The animal origin of SARS-CoV-2

  1. Authors: Spyros Lytras1, Wei Xia2, Joseph Hughes1, Xiaowei Jiang3, David L. Robertson1
  2.  See all authors and affiliationsScience  27 Aug 2021:Vol. 373, Issue 6558, pp. 968-970
  3. DOI: 10.1126/science.abh0117

Although first detected in December 2019, COVID-19 was inferred to be present in Hubei province, China, for about a month before (1). Where did this new human disease come from? To understand the origin of the COVID-19 pandemic, it is necessary to go back to 2002. At that time a novel respiratory coronavirus appeared in Foshan, Guangdong province, China, and spread to 29 countries (2). Altogether ∼8000 people were infected with severe acute respiratory syndrome coronavirus (SARS-CoV) before public health measures controlled its spread in 2003. The zoonotic origin of SARS-CoV was subsequently linked to live animals available at markets. Further sporadic spill-over events of SARS-CoV from animals took place in Guangzhou, Guangdong, and some researchers working with cultured virus were infected in laboratory accidents (3), but ultimately SARS-CoV was removed from the human population. Trading of susceptible host animals is an important common theme in the emergence of SARS and COVID-19.

Three years after the SARS epidemic began, investigations revealed that horseshoe bats (Rhinolophus) in China were harboring related coronaviruses (4). These collectively form the species SARS-related coronavirus (SARSr-CoV), which comprises the Sarbecovirus subgenus of the Betacoronavirus genus. It was inferred that a sarbecovirus circulating in horseshoe bats seeded the progenitor of SARS-CoV in an intermediate animal host, most probably civet cats (3). Although other possible intermediate hosts for SARS-CoV were identified, in particular raccoon dogs and badgers (for sale with civet cats in animal markets), it is a population of civet cats within markets that appear to have acted as the conduits of transmission to humans from the horseshoe bat reservoir of SARS-CoV, rather than civet cats being a long-term reservoir host species. Presumably a captive civet cat initially became infected by direct contact with bats—e.g., as a result of bats foraging in farms or markets—or was infected prior to capture. Following the SARS epidemic, further surveillance revealed the immediate threat posed by sarbecoviruses from horseshoe bats. Despite this clear warning, another member of the SARSr-CoV species, SARS-CoV-2, emerged in 2019 that spread with unprecedented efficiency among humans. There has been speculation that the Wuhan Institute of Virology (WIV) in Hubei was the source of the pandemic because no SARS-CoV-2 intermediate host has been identified to date and owing to the WIV’s geographic location.

SARS-CoV-2 first emerged in Wuhan city, which is >1500 km from the closest known naturally occurring sarbecovirus collected from horseshoe bats in Yunnan province, leading to an apparent puzzle: How did SARS-CoV-2 arrive in Wuhan? Since its emergence, sampling has revealed that coronaviruses genetically close to SARS-CoV-2 are circulating in horseshoe bats, which are dispersed widely from East to West China, and in Southeast Asia and Japan (5). The wide geographic ranges of the potential reservoir hosts—for example, intermediate (R. affinis) or least (R. pusillus) horseshoe bat species, which are known to be infected with sarbecoviruses—indicate that the singular focus on Yunnan is misplaced (5). Confirming this assertion, the evolutionarily closest bat sarbecoviruses are estimated to share a common ancestor with SARS-CoV-2 at least 40 years ago (5), showing that these Yunnan-collected viruses are highly divergent from the SARS-CoV-2 progenitor. The first of these viruses reported by WIV, RaTG13 (6), is certainly too divergent to be the SARS-CoV-2 progenitor, providing key genetic evidence that weakens the “lab-leak” notion. Additionally, three other sarbecoviruses collected in Yunnan independently of the WIV are now the closest bat coronaviruses to SARS-CoV-2 that have been identified: RmYN02, RpYN06, and PrC31 (see the figure).

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What is OC43?

Authors: By Benedette Cuffari, M.Sc.Reviewed by Emily Henderson, B.Sc.

In an effort to further understand and predict the health effects that can arise following infection by SARS-CoV-2, which is the infection that causes the disease COVID-19, many researchers have reevaluated the pathogenesis associated with coronaviruses that have already been identified. One type of coronavirus that has infected individuals around the world is HCoV-OC43.

A history of coronaviruses

In 1965, the first human coronavirus (HCoV) strain, which was eventually named B814, was identified from a patient’s nasal discharge. Since then, over 30 different HCoV strains have been isolated, the most notable of which include HCoV-229E, HCoV-NL63, HCoV-HLU1, and HCoV-0C43.

In addition to the aforementioned human-infecting coronavirus strains, several highly pathogenic zoonotic strains such as the severe acute respiratory syndrome coronavirus (SARS-CoV) of 2002, the Middle East respiratory syndrome coronavirus (MERS-CoV) of 2011 and the novel coronavirus COVID-19 that has, as of June 18, 2020, infected 8.24 million people and claimed the lives of over 446,000 thousand individuals around the world.

Classification of HCoV-OC43

Within the virus order of Nidiovirules is the suborder of Cornidovirineae. Within Cornidovirineae are two subfamilies known as Letovirinae and Orthocoronairinae.

All coronaviruses are within the subfamily of Orthocornavirinae; however, specific coronavirus strains can be further classified into one of four genera including Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. Whereas HCoV and HCoV-NL63 are found in the Alphacoronavirus genus, HCoV-OC43, as well as HCoV-HKU1, MERS-CoV, SARS-CoV and SARS-CoV-2 are all classified within the Betacoronavirus genus.

How does HCoV-OC43 enter cells?

The entry of HCoV-OC43 into human cells is largely achieved through the caveolin-1-dependent pathway of endocytosis; however, virus-containing vesicles at the cell surface can also undergo scission to also penetrate human cells.

Notably, while host factors like interferon-inducible transmembrane proteins (IFITMs) often prevent the entry of coronaviruses like HCoV-229E, -NL63, SARS-CoV and MERS-CoV from entering cells through its various antiviral functions, IFITM2 and IFITM3 promote the entry and subsequent infection of HCoV-OC43 into human cells.

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COVID-19: an update and cardiac involvement

Authors: Nizar R. Alwaqfi & Khalid S. Ibrahim 


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through angiotensin converting enzyme 2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, and also causing acute cardiac injury and chronic damage to the cardiovascular system. The purpose of this review is primarily reviewing the COVID-19 disease, including pathogen, clinical features, diagnosis, and treatment with particular attention to cardiovascular involvement based on the current evidence. COVID-19 remains a threat to global public health. The associated extra-pulmonary manifestations and their prolonged consequences are frequently overlooked. Pre-existing cardiovascular disease or acute cardiac complications may contribute to adverse early clinical outcome. At the moment, there is no specific treatment for COVID-19, but multiple randomized controlled trials (RCT) are being conducted. New supportive therapies are being evaluated with promising results.


In the last two decades the family coronaviruses (CoVs) was responsible for two severe epidemics of zoonotic origin. In 2003 a mysterious pneumonia, originated from southeast China, caused by a new CoV and was named severe acute respiratory syndrome CoV (SARS-CoV), it infected more than 8000 with a mortality rate around 10–15% with no available proper treatment or vaccination. Then emergence of another outbreak in 2012 in the Middle East of a novel CoV called Middle East respiratory syndrome CoV (MERS-CoV), it infected 857 cases with 35% mortality rate [1,2,3].

In late December 2019, an outbreak of a mysterious pneumonia happened in a seafood wholesale wet market, the Huanan Seafood Wholesale Market, in Wuhan, Hubei, China [45]. The underlying causative agent of this outbreak was identified as a novel coronavirus, that was named severe acute respiratory syndrome CoV 2 (SARS-CoV-2) and the disease related to it as CoV disease 2019 (COVID-19) by the World Health Organization (WHO). Later, WHO named this pathogenic virus for 2019-nCoV [67]. The market was closed on 1 January 2020 [5]. SARS-CoV-2 genetic sequence was shared publicly on 11–12 January, it is an enveloped virus with a genetic material made up of a positive–sense single–stranded RNA [58]. On march 11, 2020 WHO declared COVID-19 a pandemic disease and by May 12, 2020 the virus has spread to more than 200 countries worldwide with more than 4 million cases and more than 283 thousand deaths [5]. Till now, all available evidence for COVID-19 suggests that SARS-CoV-2 has a zoonotic origin in bats and not a laboratory construct [5].

Many literature reported the clinical features, virology, pathophysiology, epidemiology, and radiology of COVID-19, but the comprehensive review is few. And although COVID-19 is predominantly a respiratory disease, some patients develop severe cardiovascular disease [1]. In addition, patients with underlying cardiovascular disease might have an increased risk of mortality [1]. The purpose of this review is to summarize the current literature on COVID-19 disease, including pathogen, clinical features, diagnosis, and treatment based on the current evidence, with emphasis on understanding the mechanisms of cardiac involvement, cardiac complications, so that treatment of these patients can be timely and effective and mortality reduced.

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The Severe Acute Respiratory Syndrome

Authors: Joseph S.M. Peiris, M.D., D.Phil., Kwok Y. Yuen, M.D., Albert D.M.E. Osterhaus, Ph.D., and Klaus Stöhr, Ph.D.

The severe acute respiratory syndrome (SARS) is responsible for the first pandemic of the 21st century. Within months after its emergence in Guangdong Province in mainland China, it had affected more than 8000 patients and caused 774 deaths in 26 countries on five continents. It illustrated dramatically the potential of air travel and globalization for the dissemination of an emerging infectious disease and highlighted the need for a coordinated global response to contain such disease threats. We review the cause, epidemiology, and clinical features of the disease.


An unusual atypical pneumonia emerged in Foshan, Guangdong Province, mainland China, in November 2002.1,2 In February and March 2003, the disease spread to Hong Kong and then to Vietnam, Singapore, Canada, and elsewhere (Table 1).3,4 The new disease was named the severe acute respiratory syndrome (SARS), and a preliminary case definition was established.4 A novel coronavirus (SARS-CoV) was identified as the causative agent.5-10 Coronaviruses are a family of enveloped, single-stranded–RNA viruses causing disease in humans and animals, but the other known coronaviruses that affect humans cause only the common cold.

The presence of SARS-CoV has been demonstrated by reverse-trancriptase polymerase chain reaction (RT-PCR) and the isolation of the virus from respiratory secretions, feces, urine, and tissue specimens from lung biopsy,11,12 indicating that the infection is not confined to the respiratory tract. The experimental infection of cynomolgus macaques with SARS-CoV produced a pneumonia that was pathologically similar to SARS in humans.8,9 Other pathogens, including human metapneumovirus13,14 and chlamydia,7,15 have been detected together with SARS-CoV in some patients with SARS, but they have not been found consistently.5,9 The experimental infection of macaques with human metapneumovirus did not lead to a SARS-like disease, and coinfection of macaques with human metapneumovirus and SARS-CoV did not enhance the pathogenicity of the SARS-CoV in this animal model.8 Thus, all the information that is available to date suggests that SARS-CoV is necessary and sufficient for the causation of SARS in humans, but it remains to be determined whether microbial or other cofactors enhance the severity or transmissibility of the disease. The complete genetic sequence of the SARS-CoV genome was determined, and it provided confirmation that SARS-CoV belongs to a new group within the coronavirus family.

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