A Review on COVID-19 Pandemic

1. Assistant Professor, Department of Microbiology, Mahatma Gandhi University of Medical Sciences, Jaipur, Rajasthan, India. 2. Assistant Professor, Department of Emergency Medicine, Mahatma Gandhi University of Medical Sciences, Jaipur, Rajasthan, India. 3. Demonstrator, Department of Microbiology, Mahatma Gandhi University of Medical Sciences, Jaipur, Rajasthan, India. 4. Demonstrator, Department of Microbiology, Mahatma Gandhi University of Medical Sciences, Jaipur, Rajasthan, India. 5. Lab Director, Central Research Laboratory, Mahatma Gandhi University of Medical Sciences, Jaipur, Rajasthan, India.

Abstract

Coronavirus associated with Severe Acute Respiratory Syndrome (SARS) has been identified as Coronavirus Disease-2019 (COVID-19) Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), first detected in Wuhan, Hubei province, China, the National Health Commission of China received reports of 27 cases of pneumonia, including seven severe cases of unknown origin, on 30^th December 2019. In order to diagnose COVID-19, the virus responsible for the pandemic, SARS-CoV-2, was analysed for its Ribonucleic Acid (RNA). It is possible to detect specific sequences of genes encoding the RNA dependent RNA polymerase (RdRP), nucleocapsid (I#INI?I), envelope (I#IEI?I), and spike (I#ISI?I) proteins of viruses using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). There are four major groups of drugs recommended by treatment guidelines worldwide: antiviral drugs (eight drugs), antimalarial drugs (two drugs), systemic corticosteroids (five drugs), and immune-based therapy (seven drugs). The recommendations for the treatment with these drugs in all of the guidelines differ depending on the severity of the case and the health conditions of the patient. A successful preventative vaccine is the most important and time-sensitive measure in combating the COVID-19 pandemic. There were 12 SARS-CoV-2 vaccines approved/authorised for full or emergency use in various parts of the world as of 25^th February 2021, with more than 200 million doses administered worldwide. Because the disease is still relatively new and healthcare is under considerable pressure, many questions remain unanswered. There is a lack of publications regarding the effectiveness and safety of these drugs in COVID-19 patients. In addition, community members with limited financial resources must still consider the costs associated with some of the proposed treatment regimens.

Coronavirus disease-2019, Pneumonia, Vaccine

Acute respiratory disease caused by SARS-CoV-2 caused an explosive catastrophic pandemic which affected almost all part of the world produced significant loss of lives and the worst financial crisis recorded ever, since World War II. SARS-CoV-2 comprises of a nucleocapsid, surrounded by an envelope, measures 120 nm in size; has a helical symmetry (1),(2). Therefore, to diagnose COVID-19, early identification of SARS-CoV-2 infection is important. Also, to develop rapid diagnostic methods in outpatient clinics and regional medical facilities are also important in order to prevent and control the pandemic, besides improving high-throughput accurate diagnostic technology in big laboratories. To find out the origin of the COVID-19 pandemic, one should also consider intelligent medicine as an emerging technology in healthcare (1),(3). In this review, authors have explored the diagnostic information provided by each diagnostic tool and some known shortcomings, as well as the way each diagnostic tool complements the others to provide more comprehensive clinical guidance (1).

A few of the new detection technologies are summarised that have already been adopted or that may find applications in COVID-19, and the kinds of technologies that have been employed in commercial products. The concept of “intelligent medicine” for infectious epidemics is conceived to offer more options for anti-infectious disease management now or in the future (1).

EPIDEMIOLOGY

SARS-CoV-2 originated from China had spread rapidly to affect rest the world over a period of three-four months. First identified in December 2019 in Wuhan, China produced a large cluster of pneumonia cases initially called as the ‘Wuhan Virus’. Subsequently-named as the 2019-novel coronavirus (2019-nCoV). On 11^th February 2020, World Health Organisation (WHO) announced the official name ‘COVID-19’ for this new coronavirus disease also renamed the virus as SARS-CoV-2. On 11^th March 2020, WHO declared it as a global pandemic and India was one among those countries where the COVID-19 pandemic had a slower growth curve to reach its peak. Globally, as 15^th July 2022, there have been 557,917,904 confirmed cases of COVID-19, including 6,358,899 deaths, reported to WHO. As of 11^th July 2022, a total of 12,130,881,147 vaccine doses have been administered. Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2)-coronaviruses have been identified (4).

The WHO was informed by South Africa on November 24, 2021, of a new COVID-19 variant, omicron (B1.1.529). The first detection of omicron (B.1.1.529) occurred on November 11, 2021, in Botswana and on November 14, 2021, in South Africa (5).

TRANSMISSION

Primarily transmitted via respiratory droplets and contact routes.

Droplet and aerosol transmission: Occurs when a person is in close contact (within one meter) with an infected person. Occurs through coughing, sneezing or very close personal. Use of mask can prevent droplet transmission. Spread of the infected droplet nuclei beyond one meter-not documented yet. Specific settings in which aerosol-generating procedures are performed (e.g. endotracheal intubation), aerosol transmission of the COVID-19 virus may be possible. Use of N95 respirator-important to prevent this type of transmission.

Contact transmission: COVID-19 virus can spread directly via contact with infected people, or indirectly. In direct or indirect contact, the virus can only be transmitted by touching the contaminated surfaces and those who already infected. Frequent hand hygiene following potential contact exposure is crucial to prevent this type of transmission.

Presymptomatic transmission: Defined as the transmission of the COVID-19 virus from a person who is infected and shedding the virus but has not yet developed symptoms. Observed in people 1-3 days before the onset of their symptom (4).

Vertical transmission: The high expression of Angiotensin Converting Enzyme-2 (ACE-2) receptors in the human maternal-foetal interphase may allow COVID-19 to be transmitted vertically. People suffered with COVID-19 in pregnancy are at high-risk for complications that can affect the pregnancy and the developing embryo. For example, COVID-19 during pregnancy increases the risk of delivering a preterm (earlier than 37 weeks) and/or a stillborn infant. When comparing pregnant women in pre-Delta period aged 15-44 (January 1, 2020-June 26, 2021) with those in the Delta period (June 27, 2021-December 25, 2021), it was observed that,

• The risk of admission to an Intensive Care Unit (ICU) was 41% higher in the Delta period.
• The risk of invasive ventilation or Extracorporeal Membrane Oxygenation (ECMO) was 83% higher in the Delta period.
• The risk of death in the Delta period was 3.3 times the risk in the pre-Delta period.

The emergence of the Delta variant in June of 2021 in pregnant people was associated with severe outcomes including a rise in ICU admissions, an increase in required medical interventions such as invasive ventilation and ECMO, and an increased mortality that was previously seen in the pre-Delta period (January 1, 2020-June 26, 2021).

DIAGNOSIS OF COVID-19

Clinical symptoms: COVID-19 patients have reported mild to severe symptoms ranging from flu-like symptoms to other severe illnesses. There may be 2-14 days between exposure to the virus and the onset of symptoms. COVID-19 may be present in people with these symptoms (5). Most common symptoms are fever, cough, tiredness, loss of taste or smell. Less common symptoms are sore throat, headache, aches and pains, diarrhoea, a rash on skin, or discolouration of fingers or toes, red or irritated eyes. Serious symptoms are difficulty breathing or shortness of breath, loss of speech or mobility, or confusion, chest pain. If patient presents with serious symptoms, seek medical attention immediately. Before visiting the doctor, always call ahead. Mild symptoms should be managed at home by people who are otherwise healthy. An infection with the virus typically takes 5-6 days to manifest its symptoms, but it can take up to 14 days (5).

LABORATORY DIAGNOSIS

Non specific Laboratory test: Test for COVID-19 cases include Complete Blood Count (CBC),C-reactive Protein (CRP), Random Blood Sugar Test (RBS), Haemoglobin A1C (HbA1C), D-Dimer, Lactate Dehydrogenase (LDH), Serum Ferritin, High-Resolution Computed Tomography (HRCT) Chest on day five of symptom onset tests related to pre-existing illness Repeat CBC/Liver Function Test (LFT)/Renal Function Test (RFT)/Electrolytes/CRP/D-Dimer every 72 hours case based: Procalcitonin, Interleukin-6 (IL6), AQT Panel, Arteria Blood Gas (ABG) (6),(7).

Monitoring: Clinical: Haemodynamic, work of breathing, change in O₂ requirement, Serial: chest X-Ray (CXR)/HRCT if worsening, Lab: CRP, D-Dimer 48-72 hourly, CBC, Electrolytes, Kidney function test KFT, LFT 24-48 hourly, IL6 if patient deteriorating (6),(7).

Specific Test

RT PCR Test: A COVID-19 diagnosis is based primarily on epidemiological data, clinical symptoms, as well as some adjuvant technologies, such as nucleic acid detection and immunological testing. In addition, in order to ensure personnel safety, SARS-CoV-2 isolation requires high-throughput equipment (biosafety level-2) (8). In order to diagnose COVID-19, the virus responsible for the pandemic, SARS-CoV-2, is analysed for its RNA. It is possible to detect specific sequences of genes encoding the RdRP, N, E, and S proteins of viruses using RT-PCR (8).

Heating methods that do not require extraction, such as those that lyse viral particles to release RNA for subsequent analysis, are more convenient and suitable for point-of-care testing (9).

The genes encoding N, E, and S proteins, open reading frame 1ab (Orf1ab), and RdRP are targets for the detection of SARS-CoV-2. It is important to choose the targets carefully, since the E gene is highly conserved throughout all beta coronaviruses while the N gene is cross-reactive with other coronaviruses. SARS-CoV-2 can be distinguished from SARS-CoV by analyzing its RdRP gene. The S gene is also useful for distinguishing SARS-CoV-2 from other coronaviruses because of its high divergence (10).

Cycle Threshold (CT) values less than 40 are considered positive for SARS-COV, while CT values of 40 or more are considered negative for SARS-COV (11).

It is recommended that commercial RT-PCR-based tests be used under Biosafety Level 2 conditions, under notification of Drug Controller General of India (DCGI) and Ministry of Health and Family Welfare (MoH and FW), with appropriate biosafety precautions. Indian Council of Medical Research (ICMR) also validates commercial testing kits (RT-PCR, CRISPR, NAAT, Rapid antigen, IgG ELISA etc.) before they are used in mass testing. The tests are validated at the National Institute of Virology (NIV), Pune, and at 14 other ICMR-approved validation centers (12).

CLINICAL MANAGEMENT

Clinical Severity of COVID-19 (13)

Mild disease: Iinfluenza-Like Illness (ILI): Patients with uncomplicated upper respiratory tract infection with mild symptoms (fever, cough, sore throat, nasal congestion, malaise, headache without evidence of breathlessness or hypoxia).

Moderate disease: Pneumonia with no signs of severe disease-dyspnoea, fever and cough hypoxia, SpO₂<94%, respiratory rate ≥24 per minute.

Severe disease: Called as severe acute respiratory illness (SARI).

Severe pneumonia: Clinical signs of pneumonia plus one of the following sign of severe respiratory distress: (i) Respiratory rate>30/min or (ii) SpO₂<90%.

Acute Respiratory Distress Syndrome (ARDS): Symptoms: Onset of new or worsening respiratory symptoms within one week. Chest imaging: Shows bilateral opacities, not fully explained by effusions, lobar or lung collapse, or nodules decreased PaO₂/FiO₂ (normal value?500): ARDS can be classified into-mild (<300), moderate (<200), and severe (<100); (when Positive End Expiratory Pressure (PEEP) or Continuous Positive Airway Pressure (CPAP) is maintained at ≥5 cm H₂O).

Sepsis: Acute life-threatening multiorgan dysfunction: Clinically diagnosed by Sequential Organ Failure Assessment (SOFA) score.

Septic shock: Persisting hypotension despite volume resuscitation, requiring vasopressors to maintain mean arterial pressure ≥65 mm Hg and serum lactate level >18 mg/dL (Table/Fig 1) shows clinical management in Mahatma Gandhi University of Medical Sciences, Jaipur, Rajasthan, India (6),(14).

VACCINATION

SARS-CoV-2 vaccines are targeting the viral S glycoprotein. The coronavirus was also the target for the development of vaccines against other coronaviruses, and attempts were made in the past to develop vaccines against SARS and MERS based on S glycoproteins (15). In viral replication, the S glycoprotein is responsible for binding to the ACE-2 receptor on the host cell, as well as fusion of the host cell membrane with the viral membrane. Therefore, it is believed that vaccines based on S glycoproteins should elicit antibodies that block viral genome attachment and uncoating from receptors (16). The S glycoprotein’s immunogenicity and ability to bind to the ACE2 receptor are not affected by the presence or absence of other viral glycoproteins, making it a strong candidate for vaccine development (17). There is also consideration of developing a ‘pan-CoV’ vaccine due to the genetic homogeneity among coronaviruses. There is evidence that the S glycoproteins of SARS-CoV-1 and SARS-CoV-2 contain different residues; as a result, antibodies produced against SARS-CoV-1 may not be effective against SARS-CoV-2 (18).

The COVID-19 vaccine is currently approved for full use by six countries and authorised for limited use by another six (19). Details on each of the approved/authorised vaccines are provided in (Table/Fig 2) (20),(31). The vaccines are inactivated, recombinant adenovirus vaccines (human and nonhuman), and novel mRNA vaccines. There has been considerable evidence that many of these vaccines offer significant protection against severe COVID-19 (often up to 100%), and to a lesser degree, symptomatic COVID-19. The side effects of these vaccines are generally mild to moderate and acute (20),(21),(22),(23),(24),(25),(26),(27),(28),(29),(30),(31). However, there is no data on their long-term efficacy or effectiveness in preventing transmission (sterilising immunity).

Conclusion

The COVID-19 pandemic is becoming more severe, with an increase in infections and deaths. The pandemic prompts the use of off-label or consideration of pharmacologic treatments throughout the world. Various drugs were recommended for treating patients with COVID-19 infection.

In most of the guidelines, these drug classes were mentioned, either with compressions on their use or with restrictions for their use only in clinical trials. Generally, there is a big difference between these guidelines. These included indications for using drugs, types of drugs, dosage regimen, period of treatment, and safety of use among different patient groups. The recommendations for the treatment with these drugs in all of the guidelines differ depending on the severity of the case and the health conditions of the patient.

DOI and Others

DOI: 10.7860/JCDR/2022/57182.16909

Date of Submission: Apr 19, 2022
Date of Peer Review: May 13, 2022
Date of Acceptance: Jul 23, 2022
Date of Publishing: Sep 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? NA
• For any images presented appropriate consent has been obtained from the subjects. NA

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ETYMOLOGY: Author Origin