A review on COVID-19 for medical students

INTRODUCTION

Coronaviruses (CoVs), primarily of zoonotic origin, made their presence felt among humans through the SARS-CoV and MERS-CoV infections not so long ago. COVID-19, a new strain of the coronavirus, is currently a pandemic, with 1,780,356 reported cases and 108,828 reported fatalities worldwide.

CoVs belong to the genus Coronavirus in the Coronaviridae family of viruses. They are pleomorphic RNA viruses, 80–160 nm in size with 2–32 kb positive polarity, possessing multiple crown-shaped peplomers. Their recombination rate is very high due to continuous development of transcription errors and RNA-dependent RNA polymerase (RdRP) jumps contribute to their high mutation rate.^[1,2]

There are four genera of the CoV which are α, β, γ, and δ-CoV. All four genera do not cause serious illness among humans. Variants of the α and β genera have low pathogenicity, producing mild respiratory symptoms like the common cold. The γ and δ-CoV variants tend to infect birds. SARS-CoV and MERS-CoV are β-CoVs with the potential to produce acute respiratory distress syndrome (ARDS) associated with high mortality rates.^[3]

In December 2019, SARS-CoV-2 also known as the novel CoV-19 emerged in Wuhan, Hubei Province, China. Within a month, the virus made its way to other countries. On March 11, 2020, the World Health Organization (WHO) declared COVID-19 as a pandemic.^[4]

EPIDEMIOLOGY

It is hypothesized that wild bats are the reservoir of SARS-CoV-2. Theory says that infected wild bats were being traded along with livestock in the Huanan Seafood Market in Wuhan from where nCoV-19 infected the index cases. Among humans, the virus is transmitted through nasopharyngeal droplets and fomites.^[5-7]

On December 12, 2019, a case of pneumonia not caused by influenza or other known CoV was first reported in Wuhan. By December 31, 2019, 27 similar cases were diagnosed in the same province.^[8,9] All cases reported a history of animal contact in the above-mentioned market.

On January 7, 2020, the Government of China announced that nCoV-19 was isolated from all the above cases.^[10,11]

Like other coronavirus outbreaks, COVID-19 seems to exhibit high incidence in the spring season across the globe. Being the season of celebrations and gatherings, high population densities in smaller areas assist in the easy transmission of the virus among humans. Compounded by the increase in international travel, the above-mentioned factors pose significant difficulties for countries to contain the spread of the virus.^[12]

GENETICS

According to research, SARS-CoV-2 is like SARS-CoV in 70% of its genome and to MERS-CoV in 50% of its genome. It has approximately 89% similarity with two bat-derived SARS-like CoVs.^[13-15] Metagenomic next-generation sequencing revealed the entire 29,881 base pair genome of the virus with 6–11 open reading frames (ORFs).^[16] Evolutionary analysis based on ORF1a/1b, S, and N genes suggests that SARS-CoV-2 was independently introduced from animals to humans.^[17,18]

Two-thirds of the viral RNA, located in the first ORF (ORF1a/b), translates to two polyproteins, PP1a and PP1ab and encodes 16 non-structural proteins (NSP). One-third of the viral genome encodes four essential structural proteins and several accessory proteins that interfere with the host innate immune response:^[19]

1. Spike (S) glycoprotein

2. Small envelope (E) protein

3. Matrix (M) protein

4. Nucleocapsid (N) protein

SARS-CoV-2 possesses the S-glycoprotein gene and receptor-binding domain (RBD) which confer the ability to be transmitted between two humans by direct contact.

When comparing SARS-CoV-2 with other known CoVs, no difference was found in the amino acid sequences of NSP7, NSP13, envelope, matrix, or accessory proteins p6 and 8b. A few differences were found in the NSP2, NSP3, spike protein, and underpinning subdomain (RBD).^[20] Mutations in NSP2 and NSP3 play a role in the infectious potential and differentiation mechanism of the virus.^[21]

Zhang et al.^[22] found that as the virus spread across different provinces in China, its genotype exhibited several mutations.^[23]

PATHOGENESIS

Close

Export to PPT

Close

Export to PPT

CLINICAL FEATURES

Viral load at the time of infection determines the clinical features in a host. The incubation period is approximately 14 days.

The most common clinical presentation is fever, headache, sore throat, productive wet cough, myalgia, diarrhea, and dyspnea.^[33-35] The spectrum of clinical cases includes asymptomatic carriers and mild respiratory infection that recover within a week, severe progressive respiratory distress and death.^[34,36]

In severe respiratory distress, respiratory system examination reveals reduced tactile fremitus, dullness to percussion, and reduced air entry associated with rales.

Majority of the case fatalities have been reported among the middle-aged and elderly population associated with multiple comorbidities such as diabetes mellitus, hypertension, coronary artery disease, liver cirrhosis, and cancer.^[37]

INVESTIGATIONS

Investigations can be divided into two classes:

1. Tests to confirm the diagnosis of COVID 19 – a positive RT-PCR test.

2. Tests to monitor and assess the severity of the disease and its progression – performed in critically ill-hospitalized patients.

A patient is declared as recovered from the infection if two samples taken on different days give a negative RT-PCR result.

Routine blood tests include the following:

1. Complete blood count: It shows decrease in lymphocytes and white blood cells with specific reduction in CD4 and CD8 T-cells.

2. Arterial blood gas analysis.

3. Lipid profile.

4. Renal function tests.

5. Liver function tests.

6. Myocardial enzymes.

7. Urine analysis.

8. Inflammatory factors – interleukin 6 (IL-6), IL-10, and TNF-α.

9. ESR and CRP.

10. Coagulation profile with D-dimer

IMAGING

Chest X-rays are the initial imaging modality followed by CT thorax without contrast.

Clues to the diagnosis of COVID-19 on a chest X-ray are as follows:

• Bilateral lung infiltrates along the subpleural plane and bronchial vascular bundles, singular or multiple patchy, nodular, and honeycomb- or cord-like infiltrates, particularly involving the middle and lower lobes of the lung.

• Typical bilateral subsegmental ground-glass appearance

• Interlobular thickening

• Consolidation and thickening of bronchial walls

Atypical findings on imaging include:

• Pleural effusion

• Enlargement of mediastinal lymph nodes

• Single or multiple solid nodules or consolidated nodules in the center of lobule surrounded by ground-glass opacities.

CT STAGING^[38]

CONCLUSION

From the time, SARS-CoV-2 made its appearance among humankind, several researchers and health-care professionals have been risking their lives to understand the properties of the virus and aid in the recovery of infected individuals while preventing its spread among communities. By implementing lessons learned from the previous coronavirus epidemics, we can design an effective vaccine and antiviral drug that will help combat the virus. A lot more knowledge is yet to be obtained regarding the virus and the disease which will better enable us to manage patients and reduce mortality rates.