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.
- COVID-19 is the infectious disease caused by the most recently discovered coronavirus SARS-CoV-2.
- Incubation period : 2–14 days
- Causing agent : Coronavirus SARS-CoV-2 (Novel coronavirus, nCoV, Wuhan virus, China virus)
- Reservoir : Undefined (?bats, snakes)
- Origin: Wuhan, Hubei, China
- 31 Dec 2019: WHO China office reported cases of pneumonia of unknown etiology.
- 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)
- 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.
- 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;
- 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
Entry into host cell
Primarily causing infection of airway epithelial cells → Respiratory symptoms
Later on, additionally infect surrounding cells like macrophages, dendritic cells → Release of cytokines → Systemic symptoms
Spike molecules of virus interact with ACE-2 receptor on host cell
Virus particle uncoated
Genome enters cell cytoplasm
Coronavirus RNA Genome has a 5’ methylated cap & a 3’ polyadenylated tail which allows RNA to attach to Host cell ribosome for Translation
Coronavirus also have RNA-dependent RNA polymerase (RdRP) which allows viral genome to Transcribe into new RNA copies using Host cell machinery
RdRP is first protein to be made
After RdRP gene coding, Translation stops by Stop Codon called as Nested Transcript
- Dry cough,
- Shortness of breath (SOB),
- Aches and pains,
- Nasal congestion,
- Runny nose (Rhinorrhea),
- Anosmia, Ageusia,
- Sore throat,
- Gastrointestinal symptoms like Diarrhea.
Pneumonia appears to be the most common and severe manifestation of infection.
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)
- ARDS (M/C cause of death)
- 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)
- 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.
- 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.
- 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.
- 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.
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
- 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.
- 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)
- 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)
- 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.
- 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)
- Flu A & B
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
- 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
Recommendation: Consider for Admission in Hospital isolation room.
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