Lung nontumor
Infections
COVID-19
Editor-in-Chief: Debra Zynger, M.D.
Topic Completed: 7 April 2020
Minor changes: 4 July 2020
Copyright: 2020, PathologyOutlines.com, Inc.
PubMed Search: COVID-19[TI] lung
See also COVID-19 testing topic
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Diagrams / tables | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Cytology description | Cytology images | Positive stains | Negative stains | Electron microscopy description | Electron microscopy images | Molecular / cytogenetics description | Videos | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review answer #1 | Board review style question #2 | Board review answer #2Cite this page: Yoshikawa A, Bychkov A. COVID-19. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lungnontumorcovid.html. Accessed July 7th, 2020.
Definition / general
- Coronavirus disease 2019 (COVID-19) is an infectious respiratory disease caused by a novel coronavirus that emerged in Wuhan, China at the end of 2019, resulting in a worldwide pandemic
Essential features
- COVID-19 can progress to severe acute respiratory syndrome with pneumonia and acute respiratory distress syndrome
- The disease spreads rapidly and became a global outbreak approaching 1 million cases at the start of April 2020
- Definite diagnosis is based on detection of viral RNA by RT-PCR
- Histologically, COVID-19 shows diffuse alveolar damage corresponding to the phase of the disease (acute to fibrotic)
Terminology
- COVID-19 is also called novel coronavirus pneumonia
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is also called 2019 novel coronavirus (2019-nCoV)
ICD coding
Epidemiology
- COVID-19 pandemic
- In December 2019, cases of pneumonia with unknown etiology were reported from Wuhan, Hubei Province, China to WHO (WHO: Novel Coronavirus (2019-nCoV) Situation Report - 1 [Accessed 31 March 2020])
- In January 2020, the Chinese authorities identified a novel type of coronavirus, which was later named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
- At the beginning of February 2020, almost 10,000 cases of COVID-19 were confirmed in China and 100+ cases were detected outside of China (WHO: Novel Coronavirus (2019-nCoV) Situation Report - 11 [Accessed 31 March 2020])
- The disease spread rapidly and became a global outbreak approaching 1 million cases and 50,000 deaths at the start of April 2020 (WHO: Coronavirus Disease 2019 (COVID-19) Situation Report - 72 [Accessed 2 April 2020])
- Coronavirus maps:
- Person to person transmission is suspected to occur via respiratory droplets (cough, sneeze)
Sites
- Upper respiratory tract in mild disease
- Bilateral lobes of the lung in more severe disease
Pathophysiology
- Spike surface glycoprotein of the virus binds to the host via receptor binding domains of the angiotensin converting enzyme 2 (ACE2), which is most abundant in type II alveolar cells (J Virol 2020;94:e00127-20)
- After a SARS-CoV-2 attaches to a target cell, the virion releases RNA into the cell, initiating replication of the virus which further disseminates to infect more cells (Cell 2020 Mar 4 [Epub ahead of print])
- SARS-CoV-2 produces several virulence factors that promote shedding of new virions from host cells and inhibit immune response
Etiology
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive sense, single stranded RNA virus having close genetic similarity to bat coronaviruses (Nature 2020;579:270)
Diagrams / tables
Images hosted on other servers:
SARS-CoV-2
Epidemic timeline of COVID-19 in China
Clinical features
- Median incubation period estimated to be 5.1 days (Ann Intern Med 2020 Mar 10 [Epub ahead of print])
- Manifestations based on meta analysis of more than 650+ symptomatic cases (Travel Med Infect Dis 2020 Mar 13 [Epub ahead of print]):
- Fever (88%), more frequently in adults
- Cough (58%)
- Dyspnea (46%)
- Fatigue and myalgias are frequent (JAMA 2020 Feb 7 [Epub ahead of print])
- COVID-19 can progress to severe acute respiratory syndrome and its major clinicopathological phenotypes include pneumonia and acute respiratory distress syndrome
- Distribution of severity (JAMA 2020 Feb 24 [Epub ahead of print])
- Mild or no disease: 81%
- Severe disease: 14%
- Critical disease: 5%
- Overall case fatality rate: 2.3%
- 20 - 42% of hospitalized patients developed acute respiratory distress syndrome (JAMA Intern Med 2020 Mar 13 [Epub ahead of print], JAMA 2020 Feb 7 [Epub ahead of print])
- Distribution of severity (JAMA 2020 Feb 24 [Epub ahead of print])
- Patients who required ICU supportive care presented with acute respiratory distress syndrome, acute cardiac injury, acute kidney injury and shock; up to 15% of them had fatal outcomes (Travel Med Infect Dis 2020 Mar 13 [Epub ahead of print])
Diagnosis
- Nasopharyngeal swab is recommended for the specimen; oropharyngeal swab, sputum and bronchoalveolar lavage may be used alternatively (CDC: Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons for Coronavirus Disease 2019 (COVID-19) [Accessed 31 March 2020])
- Definite diagnosis is based on detection of viral RNA by real time RT-PCR via many available laboratory tests (CDC: Information for Laboratories [Accessed 31 March 2020])
Laboratory
- Meta analysis data (Travel Med Infect Dis 2020 Mar 13 [Epub ahead of print]):
- Decreased albumin
- High C reactive protein
- High lactate dehydrogenase (LDH)
- Lymphopenia
- High erythrocyte sedimentation rate (ESR)
Radiology description
- Ground glass opacities, crazy paving pattern and consolidation in bilateral lobes are common findings (Radiology 2020 Feb 13 [Epub ahead of print])
- These CT findings peak 10 days after onset
Radiology images
Images hosted on other servers:
Chest CT images
Severe changes
Prognostic factors
- Risks of acute respiratory distress syndrome development include age (> 65 years), underlying diseases (diabetes mellitus) and secondary infection (JAMA Intern Med 2020 Mar 13 [Epub ahead of print], Intensive Care Med 2020 Mar 3 [Epub ahead of print])
- Risk factors for death among hospitalized Chinese patients, in order of strength of association (Lancet 2020;395:1054)
- Coronary heart disease (p < 0.0001)
- Hypertension
- Diabetes
- Chronic kidney disease
- Chronic obstructive lung disease (p = 0.047)
Case reports
- 73 year old man and 84 year old woman with lung cancer and coincidental COVID-19 (J Thorac Oncol 2020 Feb 28 [Epub ahead of print])
- Autopsy case series (Lancet Respir Med 2020 Feb 18 [Epub ahead of print], Preprints 2020;2020030311)
Treatment
- Home management is recommended for patients with mild symptoms
- Optimal duration of home isolation is under investigation but virus is shed for an average of approximately 20 days after disease onset in hospitalized patients (Lancet 2020;395:1054)
- Patients with severe disease require hospital care
- May need oxygenation support, ranging from low dose oxygen supplement to invasive ventilation and extracorporeal membrane oxygenation (ECMO)
- Several antiviral agents are under investigation
- WHO and CDC recommend NOT to use glucocorticoids unless indicated otherwise as this has been associated with increased risk of death (Lancet 2020;395:1054, CDC: Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19) [Accessed 31 March 2020], WHO: Coronavirus disease (COVID-19) Technical Guidance - Patient Management [Accessed 31 March 2020])
Gross description
- From pulmonary edema to lung consolidation (J Clin Pathol 2020 Mar 20 [Epub ahead of print])
- Increased lung weight
- Pleurisy (pleural inflammation) may be seen
- First reports described unusual and excessive sticky liquid on cut surface (J Forens Med 2020;36:16)
- Purulent inflammation, if secondary infection superimposed
Gross images
- Not available
Microscopic (histologic) description
- Pulmonary changes are the most significant, although nonspecific (Lancet Respir Med 2020 Feb 18 [Epub ahead of print], J Thorac Oncol 2020 Feb 28 [Epub ahead of print], Preprints 2020;2020030311)
- Findings of diffuse alveolar damage corresponding to the phase of disease
- Exudative phase: hyaline membrane formation, desquamation of pneumocytes, cellular or proteinaceous exudates, alveolar hemorrhage, fibrinoid necrosis of small vessels
- Organizing phase: interstitial and intraalveolar proliferation of fibroblasts, lymphocytic infiltration, type II pneumocyte hyperplasia, fibrin deposition
- Findings representing the fibrotic phase (e.g. dense collagenous fibrosis, architectural remodeling) are not reported so far
- Viral infection changes
- Multinucleated enlarged pneumocytes with large nuclei, amphophilic cytoplasm and prominent nucleoli in alveolar spaces
- Intranuclear inclusions
- Bacterial pneumonia may be superimposed
- Findings of diffuse alveolar damage corresponding to the phase of disease
- Extrapulmonary changes: various levels of cell injury and microvascular disorders in parenchymal organs (Zhonghua Bing Li Xue Za Zhi 2020;49:E009)
- Pathological findings are primarily based on minimally invasive autopsies
Microscopic (histologic) images
Images hosted on other servers:
Lung, liver and myocardium
Diffuse alveolar damage
Marked alveolar hemorrhage
Virtual slides
Cytology description
- Bronchoalveolar lavage (BAL)
- Abundant activated plasma cells, as per a single case report (J Thorac Oncol 2020 Mar 17 [Epub ahead of print])
- Alveolar macrophages may feature nuclear clearing or intranuclear cytopathic inclusions
Cytology images
Images hosted on other servers:
BAL specimen
Positive stains
- 2019-nCoV antigen expressed in alveolar epithelia and macrophages (Zhonghua Bing Li Xue Za Zhi 2020;49:E009)
- The antibody needs further validation
Negative stains
- Not applicable
Electron microscopy description
- Spherical particles sized 60 - 140 nm
- Distinctive spikes on the surface (9 - 12 nm) giving virions the appearance of a solar corona, consistent with the Coronaviridae family
- Inclusion bodies filled with virus particles in membrane bound vesicles in cytoplasm of the respiratory epithelium (N Engl J Med 2020;382:727)
Electron microscopy images
Images hosted on other servers:
Scanning electron microscopy
Transmission electron microscopy
Molecular / cytogenetics description
- Guidelines from CDC (CDC: Information for Laboratories [Accessed 31 March 2020])
Videos
Histology of acute respiratory distress syndrome
First forensic report
Sample pathology report
- Usually reported as part of autopsy findings:
- Diffuse alveolar damage with changes compatible with viral infection
Differential diagnosis
- Other viral pneumonias such as cytomegalovirus, respiratory syncytial virus and herpes simplex virus
- Severe acute respiratory syndrome
- Acute respiratory distress syndrome of other etiology
- Acute interstitial pneumonia
Additional references
Board review style question #1
Which is the target organ affected by SARS-CoV-2 and responsible for the major manifestation of COVID-19?
- Brain
- Heart
- Kidney
- Liver
- Lung
Board review answer #1
Board review style question #2
Which of the following findings suggests viral infection of the lung?
- Alveolar hemorrhage
- Fibrin deposition
- Neutrophilic aggregation
- Nuclear inclusions
- Type II pneumocyte hyperplasia
Board review answer #2
