Characteristics of SARS-CoV-2

Coronaviruses (Coronaviridae, of the order Nidovirales) are large, single stranded RNA viruses.^56,57 Currently, there are four known genera of coronaviruses: α-CoV, β-CoV, γ-CoV, and δ-CoV.^58,59 Coronaviruses have been identified as the causative agents of diseases in humans and other vertebrates. In particular, it is estimated that 15-35% of common cold cases are caused by coronaviruses.⁶⁰ SARS-CoV-2 belongs to the β-COV family, which along with α-CoV viruses, are known to infect a variety of mammals and humans.^{49,53,54,56,61,62} SARS-CoV-2 possesses an ultrastructure typical of other coronaviruses, namely a membrane envelope with multiple “spike glycoprotein” (S-protein) extensions (Figure 1).⁶³ The viral capsule has also been found to express other polyproteins, nucleoproteins, and membrane proteins, including specifically RNA polymerase, 3-chymotrypsin-like protease, papain-like protease, helicase, glycoprotein, and accessory proteins.^7,63,64 The S-proteins from coronaviruses binds to receptors on host cells to facilitate viral entry into the target cells. For SARS-CoV-2 the target receptor is the human angiotensin-converting enzyme 2 receptor (ACE2).^65-68 Affinity for the ACE2 receptor is postulated to explain increased viral loads seen in older individuals, since ACE2 expression increases with age.⁶⁹

Figure 1. Diagram of the ultrastructure of the SARS-CoV-2 virus.¹⁰⁵

Figure 1. Diagram of the ultrastructure of the SARS-CoV-2 virus.¹⁰⁵

It is well-established that RNA viruses have higher rates of mutation than DNA-viruses.⁷⁰ On a per-site level, DNA viruses typically have mutation rates on the order of 10⁻⁸ to 10⁻⁶ substitutions per nucleotide site per cell infection (s/n/c). RNA viruses have mutation rates that range between 10⁻⁶ and 10⁻⁴ s/n/c. Given this rapid mutation rate, RNA viruses with high rates of pathogenicity are able generally to develop and propagate more frequently in the environment.⁷⁰ It should also be noted that an evolutionary advantage for a mutating pathogen includes increasing infectivity and decreasing virulence and/or longer latency periods to allow for increased replication rates. Data suggest that coronavirus variants differ in thermal stability, replication rate, and size, which may influence their transmissibility.⁷¹ The reproduction number (R₀) of SARS-CoV-2 has been estimated to be between 1.5-6.49 with a median value of 2.78.⁷² As variants changed during the pandemic an adjusted R₀ of 1.86 for COVID-19 cases and 1.34 for excess COVID-19 deaths.⁷³ This R₀ is greater than that of SARS-CoV-1 (median R₀=1.3)⁷⁴ and H1N1 influenza (median R₀=1.46),⁷⁵ but less than that of measles (median R₀=16.1).⁷⁶

SARS-CoV-2 shares numerous similarities with SARS-CoV-1 [the causative agent in the severe acute respiratory syndrome (SARS) outbreak in 2002-2003], but there are some significant differences. Both originated in China and both demonstrate stability in the environment. In an in vitro study, SARS-CoV-2 was detectable in aerosols for up to three hours, up to four hours on copper, up to 24 hours on cardboard and up to two to three days on plastic and stainless steel.⁷⁷ However, while SARS-CoV-1 was eradicated by intensive contact tracing and case isolation measures and no cases have been detected since 2004.⁷⁸ SARS-CoV-2 has proven to be significantly more difficult to eradicate. Emerging evidence suggests that asymptomatic people infected with SARS-CoV-2 are able to transmit the virus prior to onset of symptoms.⁷⁹ This occurrence of asymptomatic transmission decreases the effectiveness of symptom screening and disease control measures that were effective against SARS-CoV-1.⁷⁹

Both SARS-CoV-2 and SARS-CoV-1 viruses demonstrate binding affinity to the ACE2 receptor to enter host cells. However, the S-proteins from SARS-CoV-2 are less stable than those of SARS-CoV-1 and polyclonal anti-SARS S1 antibodies that inhibit entry of SARS-CoV-1, are not effective against SARS-CoV-2 pseudovirions.⁸⁰ Further studies using recovered SARS and COVID-19 patients’ sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other, but there does seem to be some protection from previous SARS-CoV-2 infections, even with infections across viral variants. ^80,81