Review Article

Retrospective View of COVID-19 Pandemic: Treatment, Management and Development of Preventive Measures

Petersen Tym S1, El Bayey P1, Brittain A2, Huang A1, Nandagopal V1Singh A1, Scarlett C3, Chin BY4,5, Wong CY4,6*

1University of New South Wales, High Street, Kensington, New South Wales, 2052, Australia

2University of Wollongong, Northfields Ave, Wollongong, New South Wales, 2522, Australia

3University of Newcastle, University Dr, Callaghan, New South Wales, 2308, Australia

4School of Health Sciences, International Medical University, 57000 Kuala Lumpur, Malaysia

5Centre for Cancer and Stem Cell Research, Institute for Research, Development and Innovation, International Medical University, 57000 Kuala Lumpur, Malaysia

6Centre for Environmental and Population Health, Institute for Research, Development and Innovation, International Medical University, 57000 Kuala Lumpur, Malaysia

*Corresponding author: Wong CY, School of Health Sciences; Centre for Environmental and Population Health, Institute for Research, Development and Innovation, International Medical University, 57000 Kuala Lumpur, Malaysia.

Received Date: 19 May, 2023

Accepted Date: 25 May, 2023

Published Date: 01 June, 2023

Citation: Petersen Tym S, El Bayey P, Brittain A, Huang A, Nandagopal V,  et al. (2023) Retrospective View of COVID-19 Pandemic: Treatment, Management and Development of Preventive Measures. Rep Glob Health Res 6: 158. https://doi.org/10.29011/2690-9480.100158.

Abstract

SARS-CoV-2 has held the world hostage over the last 3 years, constantly mutating to elude therapeutic measures, with 765,903,278 documented cases and 6,927,378 deaths as of May 17th, 2023. During this time, biotechnology hastened advancement of preventive measures, with healthcare professionals repurposing the use of existing medications to manage the onslaught of infections and deaths. In this retrospective review, we revisit the emergency use authorization of nascent vaccines, repurposing of non-antiviral medications and stand-by convalescent plasma and immunotherapies while welcoming the development of innovative gene editing tools.


Figure 1: Graphical Abstract summarizing current and emerging biotechnology utilized medically for the prevention, diagnosis, andtreatment of COVID-19. Graphic made with BioRender.com.

Keywords: COVID-19; CRISPR;  Immunotherapy; Management; Prevention; Repurposing; SARS-CoV-2; Treatment; Vaccine.

Introduction

Coronavirus disease 2019 (COVID-19), caused by the pathogenic virus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was first identified in December 2019 [1], ultimately resulting in the largest global health crisis in a century. On March 12, 2020, World Health Organization (WHO) declared COVID-19 a global pandemic [2]. Since then, SARS-CoV-2 has wreaked havoc on global health and economics. At the time of writing (May 17th, 2023), the virus is responsible for over 765 million infections and 6.9 million deaths worldwide [3]. A timeline of SARS-CoV-2 development is shown in Figure 2. 

 

Figure 2: Timeline of major COVID-19 events and the development of SARS-CoV-2. Graphic made with BioRender.com. 

SARS-CoV-2 shares approximately 80% homology with SARS-CoV-1, with the disparity responsible for mutations in the COVID-19 spike protein [4]. SARS-CoV-2 enters through the respiratory tract before attaching to cell surface receptor proteins, like Angiotensin-Converting Enzyme 2 (ACE2), through its homotrimer spike. Following receptor-mediated cell-entry it is directly translated by host ribosomes, particularly in the epithelial linings of the lungs, kidneys, and heart [5].

SARS-CoV-2 mutates rapidly. In February 2020 spike protein mutation A23403G (D614G) emerged, increasing viral fitness and infectivity [6]. The single nucleotide substitution in the spike protein receptor binding domain increased affinity to the ACE2 receptor and heightened its replication in human cells [7]. Rolling genomic mutations continue to affect both broader viral fitness, such as transmissibility and infectivity, and pandemic containment measures such as detection and vaccination [8]. Notable strains include Alpha (B.1.1.7), Beta (B.1.351.), Gamma (P.1) and Delta (B.1.617.2), the latter of which developed a significantly higher viral load (up to 1,200 times greater than the ancestral virus) and a shorter incubation period [9].

The dominant strain Omicron (B.1.1.529), first reported in South Africa in late 2021 [10], was classified as a ‘variant of concern’ (VOC) by WHO from initial detection [11]. Though health outcomes are less severe, it is highly contagious and carries genetic variations causing increased transmissibility and vaccine evasion [12]. One of these genetic variations also leads to ‘S gene dropout’ or ‘target failure’, where one of the genetic sections targeted by  polymerase chain reaction (PCR) testing gives a false negative [13]. Omicron (BA.5) and its subvariants have dominated the sequenced cases lodged with GISAID since May 2022 through the end of the year (85%) [14]. WHO’s most recent variant of interest is Arcturus (XBB.1.16), due to its growth advantage and immune evasion [15]. First discovered in January 2023 in India, it has spread to 31 countries [15].

As of May 17th, 2023, there are 199 vaccines in preclinical development. Eleven vaccines have WHO emergency authorization [16] via four main platforms: mRNA, viral vector, inactivated  and protein subunit.

Repurposing pre-existing drugs for the treatment of SARSCoV-2 is efficient and cost-effective [17].{Singh, 2020 #63} Computational and biological experimental methods can identify approved pharmaceuticals that target specific SARS-CoV-2 mechanisms using molecular docking, signature matching and genome-wide associated studies [18]. Alternatively, experimental methods including assays and phenotypic screening can identify effective drugs [19]. Pre-existing candidates have already undergone risk assessments in both preclinical models and humans, making this significantly more efficient and economical than standard drug development [17, 19]. For example, nirmatrelvir was originally developed for the treatment of hepatitis C, it is now packaged alongside ritonavir as Paxlovid by Pfizer. Phase 3 trials showed that among people with COVID-19 who were at high risk of hospitalization or death, those who received Paxlovid had a 90% lower risk of the above than placebo [20].

Immunotherapeutic approaches have shown clinical benefits in patients with Influenza, SARS, and Middle East Respiratory Syndrome (MERS) [21], suggesting potential for SARS-CoV-2 treatment. However, the complexity of COVID-19’s immune avoidance mechanisms and associated pro-inflammatory events, such as cytokine storm and T cell exhaustion, have prevented isolating a single effective approach. In response to the pandemic’s urgency, the Food and Drug Administration (FDA) authorized emergency use of immunotherapy methods such as recombinant monoclonal antibodies (rMAB) and convalescent plasma (CP) therapy. Alternatively, CP therapy utilizes plasma from recovered COVID-19 patients to impede infection and mitigate hyperactivated immune reaction. Some promising immunotherapeutic approaches are undergoing trials. The most notable are the inhaled interferon β-1α (IFNβ-1α) and peg-interferon λ-1 (peg-IFNλ-1) based immunotherapies, interleukin-6 (IL-6) blockade and Janus kinase (JAK) inhibition [22].

Gene-editing is the most novel technology applied to SARSCoV-2. It has been tailored to virus degradation, detection, and diagnosis [23-25]. The CRISPR/Cas systems have enormous potential due to their precision, efficiency and cost-effectiveness [24]. Figure 3 explains the guide RNA and Cas enzyme process. CRISPR-based diagnostic technologies include endonucleasetargeted CRISPR trans reporter (DETECTR) and Specific Highsensitivity Enzymatic Reporter un-LOCKing (SHERLOCK). As a treatment, CRISPR-Cas13-based strategies such as Prophylactic Antiviral CRISPR in huMAN cells (PAC-MAN) have strong potential for virus degradation in humans [26].