Issue 2: Basic science of SAR2-CoV-2 (MARCH 12, 2020)

VIRUS DESCRIPTION

  • The SARS-CoV-2 or COVID-19-virus is a novel beta-coronavirus, and is the fifth of this group to be identified1.
  • To date, two active strains have been characterized: the  less-aggressive ancestral S strain and the evolved, prevalent variant L strain; the latter accounts for ~70%  of cases2.
  • The genomic sequences of SARS-CoV-2 viruses isolated from a number of patients share sequence identity higher than 99.9%, suggesting a very recent host shift into humans; where pangolins possibly provided a partial spike gene (S) to SARS-CoV-23,4.

BASIC SCIENCE

  • The SARS-CoV-2 binds to the angiotensin converting enzyme II (ACE2) via the receptor binding domain of the  S protein, where membrane fusion  and entry into human cells is initiated 1.

INCUBATION PERIOD

  • A pooled analysis of COVID-19 cases reported a median incubation time of 5.1 days, and 97.5% of cases developed within  11.5 days (95% CI: 8.2-15.6 days). Conservatively therefore, 101 out of every 10,000 cases (99th percentile, 482) will develop symptoms after 14 days of active monitoring or quarantine5.
  • Another recent, but small, study suggests that the serial interval (i.e., time between disease onset in direct infector-infectee pairs) is shorter, at 4.0 days6.
  • Notably, virus reproduction follows exponential growth with a reproduction number  between 2.24-3.587.

TESTING

  • Confirmation of cases of COVID-19 is based on detection of unique sequences of virus RNA by nucleic acid amplification tests (NAAT) such as real-time reverse transcription polymerase chain reaction (rRT-PCR)  and confirmation by nucleic acid sequencing when necessary8.
  • Viral genes targeted so far include the N, E, S and RdRP genes.
  • A negative test does not necessarily rule out COVID-19 infection.  Assessment of overall specimen quality and repeat testing may be warranted8.
  • At minimum, respiratory material should be collected from upper respiratory specimens: nasopharyngeal and oropharyngeal swab or wash in ambulatory patients; and/or lower respiratory specimens from sputum (if produced) and/or endotracheal aspirate or bronchoalveolar lavage in patients with more severe respiratory disease8.

POTENTIAL  THERAPIES

  • There are no specific therapies directed at SARS-CoV-2, but broad-spectrum antiviral agents such as remdesivir have shown good effects9.
  • Several clinical trials are being conducted in China to assess efficacy of LPV/RTV and 157 IFNα-2b  or chloroquine in hospitalized  COVID-19 patients.

REFERENCES:

  1. https://www.cdc.gov/coronavirus/types.html Accessed March 12, 2020
  2. Tang et al. National Science Review, nwaa036
  3. Lu et al. . Lancet. 2020. Epub 2020/02/03. doi: 10.1016/S0140-6736(20)30251-8. PubMed PMID: 32007145
  4. Xiao et al., bioRxiv. 2020:2020.02.17.951335. doi: 10.1101/2020.02.17.951335.
  5. Lauer et al., Ann Intern Med. 2020. DOI: 10.7326/M20-0504
  6. Nishiura et al., Int. J Infect Dis. 2020. https://www.sciencedirect.com/science/article/pii/S1201971220301193?via%3Dihub
  7. Zhao et al., Int. J Infect Dis 92:214-217; 2020
  8. WHO website, Accessed Mar 12, 2020
  9. Martinez. https://aac-asm-org.libproxy.lib.unc.edu/content/aac/early/2020/03/03/AAC.00399-20.full.pdf