COVID-19-associated pneumonia
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Usman Ali Akbar, M.B.B.S.[2]
Synonyms and keywords:2019 novel coronavirus disease, COVID19,Wuhan virus, L type COVID pneumonia, H type Pneumonia
Overview
- The severe acute respiratory syndrome caused by SARS-CoV-2 is the cause of global pandemic that began in the Chinese city of Wuhan late 2019.
- In December 2019, a novel coronavirus was detected in pneumonia patients which were later named as 2019-nCoV.
- Pneumonia appears to be the most frequent manifestation of infection.
- COVID-19 pneumonia despite mimicking the symptoms and criteria according to Berlin definition of ARDS is a specific disease whose particular features are severe hypoxemia often associated with normal or near-normal respiratory system compliance. [1]
Historical Perspective
- In December 2019, there were case reports of a cluster of acute respiratory illness in the Wuhan, Hubei Province, China.
- In January 2020, novel coronavirus was identified in the samples of bronchoalveolar lavage fluid from a patient in Wuhan.[2]
- Later this has been confirmed as the cause of novel corona virus-infected pneumonia.
- The first cases were reported by Huang et al in which most of the patients had a history of exposure to the seafood wholesale market.
- There have been no effective therapies or vaccines available for NCIP as of yet.
Classification
There is no established system for the classification of coronavirus infected pneumonia. Based on the detailed observation of case reports and case series, it has been found that COVID-19 patients differ in their presentation at the emergency department based on three factors.
1) The severity of infection, host immune response, preserved physiological reserve and associated comorbidities.
2) Response of patient to the hypoxemia in terms of ventilator
3) the time between the presentation of patient to the emergency department and the onset of the disease.
Based on these factors, NCIP has been divided into two different phenotypes.
| COVID‑19 pneumonia, Type L | COVID‑19 pneumonia, Type H |
|---|---|
| Low elastance | High elastance |
| Low ventilation to perfusion ratio | High Left to right shunt |
| Low lung weight | High lung weight |
| Low lung recruitability. | High lung recruitability |
The H type pattern has been reported to present in 20-30 % patients in one case series. It usually fits the criteria of severe ARDS or progresses rapidly towards ARDS. In May 2020, it has been postulated that there is also third distinctive types. This phenotype usually mimics the patchy ARDS phenotype.
Pathophysiology
The exact pathogenesis of COVID 19 associated pneumonia is not fully understood.
- COVID-19 usually express trans-membrane glycoproteins which are called "spike proteins" that allow the virus to attach itself to the target organ and enter into the cell
- Spike proteins bind to surface angiotensin converting enzyme 2 (ACE2) receptors.Specifically the RBD of the S protein of SARS-CoV-2 recognize ACE2 receptors.
- ACE2 is predominately expressed on type II pneumocytes. Other proteins such TMPRSS2 is also required for complete binding and transmissibility.
- TMPRSS2 cleaves the S protein and results into the fusion of the viral and host cell membrane.
- The virus replicates itself in the target cell using RNA dependent RNA polymerase.
- Lungs seems to be more vulnerable to the SARS-CoV-2 because of the large surface area.
- Direct lung injury leading to release of various cytokines such as (IL)–1β, IL-2, IL-6, IL-7, IL-12, IL-18, tumor necrosis factor (TNF)–α, interferon (IFN)–γ, and granulocyte colony-stimulating factor (GCSF) initiates local inflammatory response and is responsible for the pulmonary manifestations of COVID-19.
- This leads to a modest local subpleural interstitial edema (ground glass lesions) at the interfaces between lung structures
- Vasoplegia results which further accounts for severe hypoxemia.
Differentiating COVID-19-associated pneumonia from other Diseases
- COVID-19 associated pneumonia can be classified from other viral pneumonia caused based on history of exposure to COVID-19, positive SARS-CoV-2 PCR , dyspnea, fever, cough,expectoration and uncommon associated findings like diarrhea, headache,vomiting and myalgias.
- Chest X-ray and other imaging modalities can further help us differentiate COVID-19 associated pneumonia from other causes.
- Chest X-ray usually shows bilateral, almost symmetrical areas of peripheral consolidation with perihilar infiltrates and an indistinct left heart border.
- CT-scan chest may show classical appearances of subpleural organizing areas of consolidation with patchy peripheral ground-glass opacities.
Epidemiology and Demographics
- In a study performed in spain COVID-19 pneumonia was diagnosed in 32 (61.5%) patients, whereas the remaining 20 cases were categorized as URTI.
Risk Factors
The risk factors for COVID-19 has not been properly established.Multiple studies show following factors to be the key to the progression of disease severity. [3]
- Diarrhea
- Lymphocyte count ≤ 1000 microlitre
- Ferritin ≥ 430 ng/ml
- CRP ≥ 2.5 mg/dL
- Consolidation on CT-scan chest
- Declining Neutrophil count
- COPD history
Screening
There is insufficient evidence to recommend routine screening for COVID-19 associated pneumonia.
Natural History, Complications, and Prognosis
- The Type L COVID-19 pneumonia patients may progress to Type H pneumonia over time due to evolution of pneumonia and high stress ventilation given as a part of treatment.
- The key feature that regulate this transition is the depth of the negative inspiratory intrathoracic pressure that is associated with increased tidal volume in spontaneous breathing.
- This is based on experimental observation by Barach and Mascheroni. This has been termed as patient self inflicted lung injury. Over time the increased edema causes lung weight to increase.
- There is superimposed pressure and dependent atelectasis that develops over the progression of time.
- When the lung edema increases massively , lung's gas volume decreases and then tidal volumes that is usually generated for a given pressure also decreases.
- This leads to development of dyspnea and worsening of patient self inflicted lung injury.
Complications
Pneumonia due to SARS-CoV-2 can further lead to following complications
- Worsening hypoxemia
- ARDS
- Barotrauma due to mechanical breathing support
- Acute cor-pulmonale
- Ventilator associated pneumonia
Prognosis
The progression L Type pneumonia to H type generally co-relates to poor prognosis as it progress rapidly towards ARDS. A study reported development of ARDS in 20 percent patient with a median of eight days after the onset of symptoms. [2]
Diagnosis
Diagnostic Study of Choice
There are no established criteria for the diagnosis of COVID-19 associated pneumonia. Initial chest x-rays maybe normal. CT-scan chest is more sensitive than chest x-ray but there is no set criteria to diagnose COVID-19 associated pneumonia in COVID-19 patients.
History and Symptoms
Exposure to SARS-CoV-2 can result into patients exhibiting signs and symptoms of upper respiratory tract infection such as sore throat, rhinorrhea, low to high-grade fever, non productive cough, myalgias, dyspnea and generalised fatigue.One study showed that Among 138 hospitalized patients, the most common general symptoms at disease onset included fever (98.6%), dry cough (59.4%), fatigue (69.6%), dyspnea (31.2%), and myalgia (34.8%). Less common symptoms of SARS-CoV-2 infection include headache, abdominal pain, dizziness, nausea, vomiting, and diarrhea. [2]
| Mild Illness | Moderate Pneumonia | Severe Pneumonia |
|---|---|---|
| Mild fever, cough (dry), sore throat, nasal congestion, malaise,headache, muscle pain, may be present. | Cough is the most predominant symptom. | Respiratory distress |
| Anosmia, diarrhea and vomiting can present in some patients. | Dyspnea or tachypnea ( children) | Tachypnea (> 30 breaths/min) |
| Dyspnea is not usually observed in mild cases. | Hypoxia (SpO2 < 90% on room air) |
Physical Examination
On physical examination, fever is most commonly present in COVID-19 patients.
- A respiratory rate above 24 breaths/minute is noted in almost all patients.
- Pulse rate > per 100 min.
- Chest examination can reveals audible crackles.
- Signs of consolidation, such as decreased or bronchial breath sounds, dullness to percussion, tactile fremitus, and egophony can be present in as early signs of pneumonia in COVID-19 patients.
Laboratory Findings
Common laboratory findings among hospitalized patients with COVID-19 include
- Lymphopenia (lymphocyte count, 0.8 × 109/L [interquartile range {IQR}, 0.6-1.1])
- Elevated aminotransaminase levels
- Elevated lactate dehydrogenase levels
- Elevated ferritin
- Elevated CRP
- Elevated ESR
- Elevated procalcitonin levels in those requiring ICU care
Electrocardiogram
There are no specific ECG findings associated with COVID-19 associated pneumonia.
X-ray
- Chest radiograph may show bilateral, almost symmetrical areas of peripheral consolidation with perihilar infiltrates . In an endemic area, these appearances are highly suggestive of COVID-19. The primary findings of COVID-19 are those of atypical or organizing pneumonia. [4]
- 18 % of the patient can have normal chest x-ray findings early in the disease course but only 3% in severe disease.[5]
- Bilateral and/or multilobar involvement is common.
- CXR typically shows patchy or diffuse asymmetric airspace opacities which is also seen in other coronaviruses cases.[6]
Echocardiography or Ultrasound
There are no specific echocardiography/ultrasound findings associated with COVID-19 associated pneumonia.
CT scan
CT-scan chest findings in patient with COVID-19 pneumonia may show following abnormalities [7]
- ground-glass opacities
- crazy paving appearance
- air space consolidation
- bronchovascular thickening in the lesion
- traction bronchiectasis
Other Diagnostic Studies
Bronchoalveolar Lavage
Bronchoalveolar lavage may not be useful in diagnosing COVID-19 pneumonia, However various case reports suggest a collection of BAL fluid when consecutive nasopharyngeal swabs are negative, to confirm or exclude the diagnosis of COVID-19-associated pneumonia.[8]
Treatment
Medical Therapy
There is no treatment for COVID-19 associated pneumonia; the mainstay of therapy is supportive care and mechanical respiratory support. As there have been 3 distinct phenotypes of COVID-19 pneumonia, so there have been different treatment modalities for each of them.
- The first step is to reverse hypoxemia which can be done through increase in FiO2. This is well tolerated in patients with Type L pneumonia.
- For L Type with dyspnea, different non-invasive options are available: high flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), or non-invasive ventilation (NIV).
- Esophageal manometry pressure is measured to prevent swings of central venous pressure.
- P0.1 and Pocclusion should be measured in intubated patient.
- Mechanical Ventilation should be instituted at appropriate time.
Primary Prevention
The best way to prevent infection is to avoid being exposed to this virus. The following practices should be adopted for infection control:
- Hand washing often with soap and water for at least 20 seconds.
- Using an alcohol-based hand sanitizer that contains at least 60% alcohol if soap and water are not available.
- Avoid touching eyes, nose, and mouth with unwashed hands.
- Avoid close contact with people who are sick
- Stay home when symptomatic
- Cover cough or sneeze with a tissue paper, then throw the tissue in the trash
- Clean and disinfect frequently touched objects and surfaces
There is currently no vaccine to prevent COVID-19.
Secondary Prevention
The secondary prevention measures of Coronavirus disease 2019 (COVID-19) constitutes protective measures to make sure that an infected individual does not transfer the disease to others by maintaining self isolation at home or designated quarantine facilities.
References
- ↑ Gattinoni, Luciano; Chiumello, Davide; Caironi, Pietro; Busana, Mattia; Romitti, Federica; Brazzi, Luca; Camporota, Luigi (2020-04-14). "COVID-19 pneumonia: different respiratory treatments for different phenotypes?". Intensive Care Medicine. Springer Science and Business Media LLC. 46 (6): 1099–1102. doi:10.1007/s00134-020-06033-2. ISSN 0342-4642.
- ↑ 2.0 2.1 2.2 Wang, Dawei; Hu, Bo; Hu, Chang; Zhu, Fangfang; Liu, Xing; Zhang, Jing; Wang, Binbin; Xiang, Hui; Cheng, Zhenshun; Xiong, Yong; Zhao, Yan; Li, Yirong; Wang, Xinghuan; Peng, Zhiyong (2020-03-17). "Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China". JAMA. American Medical Association (AMA). 323 (11): 1061. doi:10.1001/jama.2020.1585. ISSN 0098-7484.
- ↑ Wang, Chang‐Zheng; Hu, Shun‐Lin; Wang, Lin; Li, Min; Li, Huan‐Tian (2020-05-29). "Early risk factors of the exacerbation of Coronavirus disease 2019 pneumonia". Journal of Medical Virology. Wiley. doi:10.1002/jmv.26071. ISSN 0146-6615.
- ↑ Rodrigues, J.C.L.; Hare, S.S.; Edey, A.; Devaraj, A.; Jacob, J.; Johnstone, A.; McStay, R.; Nair, A.; Robinson, G. (2020). "An update on COVID-19 for the radiologist - A British society of Thoracic Imaging statement". Clinical Radiology. Elsevier BV. 75 (5): 323–325. doi:10.1016/j.crad.2020.03.003. ISSN 0009-9260.
- ↑ Guan, Wei-jie; Ni, Zheng-yi; Hu, Yu; Liang, Wen-hua; Ou, Chun-quan; He, Jian-xing; Liu, Lei; Shan, Hong; Lei, Chun-liang; Hui, David S.C.; Du, Bin; Li, Lan-juan; Zeng, Guang; Yuen, Kwok-Yung; Chen, Ru-chong; Tang, Chun-li; Wang, Tao; Chen, Ping-yan; Xiang, Jie; Li, Shi-yue; Wang, Jin-lin; Liang, Zi-jing; Peng, Yi-xiang; Wei, Li; Liu, Yong; Hu, Ya-hua; Peng, Peng; Wang, Jian-ming; Liu, Ji-yang; Chen, Zhong; Li, Gang; Zheng, Zhi-jian; Qiu, Shao-qin; Luo, Jie; Ye, Chang-jiang; Zhu, Shao-yong; Zhong, Nan-shan (2020-04-30). "Clinical Characteristics of Coronavirus Disease 2019 in China". New England Journal of Medicine. Massachusetts Medical Society. 382 (18): 1708–1720. doi:10.1056/nejmoa2002032. ISSN 0028-4793.
- ↑ Chen, Simiao; Yang, Juntao; Yang, Weizhong; Wang, Chen; Bärnighausen, Till (2020). "COVID-19 control in China during mass population movements at New Year". The Lancet. Elsevier BV. 395 (10226): 764–766. doi:10.1016/s0140-6736(20)30421-9. ISSN 0140-6736.
- ↑ Bai, Harrison X.; Hsieh, Ben; Xiong, Zeng; Halsey, Kasey; Choi, Ji Whae; Tran, Thi My Linh; Pan, Ian; Shi, Lin-Bo; Wang, Dong-Cui; Mei, Ji; Jiang, Xiao-Long; Zeng, Qiu-Hua; Egglin, Thomas K.; Hu, Ping-Feng; Agarwal, Saurabh; Xie, Fangfang; Li, Sha; Healey, Terrance; Atalay, Michael K.; Liao, Wei-Hua (2020-03-10). "Performance of radiologists in differentiating COVID-19 from viral pneumonia on chest CT". Radiology. Radiological Society of North America (RSNA): 200823. doi:10.1148/radiol.2020200823. ISSN 0033-8419.
- ↑ Gualano, Gina; Musso, Maria; Mosti, Silvia; Mencarini, Paola; Mastrobattista, Annelisa; Pareo, Carlo; Zaccarelli, Mauro; Migliorisi, Paolo; Vittozzi, Pietro; Zumla, Alimudin; Ippolito, Giuseppe; Palmieri, Fabrizio (2020). "Usefulness of bronchoalveolar lavage in the management of patients presenting with lung infiltrates and suspect COVID-19-associated pneumonia: A case report". International Journal of Infectious Diseases. Elsevier BV. 97: 174–176. doi:10.1016/j.ijid.2020.05.027. ISSN 1201-9712.