors=Glowacka I, Bertram S, Herzog P, Pfefferle S, Steffen I, Muench MO, Simmons G, Hofmann H, Kuri T, Weber F, Eichler J, Drosten C, Pöhlmann S |title=Differential downregulation of ACE2 by the spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus NL63 |journal=J. Virol. |volume=84 |issue=2 |pages=1198–205 |date=January 2010 |pmid=19864379 |pmc=2798380 |doi=10.1128/JVI.01248-09 |url=}}</ref>
-* ACE2  has anti inflammation effect and protected  the lung from acute lung injury.(4)
+*Lack of ACE2 causes elevation in angiotensin 2 level causing vascular permeability and lung edema and [[neutrophil]] infiltration and further lung deterioration.
-* Phosphorilized ACE2 is much more stable form in which converts angiotensin 2 to angiotensin 1-7 and increases endothelial nitric oxide synthase-derived NO bioavailability ,
+*ACE2 has anti inflammation effect and protected the lung from acute [[lung injury]].<ref name="ImaiKuba2005">{{cite journal|last1=Imai|first1=Yumiko|last2=Kuba|first2=Keiji|last3=Rao|first3=Shuan|last4=Huan|first4=Yi|last5=Guo|first5=Feng|last6=Guan|first6=Bin|last7=Yang|first7=Peng|last8=Sarao|first8=Renu|last9=Wada|first9=Teiji|last10=Leong-Poi|first10=Howard|last11=Crackower|first11=Michael A.|last12=Fukamizu|first12=Akiyoshi|last13=Hui|first13=Chi-Chung|last14=Hein|first14=Lutz|last15=Uhlig|first15=Stefan|last16=Slutsky|first16=Arthur S.|last17=Jiang|first17=Chengyu|last18=Penninger|first18=Josef M.|title=Angiotensin-converting enzyme 2 protects from severe acute lung failure|journal=Nature|volume=436|issue=7047|year=2005|pages=112–116|issn=0028-0836|doi=10.1038/nature03712}}</ref>
-* then  lack of phosphorilized ACE2 caused vasoconstriction and  pulmonary hypertension (5)
+*[[Phosphorilized ACE2]] is a much more stable form in which it converts [[angiotensin 2]] to [[angiotensin 1-7]] and increases the bioavailability of endothelial [[nitric oxide]] synthase-derived NO.
-* Nitric oxide inhalation for SARS-corona patients was correlated with  vasodilation  and relaxation of pulmonary artery, reduction in  pulmonary artery pressure  and improvement in arterial oxygenation. (6)
+*Lack of phosphorilized ACE2 causes vasoconstriction and [[pulmonary hypertension]].<ref name="ZhangDong2018">{{cite journal|last1=Zhang|first1=Jiao|last2=Dong|first2=Jianjie|last3=Martin|first3=Marcy|last4=He|first4=Ming|last5=Gongol|first5=Brendan|last6=Marin|first6=Traci L.|last7=Chen|first7=Lili|last8=Shi|first8=Xinxing|last9=Yin|first9=Yanjun|last10=Shang|first10=Fenqing|last11=Wu|first11=Yan|last12=Huang|first12=Hsi-Yuan|last13=Zhang|first13=Jin|last14=Zhang|first14=Yu|last15=Kang|first15=Jian|last16=Moya|first16=Esteban A.|last17=Huang|first17=Hsien-Da|last18=Powell|first18=Frank L.|last19=Chen|first19=Zhen|last20=Thistlethwaite|first20=Patricia A.|last21=Yuan|first21=Zu-Yi|last22=Shyy|first22=John Y.-J.|title=AMP-activated Protein Kinase Phosphorylation of Angiotensin-Converting Enzyme 2 in Endothelium Mitigates Pulmonary Hypertension|journal=American Journal of Respiratory and Critical Care Medicine|volume=198|issue=4|year=2018|pages=509–520|issn=1073-449X|doi=10.1164/rccm.201712-2570OC}}</ref>
-* Endothelin-1 caused  downregulated  ACE2 expression in lung epithelial cells and pulmonary vasoconstriction.(7)
+*[[Nitric oxide]] inhalation for SARS-corona patients was correlated with [[vasodilation]] and relaxation of [[pulmonary artery]], reduction in pulmonary artery pressure and improvement in arterial oxygenation.<ref name="ChenLiu2004">{{cite journal|last1=Chen|first1=L.|last2=Liu|first2=P.|last3=Gao|first3=H.|last4=Sun|first4=B.|last5=Chao|first5=D.|last6=Wang|first6=F.|last7=Zhu|first7=Y.|last8=Hedenstierna|first8=G.|last9=Wang|first9=C. G.|title=Inhalation of Nitric Oxide in the Treatment of Severe Acute Respiratory Syndrome: A Rescue Trial in Beijing|journal=Clinical Infectious Diseases|volume=39|issue=10|year=2004|pages=1531–1535|issn=1058-4838|doi=10.1086/425357}}</ref>
-*
+*[[Endothelin-1]] caused downregulated ACE2 expression in lung epithelial cells and  reduced pulmonary vasoconstriction.<ref name="pmid23751363">{{cite journal |vauthors=Zhang H, Li Y, Zeng Y, Wu R, Ou J |title=Endothelin-1 downregulates angiotensin-converting enzyme-2 expression in human bronchial epithelial cells |journal=Pharmacology |volume=91 |issue=5-6 |pages=297–304 |date=2013 |pmid=23751363 |doi=10.1159/000350395 |url=}}</ref>
-* On microscopic histopathological analysis, pulmonary wall edema,hyalin thrombosis , inflammatory cell infiltration of pulmonary microvasculature , vessle thrombosis due to diffuse alveolar damage and septal inflammation  are characteristic findings of PH in covid19.(9)
+*On microscopic histopathological analysis, pulmonary wall edema,hyalin thrombosis, inflammatory cell infiltration of pulmonary microvasculature , vessle thrombosis due to diffuse alveolar damage and septal inflammation are characteristic findings of PH in [[COVID-19]].<ref name="FoxAkmatbekov2020">{{cite journal|last1=Fox|first1=Sharon E.|last2=Akmatbekov|first2=Aibek|last3=Harbert|first3=Jack L.|last4=Li|first4=Guang|last5=Brown|first5=J. Quincy|last6=Vander Heide|first6=Richard S.|year=2020|doi=10.1101/2020.04.06.20050575}}</ref>
-*
+{|
-*
+|
-*
+[[File:1280px-Coronavirus virion structure.svg.png|thumb|400px|none|Coronavirus virion structure [https://commons.wikimedia.org/wiki/File:Coronavirus_virion_structure.svg#/media/File:Coronavirus_virion_structure.svg]]]
-*
+|}
-*
+== Causes ==
-<br />
-==Causes==
+*Factors contributing to the microthrombi formation in the pulmonary artery in [[COVID-19]] include:
-Disease name] may be caused by [cause1], [cause2], or [cause3].
-OR
+#[[Hypoxia]] following diffuse alveolar and interestitial  inflammation.  [[Hypoxia]]  may induce endothelial dysfunction and activation of [[coagulation cascade]] in small vessles.<ref name="TenPinsky2002">{{cite journal|last1=Ten|first1=Vadim S.|last2=Pinsky|first2=David J.|title=Endothelial response to hypoxia: physiologic adaptation and pathologic dysfunction|journal=Current Opinion in Critical Care|volume=8|issue=3|year=2002|pages=242–250|issn=1070-5295|doi=10.1097/00075198-200206000-00008}}</ref>
+#[[ACE2]] receptor expression downregulation after attaching the [[sparkle site|spike site]] of [[COVID-19]] to [[pneumocytes type2]].
-Common causes of [disease] include [cause1], [cause2], and [cause3].
+# Activation of the innate coagulation cascade in older age.
+#[[Mechanical ventilation]] may induce immune micro thrombosis in small arteries.<ref name="pmid23222502">{{cite journal |vauthors=Engelmann B, Massberg S |title=Thrombosis as an intravascular effector of innate immunity |journal=Nat. Rev. Immunol. |volume=13 |issue=1 |pages=34–45 |date=January 2013 |pmid=23222502 |doi=10.1038/nri3345 |url=}}</ref>
-OR
+#[[Bacterial superinfection.]]
-The most common cause of [disease name] is [cause 1]. Less common causes of [disease name] include [cause 2], [cause 3], and [cause 4].
-OR
-The cause of [disease name] has not been identified. To review risk factors for the development of [disease name], click [[Pericarditis causes#Overview|here]].
 ==Differentiating COVID-19-associated pulmonary hypertension from other Diseases==
-* Pulmonary intravascular coagulopathy causing pulmonary hypertention  in covid19 must be differentiated from  disseminated intravascular coagulation(DIC) based on clinical features including and lab data including:(lancet rheumatology)
+* Pulmonary intravascular coagulopathy causing pulmonary hypertention  in [[COVID-19]] must be differentiated from  [[disseminated intravascular coagulation(DIC)|disseminated intravascular coagulation (DIC)]] based on clinical features  and lab data:<ref name="McGonagleSharif2020">{{cite journal|last1=McGonagle|first1=Dennis|last2=Sharif|first2=Kassem|last3=O'Regan|first3=Anthony|last4=Bridgewood|first4=Charlie|title=The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease|journal=Autoimmunity Reviews|volume=19|issue=6|year=2020|pages=102537|issn=15689972|doi=10.1016/j.autrev.2020.102537}}</ref>
 {| class="wikitable"
-|
+!style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|}}
-|Disseminated intravascular coagulopathy
+!style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Disseminated intravascular coagulopathy}}
-|Pulmonary intravascular coagulopathy
+!style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Pulmonary intravascular coagulopathy}}
 |-
-|Onset
+|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |Onset
 |Acute
 |Subacute
 |-
-|Pulmonary involvement (%)
+|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |Pulmonary involvement (%)
 |50%
 |100%
 |-
-|Thrombosis
+|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Thrombosis]]
 |Multi-organ clotting
-|Mainly lung (occasional CNS and peripheral thrombosis reported; related to DIC evolution?)
+|Mainly lung
 |-
-|Bleeding
+|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Bleeding]]
 |Generalised
 |Intrapulmonary microhaemorrhage
 |-
-|Liver function
+|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Liver]] function
-|Decreased synthetic function including fibrinogen and other clotting factors; raised               transaminase +++
+|Decreased  fibrinogen and other clotting factors; increased            transaminase +++
 |Preservation of liver synthetic function; +/−
 |-
-|Anaemia
+|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Anemia]]
 | +++
 |−
 |-
-|Thrombocytopenia
+|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Thrombocytopenia]]
 | +++
 |Normal or low
 |-
-|Immune cell cytopenia
+|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[cytopenia]]
 | ++
-|No but lymphopenia is a feature of COVID-19 in general
+|No.may be  lymphopenia is a finding  of COVID-19
 |-
-|Creatine kinase
+|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Creatine kinase-myocardial type|Creatine kinase]]
-| + (skeletal and cardiac origin)
+|  +
-| + (worse prognosis)
+|  +
 |-
-|Troponin T
+|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Troponin T]]
 | +
-| ++ with high levels associated with worse outcome
+|  ++
 |-
-|Elevated prothrombin time or activated partial thromboplastin time
+|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |Elevated [[prothrombin time]] or activated [[partial thromboplastin time]]
 | +++/+++
 | + or normal
 |-
-|Fibrinogen levels
+|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Fibrinogen]] levels
 |Decreased
 |Normal or slight increase
 |-
-|Fibrin degradation products or D-dimer
+|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Fibrin degradation products]] or [[D-dimer]]
 |Increased
 |Increased
 |-
-|C-reactive protein
+|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[C-reactive protein]]
 |Elevated
 |Elevated
 |-
-|Ferritin elevation
+|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Ferritin]] elevation
 | +++
 |Elevated
 |-
-|Hypercytokinaemia
+|style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Hypercytokinaemia]]
 | +++
 | ++
 |}
-<br />
 ==Epidemiology and Demographics==
-The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.
-OR
-In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.
-OR
-In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate of [number range]%.
-Patients of all age groups may develop [disease name].
-OR
-The incidence of [disease name] increases with age; the median age at diagnosis is [#] years.
-OR
-[Disease name] commonly affects individuals younger than/older than [number of years] years of age.
-OR
-[Chronic disease name] is usually first diagnosed among [age group].
-OR
-[Acute disease name] commonly affects [age group].
-There is no racial predilection to [disease name].
-OR
-[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].
-[Disease name] affects men and women equally.
-OR
-[Gender 1] are more commonly affected by [disease name] than [gender 2]. The [gender 1] to [gender 2] ratio is approximately [number > 1] to 1.
+* Data on the incidence of pulmonary hypertension in [[COVID-19]] patients is limited.
+*There is no racial predilection to pulmonary hypertension in [[COVID-19]].
+* Male are more commonly affected by [[COVID-19]] than female, therefore, the prevalence of [[pulmonary hypertension]] induced by [[Covid-19]] is higher in the male gender.
+==Risk Factors==
-The majority of [disease name] cases are reported in [geographical region].
+* Common risk factors in the development of [[pulmonary hypertention]] in [[COVID-19]] include the following:<ref name="McGonagleO'Donnell2020">{{cite journal|last1=McGonagle|first1=Dennis|last2=O'Donnell|first2=James S|last3=Sharif|first3=Kassem|last4=Emery|first4=Paul|last5=Bridgewood|first5=Charles|title=Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia|journal=The Lancet Rheumatology|volume=2|issue=7|year=2020|pages=e437–e445|issn=26659913|doi=10.1016/S2665-9913(20)30121-1}}</ref>
+**[[Male sex]]
-OR
+**[[Hypertension]]
+**[[Obesity]]
-[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].
+**[[Diabetes]]
-==Risk Factors==
-Common risk factors in the development of pulmonary hypertention in covid 19 are male sex, hypertension, obesity, and diabetes (lancet rheumato)
 ==Screening==
-There is insufficient evidence to recommend routine screening for [disease/malignancy].
-OR
+* There is insufficient evidence to recommend routine screening for [[pulmonary hypertension]] in [[COVID-19]].
-According to the [guideline name], screening for [disease name] is not recommended.
-OR
-According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].
 ==Natural History, Complications, and Prognosis==
-If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
-OR
-Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
-OR
-Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.
+*Severe [[COVID-19]]  infection induces [[cytokine storm]] which leads to activation of the [[coagulation cascade]] and thrombotic process.
+*Inflammatory markers including [[IL-1]],[[IL-6]] and [[tumor necrosis factor]] and [[ferritin]] concentration, cause [[pulmonary endothelial dysfunction]]  and [[thromboinflammatory process]].<ref name="pmid27886531">{{cite journal |vauthors=Levi M, van der Poll T |title=Coagulation and sepsis |journal=Thromb. Res. |volume=149 |issue= |pages=38–44 |date=January 2017 |pmid=27886531 |doi=10.1016/j.thromres.2016.11.007 |url=}}</ref>
+*[[Hypoxia]] in [[COVID-19]] pneumonia will cause endothelial dysfunction and expression of active [[tissue factor]] on [[endothelium]], [[macrophage]], [[neutrophils]], and finally activation of [[coagulation cascade]] and reduction of [[fibrinolysis]] and [[plasminogen activation inhibitor 1]].
+*Thrombosis and hemorrhage occur in small vessels of the lung and [[thrombin generation]] and [[fibrin]] deposition enhances in the [[bronchoalveolar]] system.
+*These show the severity of inflammation.
+*[[D-dimer]] level correlated with severe [[COVID-19]] and indicates activation [[fibrinolysis]] and plasmin generation.<ref name="pmid32216698">{{cite journal |vauthors=Ji HL, Zhao R, Matalon S, Matthay MA |title=Elevated Plasmin(ogen) as a Common Risk Factor for COVID-19 Susceptibility |journal=Physiol. Rev. |volume=100 |issue=3 |pages=1065–1075 |date=July 2020 |pmid=32216698 |pmc=7191627 |doi=10.1152/physrev.00013.2020 |url=}}</ref>
+*[[COVID-19]] downregulates [[ACE2]] on pneumocytes type2 which are adjusted pulmonary vascular bed, then vasculopathy and [[thrombosis]] happens.
+*Prognosis is generally  poor in older  patients and in patients with high level of [[fibrin degeredated factors]], including, [[D-dimer]] and  cardiac troponin T due to [[right ventricular failure]].<ref name="ZhouYu2020">{{cite journal|last1=Zhou|first1=Fei|last2=Yu|first2=Ting|last3=Du|first3=Ronghui|last4=Fan|first4=Guohui|last5=Liu|first5=Ying|last6=Liu|first6=Zhibo|last7=Xiang|first7=Jie|last8=Wang|first8=Yeming|last9=Song|first9=Bin|last10=Gu|first10=Xiaoying|last11=Guan|first11=Lulu|last12=Wei|first12=Yuan|last13=Li|first13=Hui|last14=Wu|first14=Xudong|last15=Xu|first15=Jiuyang|last16=Tu|first16=Shengjin|last17=Zhang|first17=Yi|last18=Chen|first18=Hua|last19=Cao|first19=Bin|title=Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study|journal=The Lancet|volume=395|issue=10229|year=2020|pages=1054–1062|issn=01406736|doi=10.1016/S0140-6736(20)30566-3}}</ref>
+*[[COVID-19]] associated [[pulmonary hypertension]] is a [[chronic]] progressive [[disease]] with a high [[mortality rate]].
 ==Diagnosis==
 ===Diagnostic Study of Choice===
-The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].
-OR
-The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].
-OR
-The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].
-OR
+* The diagnosis of pulmonary hypertension is made when at least three of the following diagnostic criteria in [[right heart catheterization(RHC)|right heart catheterization (RHC)]] are met:
+*[[mPAP|Mean PAP]]≥25 mmHg,
-There are no established criteria for the diagnosis of [disease name].
+*[[Pulmonary artery wedge pressure]]≤15 mmHg.
+*[[Pulmonary vascular resistance]]>3 wood units.
 ===History and Symptoms===
-The majority of patients with [disease name] are asymptomatic.
+*The most common symptoms of pulmonary hypertension include:
+**[[Exertional dyspnea]]
-OR
+**[[Chest pain]]
+**[[Fatigue]]
-The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3]. Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3]. Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].
+**[[Lightheadedness]]
+*Less common symptoms include:
+**[[Syncope]]
 ===Physical Examination===
-* Physical examination  in PH may be remarkable for:
+*Physical examination in PH may be remarkable for:
+**[[Rales]]
-:* Rale,dulness or decreased breath sound due to pulmonary congestion or effusion
+**Dullness or decreased breath sound due to [[pulmonary congestion]] or [[effusion]].
-:* central cyanosis due to hypoxia
+**[[Central cyanosis]] due to [[hypoxia]].
-:* Holosystolic murmur increased with inspiration due to tricuspid regurgitation (TR)
+**[[Holosystolic murmur]] with increased intensity during inspiration due to [[tricuspid regurgitation]] (TR).
-:* Diastolic murmur due to pulmonary regurgitation
+**[[Diastolic murmur]] due to [[pulmonary regurgitation]].
-:* Hepatojugular reflux
+**[[Hepatojugular reflux]].
-:* Right ventricular S3 due to RV  dysfunction
+**[[Right ventricle|Right ventricular]] [[S3]] due to [[RV  dysfunction]].
-:* Distention of jugular veinsdue to RV dysfunction and TR
+**[[Distention of jugular vein]]<nowiki/>[[Distention of jugular vein|s]] due to [[RV dysfunction]] and [[Tricuspid regurgitation|TR]]
-:* Peripheral edema and ascites
+** Peripheral [[edema]] and ascites.
-:* Low blood Pressure , diminished pulse pressure , cool extremities due to reduced cardiac out put ,prepheral vasoconstriction
+** Low [[blood Pressure]].
+**[[Diminished pulse pressure]].
-<br />
+**Cool extremities due to reduced [[cardiac output]] and peripheral [[vasoconstriction]].
+**[[Abdominal distention]]
+**Lower extremity [[edema]] (seen in advanced disease and [[right ventricular failure]]).
+**[[Racing pulse]]
 ===Laboratory Findings===
-* laboratory findings consistent with the diagnosis of pulmonary hypertension in covid19 include:(lancet rheumato)
+*Laboratory findings consistent with the diagnosis of pulmonary hypertension in [[COVID-19]] include:
+#<nowiki/>Increased [[D-dimer]] <nowiki/>(due to pulmonary vascular bed [[thrombosis]] with [[fibrinolysis]]).
-Increased D-dimer(due to pulmonary vascular bed thrombosis with fibrinolysis)
+#Elevated concentra<nowiki/>tion of cardiac enzymes due to [[right ventricular strain]] induced by [[pulmonary hypertension]].
+# Normal [[fibrinogen]] and [[Platelet|platele]]<nowiki/>t level.
-Elevated cardiac enzyme concentration due to right ventriclular strain induced by pulmonary hypertention
-Normal fibrinigen and platelet level
-<br />
 ===Electrocardiogram===
+*An [[ECG in Covid-19|ECG]] may be helpful in the diagnosis of pulmonary hypertension. Findings on an ECG suggestive [[pulmonary hypertension]] include:
-An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of pulmonary hypertension  include right atrial enlargement, right axis deviation,right ventricular enlargement with strain pattern
+**[[Right atrial enlargement]].
+**[[Right axis deviation]].
+**[[Right ventricular enlargement]] with [[strain pattern]].
 ===X-ray===
+*[[Chest x-ray]] may be helpful in the diagnosis of pulmonary hypertension in [[COVID-19]]. Findings on [[chest x-ray]] suggestive of [[pulmonary hypertension]] include:
-An x-ray may be helpful in the diagnosis of pulmonary hypertension in covid 19. Findings on an x-ray suggestive of pulmonary hypertension include enlarged main pulmonary artery, prunning ot attenuation of peripheral vascultureand right ventricular enlargement specially in lateral view with other evidence of lung involvement in covid19
+**Enlarged [[main pulmonary artery]].
+**[[Prunning]] or [[attenuation of the peripheral vasculature]].
-OR
+**[[Right ventricular]] enlargement especially in [[lateral view]].
+**With other evidence of lung involvement in [[COVID-19]].
-There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
 ===Echocardiography or Ultrasound===
-There are no echocardiography/ultrasound  findings associated with [disease name].
-OR
-Echocardiography/ultrasound  may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
-OR
+*[[Echocardiography]] is the first modality in the diagnosis of [[pulmonary hypertension]]. Findings on an echocardiography suggestive of pulmonary hypertension include:
+**[[Right atria]]<nowiki/>l enlargement
-There are no echocardiography/ultrasound  findings associated with [disease name]. However, an echocardiography/ultrasound  may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
+**[[Right ventricular]] enlargement and dysfunction
+**Small left side chambers
+**[[Interventricular setal flattening]]
+**[[Tricuspid regurgitation]]
 ===CT scan===
-There are no CT scan findings associated with [disease name].
-OR
+*[[Chest CT|Chest CT scan]] even unenhanced may be helpful  in the diagnosis of pulmonary hypertension in [[COVID-19]].. Findings on CT scan suggestive pulmonary hypertension in [[COVID-19]] in comparison with baseline chest CT scan include:<ref name="SpagnoloCozzi2020">{{cite journal|last1=Spagnolo|first1=Pietro|last2=Cozzi|first2=Andrea|last3=Foà|first3=Riccardo Alessandro|last4=Spinazzola|first4=Angelo|last5=Monfardini|first5=Lorenzo|last6=Bnà|first6=Claudio|last7=Alì|first7=Marco|last8=Schiaffino|first8=Simone|last9=Sardanelli|first9=Francesco|title=CT-derived pulmonary vascular metrics and clinical outcome in COVID-19 patients|journal=Quantitative Imaging in Medicine and Surgery|volume=10|issue=6|year=2020|pages=1325–1333|issn=22234292|doi=10.21037/qims-20-546}}</ref>
-[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
+# Pulmonary artery dilation above 27mm in women and 29mm in men.
+# Increased median [[Pulmonary Artery/Aorta ratio]] from 26mm to 31mm after [[SARS-COVID]] infection.
-OR
+*In one study, pulmonary artery dilation was correlated with high level of [[D-dimer]] and [[pulmonary artery thrombosis]] and poor outcome in [[COVID-19]].<ref name="DolhnikoffDuarte‐Neto2020">{{cite journal|last1=Dolhnikoff|first1=Marisa|last2=Duarte‐Neto|first2=Amaro Nunes|last3=Almeida Monteiro|first3=Renata Aparecida|last4=Silva|first4=Luiz Fernando Ferraz|last5=Oliveira|first5=Ellen Pierre|last6=Saldiva|first6=Paulo Hilário Nascimento|last7=Mauad|first7=Thais|last8=Negri|first8=Elnara Marcia|title=Pathological evidence of pulmonary thrombotic phenomena in severe COVID‐19|journal=Journal of Thrombosis and Haemostasis|volume=18|issue=6|year=2020|pages=1517–1519|issn=1538-7933|doi=10.1111/jth.14844}}</ref>
-There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
 ===MRI===
-There are no MRI findings associated with [disease name].
-OR
-[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
-OR
+*[[Cardiac MRI]] is one of the most accurate method in the diagnosis of pulmonary hypertension. Findings on MRI for evaluation of pulmonary hypertension include :<ref name="pmid23168063">{{cite journal |vauthors=Frazier AA, Burke AP |title=The imaging of pulmonary hypertension |journal=Semin. Ultrasound CT MR |volume=33 |issue=6 |pages=535–51 |date=December 2012 |pmid=23168063 |doi=10.1053/j.sult.2012.06.002 |url=}}</ref>
+**Assessment of the anatomy of the [[pulmonary arteries]].
-There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
+**Assessment of [[pulmonary blood flow]].
+**Assessment of [[right ventricular size]], morphology, and function.
 ===Other Imaging Findings===
-There are no other imaging findings associated with [disease name].
+*[[Perfusion ventilation scan]] may be helpful in the diagnosis of chronic thromboembolic pulmonary hypertension without the ventilation portion due to difficulty in disinfecting the ventilation system in [[COVID-19]] pandemic.
+*If [[lung perfusion image]] is normal, [[chronic thromboembolism]] is ruled out and further invasive [[catheterization]] may be avoided.<ref name="GalièHumbert2016">{{cite journal|last1=Galiè|first1=Nazzareno|last2=Humbert|first2=Marc|last3=Vachiery|first3=Jean-Luc|last4=Gibbs|first4=Simon|last5=Lang|first5=Irene|last6=Torbicki|first6=Adam|last7=Simonneau|first7=Gérald|last8=Peacock|first8=Andrew|last9=Vonk Noordegraaf|first9=Anton|last10=Beghetti|first10=Maurice|last11=Ghofrani|first11=Ardeschir|last12=Gomez Sanchez|first12=Miguel Angel|last13=Hansmann|first13=Georg|last14=Klepetko|first14=Walter|last15=Lancellotti|first15=Patrizio|last16=Matucci|first16=Marco|last17=McDonagh|first17=Theresa|last18=Pierard|first18=Luc A.|last19=Trindade|first19=Pedro T.|last20=Zompatori|first20=Maurizio|last21=Hoeper|first21=Marius|title=2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension|journal=European Heart Journal|volume=37|issue=1|year=2016|pages=67–119|issn=0195-668X|doi=10.1093/eurheartj/ehv317}}</ref>
-OR
-[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 ===Other Diagnostic Studies===
-There are no other diagnostic studies associated with [disease name].
+*There are no other diagnostic studies associated with pulmonary hypertension in [[COVID-19]].
-OR
-[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
-OR
-Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].
 ==Treatment==
 ===Medical Therapy===
-* The mainstay of therapy for pulmonary hypertension in covid19  is(10)(13)
+*The mainstay of therapy for [[pulmonary hypertension]] in [[Covid-19]] including:<ref name="GordonCollard2010">{{cite journal|last1=Gordon|first1=Claire|last2=Collard|first2=Charles D|last3=Pan|first3=Wei|title=Intraoperative management of pulmonary hypertension and associated right heart failure|journal=Current Opinion in Anaesthesiology|volume=23|issue=1|year=2010|pages=49–56|issn=0952-7907|doi=10.1097/ACO.0b013e3283346c51}}</ref><ref name="PrittsPearl2010">{{cite journal|last1=Pritts|first1=Chad D|last2=Pearl|first2=Ronald G|title=Anesthesia for patients with pulmonary hypertension|journal=Current Opinion in Anaesthesiology|volume=23|issue=3|year=2010|pages=411–416|issn=0952-7907|doi=10.1097/ACO.0b013e32833953fb}}</ref>
+#[[Pulmonary vasodilation]].[[Nitric oxide]] has  antiviral  and anti inflammatory effect in [[SARS-CoV]] .<ref name="pmid15546092">{{cite journal |vauthors=Chen L, Liu P, Gao H, Sun B, Chao D, Wang F, Zhu Y, Hedenstierna G, Wang CG |title=Inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: a rescue trial in Beijing |journal=Clin. Infect. Dis. |volume=39 |issue=10 |pages=1531–5 |date=November 2004 |pmid=15546092 |pmc=7107896 |doi=10.1086/425357 |url=}}</ref>
-# Pulmonary vasodilator
+#Supplement [[oxygen]] for correction of [[hypoxia]] and prevention of pulmonary vasoconstriction  to maintain [[oxygen saturation]] above 92%.
-# Supplement oxygen for correction of  hypoxia to maintain oxygen saturation above %90 ,
+#Avoidance of inhaled prostacyclin for prevention of spreading [[COVID-19]] and using the parenteral form for the protection of health care providers.
-# Correction of hypotension  with  fluild and inotropic agents to avoid decreased RV coronary perfusion and RV ejection.
+#[[Endothelin receptor antagonist]] agents.
-# Correction of  acidosis, hypercarbia,hypothermia, hypervolemia
+#[[Anticoagulation therapy]] if there is evidence of thromboembolic mechanism.<ref name="pmid32299776">{{cite journal |vauthors=Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, Baxter-Stoltzfus A, Laurence J |title=Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases |journal=Transl Res |volume=220 |issue= |pages=1–13 |date=June 2020 |pmid=32299776 |pmc=7158248 |doi=10.1016/j.trsl.2020.04.007 |url=}}</ref>
-# Intubation is not recommended due to  effect of positive pressure ventilation on increased RV  preload and vasodilatory effect of sedation agents  impending systemic hypotension and                                  hemodynamic collapse.
+# Correction of [[hypotension]] with fluild and [[inotropic agent]]<nowiki/>s in order to avoid [[RV coronary perfusion|decreased RV coronary perfusion]] and [[RV ejection fraction]].
-# If intubation is indicated , vasoactive agent should be given before anesthesia. Etomidate  is recommended for general anesthesia due to  little effect on cardiac contractiliy and vascular tone.
+# Correction of acidosis, [[hypercarbia]], [[hypothermia]], [[hypervolemia]].
-# Ventilator should be set with low tidal volumes and moderate positive end expiratory pressure for minimum air way pressure and sufficient oxygenation and ventilation.
+#[[Intubation]] is not recommended due to the effect of [[positive pressure ventilation]] in increasing  [[RV  preload]] and also [[vasodilatory effect]] of [[sedation agents]] impending [[systemic hypotension]] and hemodynamic [[collapse]].
+# If [[intubation]] is indicated, a [[vasoactive]] agent should be given before [[anesthesia]]. [[Etomidate]] is recommended for [[general anesthesia]] due to little effect on [[cardiac contractility]] and [[vascular tone]].
-<br />
+#[[Ventilator]] should be set with low tidal volumes and moderate [[positive end-expiratory pressure]] for minimum [[airway pressure]] and sufficient [[oxygenation]] and [[ventilation]].
 ===Surgery===
-Surgical intervention is not recommended for the management of pulmonary hypertension in covid 19
+*Surgical intervention is not recommended for the management of [[pulmonary hypertension]] in [[COVID-19]].
-<br />
 ===Primary Prevention===
-There are no established measures for the primary prevention of [disease name].
+*Effective measures for the primary prevention of PH and [[COVID-19]] include [[keeping social distancing]] and maintaining the medication used for pulmonary hypertension.
-OR
+===Secondary Prevention===
+*There are no established measures for the secondary prevention of pulmonary hypertension in [[COVID-19]].
-There are no available vaccines against [disease name].
+==References==
+{{Reflist|2}}
+[[Category:Up-To-Date]]
-OR
+{{WikiDoc Help Menu}}
+{{WikiDoc Sources}}
-Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
-OR
-[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].
-===Secondary Prevention===
-There are no established measures for the secondary prevention of [disease name].
-OR
-Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].
-==References==
-{{reflist|2}}
-{{WikiDoc Help Menu}}
+.
-{{WikiDoc Sources}}