Combating the Coronavirus Pandemic: Early Detection, Medical Treatment, and a Concerted Effort by the Global Community

Abstract

The World Health Organization (WHO) has declared the outbreak of 2019 novel coronavirus, known as 2019-nCoV, a pandemic, as the coronavirus has now infected over 2.6 million people globally and caused more than 185,000 fatalities as of April 23, 2020. Coronavirus disease 2019 (COVID-19) causes a respiratory illness with symptoms such as dry cough, fever, sudden loss of smell, and, in more severe cases, difficulty breathing. To date, there is no specific vaccine or treatment proven effective against this viral disease. Early and accurate diagnosis of COVID-19 is thus critical to curbing its spread and improving health outcomes. Reverse transcription-polymerase chain reaction (RT-PCR) is commonly used to detect the presence of COVID-19. Other techniques, such as recombinase polymerase amplification (RPA), loop-mediated isothermal amplification (LAMP), clustered regularly interspaced short palindromic repeats (CRISPR), and microfluidics, have allowed better disease diagnosis. Here, as part of the effort to expand screening capacity, we review advances and challenges in the rapid detection of COVID-19 by targeting nucleic acids, antigens, or antibodies. We also summarize potential treatments and vaccines against COVID-19 and discuss ongoing clinical trials of interventions to reduce viral progression.

Figure 1

Biological and genomic structure of 2019-nCoV. (a) Classification of coronavirus genera. (b) Schematic structure of 2019-nCoV. (c) The whole-genome structure of 2019-nCoV.

Figure 2

High-throughput sequencing and real-time qRT-PCR-based detection of 2019-nCoV. (a) Four steps of high-throughput sequencing technology. (b) Steps for real-time RT-PCR analysis.

Figure 3

Isothermal amplification of nucleic acids for detecting 2019-nCoV. (a) The mechanism and process of loop-mediated isothermal amplification technology. (b, c) RT-LAMP combination with SYBR Green for detection of 2019-nCoV. The signal of SYBR Green dye was detected with a gel imaging system (b) and was visible with the naked eye under blue light (c). (d) The mechanism and process of recombinase polymerase amplification technology. Adapted and copyright with permission (b, c) [42], medRxiv.

Figure 4

CRISPR-Cas system-based detection of 2019-nCoV. (a) Mechanism of SHERLOCK and DETECTR for 2019-nCoV detection. (b, c) Typical images of lateral flow readout for CRISPR-based detection at various concentrations [60].

Figure 5

Microfluidic-based detection of 2019-nCoV. (a) Design and fabrication of a spiral chip. (b) Operation procedures for sample introduction and partition on the chip. PDMS: polydimethylsiloxane. (c) Raw (upper) and software-extracted images (down) of the chip after nucleic amplification. Adapted and copyright with permission (a–c) [70], American Chemical Society.

Figure 6

Lateral flow assays for detecting 2019-nCoV antigens or antibodies to 2019-nCoV. (a) Diagram showing LFA-based quick detection of 2019-nCoV in an IgM-IgG combined antibody assay. (b) A diagram showing different test results. (c) Representative assay test showing results from blood of different patients. Patient #13: IgM and IgG positive; #14: IgM weak positive; #15: IgM and IgG negative; #16: IgG weakly positive; #17: IgG positive only; #18: IgM positive only. Adapted and copyright with permission (c) [84], Wiley.

Figure 7

Computed tomography and transmission electron microscopy characterizations of 2019-nCoV. (a) Cross-sectional noncontrast enhanced chest CT radiographs of a man's lungs with COVID-19. The figure shows enlarged lesions and increased density of the lesions at the outer edge of the lungs (yellow arrows) [93]. (b) A TEM image of the 2019-nCoV grown in cells at the University of Hong Kong [97].

Figure 8

Proposed schematic of 2019-nCoV replication and potential treatment options targeting the coronavirus replication cycle. ACE2: angiotensin-converting enzyme 2; +: positive-strand RNA; AP: accessory protein; E: envelope protein; ER: endoplasmic reticulum; N: nucleocapsid protein; M: membrane protein; ERGIC: endoplasmic reticulum-Golgi intermediate compartment; S: spike glycoprotein.

Figure 9

Chemical structure of drugs used to treat COVID-19. (a) Chemical structures of entry inhibitors. (b) Chemical structures of protease inhibitors. (c) Chemical structures of replication inhibitors.

Figure 10

Procedures for identifying COVID-19 cases.