Introduction

COVID-19 is an infectious disease that is caused by a newly discovered viral strain, SARS-CoV-2 that belongs to the coronavirus group and causes mild to severe respiratory disease in humans. The strain was first identified in the city of Wuhan, Hubei Province, China. (1) 

The virus has a high rate of human-to-human transmission and it is also suspected to have had an animal host but research regarding this is still underway with no clear evidence available regarding the presence of a specific intermediate animal host. (2) 

History of Coronavirus

Coronaviruses are a group of RNA viruses that are known to cause a wide variety of respiratory, enteric, and other systemic infections in several organisms such as fish, birds, humans, and mammals. (3)

The term “corona” means “crown” and it refers to the surface projections present on the virus that give it a crown-like appearance. (4)

In the early 20th century coronaviruses were thought to infect animals only. (5) In 1960 it was discovered that certain strains of coronaviruses can cause mild to severe respiratory infections in humans. In the last two decades, there have been three major outbreaks of respiratory infections caused by strains from the coronavirus group, they are as follows: (6), (7)

1. Severe Acute Respiratory Syndrome (SARS)    2002-2003
2. Middle East Respiratory Syndrome    (MERS) – 2012
3. Novel Coronavirus (nCOV-19), (COVID-19), (SARS-CoV2) – 2019  

Current Condition

The COID-19 strain was first identified in December 2019. On 30th January 2020, the outbreak was declared a Public Health Emergency of International Concern (8) and on 11th March 2020, a Pandemic by the WHO. (9) 

According to the World Health Organisation (WHO) over 6 million cases of infection have been confirmed globally and more than three hundred thousand deaths have been recorded as of 4th June 2020. (10)

Transmission

SARS-CoV 2 is a highly transmissible and pathogenic virus. The intermediate host is yet to be discovered, but the rate of transmission among humans is very high. (11)  

The virus can be transmitted directly by coughing and sneezing and indirectly by touching your face after your hands if they have touched contaminated surfaces. The virus remains suspended in the air for approximately 3 hours and can travel almost 2 meters. The droplets penetrate the respiratory tract after inhalation and cause infection. The infection can also be spread by asymptomatic individuals. Pregnant women and newborns are at an increased risk of infection. (12)

The virus is transmissible 3 days before symptoms develop and viral shedding continues for almost a week after onset of symptoms. It can also be shed in the stool for approximately 5 weeks. (12)

Epidemiology 

COVID-19 is a global disease and there has been a rapid growth in cases all over the world. The virus infects individuals of all ages, races, and genders. Individuals on extremes of age i.e. under 1 year and above 65 years and those with comorbidities have the highest risk of developing severe disease. (12)

Microbiology

SARS-CoV-2 is an enveloped positive single-strand RNA virus, it has a protein-coding sequence similar to SARS-CoV and MERS-CoV and it uses Angiotensin 2 Converting Enzyme 2 (ACE 2) Receptors that are present in the alveolar cells (lungs), enterocytes ( small intestine), and some parts of the brain to gain entry into the cells. The similarity suggests that treatments that were employed to treat previous outbreaks might prove useful in treating the current COVID-19 pandemic but the evidence is limited. (12)

Pathogenesis of Novel Coronavirus (COVID-19)

The mean incubation period of the virus is 5.2 days and the range is 3-14 days. The life cycle of the virus follows the following steps: 

1. Attachment

The virus binds to receptors present on the host cells.

1. Penetration

The virus invades the host cell by endocytosis or membrane fusion.

1. Biosynthesis

Viral contents are released inside the host cells and the viral RNA now directs the production of viral proteins.

1. Maturation

The host cells make viral proteins that consist of membrane, nucleocapsid, spike, and envelope.

1. Release

The virus is released from the cell via exocytosis and infects other cells and the cycle repeats. (13)

Signs and Symptoms of COVID-19

COVID-19 can cause no to mild symptoms and can also progress to moderate to severe disease followed by death.

Mild symptoms require no treatment or symptomatic relief but moderate to severe disease may require ICU admission and ventilatory support. (14)

The common symptoms of the disease are as follows:

• Fever
• Fatigue
• Dry Cough
• Shortness of Breath
• Myalgia and Arthralgia
• Sore throat
• Headache
• Chills
• Diarrhea and nausea/vomiting
• Anosmia (Loss of Sense of Smell)
• Nasal Congestion and Rhinorrhea
• Chest pain
• Dizziness
• Increased Sputum Production

Complications

The presentation of symptoms varies in individuals and many recover with symptomatic treatment. If the disease progresses it can cause: 

• Pneumonia
• Severe acute respiratory distress syndrome (14)

It may also cause multi-organ failure and septic shock. (15) The severe cases may recover after ventilatory support or result in death. (14)

Lab reports show elevated enzyme levels, an increased leukocyte count, and a ground-glass appearance on chest CT radiograph but these findings are non-specific and cannot be used alone to diagnose the infection. (14)

What to do if you experience the symptoms?

If you experience the symptoms, immediately visit your health care provider or contact your nearest response center or helpline for further guidance.

Self-isolation is recommended while waiting for test results to limit the spread of infection.

Who should get tested?

You should consider getting tested if :

1. You have a recent history of travel
2. If you were in contact with an infected individual
3. If you are experiencing symptoms
4. You are a healthcare worker
5. You work in a/ stay in a nursing care facility
6. You had a prolonged hospital stay 
7.  Are scheduled to have surgery 

Diagnostic Strategies

The symptoms of COVID-19 are similar to symptoms of the common cold, flu, and sometimes widely non-specific. It is essential to get COVID-19 testing done in the early stages of infection so that the affected individuals can be separated and quarantined. Efficient testing with prompt results of greater specificity would be beneficial in preventing the quarantine of unaffected individuals and immediate treatment of those who have a severe form of the infection. (16)

Researchers are working vigorously to develop time and cost-effective COVID-19 testing kits with high sensitivity and specificity. Currently, two major testing modalities are commercially available for COVID-19 diagnosis. They are as follows:

1. Molecular assay testing
2. Serology (Antigen and Antibody Testing) (16)

1. Molecular Assay Testing

The COVID-19 strain used for diagnosis was isolated by Chinese scientists who were successful in identifying the novel coronavirus strain and publishing a genetic sequence so that laboratories around the world could independently establish polymerase chain reaction ( PCR) experiments to diagnose the viral infection. (17)

The different types of molecular assays are as follows:

• Reverse Transcription Polymerase Chain Reaction (RT-PCR)
• Iso-thermal Nucleic Acid Amplification

The aforementioned are the most commonly used molecular assay tests. Several other molecular tests such as Amplicon-Based Metagenomic Sequencing,  Nucleic Acid Hybridization Using Microarray, etc. The other tests have their own advantages and limitations but are not currently commonly utilized. Nasopharyngeal swabs, nasal swabs, saliva, and sputum contents are used as samples for RT-PCR. (16)   

Reverse Transcription Polymerase Chain Reaction (RT-PCR)

Considered the gold standard test for diagnosing COVID-19, RT-PCR works by amplifying small samples of the viral genetic material obtained from the upper respiratory tract. 

PCR starts with the conversion of RNA into DNA. The DNA is then amplified and monitored as the PCR progresses in real-time. The amplification automatically continues for 40 cycles after which the DNA can be detected by electrical or fluorescent signals. (16), (17)

RT-PCR is the most widely used diagnostic tool as it targets the specific pathogen and can diagnose current infection but it has certain disadvantages such as it requires expensive laboratory equipment, specialized centers, and skilled lab technicians and it also takes days to provide results. (16)

Iso-thermal Nucleic Acid Amplification

In contrast to PCR, isothermal amplification is an alternate method that allows amplification at a constant temperature, so there is no need for a thermal cycler. There are several methods that have been based on this principle but due to limited research and evidence of effectivity, it is not commonly used. (16)

Few types of iso-thermal nucleic acid amplification tests re as follows:

•  Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP)

It is a promising new technique that can help in early diagnosis as it only requires heating and visual detection of turbidity reducing the need for special reading equipment as in the case of PCR. The research is underway and we might soon see it being widely used as an alternative to PCR. (16)

• Transcription-Mediated Amplification (TMA), CRISPR-Based Assays (Clustered Regularly Interspaced Short Palindromic Repeats),  Rolling Circle Amplification

TMA, CRISPR, and Rolling circle amplification are other tests based on the isothermal principle but the research evidence regarding their effectiveness is limited. (16)

Serology

Serological tests analyze blood, plasma, sputum, saliva, and other biological fluids to detect immunoglobulins formed by the immune system in response to an infection.  Serologic testing helps in contact tracing, identifying past infections, and asymptomatic individuals who were infected with the virus. (16)

Serology testing may help predict post-infection immunity and the possible development of vaccination and herd immunity but cannot be used as a reliable diagnostic tool as it can not detect current infection. (16), (17)

The two most common types of serologic tests are as follows:

1. Enzyme-linked Immunosorbent Assay (ELISA)
2. Lateral Flow Immunoassay

Enzyme-Linked Immunosorbent Assay (ELISA)

ELISA can be used to detect viral antigens and antibodies. The research regarding viral antigen testing is very limited and not well developed as the viral antigens have cross-reactivity and similarity to other viruses and may give false-positive results.

Viral antibody testing using ELISA can give quick results, test multiple samples simultaneously, and does not require expensive equipment or highly trained staff. 

The test is performed on testing plates in which the patient sample is added in a vial that already contains specific enzyme-linked antibodies against the viral antibodies present in the serum. If the test is positive a color change is observed. (16)

Lateral Flow Immunosorbent Assay

The test detects antibodies in patient samples and checks the host’s response to viral invasion. They detect the previous infection, exposure in asymptomatic individuals, and may prove to be a predictor of long term immunity. (16), (17)

The test consists of a strip that can be used at the point of care. The sample is mixed with a diluting agent and applied on the strip. The positive control shows the kit is viable and the other two lines show the detected antibodies. (16)

How to read the strip?

IgM positive: Early infection

IgG positive: Past Exposure or Current Infection, may also predict long-term immunity

IgM and IgG positive: Current infection

The lateral flow assay tests are inexpensive and easy to perform but have a low analytical sensitivity when compared to RT-PCR and thus are not used as a sole diagnostic tool. (17)

Other tests based on the serologic testing include neutralization assay, luminescent immunoassay, rapid antigen test, etc. but their use is not currently widespread.

Treatments

There is no conclusive evidence of antiviral drugs being effective against the novel coronavirus and no vaccine is available. Thus, the treatment mainly relies on providing symptomatic relief and ventilatory support. (18) 

Potential Drugs

Certain clinical trials have been performed with antiviral drugs such as lopinavir and ritonavir but further assessment is required before adding it to the treatment regime. (18)

Corticosteroids have also shown improvement in some patients by reducing lung inflammation but more research is necessary to outline benefits and weigh them against potential harm. (18)  

Chloroquine and hydroxychloroquine are also under study as an anti-SARS-CoV drug and as potential prophylaxis agents but more data is required to outline the benefits as the side effect profile of both the drugs is not negligible. (18)

Convalescent Plasma Transfusion Therapy

Clinical trials suggest that transfusing patients in the early stages of infections with the plasma of recovered patients can result in a decrease in mortality and some improvement. Clear evidence regarding efficacy and safety is still limited but it is encouraged to obtain plasma from patients within two weeks after recovery to ensure the presence of high neutralizing antibody titers. (18)

Rehabilitation after Severe Illness

Severe disease may cause physical, social, and psychosocial impairment. Post intensive care unit recovery and rehabilitation is one of the many challenges the pandemic has brought on the healthcare system. Rehabilitation experts, physiotherapists, and occupational therapists have started working on strategies that will help patients recover quickly and return to daily activities with minimum disability. (19), (20)

It is recommended to use an interdisciplinary rehabilitation approach that should continue throughout the hospital stay. (19)

Patients, family members, and any other care provider at home should be educated regarding patient care after discharge and the rehabilitative care monitored and continued in out-patient settings, through home visits or via telehealth. (19) 

Conclusive treatment strategies are still under research but safety and preventive measures are not to be ignored during rehabilitation. It would be beneficial if separate rehabilitative centers are made for COVID-19 patients under-recovery. (21) 

Prevention and Vaccination

Since the treatment is limited to symptomatic relief and ventilatory support our best course of action to limit the spread of the disease is prevention so that we can flatten the curve. The following measures have to be taken for effective prevention.

1. Frequent handwashing with soap and water
2. Using sanitizer
3. Covering the mouth and the nose with a mask
4. Avoiding mass gatherings
5. Social distancing measures
6. Regular disinfection of surfaces and public spaces, public transports and other items used by the public for example shopping carts
7. Avoid touching your face
8. Avoid unnecessarily leaving your home 
9. Self isolate if you suspect you have the infection or are showing symptoms and immediately contact your healthcare provider for guidance
10. Avoid traveling (22)

The research for developing a vaccine is being conducted day in and day out but so far prevention is the only effective option. (18) 

Summary and Social Impact

COVID-19 is a pandemic disease with high transmission rates, no vaccine, and no specific treatment. The only effective measure is prevention and mass testing to accurately record the cases and outcomes. The disease has a moderate mortality rate but the high rates of infection overwhelm the healthcare resources resulting in greater deaths due to the unavailability of test kits, manpower, and ventilators.

It is our social responsibility as inhabitants of the planet earth to follow standard operating protocols (SOPS) for the sake of our fellow humans without religious intolerance, racism, and xenophobia.

The governments of all countries are making masks and gloves mandatory in public spaces, starting online classes, and providing the latest updates regarding the virus. It is our responsibility to not spread fake news and follow preventive measures.

References

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