COVID-19-associated hypoxemia: Difference between revisions

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


{{CMG}}; {{AE}}
'''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.]]


{{SK}}  
{{SK}}  


==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]], 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==
Line 12: Line 17:
* In December 2019, novel coronavirus outbreak occurred in Wuhan, China<ref name="pmid32134861">{{cite journal |vauthors=Wu YC, Chen CS, Chan YJ |title=The outbreak of COVID-19: An overview |journal=J Chin Med Assoc |volume=83 |issue=3 |pages=217–220 |date=March 2020 |pmid=32134861 |pmc=7153464 |doi=10.1097/JCMA.0000000000000270 |url=}}</ref>
* In December 2019, novel coronavirus outbreak occurred in Wuhan, China<ref name="pmid32134861">{{cite journal |vauthors=Wu YC, Chen CS, Chan YJ |title=The outbreak of COVID-19: An overview |journal=J Chin Med Assoc |volume=83 |issue=3 |pages=217–220 |date=March 2020 |pmid=32134861 |pmc=7153464 |doi=10.1097/JCMA.0000000000000270 |url=}}</ref>


* On 11th March 2020 it was declared as Pandemic by WHO.
* On 11th March 2020, it was declared as Pandemic by WHO.


==Classification==
==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.
*There is no established system for the classification of COVID-19 associated hypoxemia.
 
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].


==Pathophysiology==
==Pathophysiology==
The exact pathogenesis of [disease name] is not fully understood.


OR
* [[COVID-19]] is caused by the novel [[Coronavirus]]. It binds to [[Angiotensin-converting enzyme|ACE]]-2 receptors in the lower respiratory tract which causes pulmonary manifestations.
* The [[Virus (biology)|virus]] causes [[Alveolus|alveolar]] injury which stimulates an [[inflammatory]] response in the host tissue.
*[[Mononuclear cells|Mononuclear]] inflammatory [[Cells (biology)|cells]] are recruited at the site of injury which release [[cytokines]] e.g [[Interleukin-6]] and activate procoagulants
* As a result of this insult, the [[Alveolar-capillary barrier|alveolar epithelium]] and [[Capillary bed|capillary endothelium]] are damaged.
* 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]].
* 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 support the lack of [[dyspnea]] in proportion to the severity of [[hypoxemia]], on clinical presentation, a phenomenon known as "happy hypoxemia".


It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
===Mechanisms of Hypoxemia in COVID-19===


OR
* [[Hypoxemia]] in [[COVID-19]] is marked by an increased [[Alveolar-arterial gradient|A-a gradient.]]


[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
====Ventilation Perfusion Mismatch====


OR
*[[Ventilation-perfusion mismatch|V/Q mismatch]] is typically seen due to [[ARDS]].
* Initially the [[lungs]] have good [[compliance]] but there is marked [[hypoxemia]].
* 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.
* 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]].
* Pulmonary vascular [[thrombi]] also contributes to [[Ventilation-perfusion mismatch|Va/Q mismatch]].
* 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]].


Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
====Intrapulmonary Shunt====
*[[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 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]].


OR
====Diffusion Impairment====
* Persistent [[hypoxemia]] has been seen in recovered patients, due to postviral [[fibrosis]].<ref name="GeorgeWells2020">{{cite journal|last1=George|first1=Peter M|last2=Wells|first2=Athol U|last3=Jenkins|first3=R Gisli|title=Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy|journal=The Lancet Respiratory Medicine|year=2020|issn=22132600|doi=10.1016/S2213-2600(20)30225-3}}</ref>


 
* 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.<ref name="MoJian2020">{{cite journal|last1=Mo|first1=Xiaoneng|last2=Jian|first2=Wenhua|last3=Su|first3=Zhuquan|last4=Chen|first4=Mu|last5=Peng|first5=Hui|last6=Peng|first6=Ping|last7=Lei|first7=Chunliang|last8=Chen|first8=Ruchong|last9=Zhong|first9=Nanshan|last10=Li|first10=Shiyue|title=Abnormal pulmonary function in COVID-19 patients at time of hospital discharge|journal=European Respiratory Journal|volume=55|issue=6|year=2020|pages=2001217|issn=0903-1936|doi=10.1183/13993003.01217-2020}}</ref>
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
 
OR
 
The progression to [disease name] usually involves the [molecular pathway].
 
OR
 
The pathophysiology of [disease/malignancy] depends on the histological subtype.


==Causes==
==Causes==
The table below describes the most common [[causes]] of [[hypoxemia]] in [[COVID-19]]:
{| class="wikitable"
|+<big>Common Causes of [[Hypoxemia]] in COVID-19</big>
!style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Pulmonary causes}}
!style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Cardiac causes}}
|-
|[[Pneumonia]]
|[[Myocardial Infarction]]
|-
|Non cardiogenic Pulmonary Edema
|[[Myocarditis]]
|-
|[[Pulmonary hypertension|Pulmonary Hypertension]]
|[[Heart Failure]]
|-
|[[Pulmonary embolism]]
|[[Cardiogenic Shock]]
|-
|Super imposed bacterial infection
|[[Arrhythmia]]
|}


* Acute Respiratory Distress Syndrome
==Differentiating COVID-19-associated hypoxemia from other Diseases==
 
* COVID-19-associated hypoxemia should be differentiated from other potential causes of [[hypoxemia]].
* Microvascular Thrombi<ref>{{cite journal|doi=10.1016/ S1473-3099(20)30367-4}}</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>
 
*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=
* COVID-19 Pneumonia
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>
 
==Differentiating COVID-19-associated encephalopathy from other Diseases==
[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].


OR
*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"
[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].
!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==
The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.
*[[COVID-19]] is seen more commonly in men.
 
* 80% of patients with [[Coronavirus]] disease develop a respiratory infection.<ref>{{cite journal|doi=10.1161/CIRCULATIONAHA.120.047915Circulation}}</ref>
OR
* 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 [[Acute respiratory distress syndrome|ARDS.]]<ref name="GreenlandMichelow2020">{{cite journal|last1=Greenland|first1=John R.|last2=Michelow|first2=Marilyn D.|last3=Wang|first3=Linlin|last4=London|first4=Martin J.|title=COVID-19 Infection|journal=Anesthesiology|volume=132|issue=6|year=2020|pages=1346–1361|issn=0003-3022|doi=10.1097/ALN.0000000000003303}}</ref>
 
* There is no geographical association of [[hypoxemia]] in [[COVID-19|COVID-19.]]
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.
 
 
 
The majority of [disease name] cases are reported in [geographical region].
 
OR
 
[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].


==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)
 
**Male sex
* Older age ( median - 60 years)
**[[Hypertension]]
 
**[[Dyspnea]] on clinical presentation
* Male sex
 
* Hypertension
 
* Dyspnea on clinical presentation
 
==Screening==
There is insufficient evidence to recommend routine screening for [disease/malignancy].
 
OR
 
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==
==Natural History, Complications, and Prognosis==
If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
* [[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>
OR
* 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]].
Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
*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===
OR
*[[Hypoxemia]] in COVID-19 patients is associated with the development of the following:
 
**[[Acute respiratory distress syndrome|Acute Respiratory Distress Syndrome]]
Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.
** 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 [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].
*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]]
OR
**[[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
The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].
**Oxygen Saturation below 90% on Pulse oximeter
 
OR
 
There are no established criteria for the diagnosis of [disease name].


===History and Symptoms===
===History and Symptoms===
The majority of patients with [disease name] are asymptomatic.


OR
* 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>
 
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].
* [[Fever]]
 
* [[Tachypnea]]
===Physical Examination===
* [[Nausea]]
Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].
* [[Vomiting]]
 
* [[Diarrhea]]
OR
* Loss of sense of [[smell]] and [[taste]]
 
Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
The presence of [finding(s)] on physical examination is diagnostic of [disease name].
 
OR
 
The presence of [finding(s)] on physical examination is highly suggestive of [disease name].


===Laboratory Findings===
===Laboratory Findings===
An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].
OR
Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
OR
[Test] is usually normal among patients with [disease name].
OR
Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].
OR
There are no diagnostic laboratory findings associated with [disease name].


* [[Lymphopenia]] (80% of patients)
* [[Thrombocytopenia]]
* Elevated C- Reactive Protein
* Elevated [[LDH]] (40% of patients)
* ELevated [[D-Dimer]]
* Elevated level of IL-1, [[IL-6]]
===Electrocardiogram===
===Electrocardiogram===
There are no ECG findings associated with [disease name].
* 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 />
OR
===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=
An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
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 />
===X-ray===
There are no x-ray findings associated with [disease name].
 
OR
 
An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
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===
===Echocardiography or Ultrasound===
There are no echocardiography/ultrasound  findings associated with [disease name].
* 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 />
OR
===CT Scan===
 
*[[Ct scan|Computed Tomography]] shows consolidation and bilateral ground-glass opacities located peripherally.
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].
*To view the CT scan findings on COVID-19, [[COVID-19 CT scan|click here]].
 
OR
 
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].
 
===CT scan===
There are no CT scan findings associated with [disease name].
 
OR
 
[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].
 
OR
 
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===
===MRI===
There are no MRI findings associated with [disease name].
* 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 />
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
 
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].


===Other Imaging Findings===
===Other Imaging Findings===
There are no other imaging findings associated with [disease name].
* To view other imaging findings on COVID-19, [[COVID-19 other imaging findings|click here]].<br />
 
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===
===Other Diagnostic Studies===
There are no other diagnostic studies associated with [disease name].
* To view other diagnostic studies for COVID-19, [[COVID-19 other diagnostic studies|click here]].<br />
 
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==
==Treatment==
===Medical Therapy===
===Treatment of Hypoxemia due to COVID-19===
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
====Overview====
 
* [[Hypoxia]] due to [[COVID-19]] warrants hospital admission.
OR
*[[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>
* Invasive mechanical Ventilation by early [[intubation]] is recommended for [[hypoxemia]] not responding to Non-Invasive Ventilation.


Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
====Venturi Mask====
* SpO2< 93%-94%
* [[Respiratory rate]] > 28-30 breaths per minute.
* Deliver [[oxygen]] via 40% [[Venturi mask|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.


OR
====High Flow Nasal Oxygenation(HFNO)====
* Use is recommended in a negative pressure environment due to [[Aerosols|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%.


The majority of cases of [disease name] are self-limited and require only supportive care.
====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 [[FiO2]]of 60%.
* Monitor with hourly [[Arterial blood gas|Arterial Blood Gas]] sampling.
* Use for 4-6 hours, allowing 1-hour break for feeding.


OR
====Invasive Mechanical ventilation====
* 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.
* 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.
* Plateau Pressure(Pplat) < 30cm H2O.
* High Positive End Expiratory Pressure (PEEP) is recommended to keep driving pressure (Pplat-PEEP)<14cm H2O.


[Disease name] is a medical emergency and requires prompt treatment.
====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 [[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>
* 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.


OR
====Extra Corporeal Membrane Oxygenation====
 
* Used in refractory hypoxemic [[respiratory failure]].
The mainstay of treatment for [disease name] is [therapy].
* PaO2/Fio2 < 50mmHg for more than 1 hour.
 
* PaO2/FiO2 < 80mmHg for more than 2 hours.
OR
*[[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>
The optimal therapy for [malignancy name] depends on the stage at diagnosis.
 
OR
 
[Therapy] is recommended among all patients who develop [disease name].
 
OR
 
Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
 
OR
 
Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
 
OR
 
Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
 
OR
 
Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
 
===Surgery===
Surgical intervention is not recommended for the management of [disease name].
 
OR
 
Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]
 
OR
 
The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].
 
OR
 
The feasibility of surgery depends on the stage of [malignancy] at diagnosis.
 
OR
 
Surgery is the mainstay of treatment for [disease or malignancy].


==Prevention==
===Primary Prevention===
===Primary Prevention===
There are no established measures for the primary prevention of [disease name].
* Infection with COVID-19 can be prevented by practicing the following:
 
**Social distancing
OR
** Frequent hand washing
 
** Personal Hygiene
There are no available vaccines against [disease name].
** 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=
OR
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>
 
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==
==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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