Etiology

Version 1: 01-04-2020

Virology

  • Outbreak in Wuhan: In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood and wet animal wholesale market in Wuhan, Hubei Province, China.[1] By Jan 7, 2020, the novel beta-coronavirus (CoV) was isolated from patients’ airway epithelial cells.[1]

  • Genome sequencing: SARS-CoV-2 is an RNA virus that is 75–80% identical to the SARS-CoV and 40% identical to the MERS-CoV. [2]

  • Origin: Bats might be the original host of this virus, but an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans.

  • Cell host: SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) receptor on lung epithelial cells.[2,3]

  • Mutations: SARS-COV-2 may mutate to become more or less virulent.4, 5 The estimated mean evolutionary rate for SARS-COV-2 is 1.8 × 10−3 substitutions per site per year. It is predicted that one or more mutations may be selected and sustained during this outbreak.[5] Mutations of surface proteins conferring stability have been shown.[6]

  • 2 subtypes of SARS-COV-2: The L type (~70%) is more prevalent and more aggressive than the S type (~30%), but the S type is the ancestral version. [7]

Transmission

  • Contact and droplet transmission: Person-to-person transmission occurs primarily via direct contact or through droplets spread by coughing or sneezing from an infected individual. [3]

  • Other possible modes of transmission: The virus has been found in stool and blood. [8]

  • Health care–associated transmission: 41% of 138 cases in a study were health care acquired. [9]

  • Asymptomatic transmission: Transmission from asymptomatic carriers appears was reported. [10]

  • No evidence of vertical transmission: A study on 9 women with confirmed COVID-19 who had a caesarean section in their third trimester showed no evidence of transmission from mother to child. Amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients were tested for SARS-CoV-2, and all samples tested negative for the virus. It is unclear whether transmission can occur during vaginal birth. [11]

  • Consequences of perinatal COVID-19 infection: Problems such as fetal distress, premature labor, respiratory distress, thrombocytopenia accompanied by abnormal liver function, and even death were reported in a study on 10 neonates born to mothers with COVID-19. [12]

  • Duration of viral shedding: Median duration of viral shedding was 20.0 days (IQR 17.0–24.0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. [13]

  • Incubation period: In the first 425 patients with confirmed COVID-19, the mean incubation period was 5.2 days (95% CI, 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days.14 Current estimates of the incubation period range from 1 to 14 days with a median of 5-6 days, although recent case reports suggest that the incubation period may be as long as 24 days.[8]

  • The reproductive number (R0): On average, an infected person will infect 2-3 other people, resulting in a higher pandemic potential than SARS. 8 The reproduction number is estimated to range from 2.24 [95% CI 1.96–2.55] to 3.58 (95% CI 2.89–4.39). [15]

  • Aerosol stability: In a recent experiment, SARS-CoV-2 remained viable in aerosols for 3 hours, with a reduction in infectious titer from 103.5 to 102.7 TCID50 per liter of air. This reduction was similar to that observed with SARS-CoV-1, from 104.3 to 103.5 TCID50 per milliliter.[16]

  • Surface stability: SARS-CoV-2 was more stable on plastic and stainless steel than on copper and cardboard, and viable virus was detected up to 72 hours after application to these surfaces.[16]

Illustration of the ultrastructure of the Covid-19 virus

CDC/SCIENCE PHOTO LIBRARY
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Illustration by Mohamed Hassan

References

1.    Zhu, N. et al. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 382, 727–733 (2020).
2.    Lu, R. et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 395, 565 (2020).
3.    Rothan, H. A. & Byrareddy, S. N. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J. Autoimmun. 102433 (2020). doi:10.1016/j.jaut.2020.102433
4.    Chan, J. F. W. et al. A novel coronavirus outbreak of global health concern. Lancet 395, 514–523 (2020).
5.    Li, X. et al. Transmission dynamics and evolutionary history of 2019-nCoV. J. Med. Virol. 501–511 (2020). doi:10.1002/jmv.25701
6.    Benvenuto, D. et al. The 2019-new coronavirus epidemic: Evidence for virus evolution. J. Med. Virol. 92, 455–459 (2020).
7.    Tang, X. et al. On the origin and continuing evolution of SARS-CoV-2. Natl. Sci. Rev. 213, 54–63 (2020).
8.    Del Rio, C. & Malani, P. N. New Insights on a Rapidly Changing Epidemic. Jama 30303, 2019–2020 (2020).
9.    Wang, D. et al. Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA - J. Am. Med. Assoc. 1–9 (2020). doi:10.1001/jama.2020.1585
10.    Peng, D. et al. Presumed Asymptomatic Carrier Transmission ofCOVID-19 Anovel. N. Engl. J. Med. 19–20 (2020). doi:10.1056/nejmoa2001316
11.    Chen, H. et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. www.thelancet.com (2020). doi:10.1016/S0140-6736(20)30360-3
12.    Zhu, H. et al. Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia. Transl. Pediatr. 9, 51–60 (2020).
13.    Zhou, F. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan , China : a retrospective cohort study. Lancet 6736, 1–9 (2020).
14.    Chen, Y., Liu, Q. & Guo, D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J. Med. Virol. 92, 418–423 (2020).
15.    Lai, C. C., Shih, T. P., Ko, W. C., Tang, H. J. & Hsueh, P. R. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. International Journal of Antimicrobial Agents (2020). doi:10.1016/j.ijantimicag.2020.105924
16.    Zou, L. et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N. Engl. J. Med. (2020). doi:10.1056/NEJMc2001737
17.    Guan, W.-J. et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N. Engl. J. Med. (2020). doi:10.1056/NEJMoa2002032
18.    https://www.worldometers.info/coronavirus/

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