Recent Developments on Therapeutic and Diagnostic Approaches for COVID-19

Abstract

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious public health threat worldwide with millions of people at risk in a growing number of countries. Though there are no clinically approved antiviral drugs and vaccines for COVID-19, attempts are ongoing for clinical trials of several known antiviral drugs, their combination, as well as development of vaccines in patients with confirmed COVID-19. This review focuses on the latest approaches to diagnostics and therapy of COVID-19. We have summarized recent progress on the conventional therapeutics such as antiviral drugs, vaccines, anti-SARS-CoV-2 antibody treatments, and convalescent plasma therapy which are currently under extensive research and clinical trials for the treatment of COVID-19. The developments of nanoparticle-based therapeutic and diagnostic approaches have been also discussed for COVID-19. We have assessed recent literature data on this topic and made a summary of current development and future perspectives.

Keywords: ARDS; anti-SARS-CoV-2 antibody; antiviral drugs; antiviral vaccines; convalescent plasma therapy; immunotherapy; nanotherapeutics.

Fig. 1

Human coronavirus. a Schematic structure of SARS-CoV-2 virus. b A transmission electron microscope image of SARS-CoV-2 spherical viral particles in cell. The virus is colorized in blue. Adapted from the US Centers for Disease Control. Reproduced with permission from (16)

Fig. 2

Overview of the coronavirus replication cycle (simplified, not to scale). The figure depicts viral development from initial binding and release of viral genome to eventual exocytosis of the mature virion. ERGIC, endoplasmic reticulum-Golgi intermediate compartment (also referred to as vesicular-tubular cluster). Drawn using a template retrieved from (18)

Fig. 3

Proposed therapeutic treatments for COVID-19. a, b Targeting viral entry mechanism. a Viral entry mechanism of SARS-CoV-2. b Possible approaches for blocking ACE2 receptors. c Antiviral drugs targeting the coronavirus replication cycle (simplified). Abbreviations: ACE2, angiotensin-converting enzyme 2; scFvs, recombinant human single-chain variable region fragments against the S1 domain of spike (S) protein of the SARS-CoV; ACE2-Fc, immunoglobulin fragment (Fc)-ACE2 fusion protein

Fig. 4

Acute Immune responses to coronaviruses. Coronaviruses are RNA viruses, some of which can infect human lung epithelium via the receptor ACE2 (1). After endocytosis (2), viral RNA activates endosomal and cytoplasmic sensors, TLR3/7 and MAVS, respectively (3). These receptors activate interferon regulatory factors (IRFs) and NFkB (4) to induce inflammatory cytokines (5), including interferons (IFNs). Dendritic cells (DCs) sample antigen and migrate to lymphoid organs to prime adaptive immunity. CD8 T cells recognize of antigen on DCs or infected cells (6) and induce apoptosis in affected lung epithelial cells (7)

Fig. 5

Common components of vaccines. Vaccines include various components such as active ingredients, adjuvants, antibiotics, stabilizers, preservatives, and traces of residual inactivating agents as schematically shown here

Fig. 6

Clinical phase vaccine candidates for COVID-19 (as of April, 2020). Based on data from (36)

Fig. 7

A typical procedure of COVID-19 diagnostics through RT-PCR. The RT-PCR method involves sample collection and extraction of viral RNA sample. The extracted RNA sample is converted to its complementary DNA (cDNA) by the reverse transcription. Finally, the amplification of this DNA sample is performed in qPCR, and the viral cDNA is detected by a fluorescent signal

Fig. 8

Assay techniques and tests for COVID-19 diagnosis. a, b The enzyme-linked immunosorbent assays (ELISA) detecting COVID-19 antibodies (a) or antigens (b). Redrawn with permission from (155). c Serologic diagnostic tests for COVID-19 antibodies

Fig. 9

Representative chest CT images. a Transverse chest CT images from a 40-year-old man showing bilateral multiple lobular and subsegmental areas of consolidation on day 15 after symptom onset. b Transverse chest CT images from a 53-year-old woman showing bilateral ground-glass opacity and subsegmental areas of consolidation on day 8 after symptom onset. c Transverse chest CT images showing bilateral ground-glass opacity on day 12 after symptom onset. Reproduced with permission from (183)