How SARS-COV-2 traveled to West Africa

Oct 6, 2020

With the onset of the COVID-19 pandemic, medical research has focused on tracing the origin of the SARS-CoV-2 infection, which was first reported in the Chinese city of Wuhan, in late 2020.

Image Credit: https://www.biorxiv.org/content/10.1101/2020.10.02.323519v1.full

By June 2020, all African countries had reported COVID-19 cases. A recent study reported on the prepress server bioRxiv * October 2020 continues the spread of the virus from China to Europe and then to West Africa.

The sequence of viral RNA has changed considerably throughout its spread, leading to the appearance of SARS-CoV-2 clades. They are found to be specific to different regions.

Previous studies have described the possible effect of the D614G mutation that is related to clade G, as linked to higher mortality in states on the east coast of the US relative to the west coast. The mechanism of increased virulence is believed to be due to the increased adherence of the virus to the cell membrane, possibly due to a hydrogen bond between the S1 unit of the spike protein and the S2 region of the cell membrane. Some evidence for this comes from mouse studies.

Other researchers have shown the rapid rise to dominance of clade G in whatever region it enters, as it replaces all other clades with the amino acid D614. In mid-March 2020, this clade was mostly confined to Europe, but was quickly introduced to other countries.

Of four samples from the Chinese clade G, one had the A23403G substitution inducing the D614G mutation, but the other two commonly associated mutations were missing. Three with the D614G mutation were traced to the German sample first sequenced in January 2020. This sample has the A23403G mutation and a C-to-T mutation at position 3037, but the one at position 14408 is missing.

The earliest sample that had all three mutations, as well as another in the Untranslated Region (UTR), was found in Italy. Furthermore, a C14408T mutation found in clades G along with the sequence encoding RNA-dependent RNA polymerase (RdRp) is believed to increase the mutation rate.

A phylogenetic tree constructed for the viruses circulating in France showed that the first introduction of the virus did not cause community spread, and clade G was introduced long before the first case was recorded. This belonged to the same clade but was presented in a patient with no history of travel or contact with a traveler.

One of the advantages of the African population with respect to this virus is the large proportion of young people, with an average age of ~ 20 years in sub-Saharan Africa, who are expected to suffer from a mild illness. Second, the risk of transmission from China via air traffic was found to be quite unlikely during the initial outbreak, except in South Africa and Ethiopia. In the latter phase, however, researchers have found that containment measures are essential given the high rates of infection that are estimated.

The current study explores the region of Africa from where the first SARS-CoV-2 sequences were isolated, to build a phylogenetic tree. This could help to understand how the virus was transmitted between countries and if different clades have different degrees of severity.

The sequences being studied come from West African countries like Gambia, Ghana, Nigeria, and Senegal. These are very similar to those in China and Europe.

The phylogenetic tree is shown to split in two at the level of the D614G mutation, indicating the importance of this single nucleotide point mutation in viral diversity. Therefore, the lower branch lacks this mutation and is linked to the early Wuhan sequences, which also contain the Nigerian viral sequences.

The upper branch has the sequences that circulate in Europe, shared by those of Senegal. Samples from Ghana are grouped equally with both branches. The three samples from the Gambia belong to three different clades (V, GR and GH).

Clade mutation association

The researchers found that the West African samples are found in all clades, which could be because they were introduced from China and European countries alike. However, the samples from each country show a characteristic cluster distribution as shown above.

Clade S has two important mutations, C24370T and G22468T, which appear to be specific to West Africa. Samples from Ghana are grouped in the branch emanating from the first mutation, while the second may give rise to a branch that is the result of virus migration, as evidenced by the presence of Mali and Tunisian strains in this branch .

The Senegal strains related to the French sequences arise from both branches, while others are closer to those of Spain at the end of February, belonging to the first clade S. This indicates that the virus was introduced several times into Senegal from France. Spain and other regions of Africa.

Timeline of clade distribution

When clades are mapped against time, it is obvious that European clade G sequences play an important role in the African outbreak, including the D614G mutation. An unexpected pattern was observed in which the G clades belonging to the later part of the pandemic in Europe, namely G, GH, GR, appeared in circulation earlier than those belonging to the first European outbreaks, namely L, S , and V.

One explanation is that the French strains introduced into Senegal showed the founder effect, being closely related to the Senegalese strains and with a similar clade distribution. Another is that the migration and travel routes affected the circulation of the different strains, as observed in the first case reported in Nigeria, which originated in Italy. The earliest clades may have arrived by a slower route, for example by ship, while the later clades traveled faster and reached these countries earlier.

Again, the sample sequences from early European clades came from mid-March, by which time the Chinese part of the epidemic was coming to an end, indicating the possibility that the virus had passed through and into from several countries before the ‘early’ samples. were sequenced.

An unexpected finding was that clade S is very abundant mainly due to strains from Nigeria and Ghana. When these strains are excluded, the pattern of abundance of strains is close to that observed throughout the world, with a delay of 2 to 4 weeks.

Distribution of clades by country

The earliest clades appear to have spread mainly in Nigeria, which produced the largest proportion of these sequences. The samples from Ghana come almost equally from China and Europe, while those from Senegal come mainly from France with some early Chinese clades.

The Gambia had two sequences from Europe and one from China, a pattern that resembles the Italian extension, but where clade G is replaced by clade GH. This change, however, is associated with the Chinese and European clades. The Gambian distribution is similar to the UK pattern, which also, however, is related to that of the Ghana clade distribution due to the presence of Chinese clades.

Finally, states on the east and west coast of the US show different distributions, with the former being similar to the Nigerian pattern, containing a large proportion of clades from China, but the latter producing more GH clades like the French and Senegalese.

Geographical distribution

The map shows that the China-based L, S, and V clades spanned Europe and the west coast of the US and make up a high percentage of Nigerian strains. These clades are found together with the later European clades G, GH and GR in almost equal proportions, such as the west coast. Senegal has the same viral distribution pattern as France, but some exceptions belong to the first clades based in China, creating some similarities to the east coast.

The researchers propose that this pattern arises from a combination of two explanations: the earliest clades may not have been active during the initial period of viral circulation in West Africa, or they may have been introduced later than the earliest strains. The later clades may also have been more virulent, leading to their earlier detection.

The bottom line is that while Senegal and Gambia hosted multiple submissions from Europe, due to the low level of air traffic to and from China. Ghana and Nigeria received the virus from Europe, as well as from China, both directly and indirectly through Asian or European countries.

Most of the cases from which strains were retrieved for sequencing came from the period when Wuhan was still blocked, between January 23 and April 8, 2020. Possibly, the researchers say, the strains of the former clades were transmitted very early in the pandemic. or through other countries, or provinces of China other than Wuhan.

As in other regions, the researchers predict that the later G clades will become predominant in Nigeria and Ghana, but it is unclear whether this will also lead to higher mortality. Some researchers feel that the D614G mutation is linked to a higher case fatality rate, but others say that the evidence points to greater infectivity and a higher viral load, but not to a greater severity of the disease.

At present, the case fatality rate in these countries is low, 0.6 in Ghana but 3.2 in The Gambia. The researchers hint that sunlight, vitamin D levels, and weather can also influence the outcome after infection with the virus. Again, some researchers predict that the continued appearance of mutations will eventually make the virus endemic with a low mortality rate.

The researchers hope that this pioneering study will be followed by more extensive analysis using a greater number of sequences. However, G clades in West Africa do not appear to correlate with mortality, so “refute fears that the pandemic would massively overwhelm health systems in Africa. “

It is not yet time to relax, and measures to prevent future outbreaks must balance the financial stability of the region and the need to protect the health of the inhabitants.

*Important news

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or be treated as established information.