Primary author: David Jorgensen

Olivia Boyd, Lily Geidelberg, David Jorgensen, Manon Ragonnet, Igor Siveroni, Erik Volz and the Imperial College COVID-19 Response Team

Report prepared on 2020-06-07

This report uses full genome sequence data for Madinah shared publicly by the Pathogen Genomics Lab at the King Abdullah University of Science and Technology. International background sequences included in the analsis are from GISAID (contributing laboratories).

Key points

  • This is a preliminary analysis, predictions are subject to change with further genetic data covering a longer time period. Out of sample predictions are made using data from the international reservoir and may not reflect local changes over the same time period.
  • In this analysis we predict a basic reproduction number (R0) for Makkah of 1.72, with the effective reproduction number (Rt) falling to 1.52 at the time of the last sample (2020-04-16). Out of sample prediction using international SARS-CoV2 data shows Rt continuing to decline following the last reported sample (Figure 5). The trajectory of this curve is likely to change with the inclusion of more recent internal sequence data.
  • We estimate that approximately 70% of SARS-CoV2 cases in Makkah have been reported over the course of the epidemic.

This is analysis is based on :

  • 34 whole genomes sampled from within Makkah
  • 72 whole genomes sampled from outside of Makkah
  • Samples within Makkah were collected between 2020-03-22 and 2020-04-16

As duplicate sequences and those with likely sequencing errors or significant gaps were removed prior to analysis this represents a smaller sample than the total number of Makkah samples uploaded to gisaid. Figure 1 shows the distribution of the included sequences over time, including external sequences.

Reported cases for comparison to our model predictions are taken from covid19.moh.gov.sa for the Makkah al Mukarramah region. These data are used for comparison purposes only and do not influence the phylodynamic analyses.

plot of chunk sampling dist

Figure 1: Sampling distributions over time of number of sequences included within the region versus sequences included from the international reservoir.

Estimated infections in Makkah

In this preliminary analysis we estimate 3623 [1107-17213] (median [95%CI]) cumulative infections at the time of the last sample (2020-04-20). At the same time point there were 1584 reported cases. The number of cases reported falls within the 95% credible interval for the number of cases predicted by the model.

plot of chunk Cumulative estimated infections through time

plot of chunk Cumulative estimated infections through time log scale

Figure 2: Estimated cumulative infections through time represented by solid black line (median) and 95% CrI (ribbon). Points represent reported cases in Makkah. The dashed line indicates the date of last sample in Makkah in this analysis.

plot of chunk daily estimated infections through time

plot of chunk daily estimated infections through time log scale

Figure 3: Estimated daily infections through time represented by solid black line (median) and 95% CrI (ribbon). Points represent reported cases in Makkah. The dashed line indicates the date of last sample in Makkah in this analysis.

plot of chunk reporting

Figure 4: Estimated percentage of cases reported in Makkah. Error bars represent the 95% credible interval.

We estimate approximately 70% of cases occuring in Makkah have been reported. Estimated reporting rates for the Kingdom of Saudi Arabia from other sources are higher with Russell et al. estimating 87% from comparison of fatality data to the number of reported cases. Our reporting rate estimates are likely to change with a longer time series of genetic data.

plot of chunk Rt

Figure 5: Reproduction number through time. The black vertical dashed line indicates the date of last sample in Makkah in this analysis.

Reproduction number at last sample (2020-04-16): 1.54 [1.01-1.88] median [95% CrI]

How quickly has the epidemic in Makkah grown?

Quantile Reproduction number Growth rate (per day) Doubling time (days)
50% 1.72 0.0785 8.83
2.5% 1.31 0.0365 5.56
97.5% 2.23 0.125 19

Table 1: Reproduction number, growth rate and doubling times

How has SARS-CoV 2 evolved in Makkah?

plot of chunk ml_tree

Figure 6: Maximum likelihood phylogeny with the x-axis representing NT substitutions per site. The colour of the tips corresponds to sampling location; red tips were sampled from within Makkah, grey tips from outside.

plot of chunk mcc_tree

Figure 7: Time scaled phylogeny co-estimated with epidemiological parameters. The colour of the tips corresponds to location sampling; red tips were sampled from within Makkah.

We present a time-scaled phylogeny for the sequence data from Makkah and the international reservoir. The majority of sequenced genomes from Makkah fall in to two distinct clusters of internal transmission with further introductions of virus not leading to onwards transmission. The sequences from Makkah are predominantly associated with sequence data from Europe and the Americas, although the majority of reported sequence data comes from these regions so this association may be heavily influenced by reporting biases. As support for internal nodes in the time scaled phylogeny is variable we have included a maximum likelihood tree showing the genetic relationship between sequences in figure 6.

Molecular clock rate of evolution: 0.00101 [0.000658-0.00127] median [95% CrI]

Methods summary

Details on methods and priors can be found here.

Statistic mean ESS
posterior -43231 237
likelihood -43124 4005
prior -107 233
treeLikelihood.algn -43124 4005
TreeHeight 0.3982 346
clockRate 0.0009941 482
kappa 5.887 30445
PhydynSEIR -75.67 237
seir.E 44.16 308
seir.S 96013 10421
seir.b 13.63 3768
seir.exog 0.008481 1065
seir.exogGrowthRate 26.05 152
seir.importRate 3.506 598
seir.p_h 0.2067 17354
seir.tau 72.16 23110
freqParameter.1 0.2974 8748
freqParameter.2 0.1822 11082
freqParameter.3 0.1953 10828
freqParameter.4 0.3251 10951

Table 2: Effective sample size of model parameters

Model version: seijr_0.1.1_coupled

Report version: 20200607-203557-f824070b

Acknowledgements

This work was supported by the MRC Centre for Global Infectious Disease Analysis at Imperial College London.

Sequence data were provided by GISAID and these laboratories.