SARS-CoV-2: From Structure to Pathology, Host Immune Response and Therapeutic Management

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Abstract

Coronaviruses are large, enveloped viruses with a single-stranded RNA genome, infecting both humans and a wide range of wild and domestic animals. SARS-CoV-2, the agent of the COVID-19 pandemic, has 80% sequence homology with SARS-CoV-1 and 96–98% homology with coronaviruses isolated from bats. The spread of infection is favored by prolonged exposure to high densities of aerosols indoors. Current studies have shown that SARS-CoV-2 is much more stable than other coronaviruses and viral respiratory pathogens. The severe forms of infection are associated with several risk factors, including advanced age, metabolic syndrome, diabetes, obesity, chronic inflammatory or autoimmune disease, and other preexisting infectious diseases, all having in common the pre-existence of a pro-inflammatory condition. Consequently, it is essential to understand the relationship between the inflammatory process and the specific immune response in SARS-CoV-2 infection. In this review, we present a general characterization of the SARS-CoV-2 virus (origin, sensitivity to chemical and physical factors, multiplication cycle, genetic variability), the molecular mechanisms of COVID-19 pathology, the host immune response and discuss how the inflammatory conditions associated with different diseases could increase the risk of COVID-19. Last, but not least, we briefly review the SARS-CoV-2 diagnostics, pharmacology, and future approaches toward vaccine development.

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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chaolin Huang, Yeming Wang, Xingwang Li … (2020)

Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Markus Hoffmann, Hannah Kleine-Weber, Simon Schroeder … (2020)

Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.

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A new coronavirus associated with human respiratory disease in China

Fan Wu, Su Zhao, Bin Yu … (2020)

Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health 1–3 . Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing 4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China 5 . This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.

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Journal

Journal ID (nlm-ta): Microorganisms

Journal ID (iso-abbrev): Microorganisms

Journal ID (publisher-id): microorganisms

Title: Microorganisms

Publisher: MDPI

ISSN (Electronic): 2076-2607

Publication date (Electronic): 24 September 2020

Publication date Collection: October 2020

Volume: 8

Issue: 10

Electronic Location Identifier: 1468

Affiliations

[1 ]Microbiology Immunology Department, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania; mihaescuapelevii@ 123456gmail.com (G.M.); ovidiu.vrancianu@ 123456yahoo.com (C.O.V.); lia_mara_d@ 123456yahoo.com (L.-M.D.); lumi.marutescu@ 123456gmail.com (L.G.M.); gratiela87@ 123456gmail.com (G.G.P.)

[2 ]Research Institute of the University of Bucharest, 050095 Bucharest, Romania

[3 ]National Institute for Research and Development in Microtechnologies—IMT, 077190 Bucharest, Romania; cipi_sil@ 123456yahoo.com

[4 ]Academy of Romanian Scientists, 010071 Bucharest, Romania

[5 ]ENT Department, University of Medicine and Pharmacy Carol Davila and Coltea Clinical Hospital, 020022 Bucharest, Romania; raluca.grigore@ 1234563f.ro (R.G.); berstein@ 123456dr.com (Ș.B.)

[6 ]Institute of Biology, 060031 Bucharest, Romania; cvgmarian@ 123456gmail.com

Author notes

[* ]Correspondence: carmen.chifiriuc@ 123456bio.unibuc.ro

Author information

Ciprian Iliescu https://orcid.org/0000-0001-7042-5248

Corneliu Ovidiu Vrancianu https://orcid.org/0000-0002-2409-0966

Lia-Mara Ditu https://orcid.org/0000-0002-6593-255X

Gratiela Gradisteanu Pircalabioru https://orcid.org/0000-0002-6384-1822

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Publisher ID: microorganisms-08-01468

DOI: 10.3390/microorganisms8101468

PMC ID: 7600570

PubMed ID: 32987852

SO-VID: 34c751a0-d51f-470c-9706-95b7b71a81a0

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

SARS-CoV-2: From Structure to Pathology, Host Immune Response and Therapeutic Management

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Novel Coronavirus Disease COVID-19

Most cited references 128

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

A new coronavirus associated with human respiratory disease in China

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