COVID-19-associated hypoxemia
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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
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 classification of COVID-19-associated hypoxemia.
Pathophysiology
- COVID-19 is caused by the novel Coronavirus. It binds to ACE-2 receptors in the lower respiratory tract which causes pulmonary manifestations.
- The virus causes alveolar injury which stimulates an inflammation response in the host tissue
- Mononuclear inflammatory 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 epithelium and capillary endothelium are damaged
- Alveoli collapse due to fluid accumulation and loss of 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 of expression of mitochondrial proteins by the Coronavirus, occurring at a cellular level.[2]
- The above mechanism supports the lack of dyspnea in proportion to the severity of hypoxemia, on clinical presentation, a phenomenon known as "happy hypoxemia".[3]
Mechanisms of Hypoxemia in COVID-19
- Hypoxemia in COVID-19 is marked by an increased A-a gradient.
Ventilation Perfusion Mismatch
- 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.[4]
- 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.
- These changes in lung dynamics promote capillary leakage which further increases alveolar exudates and the lungs become poorly compliant.
- The ventilation perfusion mismatch therefore progresses from a high Va/Q ratio to low Va/Q ratio.
- Pulmonary vascular thrombi also contribute to Va/Q mismatch.
- Both acute pulmonary embolism and small vessel thrombosis were seen on autopsy.
- This increases the alveolar dead space causing Va/Q mismatch.
Intrapulmonary Shunt
- Blood is shunted from the poorly ventilated alveoli to well aerated lung regions.
- Intra cardiac shunts can be detected in 20% of patients being treated for ARDS. Patent foramen ovale opens due to positive pressure ventilation.[5][6]
- Shunt can be differentiated from Va/Q mismatch due to lack of response to supplemental oxygen.
Diffusion Impairment
- Persistent hypoxemia has been seen in recovered patients, due to postviral fibrosis.[7]
- 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.[8]
Causes
- Acute Respiratory Distress Syndrome
- Microvascular Thrombi[9]
- COVID-19 Pneumonia
Differentiating COVID-19-associated hypoxemia from other Diseases
Dyspnea is not a prominent feature of hypoxemia due to COVID-19 in contrast to other diseases causing hypoxemia[6]
Epidemiology and Demographics
- COVID-19 is seen more commonly in men.
- 80% of patients with Coronavirus disease develop a respiratory infection.[10]
- 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.[11]
- 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%):[12]
- Older age (median - 60 years)
- Male sex
- Hypertension
- Dyspnea on clinical presentation
Natural History, Complications, and Prognosis
- COVID-19 has a 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.[13]
- Common complications of hypoxemia include acute respiratory failure, (see COVID-19-associated respiratory failure) and multiorgan failure( Acute Kidney injury, Liver dysfunction, Cardiac injury).[14]
- 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%.[15][16]
Diagnosis
Diagnostic Study of Choice
- COVID -19 associated hypoxemia can be established by the following investigations:
- Reverse Transcriptase- Polymerase Chain Reaction from nasal or throat swab sample positive for COVID-19
- Chest Tomography images showing peripheral and bilateral ground-glass opacities
- Arterial Blood gas showing Pa02(Partial Pressure of oxygen) below 60mmHg
- Oxygen Saturation below 90% on Pulse oximeter
History and Symptoms
- Drycough- most common symptom
- Fever
- Tachypnea
- Nausea
- Vomiting
- Diarrhea
- Loss of sense of smell and taste
Physical Examination
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].
OR
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
- Lymphopenia - seen in 80% patients
- Thrombocytopenia
- Elevated C- Reactive Protein
- Elevated LDH - seen in 40% patients
- ELevated D-Dimer
- Elevated level of IL-1, IL-6
Imaging Studies
- Computed Tomography shows consolidation and bilateral ground glass opacities located peripherally.
Treatment
Medical Therapy
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
OR
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
OR
The majority of cases of [disease name] are self-limited and require only supportive care.
OR
[Disease name] is a medical emergency and requires prompt treatment.
OR
The mainstay of treatment for [disease name] is [therapy].
OR
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
There are no established measures for the primary prevention of [disease name].
OR
There are no available vaccines against [disease name].
OR
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
- ↑ 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). - ↑ . doi:10.1161/CIRCULATIONAHA.120.047915Circulation. Missing or empty
|title=(help) - ↑ . doi:10.1161/CIRCULATIONAHA.120.047915Circulation. Missing or empty
|title=(help) - ↑ 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). - ↑ 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.
- ↑ 6.0 6.1 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). - ↑ 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.
- ↑ 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.
- ↑ . doi:10.1016/ S1473-3099(20)30367-4 Check
|doi=value (help). Missing or empty|title=(help) - ↑ . doi:10.1161/CIRCULATIONAHA.120.047915Circulation. Missing or empty
|title=(help) - ↑ 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.
- ↑ 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.
- ↑ 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). - ↑ 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). - ↑ 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). - ↑ 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).