Molecular mechanisms and epidemiology of COVID-19 from an allergist's perspective

Abstract

The global pandemic caused by the newly described severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused worldwide suffering and death of unimaginable magnitude from coronavirus disease 2019 (COVID-19). The virus is transmitted through aerosol droplets, and causes severe acute respiratory syndrome. SARS-CoV-2 uses the receptor-binding domain of its spike protein S1 to attach to the host angiotensin-converting enzyme 2 receptor in lung and airway cells. Binding requires the help of another host protein, transmembrane protease serine S1 member 2. Several factors likely contribute to the efficient transmission of SARS-CoV-2. The receptor-binding domain of SARS-CoV-2 has a 10- to 20-fold higher receptor-binding capacity compared with previous pandemic coronaviruses. In addition, because asymptomatic persons infected with SARS-CoV-2 have high viral loads in their nasal secretions, they can silently and efficiently spread the disease. PCR-based tests have emerged as the criterion standard for the diagnosis of infection. Caution must be exercised in interpreting antibody-based tests because they have not yet been validated, and may give a false sense of security of being "immune" to SARS-CoV-2. We discuss how the development of some symptoms in allergic rhinitis can serve as clues for new-onset COVID-19. There are mixed reports that asthma is a risk factor for severe COVID-19, possibly due to differences in asthma endotypes. The rapid spread of COVID-19 has focused the efforts of scientists on repurposing existing Food and Drug Administration-approved drugs that inhibit viral entry, endocytosis, genome assembly, translation, and replication. Numerous clinical trials have been launched to identify effective treatments for COVID-19. Initial data from a placebo-controlled study suggest faster time to recovery in patients on remdesivir; it is now being evaluated in additional controlled studies. As discussed in this review, till effective vaccines and treatments emerge, it is important to understand the scientific rationale of pandemic-mitigation strategies such as wearing facemasks and social distancing, and implement them.

Keywords: ACE2; COVID-19; TMPRSS2; allergic rhinitis; asthma; receptor-binding domain; severe acute respiratory syndrome coronavirus 2.

Fig 1

A, Structure of RBD of spike protein S1 of SARS-CoV-2 bound to ACE2. Structure of ACE2 bound to the RBD of the S1 spike protein of SARS-CoV-2., , The chimeric RBD is in orange, and human ACE2 is in green. The figure was created with Research Collaboratory for Structural Bioinformatics Protein Data Bank (https://www.rcsb.org/). RBD, RBD of S1 spike protein of SARS-CoV-2. B, Cartoon showing how SARS-CoV-2 binds to the lung epithelial cells. SARS-CoV-2 has a spike protein with transmembrane (TM), S1 and S2 part. S1 part has an RBD. The virion uses the spike protein S1 to attach with RBD of the host ACE2 receptor on the cell membrane with the help of the cellular TMPRSS2. Following attachment of S1 to ACE2, the host serine protease TMPRSS2 cleaves the S2 protein from S1, and plays a role in membrane fusion of CoVs. The figure was created using BioRender (https://biorender.com/). C, The prevalence of asthma in patients hospitalized for COVID-19 in United States. Data were extracted from April 8, 2020, MMWR report and Centers for Disease Control and Prevention. The total length of each bar represents the prevalence rates of COVID-19 in each age group. The length of the blue part of this bar is the expected prevalence rate of asthma in each age group. The orange part represents the prevalence rate of COVID-19 in excess of the expected prevalence rate of asthma in each age group.

Fig 2

Treatment strategies for COVID-19. A, Drugs that are designed to block entry of SARS-CoV into the cells. B, Drugs that act at different steps of virus replication inside the cell. The figure shows 8 steps from viral entry to virus release in airway epithelial cells. After fusion to the host cell, the viral genome RNA is released into the cytoplasm. The uncoated RNA translates pp1a and pp1ab polyproteins, and the replication-transcription complex replicates RNA for assembly and virus release. The figure was created using BioRender (https://biorender.com/). ERGIC, Reticulum-Golgi intermediate compartment; MDA5, melanoma differentiation-associated protein 5; NSP, nonstructural protein; OAS, 2'-5' oligoadenylate synthetase; PKR, protein kinase R; pp1a, polyprotein1a; pp1ab, polyprotein1ab; TLR9, Toll-like receptor 9.