References ×

Note that for about 10 out of 45 parameters, the literature values are from other coronaviruses. We await corresponding measurements for SARS-CoV-2.

Size & Content

Diameter:(Zhu et al. 2020) - “Electron micrographs of negative-stained 2019-nCoV particles were generally spherical with some pleomorphism (Figure 3). Diameter varied from about 60 to 140 nm.“

Volume: Using diameter and assuming the virus is a sphere

Mass: Using the volume and a density of ~ 1 g per mL

Number of surface spikes trimers: (Neuman et al. 2011) - “Our model predicts ∼90 spikes per particle.”

Length of surface spikes trimers: (Zhu et al. 2020) - “ Virus particles had quite distinctive spikes, about 9 to 12 nm, and gave virions the appearance of a solar corona. “

Membrane (M; 222 aa): (Neuman et al. 2011) - “Using the M spacing data for each virus (Fig.6C), this would give ∼1100 M2 molecules per average SARS-CoV, MHV and FCoV particle”

Envelope (E; 75 aa): (Godet et al. 1992) - “Based on the estimated molar ratio and assuming that coronavirions bear 100 (Roseto et al., 1982) to 200 spikes, each composed of 3 S molecules (Delmas and Laude, 1990) it can be inferred that approximately 15- 30 copies of ORF4 protein are incorporated into TGEV virions (Purdue strain).”

Nucleoprotein (364 aa): (Neuman et al. 2011) - “Estimated ratios of M to N protein in purified coronaviruses range from about 3M:1N (Cavanagh, 1983,Escors et al., 2001b) to 1M:1N (Hogue and Brian, 1986,Liu and Inglis, 1991), giving 730–2200 N molecules per virion.”

Host cell binding affinity (K d ): (Walls et al. 2020) - Walls et al. reports K d of ≈1 nM for the binding domain in Table 1 using Biolayer interferometry with k on of ≈1.5×105 M-1 s-1 and k off of ≈1.6×10-4 s-1. (Wrapp et al. 2020) - Wrapp et al. reports K d of ≈15 nM for the spike (Fig.3) and ≈35 nM for the binding domain (Fig.4) using surface plasmon resonance with k on of ≈1.9×105 M-1 s-1 and k off of ≈2.8×10-3 s-1 for the spike and k on of ≈1.4×105 M-1 s-1 and k off of ≈4.7×10-3 s-1 for the binding domain. (Lan et al. 2020) - Lan et al. reports K d of ≈5 nM for the binding domain in Extended Data Fig. 4 using surface plasmon resonance with k on of ≈1.4×106 M-1 s-1 and k off of ≈6.5×10-3 s-1. (Shang et al. 2020) - Shang et al. reports K d of ≈40 nM for the binding domain in Extended Data Fig. 6 using surface plasmon resonance with k on of ≈1.8×106 M-1 s-1 and k off of ≈7.8×10-3 s-1. The main disagreement between the studies seems to be on the k off .

Genome

Type: (ViralZone) +ssRNA “_Monopartite, linearssRNA(+) genome_”

Genome length: (Wu et al. 2020) - Figure 2

Number of genes: (Wu et al. 2020) - “SARS-CoV-2 genome has 10 open reading frames (Fig. 2A).“ or (Wu et al. 2020) - "The 2019-nCoV genome was annotated to possess 14 ORFs encoding 27 proteins".

Number of proteins: (Wu et al. 2020) -”By aligning with the amino acid sequence of SARS PP1ab and analyzing the characteristics of restriction cleavage sites recognized by 3CLpro and PLpro, we speculated 14 specific proteolytic sites of 3CLpro and PLpro in SARS-CoV-2 PP1ab (Fig. 2B). PLpro cleaves three sites at 181–182, 818–819, and 2763–2764 at the N-terminus and 3CLpro cuts at the other 11 sites at the C-terminus, and forming 15 non-structural proteins.”

Evolution rate: (Koyama et al. 2020) -“Mutation rates estimated for SARS, MERS, and OC43 show a large range, covering a span of 0.27 to 2.38 substitutions ×10-3 / site / year (10-16).” Recent unpublished evidence also suggest this rate is of the same order of magnitude in SARS-CoV-2

Mutation rate: (Sanjuan et al. 2010) - “Murine hepatitis virus … Therefore, the corrected estimate of the mutation rate is μ s/n/c = 1.9x10-6/ 0.55 = 3.5 x 10-6.”

Genome similarity: For all species except pangolin: (Wu et al. 2020) - “After phylogenetic analysis and sequence alignment of 23 coronaviruses from various species. We found three coronaviruses from bat (96%, 88% and 88% for Bat-Cov RaTG13, bat-SL-CoVZXC12 and bat-SL-CoVZC45, respectively) have the highest genome sequence identity to SARS-CoV-2 (Fig. 1A). Moreover, as shown inFig. 1B, Bat-Cov RaTG13 exhibited the closest linkage with SARS-CoV-2. These phylogenetic evidences suggest that SARS-CoV-2 may be evolved from bat CoVs, especially RaTG13. Among all coronaviruses from human, SARS-CoV (80%) exhibited the highest genome sequence identity to SARS-CoV-2. And MERS/isolate NL13845 also has 50% identity with SARS-CoV-2.” For pangolin: (Zhang et al. 2020) - Figure 3

Replication Timescales

Virion entry into cell: (Schneider et al. 2012) - “_Previous experiments had revealed that virus is internalized within 15 min”_and (Ng et al. 2003) - “Within the first 10 min, some virus particles were internalised into vacuoles (arrow) that were just below the plasma membrane surface (Fig. 2, arrows). … The observation at 15 min postinfection (p.i.), did not differ much from 10 min p.i. (Fig. 4a)”

Eclipse period: (Schneider et al. 2012) - “SARS-CoV replication cycle from adsorption to release of infectious progeny takes about 7 to 8 h (data not shown).”and (Harcourt et al. 2020) - Figure 4 shows virions are released after 12-36 hrs but because this is multi-step growth this represents an upper bound for the replication cycle.

Burst size: (Hirano et al. 1976) - “The average per‐cell yield of active virus was estimated to be about 6–7× 102plaque‐forming units.” This data is for MHV, moreore research is needed to verify these values for SARS-CoV-2.

Host Cells

Type: (Shieh et al. 2005) - “Immunohistochemical andin situ hybridizationassays demonstrated evidence ofSARS-associated coronavirus(SARS-CoV) infection in various respiratory epithelial cells, predominantly type II pneumocytes, and inalveolar macrophagesin the lung.“and (Walls et al. 2020) - “SARS-CoV-2 uses ACE2 to enter target cells”and (Rockx et al. 2020) - “In SARS-CoV-2-infected macaques, virus was excreted from nose and throat in absence of clinical signs, and detected in type I and II pneumocytes in foci of diffuse alveolar damage and mucous glands of the nasal cavity… In the upper respiratory tract, there was focal 5 or locally extensive SARS-CoV-2 antigen expression in epithelial cells of mucous glands in the nasal cavity (septum or concha) of all four macaques, without any associated histological lesions (fig. 2I)”

Type I and Type II pneumocyte and alveolar macrophage cell number: (Crapo et al. 1982) - Table 4 and (Stone et al. 1992) - Table 5

Epithelial cells in mucous gland cell number and volume: (ICRP 1975) - surface area of nasal cavity,(Tos & Mogensen, 1976) and (Tos & Mogensen, 1977) - mucous gland density, (Widdicombe 2019) - mucous gland volume, (Ordoñez et al. 2001) and (Mercer et al. 1994) - mucous cell volume. We divide the mucous gland volume by the mucous cell volume to arrive at the total number of mucous cells in a mucous gland. We multiply the surface density of mucous glands by the surface area of the nasal cavity to arrive at the total number of mucous glands, and then multiply the total number of mucous glands by the number of mucous cells per mucous gland.

Type II pneumocyte volume: (Fehrenbach et al. 1995) - “Morphometry revealed that although inter‐individual variation due to some oedematous swelling was present, the cells were in a normal size range as indicated by an estimated mean volume of 763 ± 64 μm3. “

Alveolar macrophage volume: (Crapo et al. 1982) - “Alveolar macrophages were found to be the largest cell in the populations studied, having a mean volume of 2,491 μm3”

Concentration

Nasopharynx, Throat, Stool, and Sputum: (Woelfel et al. 2020) - Figure 2. __ and (Kim et al. 2020) - Figure 1 and (Pan et al. 2020) - Figure. We took the maximal viral load for each patient in nasopharyngeal swabs, throat swabs, stool or in sputum.

Antibody Response - Seroconversion

Seroconversion time (time period until a specific antibody becomes detectable in the blood): (Zhao et al. 2020) - “The seroconversion sequentially appeared for Ab, IgM and then IgG, with a median time of 11, 12 and 14 days, respectively” and (To et al. 2020) - “For 16 patients with serum samples available 14 days or longer after symptom onset, rates of seropositivity were 94% for anti-NP IgG (n=15), 88% for anti-NP IgM (n=14), 100% for anti-RBD IgG (n=16), and 94% for anti-RBD IgM (n=15)”

Maintenance of antibody response to virus: (Wu et al. 2007) - “Among 176 patients who had had severe acute respiratory syndrome (SARS), SARS-specific antibodies were maintained for an average of 2 years, and significant reduction of immunoglobulin G–positive percentage and titers occurred in the third year.”

Virus Environmental Stability

Half life on surfaces: (van Doremalen et al. 2020) - For half-lives we use Supplementary Table 1. For time to decay from ~104 to ~10 TCID 50 /L-1 air or mL-1 medium, we use the first time titer reached detection limit in Figure 1A for surfaces. For aerosols, we use ten half-life values (1000-fold decrease from 104 to 10, meaning 10 halvings of concentration) from Supplementary Table 1. More studies are urgently needed to clarify the implications of virion stability on the probability of infection from aerosols or surfaces.

RNA stability on surfaces: (Moriarty et al. 2020) - “SARS-CoV-2 RNA was identified on a variety of surfaces in cabins of both symptomatic and asymptomatic infected passengers up to 17 days after cabins were vacated on the Diamond Princess but before disinfection procedures had been conducted (Takuya Yamagishi, National Institute of Infectious Diseases, personal communication, 2020).”

“Characteristic” Infection Progression in a Single Patient

Basic reproductive number, R 0 : (Li et al. 2020) - “Our median estimate of the effective reproductive number, Re—equivalent to the basic reproductive number (R0) at the beginning of the epidemic—is 2.38 (95% CI: 2.04−2.77)” and (Park et al. 2020) - “Our estimated R0 from the pooled distribution has a median of 2.9 (95% CI: 2.1–4.5).”

Latent period (from infection to being able to transmit): (Li et al. 2020) - ”In addition, the median estimates for the latent and infectious periods are approximately 3.69 and 3.48 days, respectively.”and Table 1 and (He et al. 2020) - We use the time it takes the infectiousness to reach half its peak, which happens two days before symptom onset based on Figure 1b. As symptoms arise after 5 days (see incubation period), this means the latent period is about 3 days.

Incubation period (from infection to symptoms): (Lauer et al. 2020) - “ The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection. These estimates imply that, under conservative assumptions, 101 out of every 10 000 cases (99th percentile, 482) will develop symptoms after 14 days of active monitoring or quarantine. ” and (Li et al. 2020) - “The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days.”

Infectious period (partially overlaps latent period): (Li et al. 2020) - ”In addition, the median estimates for the latent and infectious periods are approximately 3.69 and 3.48 days, respectively.”and Table 1 and (He et al. 2020) - We quantify the interval between half the maximal infectiousness from the infectiousness profile in Figure 1b.

Disease duration: (WHO 2020) - “Using available preliminary data, the median time from onset to clinical recovery for mild cases is approximately 2 weeks and is 3-6 weeks for patients with severe or critical disease”

Time until diagnosis: (Xu et al. 2020) - __ We used data on cases with known symptom onset and case confirmation dates and calculated the median time delay between these two dates.

Case Fatality Rate: (ECDC geographic distribution of cases from 02/04/2020) - We use data from all countries with more than 50 death cases and calculate the uncorrected raw Case Fatality Rate for each country. The range represents the lowest and highest rates observed.

Infected Fatality Rate: We rely on three independent approaches that estimate the IFR. The first relies on repartiats which came back to their home countries and were extensively tested. (Verity et al. 2020) - “We obtain an overall IFR estimate for China of 0.66% (0.39%,1.33%)” and (Ferguson et al. 2020) - “The IFR estimates from Verity et al.12 have been adjusted to account for a non-uniform attack rate giving an overall IFR of 0.9% (95% credible interval 0.4%-1.4%).” and (Nishiura et al. 2020) - “The infection fatality risk (IFR)—the actual risk of death among all infected individuals—is therefore 0.3% to 0.6%”. The second approach relies on data gathered from the Diamond Princess ship, where all passengers were tested. (Russel et al 2020) - “We estimated that the all-age cIFR on the Diamond Princess was 1.3% (95% confidence interval (CI): 0.38–3.6)”. The third approach relies on epidemiological modelling of case time-series from China “We also found that most recent crude infection fatality ratio (IFR) and time-delay adjusted IFR is estimated to be 0.04% (95% CrI: 0.03-0.06%) and 0.12% (95%CrI: 0.08-0.17%)”. Combining these three methods, and taking into account the reliability of each report, we estimate a crude range of ≈0.3%-1.3% for the IFR.

Acknowledgements

We thank Uri Alon, Niv Antonovsky, David Baltimore, Rachel Banks, Arren Bar Even, Naama Barkai, Molly Bassette, Menalu Berihoon, Biana Bernshtein, Pamela Bjorkman, Cecilia Blikstad, Julia Borden, Bill Burkholder, Griffin Chure, Lillian Cohn, Bernadeta Dadonaite, Emmie De wit, Ron Diskin, Ana Duarte, Tal Einav, Avigdor Eldar, Elizabeth Fischer, William Gelbart, Alon Gildoni, Britt Glausinger, Shmuel Gleizer, Dani Gluck, Soichi Hirokawa, Greg Huber, Christina Hueschen, Amit Huppert, Shalev Itzkovitz, Martin Jonikas, Leeat Keren, Gilmor Keshet, Marc Kirschner, Roy Kishony, Amy Kistler, Liad Levi, Sergei Maslov, Adi Millman, Amir Milo, Elad Noor, Gal Ofir, Alan Perelson, Steve Quake, Itai Raveh, Andrew Rennekamp, Tom Roeschinger, Daniel Rokhsar, Alex Rubinsteyn, Gabriel Salmon, Maya Schuldiner, Eran Segal, Ron Sender, Alex Sigal, Maya Shamir, Arik Shams, Mike Springer, Adi Stern, Noam Stern-Ginossar, Lubert Stryer, Dan Tawfik, Boris Veytsman, Aryeh Wides, Tali Wiesel, Anat Yarden, Yossi Yovel, Dudi Zeevi, Mushon Zer Aviv, and Alexander Zlokapa for productive feedback on this manuscript. Figure created using Biorender.