COVID-19-associated hypoxemia: Difference between revisions

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__NOTOC__  
__NOTOC__  
{{COVID-19}}
{{Main article|COVID-19}}
{{SI}}
 
'''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]]'''


{{CMG}}; {{AE}} [[User:Rija Gul|Rija Gul, M.B.B.S.]]
{{CMG}}; {{AE}} [[User:Rija Gul|Rija Gul, M.B.B.S.]]
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==Overview==
==Overview==
[[COVID-19]] emerged as a [[pandemic]], after its outbreak in Wuhan, China in December 2019. It is caused by a new type of [[Coronavirus]] (novel Coronavirus), based on its [[genomic]] study. The [[Virus (biology)|virus]] binds to [[Angiotensin-converting enzyme|ACE-2 receptors]] on [[Pneumocytes|Type 2 pneumocytes]] in the lower respiratory tract. Its clinical presentation varies from asymptomatic disease to severe acute respiratory distress syndrome ([[ARDS]]). [[Hypoxemia]] is present with an increased [[A-a gradient]]. [[Hypoxemia]] is diagnosed by Pa02<60mmHg in a sample of [[Arterial blood gases|Arterial Blood Gas]]. Mechanisms involved in [[hypoxemia]] are widely reported to be due to [[Ventilation-perfusion mismatch|ventilation perfusion mismatch]] and [[Shunting|intrapulmonary shunting]]. [[Diffusion]] impairment can cause [[hypoxemia]] during recovery period due to [[fibrosis]] in the [[lung]]. Older age, male sex, [[hypertension]] and [[dyspnea]] have been identified as risk factors for development of [[hypoxemia]] in [[COVID-19]]. Complications of [[hypoxemia]] include [[acute respiratory failure]] and [[Multiple organ failure|multi-organ failure]]. Treatment is based on [[oxygen]] supplementation to keep target Spo2> 90%.
[[COVID-19]] emerged as a [[pandemic]], after its outbreak in Wuhan, China in December 2019. It is caused by a new type of [[Coronavirus]], which binds to [[Angiotensin-converting enzyme|ACE-2 receptors]] on [[Pneumocytes|Type 2 pneumocytes]] in the lower respiratory tract. The clinical presentation of patients with COVID-19 varies from asymptomatic disease to severe acute respiratory distress syndrome ([[ARDS]]). [[Hypoxemia]] is present with an increased [[A-a gradient]]. [[Hypoxemia]] is diagnosed by Pa02<60mmHg in a sample of [[Arterial blood gases|Arterial Blood Gas]]. Mechanisms involved in [[hypoxemia]] are widely reported to be due to [[Ventilation-perfusion mismatch|ventilation perfusion mismatch]] and [[Shunting|intrapulmonary shunting]]. [[Diffusion]] impairment can cause [[hypoxemia]] during recovery period due to [[fibrosis]] in the [[lung|lungs]]. Older age, male sex, [[hypertension]] and [[dyspnea]] have been identified as risk factors for development of [[hypoxemia]] in [[COVID-19]]. Complications of [[hypoxemia]] include [[acute respiratory failure]] and [[Multiple organ failure|multi-organ failure]]. Treatment is based on [[oxygen]] supplementation to keep target Spo2> 90%.


==Historical Perspective==
==Historical Perspective==
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* Alveoli collapse occurs due to fluid accumulation and loss of [[Pulmonary surfactant|surfactant]]
* Alveoli collapse occurs due to fluid accumulation and loss of [[Pulmonary surfactant|surfactant]]
* Simultaneously, the activation of [[Coagulation cascade]] by [[cytokines]] leads to widespread [[thrombosis]] in multiple organs of the body, including [[lungs]].
* Simultaneously, the activation of [[Coagulation cascade]] by [[cytokines]] leads to widespread [[thrombosis]] in multiple organs of the body, including [[lungs]].
* It has also been suggested that there is down-regulation of the Hemostatic Oxygen Sensing system of the body (e.g [[Carotid bodies]]) through alteration of expression of [[Mitochondrial|mitochondrial proteins]] by the [[Coronavirus, SARS associated|Coronavirus,]] occurring at a cellular level.
* It has also been suggested that there is down-regulation of the Hemostatic Oxygen Sensing system of the body (e.g [[Carotid bodies]]) through alteration in the expression of [[Mitochondrial|mitochondrial proteins]] by the [[Coronavirus, SARS associated|Coronavirus,]] occurring at a cellular level.
* The above mechanism supports the lack of [[dyspnea]] in proportion to the severity of [[hypoxemia]], on clinical presentation, a phenomenon known as "happy hypoxemia".
* The above mechanism support the lack of [[dyspnea]] in proportion to the severity of [[hypoxemia]], on clinical presentation, a phenomenon known as "happy hypoxemia".


===Mechanisms of Hypoxemia in COVID-19===
===Mechanisms of Hypoxemia in COVID-19===
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* This can be explained by abnormal [[vasoregulation]] which disrupts the physiological, hypoxic pulmonary [[vasoconstriction]] response to [[hypoxemia]].<ref name="pmid32291463">{{cite journal |vauthors=Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, Camporota L |title=COVID-19 pneumonia: different respiratory treatments for different phenotypes? |journal=Intensive Care Med |volume=46 |issue=6 |pages=1099–1102 |date=June 2020 |pmid=32291463 |pmc=7154064 |doi=10.1007/s00134-020-06033-2 |url=}}</ref>
* This can be explained by abnormal [[vasoregulation]] which disrupts the physiological, hypoxic pulmonary [[vasoconstriction]] response to [[hypoxemia]].<ref name="pmid32291463">{{cite journal |vauthors=Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, Camporota L |title=COVID-19 pneumonia: different respiratory treatments for different phenotypes? |journal=Intensive Care Med |volume=46 |issue=6 |pages=1099–1102 |date=June 2020 |pmid=32291463 |pmc=7154064 |doi=10.1007/s00134-020-06033-2 |url=}}</ref>
* If [[hypoxemia]] is not addressed early, the patient increases inspiratory efforts which exerts more [[pressure]] on the [[tissues]], causing a rise in the [[Transpulmonary pressure|transpulmonary]] pressure.
* If [[hypoxemia]] is not addressed early, the patient increases inspiratory efforts which exerts more [[pressure]] on the [[tissues]], causing a rise in the [[Transpulmonary pressure|transpulmonary]] pressure.
* These changes in lung dynamics promote [[Capillary leak|capillary leakage]] which further increases alveolar [[Exudate|exudates]] and the [[lungs]] become poorly compliant.
* These changes in lung dynamics promote [[Capillary leak|capillary leakage]], which further increases alveolar [[Exudate|exudates]] and the [[lungs]] become poorly compliant.
* The [[Ventilation-perfusion mismatch pathophysiology|ventilation-perfusion mismatch]], therefore, progresses from a high [[Ventilation/perfusion ratio|Va/Q ratio]] to a low [[Ventilation/perfusion ratio|Va/Q ratio]].
* The [[Ventilation-perfusion mismatch pathophysiology|ventilation-perfusion mismatch]], therefore, progresses from a high [[Ventilation/perfusion ratio|Va/Q ratio]] to a low [[Ventilation/perfusion ratio|Va/Q ratio]].
* Pulmonary vascular [[thrombi]] also contribute to [[Ventilation-perfusion mismatch|Va/Q mismatch]].
* Pulmonary vascular [[thrombi]] also contributes to [[Ventilation-perfusion mismatch|Va/Q mismatch]].
* Both acute [[pulmonary embolism]] and small vessel [[thrombosis]] are seen on autopsy.
* Both acute [[pulmonary embolism]] and small vessel [[thrombosis]] are seen on autopsy.
* This increases the alveolar [[dead space]] causing [[Ventilation-perfusion mismatch pathophysiology|Va/Q mismatch]].
* This increases the alveolar [[dead space]] causing [[Ventilation-perfusion mismatch pathophysiology|Va/Q mismatch]].
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====Intrapulmonary Shunt====
====Intrapulmonary Shunt====
*[[Blood]] is shunted from the poorly [[Ventilation|ventilated]] [[Pulmonary alveolus|alveoli]] to well-aerated [[lung]] regions.
*[[Blood]] is shunted from the poorly [[Ventilation|ventilated]] [[Pulmonary alveolus|alveoli]] to well-aerated [[lung]] regions.
* Intra-cardiac shunts can be detected in 20% of the patients being treated for [[Acute respiratory distress syndrome|ARDS]]. [[Patent foramen ovale]] opens due to [[positive pressure ventilation]].<ref name="Mekontso DessapBoissier2010">{{cite journal|last1=Mekontso Dessap|first1=Armand|last2=Boissier|first2=Florence|last3=Leon|first3=Rusel|last4=Carreira|first4=Serge|last5=Roche Campo|first5=Ferran|last6=Lemaire|first6=François|last7=Brochard|first7=Laurent|title=Prevalence and prognosis of shunting across patent foramen ovale during acute respiratory distress syndrome*|journal=Critical Care Medicine|volume=38|issue=9|year=2010|pages=1786–1792|issn=0090-3493|doi=10.1097/CCM.0b013e3181eaa9c8}}</ref><ref name="pmid32634734">{{cite journal |vauthors=Fisher HK |title=Hypoxemia in COVID-19 patients: An hypothesis |journal=Med. Hypotheses |volume=143 |issue= |pages=110022 |date=June 2020 |pmid=32634734 |pmc=7308039 |doi=10.1016/j.mehy.2020.110022 |url=}}</ref>
* Intra-cardiac shunts can be detected in 20% of the COVID-19 patients treated for [[Acute respiratory distress syndrome|ARDS]]. [[Patent foramen ovale]] opens due to [[positive pressure ventilation]].<ref name="Mekontso DessapBoissier2010">{{cite journal|last1=Mekontso Dessap|first1=Armand|last2=Boissier|first2=Florence|last3=Leon|first3=Rusel|last4=Carreira|first4=Serge|last5=Roche Campo|first5=Ferran|last6=Lemaire|first6=François|last7=Brochard|first7=Laurent|title=Prevalence and prognosis of shunting across patent foramen ovale during acute respiratory distress syndrome*|journal=Critical Care Medicine|volume=38|issue=9|year=2010|pages=1786–1792|issn=0090-3493|doi=10.1097/CCM.0b013e3181eaa9c8}}</ref><ref name="pmid32634734">{{cite journal |vauthors=Fisher HK |title=Hypoxemia in COVID-19 patients: An hypothesis |journal=Med. Hypotheses |volume=143 |issue= |pages=110022 |date=June 2020 |pmid=32634734 |pmc=7308039 |doi=10.1016/j.mehy.2020.110022 |url=}}</ref>
* Shunt can be differentiated from [[Ventilation-perfusion mismatch|Va/Q mismatch]] due to the lack of response to supplemental [[oxygen]].
* Shunt can be differentiated from [[Ventilation-perfusion mismatch|Va/Q mismatch]] due to the lack of response to supplemental [[oxygen]].


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==Causes==
==Causes==
*[[Hypoxemia]] in COVID-19 patients is associated with the development of the following:
The table below describes the most common [[causes]] of [[hypoxemia]] in [[COVID-19]]:
**[[Acute respiratory distress syndrome|Acute Respiratory Distress Syndrome]]
{| class="wikitable"
** Microvascular [[Thrombi]]<ref>{{cite journal|doi=10.1016/ S1473-3099(20)30367-4}}</ref>
|+<big>Common Causes of [[Hypoxemia]] in COVID-19</big>
** COVID-19 Pneumonia (see [[COVID-19-associated pneumonia|Covid-19-associated pneumonia]])
!style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Pulmonary causes}}
 
!style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Cardiac causes}}
==Differential Diagnosis==
|-
|[[Pneumonia]]
|[[Myocardial Infarction]]
|-
|Non cardiogenic Pulmonary Edema
|[[Myocarditis]]
|-
|[[Pulmonary hypertension|Pulmonary Hypertension]]
|[[Heart Failure]]
|-
|[[Pulmonary embolism]]
|[[Cardiogenic Shock]]
|-
|Super imposed bacterial infection
|[[Arrhythmia]]
|}


==Differentiating COVID-19-associated hypoxemia from other Diseases==
==Differentiating COVID-19-associated hypoxemia from other Diseases==
* COVID-19-associated hypoxemia should be differentiated from other potential causes of [[hypoxemia]].
*[[Dyspnea]] is not a prominent feature of [[hypoxemia]] due to [[COVID-19]] in contrast to other diseases causing [[hypoxemia]]<ref name="pmid32634734">{{cite journal |vauthors=Fisher HK |title=Hypoxemia in COVID-19 patients: An hypothesis |journal=Med. Hypotheses |volume=143 |issue= |pages=110022 |date=June 2020 |pmid=32634734 |pmc=7308039 |doi=10.1016/j.mehy.2020.110022 |url=}}</ref>
*This can be explained by areas of well preserved lung compliance surrounding the damaged tissue.<ref name="DondorpHayat2020">{{cite journal|last1=Dondorp|first1=Arjen M.|last2=Hayat|first2=Muhammad|last3=Aryal|first3=Diptesh|last4=Beane|first4=Abi|last5=Schultz|first5=Marcus J.|title=Respiratory Support in COVID-19 Patients, with a Focus on Resource-Limited Settings|journal=
The American Journal of Tropical Medicine and Hygiene|volume=102|issue=6|year=2020|pages=1191–1197|issn=0002-9637|doi=10.4269/ajtmh.20-0283}}</ref>


[[Dyspnea]] is not a prominent feature of [[hypoxemia]] due to [[COVID-19]] in contrast to other diseases causing [[hypoxemia]]<ref name="pmid32634734">{{cite journal |vauthors=Fisher HK |title=Hypoxemia in COVID-19 patients: An hypothesis |journal=Med. Hypotheses |volume=143 |issue= |pages=110022 |date=June 2020 |pmid=32634734 |pmc=7308039 |doi=10.1016/j.mehy.2020.110022 |url=}}</ref>
*It is important to differentiate [[COVID-19]] associated pneumonia from Community acquired pneumonia, as both can present with [[hypoxemia]] and pulmonary [[Infection|infection.]]<ref name="LipmanChambers2020">{{cite journal|last1=Lipman|first1=Marc|last2=Chambers|first2=Rachel C|last3=Singer|first3=Mervyn|last4=Brown|first4=Jeremy Stuart|title=SARS-CoV-2 pandemic: clinical picture of COVID-19 and implications for research|journal=Thorax|year=2020|pages=thoraxjnl-2020-215024|issn=0040-6376|doi=10.1136/thoraxjnl-2020-215024}}</ref>
{| class="wikitable"
!style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Covid-19 Pneumonia}}
!style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Community Acquired pneumonia}}
|-
|[[Severe acute respiratory syndrome|Sars-Cov2]]
|[[Virus|Viral]]/ [[Bacterial]] pathogens e.g Streptococcus Pneumonia, [[Influenza]]
|-
|[[Pneumonia]] develops after 6 days of infective symptoms
|Rapid development of symptoms of [[pneumonia]]
|-
|[[Malaise]] is a prominent feature
|[[Malaise]] is not a prominent feature
|-
|Extra Pulmonary symptoms are present ( [[anosmia]], [[headache]], [[myalgia]])
|Pulmonary symptoms are more prominent ( Productive [[cough]], [[fever]])
|-
|Radiology shows Basal [[atelectasis]] / Bilateral peripheral Ground Glass opacities
|Radiology shows [[Lobar pneumonia|Lobar Consolidation]]
|}


==Epidemiology and Demographics==
==Epidemiology and Demographics==
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==Risk Factors==
==Risk Factors==
*According to a study conducted in Wuhan, China, the following risk factors were identified in patients presenting with [[hypoxemia]](Spo2< 90%):<ref name="XieCovassin2020">{{cite journal|last1=Xie|first1=Jiang|last2=Covassin|first2=Naima|last3=Fan|first3=Zhengyang|last4=Singh|first4=Prachi|last5=Gao|first5=Wei|last6=Li|first6=Guangxi|last7=Kara|first7=Tomas|last8=Somers|first8=Virend K.|title=Association Between Hypoxemia and Mortality in Patients With COVID-19|journal=Mayo Clinic Proceedings|volume=95|issue=6|year=2020|pages=1138–1147|issn=00256196|doi=10.1016/j.mayocp.2020.04.006}}</ref>
*According to a study conducted in Wuhan, China, the following risk factors were identified in patients presenting with [[hypoxemia]] (Spo2< 90%):<ref name="XieCovassin2020">{{cite journal|last1=Xie|first1=Jiang|last2=Covassin|first2=Naima|last3=Fan|first3=Zhengyang|last4=Singh|first4=Prachi|last5=Gao|first5=Wei|last6=Li|first6=Guangxi|last7=Kara|first7=Tomas|last8=Somers|first8=Virend K.|title=Association Between Hypoxemia and Mortality in Patients With COVID-19|journal=Mayo Clinic Proceedings|volume=95|issue=6|year=2020|pages=1138–1147|issn=00256196|doi=10.1016/j.mayocp.2020.04.006}}</ref>
**Older age (median - 60 years)
**Older age (median - 60 years)
**Male sex
**Male sex
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==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==
* [[COVID-19]] has a wide range of clinical presentation, varying from asymptomatic to severe disease, requiring ICU admission.  
* [[COVID-19]] has a wide range of clinical presentations, varying from asymptomatic to severe disease, requiring ICU admission.  
* Acute Respiratory Distress Syndrome (ARDS) (see [[COVID-19-associated acute respiratory distress syndrome]]) and [[pneumonia]], which are a common cause of [[hypoxemia]], can develop in 15% of patients.<ref name="pmid32195698">{{cite journal |vauthors=Greenland JR, Michelow MD, Wang L, London MJ |title=COVID-19 Infection: Implications for Perioperative and Critical Care Physicians |journal=Anesthesiology |volume=132 |issue=6 |pages=1346–1361 |date=June 2020 |pmid=32195698 |pmc=7155909 |doi=10.1097/ALN.0000000000003303 |url=}}</ref>
* Acute Respiratory Distress Syndrome (ARDS) (see [[COVID-19-associated acute respiratory distress syndrome]]) and [[pneumonia]], which are a common cause of [[hypoxemia]], can develop in 15% of patients.<ref name="pmid32195698">{{cite journal |vauthors=Greenland JR, Michelow MD, Wang L, London MJ |title=COVID-19 Infection: Implications for Perioperative and Critical Care Physicians |journal=Anesthesiology |volume=132 |issue=6 |pages=1346–1361 |date=June 2020 |pmid=32195698 |pmc=7155909 |doi=10.1097/ALN.0000000000003303 |url=}}</ref>
* Common complications of [[hypoxemia]] include acute respiratory failure, (see [[COVID-19-associated respiratory failure]]) and multiorgan failure( [[Acute Kidney injury]], Liver dysfunction, Cardiac injury).<ref name="pmid32105632">{{cite journal |vauthors=Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y |title=Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study |journal=Lancet Respir Med |volume=8 |issue=5 |pages=475–481 |date=May 2020 |pmid=32105632 |pmc=7102538 |doi=10.1016/S2213-2600(20)30079-5 |url=}}</ref>
* Common complications of [[hypoxemia]] include acute respiratory failure, (see [[COVID-19-associated respiratory failure]]) and multiorgan failure ([[Acute Kidney injury]], Liver dysfunction, Cardiac injury).<ref name="pmid32105632">{{cite journal |vauthors=Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y |title=Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study |journal=Lancet Respir Med |volume=8 |issue=5 |pages=475–481 |date=May 2020 |pmid=32105632 |pmc=7102538 |doi=10.1016/S2213-2600(20)30079-5 |url=}}</ref>
* Prognosis is generally poor for patients presenting with [[hypoxemia]]. It has been identified as an independent risk factor for [[mortality]] due to [[COVID-19]].
* Prognosis is generally poor for patients presenting with [[hypoxemia]]. It has been identified as an independent risk factor for [[mortality]] due to [[COVID-19]].
*Patients who require mechanical ventilation have a [[mortality rate]] of 50%-60%.<ref name="pmid32547323">{{cite journal |vauthors=Pan F, Yang L, Li Y, Liang B, Li L, Ye T, Li L, Liu D, Gui S, Hu Y, Zheng C |title=Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): a case-control study |journal=Int J Med Sci |volume=17 |issue=9 |pages=1281–1292 |date=2020 |pmid=32547323 |pmc=7294915 |doi=10.7150/ijms.46614 |url=}}</ref><ref name="pmid32171076">{{cite journal |vauthors=Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B |title=Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study |journal=Lancet |volume=395 |issue=10229 |pages=1054–1062 |date=March 2020 |pmid=32171076 |pmc=7270627 |doi=10.1016/S0140-6736(20)30566-3 |url=}}</ref>
*Patients who require mechanical ventilation have a [[mortality rate]] of 50%-60%.<ref name="pmid32547323">{{cite journal |vauthors=Pan F, Yang L, Li Y, Liang B, Li L, Ye T, Li L, Liu D, Gui S, Hu Y, Zheng C |title=Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): a case-control study |journal=Int J Med Sci |volume=17 |issue=9 |pages=1281–1292 |date=2020 |pmid=32547323 |pmc=7294915 |doi=10.7150/ijms.46614 |url=}}</ref><ref name="pmid32171076">{{cite journal |vauthors=Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B |title=Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study |journal=Lancet |volume=395 |issue=10229 |pages=1054–1062 |date=March 2020 |pmid=32171076 |pmc=7270627 |doi=10.1016/S0140-6736(20)30566-3 |url=}}</ref>
 
===Complications===
*[[Hypoxemia]] in COVID-19 patients is associated with the development of the following:
**[[Acute respiratory distress syndrome|Acute Respiratory Distress Syndrome]]
** Microvascular [[Thrombi]]<ref>{{cite journal|doi=10.1016/ S1473-3099(20)30367-4}}</ref>
** COVID-19 Pneumonia (see [[COVID-19-associated pneumonia|Covid-19-associated pneumonia]])
** Massive [[Pulmonary embolism]]<ref name="UllahSaeed2020">{{cite journal|last1=Ullah|first1=Waqas|last2=Saeed|first2=Rehan|last3=Sarwar|first3=Usman|last4=Patel|first4=Rajesh|last5=Fischman|first5=David L.|title=COVID-19 Complicated by Acute Pulmonary Embolism and Right-Sided Heart Failure|journal=JACC: Case Reports|year=2020|issn=26660849|doi=10.1016/j.jaccas.2020.04.008}}</ref>
**Hyper [[Inflammation]]
==Diagnosis==
==Diagnosis==
===Diagnostic Study of Choice===
===Diagnostic Study of Choice===


*The [[diagnosis]] of [[COVID-19]] associated [[hypoxemia]] can be established by the following investigations:
*The [[diagnosis]] of [[COVID-19]] associated [[hypoxemia]] can be established by the following investigations:
**[[Polymerase chain reaction|Reverse Transcriptase- Polymerase Chain Reaction]] from nasal or throat swab sample positive for [[COVID-19]]
**[[Polymerase chain reaction|Reverse Transcriptase-Polymerase Chain Reaction]] from nasal or throat swab sample positive for [[COVID-19]]
**[[CT-scans|Chest Tomography]] images showing peripheral and bilateral ground-glass opacities
**[[CT-scans|Chest Tomography]] images showing peripheral and bilateral ground-glass opacities
**[[Arterial blood gases|Arterial Blood gas]] showing Pa02 (Partial Pressure of oxygen) below 60mmHg
**[[Arterial blood gases|Arterial Blood gas]] showing Pa02 (Partial Pressure of oxygen) below 60mmHg
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===History and Symptoms===
===History and Symptoms===


* Dry [[cough]] (most common symptom)
* Dry [[cough]]<ref name="UllahSaeed2020">{{cite journal|last1=Ullah|first1=Waqas|last2=Saeed|first2=Rehan|last3=Sarwar|first3=Usman|last4=Patel|first4=Rajesh|last5=Fischman|first5=David L.|title=COVID-19 Complicated by Acute Pulmonary Embolism and Right-Sided Heart Failure|journal=JACC: Case Reports|year=2020|issn=26660849|doi=10.1016/j.jaccas.2020.04.008}}</ref>
* [[Fever]]
* [[Fever]]
* [[Tachypnea]]
* [[Tachypnea]]
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* ELevated [[D-Dimer]]
* ELevated [[D-Dimer]]
* Elevated level of IL-1, [[IL-6]]
* Elevated level of IL-1, [[IL-6]]
===Electrocardiogram===
* There are no typical [[electrocardiographic]] findings for [[hypoxemia]] related to [[COVID-19]].
* To view the electrocardiogram findings on COVID-19, [[COVID-19 electrocardiogram|click here]].<br />
===X-Ray===
* Chest x-ray demonstrates multi-lobar infiltrates<ref name="DondorpHayat2020">{{cite journal|last1=Dondorp|first1=Arjen M.|last2=Hayat|first2=Muhammad|last3=Aryal|first3=Diptesh|last4=Beane|first4=Abi|last5=Schultz|first5=Marcus J.|title=Respiratory Support in COVID-19 Patients, with a Focus on Resource-Limited Settings|journal=
The American Journal of Tropical Medicine and Hygiene|volume=102|issue=6|year=2020|pages=1191–1197|issn=0002-9637|doi=10.4269/ajtmh.20-0283}}</ref>
* To view the x-ray finidings on COVID-19, [[COVID-19 x ray|click here]].<br />
===Echocardiography or Ultrasound===
* There are no typical [[Echocardiography|echocardiographic]] findings for [[hypoxemia]] related to [[COVID-19]].
* To view the echocardiographic findings on COVID-19, [[COVID-19 echocardiography and ultrasound|click here]].<br />
===CT Scan===
*[[Ct scan|Computed Tomography]] shows consolidation and bilateral ground-glass opacities located peripherally.
*To view the CT scan findings on COVID-19, [[COVID-19 CT scan|click here]].
===MRI===
* There are no specific [[MRI]] findings for [[hypoxemia]] related to [[COVID-19]].
* To view the MRI findings on COVID-19, [[COVID-19 MRI|click here]].<br />


===Imaging Studies===
===Other Imaging Findings===
*[[Ct scan|Computed Tomography]] shows consolidation and bilateral ground glass opacities located peripherally.
* To view other imaging findings on COVID-19, [[COVID-19 other imaging findings|click here]].<br />
===Other Diagnostic Studies===
* To view other diagnostic studies for COVID-19, [[COVID-19 other diagnostic studies|click here]].<br />


==Treatment==
==Treatment==
===Treatment of Hypoxemia due to COVID-19===
===Treatment of Hypoxemia due to COVID-19===
====Overview====
====Overview====
* [[Hypoxia]] due to [[COVID-19]] warrants hospital admission
* [[Hypoxia]] due to [[COVID-19]] warrants hospital admission.
*[[Oxygen]] target should be Spo2>90%
*[[Oxygen]] target should be Spo2>90%.
* Some centres have suggested to restrict [[oxygen]] supplementation by [[High Flow Nasal Cannula]](HFNC) and [[Non Invasive Ventilation]]( Bipap, CPAP) as they generate [[aerosol]] and pose a threat to the healthcare workers<ref name="pmid32291505">{{cite journal |vauthors=Kluge S, Janssens U, Welte T, Weber-Carstens S, Marx G, Karagiannidis C |title=German recommendations for critically ill patients with COVID‑19 |journal=Med Klin Intensivmed Notfmed |volume= |issue= |pages= |date=April 2020 |pmid=32291505 |pmc=7155395 |doi=10.1007/s00063-020-00689-w |url=}}</ref>
* Some centres have suggested to restrict [[oxygen]] supplementation by High Flow Nasal Cannula (HFNC) and Non-Invasive Ventilation (Bipap, CPAP) as they generate [[aerosol]] and pose a threat to the healthcare workers.<ref name="pmid32291505">{{cite journal |vauthors=Kluge S, Janssens U, Welte T, Weber-Carstens S, Marx G, Karagiannidis C |title=German recommendations for critically ill patients with COVID‑19 |journal=Med Klin Intensivmed Notfmed |volume= |issue= |pages= |date=April 2020 |pmid=32291505 |pmc=7155395 |doi=10.1007/s00063-020-00689-w |url=}}</ref>
* Invasive mechanical Ventilation by early [[intubation]] is recommended for [[hypoxemia]] not responding to [[Non Invasive Ventilation]]
* Invasive mechanical Ventilation by early [[intubation]] is recommended for [[hypoxemia]] not responding to Non-Invasive Ventilation.


====Venturi Mask====
====Venturi Mask====
* SpO2< 93%-94%
* SpO2< 93%-94%
* [[Respiratory rate]] > 28-30 breaths per minute
* [[Respiratory rate]] > 28-30 breaths per minute.
* Deliver [[oxygen]] via 40% [[Venturi mask]]  
* Deliver [[oxygen]] via 40% [[Venturi mask|Venturi mask.]]
* If response is seen in 5-10 minutes, continue treatment for the next 6 hours  
* If a response is seen in 5-10 minutes, continue treatment for the next 6 hours.
* NIV is recommended if there is no improvement
* NIV is recommended if there is no improvement.


====High Flow Nasal Oxygenation(HFNO)====
====High Flow Nasal Oxygenation(HFNO)====
* Use is recommended in negative pressure environment due to [[Aerosols|aerosol]] generation
* Use is recommended in a negative pressure environment due to [[Aerosols|aerosol]] generation.
* Apply if SpO2< 92%
* Apply if SpO2< 92%.
* No response to [[Oxygen]] delivery is observed via [[nasal cannula]], face mask or [[Venturi mask]]
* No response to [[Oxygen]] delivery is observed via [[nasal cannula]], face mask or [[Venturi mask]].
* Use [[Oxygen]] flow of 30-50L/min
* Use [[Oxygen]] flow of 30-50L/min.
* Keep [[FiO2]] between 50%-70%
* Keep [[FiO2]] between 50%-70%.


====Non Invasive Ventilation====
====Non Invasive Ventilation====
* Used when [[dyspnea]]/ [[hypoxemia]] does not improve within 1 hour of HFNO used at 50L/min and FiO2>70%  
* Used when [[dyspnea]]/ [[hypoxemia]] does not improve within 1 hour of HFNO used at 50L/min and FiO2>70%.
* Recommended to use pressure setting of 8-10cm Hg and [[FiO2]]of 60%
* Recommended to use pressure setting of 8-10cm Hg and [[FiO2]]of 60%.
* Monitor with hourly [[Arterial blood gas|Arterial Blood Gas]] sampling
* Monitor with hourly [[Arterial blood gas|Arterial Blood Gas]] sampling.
* Use for 4-6 hours, allowing 1 hour break for feeding
* Use for 4-6 hours, allowing 1-hour break for feeding.


====Invasive Mechanical ventilation====
====Invasive Mechanical ventilation====
* Performed in patients with severe [[hypoxemia]] ( Pa02/FiO2 <200) and failure of NIV
* Performed in patients with severe [[hypoxemia]] ( Pa02/FiO2 <200) and failure of NIV.
* Rapid Sequence [[intubation]] is preferred to avoid [[Aerosols|aerosolisation]] by Bag mask ventilation
* Rapid Sequence [[intubation]] is preferred to avoid [[Aerosols|aerosolisation]] by Bag mask ventilation.
* Lung protective Ventilation is used in patients with severe [[Acute respiratory distress syndrome|ARDS]]
* Lung protective Ventilation is used in patients with severe [[Acute respiratory distress syndrome|ARDS]].
*[[Tidal volume|Tidal Volume]] at 4-6ml/kg of body weight
*[[Tidal volume|Tidal Volume]] at 4-6ml/kg of body weight.
* Plateau Pressure(Pplat) < 30cm H2O
* Plateau Pressure(Pplat) < 30cm H2O.
* High [[Positive-end expiratory pressure|Positive End Expiratory Pressure]] (PEEP) is recommended to keep [[driving pressure]](Pplat-PEEP)<14cm H2O
* High Positive End Expiratory Pressure (PEEP) is recommended to keep driving pressure (Pplat-PEEP)<14cm H2O.


====Prone Position====
====Prone Position====
* Recommended in severe [[ARDS]](PaO2/FiO2<150) along with Invasive Mechanical ventilation
* Recommended in severe [[ARDS]] (PaO2/FiO2 <150) along with Invasive Mechanical ventilation.
* Recommended for total duration of 12-16 hours daily
* Recommended for a total duration of 12-16 hours daily.
* Not recommended for infants less than 6 months of age
* Not recommended for infants less than 6 months of age.
* It decreases [[Ventilation-perfusion mismatch|Va/Q mismatch]] by eliminating gravitational forces exerted on [[lung]] portion by [[mediastinal]] structures, allowing maximum [[lung]] recruitment when positive pressure mechanical ventilation is applied<ref name="pmid32484966">{{cite journal |vauthors=Lindahl SGE |title=Using the prone position could help to combat the development of fast hypoxia in some patients with COVID-19 |journal=Acta Paediatr. |volume=109 |issue=8 |pages=1539–1544 |date=August 2020 |pmid=32484966 |pmc=7301016 |doi=10.1111/apa.15382 |url=}}</ref>
* It decreases [[Ventilation-perfusion mismatch|Va/Q mismatch]] by eliminating gravitational forces exerted on [[lung]] portion by [[mediastinal]] structures, allowing maximum [[lung]] recruitment when positive pressure mechanical ventilation is applied.<ref name="pmid32484966">{{cite journal |vauthors=Lindahl SGE |title=Using the prone position could help to combat the development of fast hypoxia in some patients with COVID-19 |journal=Acta Paediatr. |volume=109 |issue=8 |pages=1539–1544 |date=August 2020 |pmid=32484966 |pmc=7301016 |doi=10.1111/apa.15382 |url=}}</ref>
* Meta analysis have shown that [[Prone position|Prone positioning]] can decrease [[mortality]] when used for long duration within intial 48hours in severe [[Acute respiratory distress syndrome|ARDS]].<ref name="Mora-ArteagaBernal-Ramírez2015">{{cite journal|last1=Mora-Arteaga|first1=J.A.|last2=Bernal-Ramírez|first2=O.J.|last3=Rodríguez|first3=S.J.|title=The effects of prone position ventilation in patients with acute respiratory distress syndrome. A systematic review and metaanalysis|journal=Medicina Intensiva (English Edition)|volume=39|issue=6|year=2015|pages=359–372|issn=21735727|doi=10.1016/j.medine.2014.11.004}}</ref>
* Meta analysis have shown that [[Prone position|Prone positioning]] can decrease [[mortality]] when used for long duration within intial 48hours in severe [[Acute respiratory distress syndrome|ARDS]].<ref name="Mora-ArteagaBernal-Ramírez2015">{{cite journal|last1=Mora-Arteaga|first1=J.A.|last2=Bernal-Ramírez|first2=O.J.|last3=Rodríguez|first3=S.J.|title=The effects of prone position ventilation in patients with acute respiratory distress syndrome. A systematic review and metaanalysis|journal=Medicina Intensiva (English Edition)|volume=39|issue=6|year=2015|pages=359–372|issn=21735727|doi=10.1016/j.medine.2014.11.004}}</ref>
* In a pilot study performed in New York emergency, awake [[Prone position|proning]] was associated with improved [[Oxygen-16|oxygen]] saturations in non intubated patients.<ref name="pmid32320506">{{cite journal |vauthors=Caputo ND, Strayer RJ, Levitan R |title=Early Self-Proning in Awake, Non-intubated Patients in the Emergency Department: A Single ED's Experience During the COVID-19 Pandemic |journal=Acad Emerg Med |volume=27 |issue=5 |pages=375–378 |date=May 2020 |pmid=32320506 |pmc=7264594 |doi=10.1111/acem.13994 |url=}}</ref>
* In a pilot study performed in New York emergency, awake [[Prone position|proning]] was associated with improved [[Oxygen-16|oxygen]] saturations in non intubated patients.<ref name="pmid32320506">{{cite journal |vauthors=Caputo ND, Strayer RJ, Levitan R |title=Early Self-Proning in Awake, Non-intubated Patients in the Emergency Department: A Single ED's Experience During the COVID-19 Pandemic |journal=Acad Emerg Med |volume=27 |issue=5 |pages=375–378 |date=May 2020 |pmid=32320506 |pmc=7264594 |doi=10.1111/acem.13994 |url=}}</ref>
* Position should be changed every 2 hours to prevent pressure ulcer formation
* Position should be changed every 2 hours to prevent pressure ulcer formation.


====Extra Corporeal Membrane Oxygenation====
====Extra Corporeal Membrane Oxygenation====
* Used in refractory hypoxemic [[respiratory failure]]
* Used in refractory hypoxemic [[respiratory failure]].
* PaO2/Fio2 < 50mmHg for more than 1 hour
* PaO2/Fio2 < 50mmHg for more than 1 hour.
* PaO2/FiO2 < 80mmHg for more than 2 hours
* PaO2/FiO2 < 80mmHg for more than 2 hours.
*[[Arterial blood gases|Arterial Blood Gas]] indicating pH<7.2 persisting for more than 1 hour, due to uncompensated [[respiratory acidosis]]
*[[Arterial blood gases|Arterial Blood Gas]] indicating pH <7.2 persisting for more than 1 hour, due to uncompensated [[respiratory acidosis]].
* It is has shown improved clinical outcome in severe COVID-19<ref name="pmid32243266">{{cite journal |vauthors=Li X, Guo Z, Li B, Zhang X, Tian R, Wu W, Zhang Z, Lu Y, Chen N, Clifford SP, Huang J |title=Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019 in Shanghai, China |journal=ASAIO J. |volume=66 |issue=5 |pages=475–481 |date=May 2020 |pmid=32243266 |pmc=7273861 |doi=10.1097/MAT.0000000000001172 |url=}}</ref>
* It is has shown improved clinical outcome in severe COVID-19.<ref name="pmid32243266">{{cite journal |vauthors=Li X, Guo Z, Li B, Zhang X, Tian R, Wu W, Zhang Z, Lu Y, Chen N, Clifford SP, Huang J |title=Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019 in Shanghai, China |journal=ASAIO J. |volume=66 |issue=5 |pages=475–481 |date=May 2020 |pmid=32243266 |pmc=7273861 |doi=10.1097/MAT.0000000000001172 |url=}}</ref>


==Prevention==
==Prevention==
Line 178: Line 245:
** Personal Hygiene
** Personal Hygiene
** Wearing mask
** Wearing mask
** Use of Personal Protective equipment by healthcare workers<ref name="DondorpHayat2020">{{cite journal|last1=Dondorp|first1=Arjen M.|last2=Hayat|first2=Muhammad|last3=Aryal|first3=Diptesh|last4=Beane|first4=Abi|last5=Schultz|first5=Marcus J.|title=Respiratory Support in COVID-19 Patients, with a Focus on Resource-Limited Settings|journal=
The American Journal of Tropical Medicine and Hygiene|volume=102|issue=6|year=2020|pages=1191–1197|issn=0002-9637|doi=10.4269/ajtmh.20-0283}}</ref>


==References==
==References==
{{reflist|2}}
{{reflist|2}}
[[Category:Up-To-Date]]


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Latest revision as of 18:43, 29 July 2020

Main article: COVID-19

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rija Gul, M.B.B.S.

Synonyms and keywords:

Overview

COVID-19 emerged as a pandemic, after its outbreak in Wuhan, China in December 2019. It is caused by a new type of Coronavirus, which binds to ACE-2 receptors on Type 2 pneumocytes in the lower respiratory tract. The clinical presentation of patients with COVID-19 varies from asymptomatic disease to severe acute respiratory distress syndrome (ARDS). Hypoxemia is present with an increased A-a gradient. Hypoxemia is diagnosed by Pa02<60mmHg in a sample of Arterial Blood Gas. Mechanisms involved in hypoxemia are widely reported to be due to ventilation perfusion mismatch and intrapulmonary shunting. Diffusion impairment can cause hypoxemia during recovery period due to fibrosis in the lungs. Older age, male sex, hypertension and dyspnea have been identified as risk factors for development of hypoxemia in COVID-19. Complications of hypoxemia include acute respiratory failure and multi-organ failure. Treatment is based on oxygen supplementation to keep target Spo2> 90%.

Historical Perspective

  • In December 2019, novel coronavirus outbreak occurred in Wuhan, China[1]
  • On 11th March 2020, it was declared as Pandemic by WHO.

Classification

  • There is no established system for the classification of COVID-19 associated hypoxemia.

Pathophysiology

Mechanisms of Hypoxemia in COVID-19

Ventilation Perfusion Mismatch

Intrapulmonary Shunt

Diffusion Impairment

  • A study was conducted in China to measure DLCO of discharged patients. The researchers concluded that the decrease in DLCO correlated with the severity of pneumonia on admission.[6]

Causes

The table below describes the most common causes of hypoxemia in COVID-19:

Common Causes of Hypoxemia in COVID-19
Pulmonary causes Cardiac causes
Pneumonia Myocardial Infarction
Non cardiogenic Pulmonary Edema Myocarditis
Pulmonary Hypertension Heart Failure
Pulmonary embolism Cardiogenic Shock
Super imposed bacterial infection Arrhythmia

Differentiating COVID-19-associated hypoxemia from other Diseases

  • COVID-19-associated hypoxemia should be differentiated from other potential causes of hypoxemia.
  • Dyspnea is not a prominent feature of hypoxemia due to COVID-19 in contrast to other diseases causing hypoxemia[4]
  • This can be explained by areas of well preserved lung compliance surrounding the damaged tissue.[7]
  • It is important to differentiate COVID-19 associated pneumonia from Community acquired pneumonia, as both can present with hypoxemia and pulmonary infection.[8]
Covid-19 Pneumonia Community Acquired pneumonia
Sars-Cov2 Viral/ Bacterial pathogens e.g Streptococcus Pneumonia, Influenza
Pneumonia develops after 6 days of infective symptoms Rapid development of symptoms of pneumonia
Malaise is a prominent feature Malaise is not a prominent feature
Extra Pulmonary symptoms are present ( anosmia, headache, myalgia) Pulmonary symptoms are more prominent ( Productive cough, fever)
Radiology shows Basal atelectasis / Bilateral peripheral Ground Glass opacities Radiology shows Lobar Consolidation

Epidemiology and Demographics

  • COVID-19 is seen more commonly in men.
  • 80% of patients with Coronavirus disease develop a respiratory infection.[9]
  • According to a study conducted in Hubei, China, 5%-25% of patients admitted in hospital for COVID-19 needed ICU admission. Of the patients admitted in ICU, 60%-70% developed ARDS.[10]
  • There is no geographical association of hypoxemia in COVID-19.

Risk Factors

  • According to a study conducted in Wuhan, China, the following risk factors were identified in patients presenting with hypoxemia (Spo2< 90%):[11]

Natural History, Complications, and Prognosis

Complications

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Laboratory Findings

Electrocardiogram

X-Ray

  • Chest x-ray demonstrates multi-lobar infiltrates[7]
  • To view the x-ray finidings on COVID-19, click here.

Echocardiography or Ultrasound

CT Scan

  • Computed Tomography shows consolidation and bilateral ground-glass opacities located peripherally.
  • To view the CT scan findings on COVID-19, click here.

MRI

Other Imaging Findings

  • To view other imaging findings on COVID-19, click here.

Other Diagnostic Studies

  • To view other diagnostic studies for COVID-19, click here.

Treatment

Treatment of Hypoxemia due to COVID-19

Overview

  • Hypoxia due to COVID-19 warrants hospital admission.
  • Oxygen target should be Spo2>90%.
  • Some centres have suggested to restrict oxygen supplementation by High Flow Nasal Cannula (HFNC) and Non-Invasive Ventilation (Bipap, CPAP) as they generate aerosol and pose a threat to the healthcare workers.[18]
  • Invasive mechanical Ventilation by early intubation is recommended for hypoxemia not responding to Non-Invasive Ventilation.

Venturi Mask

  • SpO2< 93%-94%
  • Respiratory rate > 28-30 breaths per minute.
  • Deliver oxygen via 40% Venturi mask.
  • If a response is seen in 5-10 minutes, continue treatment for the next 6 hours.
  • NIV is recommended if there is no improvement.

High Flow Nasal Oxygenation(HFNO)

  • Use is recommended in a negative pressure environment due to aerosol generation.
  • Apply if SpO2< 92%.
  • No response to Oxygen delivery is observed via nasal cannula, face mask or Venturi mask.
  • Use Oxygen flow of 30-50L/min.
  • Keep FiO2 between 50%-70%.

Non Invasive Ventilation

  • Used when dyspnea/ hypoxemia does not improve within 1 hour of HFNO used at 50L/min and FiO2>70%.
  • Recommended to use pressure setting of 8-10cm Hg and FiO2of 60%.
  • Monitor with hourly Arterial Blood Gas sampling.
  • Use for 4-6 hours, allowing 1-hour break for feeding.

Invasive Mechanical ventilation

  • Performed in patients with severe hypoxemia ( Pa02/FiO2 <200) and failure of NIV.
  • Rapid Sequence intubation is preferred to avoid aerosolisation by Bag mask ventilation.
  • Lung protective Ventilation is used in patients with severe ARDS.
  • Tidal Volume at 4-6ml/kg of body weight.
  • Plateau Pressure(Pplat) < 30cm H2O.
  • High Positive End Expiratory Pressure (PEEP) is recommended to keep driving pressure (Pplat-PEEP)<14cm H2O.

Prone Position

  • Recommended in severe ARDS (PaO2/FiO2 <150) along with Invasive Mechanical ventilation.
  • Recommended for a total duration of 12-16 hours daily.
  • Not recommended for infants less than 6 months of age.
  • It decreases Va/Q mismatch by eliminating gravitational forces exerted on lung portion by mediastinal structures, allowing maximum lung recruitment when positive pressure mechanical ventilation is applied.[19]
  • Meta analysis have shown that Prone positioning can decrease mortality when used for long duration within intial 48hours in severe ARDS.[20]
  • In a pilot study performed in New York emergency, awake proning was associated with improved oxygen saturations in non intubated patients.[21]
  • Position should be changed every 2 hours to prevent pressure ulcer formation.

Extra Corporeal Membrane Oxygenation

  • Used in refractory hypoxemic respiratory failure.
  • PaO2/Fio2 < 50mmHg for more than 1 hour.
  • PaO2/FiO2 < 80mmHg for more than 2 hours.
  • Arterial Blood Gas indicating pH <7.2 persisting for more than 1 hour, due to uncompensated respiratory acidosis.
  • It is has shown improved clinical outcome in severe COVID-19.[22]

Prevention

Primary Prevention

  • Infection with COVID-19 can be prevented by practicing the following:
    • Social distancing
    • Frequent hand washing
    • Personal Hygiene
    • Wearing mask
    • Use of Personal Protective equipment by healthcare workers[7]

References

  1. ↑ Wu YC, Chen CS, Chan YJ (March 2020). "The outbreak of COVID-19: An overview". J Chin Med Assoc. 83 (3): 217–220. doi:10.1097/JCMA.0000000000000270. PMC 7153464 Check |pmc= value (help). PMID 32134861 Check |pmid= value (help).
  2. ↑ Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, Camporota L (June 2020). "COVID-19 pneumonia: different respiratory treatments for different phenotypes?". Intensive Care Med. 46 (6): 1099–1102. doi:10.1007/s00134-020-06033-2. PMC 7154064 Check |pmc= value (help). PMID 32291463 Check |pmid= value (help).
  3. ↑ Mekontso Dessap, Armand; Boissier, Florence; Leon, Rusel; Carreira, Serge; Roche Campo, Ferran; Lemaire, François; Brochard, Laurent (2010). "Prevalence and prognosis of shunting across patent foramen ovale during acute respiratory distress syndrome*". Critical Care Medicine. 38 (9): 1786–1792. doi:10.1097/CCM.0b013e3181eaa9c8. ISSN 0090-3493.
  4. ↑ 4.0 4.1 Fisher HK (June 2020). "Hypoxemia in COVID-19 patients: An hypothesis". Med. Hypotheses. 143: 110022. doi:10.1016/j.mehy.2020.110022. PMC 7308039 Check |pmc= value (help). PMID 32634734 Check |pmid= value (help).
  5. ↑ George, Peter M; Wells, Athol U; Jenkins, R Gisli (2020). "Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy". The Lancet Respiratory Medicine. doi:10.1016/S2213-2600(20)30225-3. ISSN 2213-2600.
  6. ↑ Mo, Xiaoneng; Jian, Wenhua; Su, Zhuquan; Chen, Mu; Peng, Hui; Peng, Ping; Lei, Chunliang; Chen, Ruchong; Zhong, Nanshan; Li, Shiyue (2020). "Abnormal pulmonary function in COVID-19 patients at time of hospital discharge". European Respiratory Journal. 55 (6): 2001217. doi:10.1183/13993003.01217-2020. ISSN 0903-1936.
  7. ↑ 7.0 7.1 7.2 Dondorp, Arjen M.; Hayat, Muhammad; Aryal, Diptesh; Beane, Abi; Schultz, Marcus J. (2020). "Respiratory Support in COVID-19 Patients, with a Focus on Resource-Limited Settings". The American Journal of Tropical Medicine and Hygiene. 102 (6): 1191–1197. doi:10.4269/ajtmh.20-0283. ISSN 0002-9637.
  8. ↑ Lipman, Marc; Chambers, Rachel C; Singer, Mervyn; Brown, Jeremy Stuart (2020). "SARS-CoV-2 pandemic: clinical picture of COVID-19 and implications for research". Thorax: thoraxjnl-2020–215024. doi:10.1136/thoraxjnl-2020-215024. ISSN 0040-6376.
  9. ↑ . doi:10.1161/CIRCULATIONAHA.120.047915Circulation. Missing or empty |title= (help)
  10. ↑ Greenland, John R.; Michelow, Marilyn D.; Wang, Linlin; London, Martin J. (2020). "COVID-19 Infection". Anesthesiology. 132 (6): 1346–1361. doi:10.1097/ALN.0000000000003303. ISSN 0003-3022.
  11. ↑ Xie, Jiang; Covassin, Naima; Fan, Zhengyang; Singh, Prachi; Gao, Wei; Li, Guangxi; Kara, Tomas; Somers, Virend K. (2020). "Association Between Hypoxemia and Mortality in Patients With COVID-19". Mayo Clinic Proceedings. 95 (6): 1138–1147. doi:10.1016/j.mayocp.2020.04.006. ISSN 0025-6196.
  12. ↑ Greenland JR, Michelow MD, Wang L, London MJ (June 2020). "COVID-19 Infection: Implications for Perioperative and Critical Care Physicians". Anesthesiology. 132 (6): 1346–1361. doi:10.1097/ALN.0000000000003303. PMC 7155909 Check |pmc= value (help). PMID 32195698 Check |pmid= value (help).
  13. ↑ Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y (May 2020). "Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study". Lancet Respir Med. 8 (5): 475–481. doi:10.1016/S2213-2600(20)30079-5. PMC 7102538 Check |pmc= value (help). PMID 32105632 Check |pmid= value (help).
  14. ↑ Pan F, Yang L, Li Y, Liang B, Li L, Ye T, Li L, Liu D, Gui S, Hu Y, Zheng C (2020). "Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): a case-control study". Int J Med Sci. 17 (9): 1281–1292. doi:10.7150/ijms.46614. PMC 7294915 Check |pmc= value (help). PMID 32547323 Check |pmid= value (help).
  15. ↑ Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B (March 2020). "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study". Lancet. 395 (10229): 1054–1062. doi:10.1016/S0140-6736(20)30566-3. PMC 7270627 Check |pmc= value (help). PMID 32171076 Check |pmid= value (help).
  16. ↑ . doi:10.1016/ S1473-3099(20)30367-4 Check |doi= value (help). Missing or empty |title= (help)
  17. ↑ 17.0 17.1 Ullah, Waqas; Saeed, Rehan; Sarwar, Usman; Patel, Rajesh; Fischman, David L. (2020). "COVID-19 Complicated by Acute Pulmonary Embolism and Right-Sided Heart Failure". JACC: Case Reports. doi:10.1016/j.jaccas.2020.04.008. ISSN 2666-0849.
  18. ↑ Kluge S, Janssens U, Welte T, Weber-Carstens S, Marx G, Karagiannidis C (April 2020). "German recommendations for critically ill patients with COVID‑19". Med Klin Intensivmed Notfmed. doi:10.1007/s00063-020-00689-w. PMC 7155395 Check |pmc= value (help). PMID 32291505 Check |pmid= value (help).
  19. ↑ Lindahl S (August 2020). "Using the prone position could help to combat the development of fast hypoxia in some patients with COVID-19". Acta Paediatr. 109 (8): 1539–1544. doi:10.1111/apa.15382. PMC 7301016 Check |pmc= value (help). PMID 32484966 Check |pmid= value (help). Vancouver style error: initials (help)
  20. ↑ Mora-Arteaga, J.A.; Bernal-Ramírez, O.J.; Rodríguez, S.J. (2015). "The effects of prone position ventilation in patients with acute respiratory distress syndrome. A systematic review and metaanalysis". Medicina Intensiva (English Edition). 39 (6): 359–372. doi:10.1016/j.medine.2014.11.004. ISSN 2173-5727.
  21. ↑ Caputo ND, Strayer RJ, Levitan R (May 2020). "Early Self-Proning in Awake, Non-intubated Patients in the Emergency Department: A Single ED's Experience During the COVID-19 Pandemic". Acad Emerg Med. 27 (5): 375–378. doi:10.1111/acem.13994. PMC 7264594 Check |pmc= value (help). PMID 32320506 Check |pmid= value (help).
  22. ↑ Li X, Guo Z, Li B, Zhang X, Tian R, Wu W, Zhang Z, Lu Y, Chen N, Clifford SP, Huang J (May 2020). "Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019 in Shanghai, China". ASAIO J. 66 (5): 475–481. doi:10.1097/MAT.0000000000001172. PMC 7273861 Check |pmc= value (help). PMID 32243266 Check |pmid= value (help).


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