COVID-19 Literature Situation Report February 4, 2020

• Tang, et al. provide a brief synopsis of two Thai cases and a case from Japan, noting that these did not enter the specific “wet market” at the epicenter of the current epidemic and were not epi-linked to each other
• They go on to cite the non-specific symptoms identified among the early cases; the lack of pediatric cases; and the need for seroprevalence surveys. 

Tang JW, et al. (2020) Emergence of a novel coronavirus causing respiratory illness from Wuhan, China, Journal of Infection. doi: https://doi.org/10.1016/j.jinf.2020.01.014

• Incubation periods were assessed by Lauer, et al. based on 101 confirmed cases with identifiable exposure windows from outside Hubei province (other parts of China plus globally). Case were 62% male with a mean age of 52 years. 
  • Mean incubation period: 5.2 days (95% CI, 4.4, 6.0 days)
  • 95% of persons developed symptoms within 10.5 days (95% CI, 7.3, 15.3 days)
  • 64/10,000 cases may develop symptoms after 14 days (<1%)
  • Median incubation time assessing fever only: 5.7 days, with 97.5% of persons experiencing fever within 11.4 days (95% CI: 6.1, 17.8 days)
• A subset of patients with symptom onset outside a facility had a mean time of 2.7 days from symptoms to hospitalization. [Note: Consistent with Sun, et al., below]
• Incubation periods appear on average almost a day shorter in China than elsewhere, possibly due to a bias that persons able to travel out of China tended to have longer incubation periods.
• These estimates are generally consistent with earlier estimates and those for SARS and MERS, though longer than the roughly 3-day period seen for other non-SARS human coronaviruses.

Lauer SA, et al. (Feb 4, 2020). The incubation period of 2019-nCoV from publicly reported confirmed cases: estimation and application. Pre-Print downloaded on 4 Feb, 2020 from, https://www.medrxiv.org/content/10.1101/2020.02.02.20020016v1

• Science news reports that the NEJM article on asymptomatic transmission erred in describing the infected traveler from China as asymptomatic. Follow-up by regional authorities in Germany found that the traveler did have respiratory and other symptoms while in Germany.
• An update in the NEJM is expected soon.

Kupferschmidt K (Feb 3, 2020, 5:30 PM) Study claiming new coronavirus can be transmitted by people without symptoms was flawed. ScienceMag.org (American Association for the Advancement of Science). Accessed 3 Feb, 2020 from, https://www.sciencemag.org/news/2020/02/paper-non-symptomatic-patient-transmitting-coronavirus-wrong   

• Train travel was correlated with the spread of 2019-nCoV through mainland China. 

Zhao S, et al. (in press) DOI: https://doi.org/10.1016/j.tmaid.2020.101568

• Airport screening will likely miss about 46% of infected travelers (in line with prior estimates)

Quilty, et al. Pre-print downloaded 2 Feb, 2020 at, https://www.medrxiv.org/content/10.1101/2020.01.31.20019265v1

• Using information from an International Air Transport Data database, SIR modeling techniques, and R0 estimates ranging from 1.4-2.9, critical timeframes for outbreak emergence (establishing transmission in a new locale) range from about 18-30 days. To gain 30 days in these scenarios, control measures must reduce connections between locales by 87-95%.

Yuan HY, et al. Pre-print downloaded 4 Feb, 2020 at, https://www.medrxiv.org/content/10.1101/2020.02.01.20019984v1

• Chances of sustained transmission from an introduced case are about 37% without surveillance and 0.5% with “intense surveillance.” 

Thompson RN (2020) Pre-print downloaded 3 Feb, 2020 at, https://www.biorxiv.org/content/10.1101/2020.01.24.919159v1

• In locations with “similar transmission potential as Wuhan,” three or more introduced cases will lead to a more than 50% chance of the infection becoming established in that locale 

Kucharski, et al. Pre-print downloaded 2 Feb, 2020 at, https://www.medrxiv.org/content/10.1101/2020.01.31.20019901v1 

• Jiang, et al. provide a review of sequence homologies among SARS, MERS, and bat-SL-CoV’s related to 2019-nCoV strains in order to predict the potential utility of viral replication inhibitors found effective for SARS and MERS in animal models 
• They align 2019-nCoV S protein sequence with those of SARS-CoV and several bat-SL-CoVs to predict the cleavage site for generating S1 and S2 subunits; likely functioning of those subunits; and specific candidate molecules to interfere with viral replication
  • Two functional domains of the S1 subunit: binding of the virion to the host cell receptor 
  • Three functional domains of the S2 subunit: fusion between viral and cellular membranes

Jiang S, et al. (2020) An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies, Emerging Microbes & Infections. 9:1, 275-277, DOI: 10.1080/22221751.2020.1723441

• Huang and Herrman perform large-scale protein-protein docking experiments to quantify the interactions of 2019-nCoV S-protein receptor-binding domain (S-RBD) with human receptor ACE2 
• Sampling a large number of thermodynamically probable binding conformations with Monte Carlo algorithm, they established an experiment-based strength reference for evaluating the receptor-binding affinity of 2019-nCoV via comparison with SARS-CoV. 
• The binding affinity of 2019-nCoV S-RBD was about 73% of that of SARS-CoV
• This method might also be applied for rapidly assessing human transmission capability of other newly emerging CoV; and shows the utility of protein-protein interaction analyses

Huang Q and Herrman A (Feb 4, 2020). Fast assessment of human receptor-binding capability of 2019 novel coronavirus (2019-nCoV). Pre-Print downloaded on 4 Feb, 2020 from, https://www.biorxiv.org/content/10.1101/2020.02.01.930537v2

Context: Based on current reports from China, the case fatality (%) among confirmed cases since the start of the epidemic is 2.1% (15% among “severe” cases; 1% among all confirmed and suspected cases).

• Sun, et al. used crowdsourced data from a Chinese healthcare professional community network site and other publicly available data to provide information on demographics, hospitalization, and reporting lag during the period of Dec 2019 – Jan 2020. Case definitions are not specified.
• They identified 288 apparently-hospitalized cases (200 in 5 provinces of mainland China; 88 international), including 39 fatalities (13.5%).
  • Cases were 63% male
  • Median age: 44 years of age, with a majority of case over 30 years.
    Seven (2.4%) cases were under 15 years (est. adjusted relative risk for age <15 yrs was 0.3).
  • Median age among those who died: 70 years. Two deaths (5%) occurred in persons <50 yrs.
  • Average lag in symptom onset to seeking care in China was 3 days, declining from 5 to 2 days before compared to after 18 January. In Hubei, the ~6 day average was probably affected by delays in the early Wuhan cases. Outside Hubei, the average was about 2 days; outside China, the average was same-day.
  • Average lag in hospitalization to report in China was 3 days, declining from 9 to 2 days before compared to after 18 January. In Hubei, the ~9 day average was probably affected by delays in the early Wuhan cases. Outside Hubei and internationally, the average was about 2 days.
  • Average lag in symptom onset to reporting was 5 days, ranging from 0-43 days.
  • Rapid growth of cases in China outside Hubei is reported as consistent with sustained transmission in those other areas.
• Crowdsourced data appeared to capture more cases in China before the 18 Jan, when compared to national reporting; and slowed compared to national reporting after that.

Sun K, et al. (Feb 4, 2020). Early epidemiological analysis of the 2019-nCoV outbreak based on a crowdsourced data. Pre-Print downloaded on 4 Feb, 2020 from, https://www.medrxiv.org/content/10.1101/2020.01.31.20019935v1