Coronavirus Disease (COVID-19): Definition, Epidemiology, Pathogenesis, Symptoms, Signs, Complications, Diagnosis, Differential Diagnosis, Management, Prognosis, Prevention, Statistics & Updates
Updated on 19th June 2020. These materials are regularly updated based on new scientific findings as the pandemic evolves.
Introduction
- COVID-19 is the infectious disease caused by the most recently discovered coronavirus SARS-CoV-2.
- Incubation period : 2–14 days
Causative Agent
- Causing agent : Coronavirus SARS-CoV-2 (Novel coronavirus, nCoV, Wuhan virus, China virus)
- Reservoir : Undefined (?bats, snakes)
Epidemiology
- Origin: Wuhan, Hubei, China
- 31 Dec 2019: WHO China office reported cases of pneumonia of unknown etiology.
Epidemiological parameters
- Causative agent: SARS-CoV-2
- Source of infection: Cases
- Mode of infection: Droplets, Contact & Fomites
- Reproductive number (R0): 2- 2.5 (Number of secondary infections generated from one infected person)
- Incubation Period: 2.2-11.5 days (Median Incubation Period: 5.1 days)
- Age group affected: All age groups (Mostly 30+ age group)
Note: Influenza spreads faster than COVID-19.
Case fatality rate (CFR)
- Overall CFR: 2.0-3.7% (0.2-15%)
- >1% CFR in age 50+ years
- >10% CFR in age 80+ years
- CFR highest if co-existing morbidities (CVD, HTN, DM)
Epidemic Curve
- More steeper the curve, More the requirements of ICU’s
WHO Risk Assessment (on 28th feb 2020)
- China: Very High
- Regional: Very High
- Global: Very High
Definitions of case
1. Suspect Case
- A. A patient with acute respiratory illness (fever and at least one sign/symptom of respiratory disease (e.g.,cough, shortness of breath), AND with no other etiology that fully explains the clinical presentation AND a history of travel to or residence in a country/area or territory reporting local transmission of COVID-19 disease during the 14 days prior to symptom onset.
OR
- B. A patient with any acute respiratory illness AND having been in contact with a confirmed or probable COVID19 case in the last 14 days prior to onset of symptoms;
OR
- C. A patient with severe acute respiratory infection (fever and at least one sign/symptom of respiratory disease (e.g., cough, shortness breath) AND requiring hospitalization AND with no other etiology that fully explains the clinical presentation.
2. Probable case
- A suspect case for whom testing for COVID-19 is inconclusive. (Inconclusive being the result of the test reported by the laboratory).
3. Confirmed case
- A person with laboratory confirmation of COVID-19 infection, irrespective of clinical signs and symptoms.
Mode of Transmission
1. Human-to-Human transmission
Mode of infection: Droplets, Contact, & Fomites
- Droplet transmission (large respiratory droplets that people sneeze, cough or drip)
- Aerosol transmission (when someone coughs or sneezes in the room)
- Contact transmission (touching a contaminated surface then touching your mouth, nose or eyes)
- Direct transmission (kissing, shaking hands etc.)
Source of infection: Cases (Asymptomatic, Symptomatic)
2. Animal-to-Human transmission
Pathogenesis
Entry into host cell
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Primarily causing infection of airway epithelial cells → Respiratory symptoms
Later on, additionally infect surrounding cells like macrophages, dendritic cells → Release of cytokines → Systemic symptoms
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Spike molecules of virus interact with ACE-2 receptor on host cell
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Virus particle uncoated
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Genome enters cell cytoplasm
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Coronavirus RNA Genome has a 5’ methylated cap & a 3’ polyadenylated tail which allows RNA to attach to Host cell ribosome for Translation
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Coronavirus also have RNA-dependent RNA polymerase (RdRP) which allows viral genome to Transcribe into new RNA copies using Host cell machinery
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RdRP is first protein to be made
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After RdRP gene coding, Translation stops by Stop Codon called as Nested Transcript
Clinical Features
- Fever,
- Dry cough,
- Shortness of breath (SOB),
- Tiredness,
- Aches and pains,
- Nasal congestion,
- Runny nose (Rhinorrhea),
- Anosmia, Ageusia,
- Sore throat,
- Headache,
- Gastrointestinal symptoms like Diarrhea.
Pneumonia appears to be the most common and severe manifestation of infection.
Clinical Spectrum
Clinical spectrum of coronavirus disease 2019 (COVID-19) range from mild symptoms to severe illness and death for confirmed cases.
- 81% Mild
- 14% Severe (needs supplemental O2)
- 5% Critical (requires ventilation)
Most infections are self limiting.
Factors determining the severity of disease are
- Age of individual (More severe in elderly)
- Immunity of host (More severe in patient with Comorbid conditions, immunocompromising conditions)
Complications
- Pneumonia
- ARDS (M/C cause of death)
Diagnosis
1. rRT-PCR
- Sensitivity-70% but Specific
- Genes: N, E, RdRP
- Specimens: URT (Nasopharyngeal swabs NPS, Oropharyngeal swabs OPS)
- Cost for rRT-PCR on NPS/OPS : 36-51 USD (∼3500 INR)
Sample collection
- Specimens: URT (Nasopharyngeal swabs NPS, Oropharyngeal swabs OPS) > LRT (BAL, Tracheal aspirate)
- Location: In OPS, Tonsillar pillars & Posterior oropharynx
- Specimen should be collected by Synthetic fiber swabs with plastic shafts (Should not use calcium alginate swabs with plastic shaft)
- Specimen should be collected as soon as PUI (Person Under Identification) is identified.
- Procedure: Tilt head → 90° parallel to palate
- Precautions to be taken: Use PPE in place, Use purple nitrite latex free glove.
- All respiratory specimen collection procedures should be done in negative pressure rooms.
- Both Induction of sputum collection OR Bronchoscopy are not recommended.
Bronchoscopy
Benefits
- Helps in obtaining BAL samples in patients who are not able to expectorate sputum for checking bacterial culture/AFB smear/gene Xpert
- Bronchoscope can be used to clear out mucous plugs in ventilated patients.
Risks
- May cause some deterioration in clinical condition, especially in patients who are on high oxygen support.
- High risk of transmission of infection to providers.
- Significant utilization of valuable resources at this point (N95 respirators, physicians, respiratory therapists) – Supply of all these resources will be limited during the time of a pandemic.
Recommendations
- Bronchoscopy should not be done only for the purpose of ruling COVID-19. Risk of transmission of infection to others is extremely high through aerosols.
- It can be performed when sputum sample cannot be obtained to rule out alternative diagnosis like (Tuberculosis, bacterial/fungal pneumonias).
- It can be performed to suction out mucous plugs in ventilated patients.
- Consideration for use of a disposable bronchoscope if available.
- Consider bronchoscopy in patient’s place of care to minimize the exposure.
- Minimize staff in room during procedure.
- Negative pressure room if available.
- All Personal Protective equipment should be used: Face shield/goggles, N95 mask, Contact isolation gown, Gloves.
- Standard disinfection protocols should be followed for cleaning your flexible bronchoscopes and video monitors.
2. IgM-IgG Combo test (COVID-19 Rapid Test)
- Principle: Lateral flow immuno-chromatography to detect IgG & IgM antibodies.
- The IgM-IgG combined assay has better utility and sensitivity compared with a single IgM or IgG test.
- It can be used for the rapid screening of SARS-CoV-2 carriers, symptomatic or asymptomatic, in hospitals, clinics, and test laboratories.
3. Radiology
a. Computed Tomography (CT Chest)
- Sensitivity-95%, Specificity-Low)
- Bilateral lung involvement on initial CT
- Usually affecting the subpleural regions and the lower lobes
- Consolidative pattern in ICU patients
- Predominanatly ground glass pattern in patients who were not in ICU
Findings
- Multifocal ground glass opacities (GGO) & consolidation with a posterior & peripheral lung predilection.
- Smooth and irregular interlobular septal thickening, crazy paving pattern, air bronchogram and irregular pleural thickening.
Stages
- Early stage (0-4 days after the onset of the symptoms), in which ground glass opacities (GGO) are frequent, with sub-pleural distribution and involving predominantly the lower lobes. Some patients in this stage could have a normal CT.
- Progressive stage (5-8 days after the onset of the symptoms), the findings usually evolved to rapidly involvement of the two lungs or multi-lobe distribution with GGO, crazy-paving and consolidation of airspaces.
- Peak stage (9-13 days after the onset of the symptoms), the consolidation becomes denser and it was present in almost all of the cases. Other finding was residual parenchymal bands.
- Absorption stage (>14 days after the onset of the symptoms), no crazy paving pattern was observed, the GGO could remain.
(b). Chest Radiography (CXR)
- The findings on CXR are not specific, and in the initial phases of the disease the studies could be normal.
- The most common features include lobar/ multi-lobar / bilateral lung consolidation.
(c). Lung ultrasound (USG)
- The USG findings are also not specific for COVID-19 infection.
- The findings include: Irregular pleural lines, sub-pleural areas of consolidation, areas of White lung and thick B lines.
- It is a tool that could be used at bed side avoiding the need for shifting infected patients to a Radiology suite.
4. Blood findings
(a). WBC Count
White blood cell count can vary. It does not provide accurate information about COVID-19.
- Leukopenia, leukocytosis, and lymphopenia have been reported. Lymphopenia is more common, seen in more than 80% of patients.
- Neutrophils: Normal to High
(b). Platelet Count
- Mild thrombocytopenia is commonly seen. However, thrombocytopenia is considered as a poor prognostic sign.
(c). Inflammatory Markers
- Serum Procalcitonin ↑ (in patients who require ICU care)
- C – reactive protein (CRP) ↑ (seems to track with disease severity and prognosis)
(d). Others
- Lactate: Mildly high
- Troponin: High
- Urea/Creatinine: Mildly high
- Albumin: Low
- Creatine kinase: High
- AST/ALT: High
- Ferritin: High
High D-dimer levels & more severe lymphopenia have been associated with mortality.
5. Pulmonary function tests (PFT)
Risks
- Sources of cross infection in pulmonary function lab can occur due to close contact, direct contact and through aerosolized particles. Among these Droplets/aerosolized particles is the most common mode of transmission of infection.
- Numerous factors play a role in the virulence of an organism: source & strain of pathogen, route of infectivity, particle size, room temperature and infective dose of pathogen.
Recommendations
- All kinds of pulmonary function tests should be avoided among patients with a strong suspicion of upper or lower Respiratory tract infection.
- In COVID 19 endemic zones it would be wise to avoid PFTs for a major proportion of patient to avoid spread of infection and usage of PFT should be limited for time being for only pre-operative fitness assessment.
- All patients who are enrolled to perform a PFT should be segregated, since this helps in preventing the spread of infection. Performing a chest x-ray prior to PFT would help to rule out Respiratory infections to certain extent.
- Contact in waiting room with potentially infectious patients should be minimized. Surgical facemasks, tissues, and waste container, alcohol-based sanitizers should be made easily available for infectious patients.
- All connections between the patient and the PFT machine (tubing’s & valves) should be cleaned and disinfected before re-use.
- Disposable items in PFT lab like mouth pieces can be a reservoir of microorganisms and hence should be disposed carefully.
- Usage of personal protective equipments helps in reducing the risk of cross contamination.
Differential Diagnosis (D/D)
- H1N1
- H5N1
- Flu A & B
- RSV
- Rhinovirus
- Parainfluenza
- Allergy
Management
There is no specific antiviral treatment recommended for COVID-19, and no vaccine is currently available.
- No drug of choice
- Oxygen support
- Oxygen saturation to be maintained above 90%
- Conservative fluid management
- Give empirical antibiotics (As per institution based CAP guidelines)/ anti-viral (Oseltamivir)
- High dependency / ICU care when needed
For treating the COVID-19 patient, various guidelines have been formulated by different hospitals & institutions.
1. AIIMS Potocol
2. Other Protocol
A. Mild Disease (81%)
These patients usually present with symptoms of
- An upper respiratory tract viral infection
- Low grade fever , cough, malaise, rhinorrhoea, sore throat without any warning signs
- Shortness of breath
Haemoptysis - Gastro-Intestinal symptoms: Nausea, vomiting, Diarrhea
- Without change in mental status ( ie: confusion, lethargy)
- Non immunocompromised
Recommendation: Consider for home isolation in asymptomatic/mild disease.
B. Severe Disease & Critically ill patients
Severe Disease (14%)
- Respiratory rate > 30/min
- SPo2 <93%
- PaO2/FiO2 <300
- Lung infiltrates >50% within 24- 48 hours
Critically ill (5%)
- Respiratory failure (need of mechanical ventilation)
- Septic shock
- MODS
Recommendation: Consider for Admission in Hospital isolation room.
Prognosis
The vast majority of infected patients (e.g. >80%) don’t get significantly ill and don’t require hospitalization.
Among hospitalized patients (Guan et al 2/28)
- 10-20% of patients are admitted to ICU.
- 3-10% requires intubation.
- 2-5% dies.
Epidemiological risk factors
- Older Age
- Male sex
- Medical comorbidities
- Chronic pulmonary diseases
- Cardiovascular disease
- Chronic kidney disease
- Diabetes
