In this online pre-print, we present a case of persistent SARS-CoV-2 infection with accelerated intra-host evolution in a patient with advanced HIV and antiretroviral treatment failure in South Africa.

Paper deposited at medRxiv &available at:… @sigallab
SARS-CoV-2 RT-PCR was positive for 216 days (27 weeks). At all time-points between day 0 and day 216 there was a mean Ct ranging from 16.4 to 31.6. The patient had HIV drug resistance and was not responding to therapy.
Over 30 mutations accumulated over time, many of them changing aminoacids that are common of variants of concern.
At day 6, the E484K substitution in the receptor-binding domain (RBD) emerged, along with a substitution in the S2 subunit (A1078V). The E484K mutation remained in the consensus sequence until day 34, but then persisted at low frequency up to day 190
At the later time points, there was a significant shift in the virus population, with the emergence at day 71 of the K417T and F490S mutations in the spike RBD, followed by the emergence of L455F and F456L at day 106. At day 190, there was the emergence of D427Y and N501Y.
Table of mutations in the Spike protein, including the appearance of 501Y, 484K and 417T (all from variants of concern) and mutations and deletion at the N-terminal domain (NTD)
All genomes fell within PANGO lineage B.1.1.2732, a South African lineage that was previously part of B.1.1.56, one of the most prevalent lineages in the first wave of the epidemic in the province of KwaZulu-Natal in South Africa.
There were the appearance of mutations also in the N protein and ORF1a
Discussion: Despite a short clinical illness of moderate severity, SARS-CoV-2 PCR positivity persisted up to 216 days. We demonstrate significant shifts in the virus population over that time, involving multiple mutations at key neutralizing antibody sites in the spike RBD & NTD
Most other cases of persistent infection have been described in people with haematological malignancies or people receiving immunosuppressive therapies for solid organ transplants or other chronic medical conditions
There is one other documented case of prolonged infection in a person with HIV - in that case the person was ART-naïve with profound immunosuppression and genome sequencing revealed only a single emergent mutation in spike (T719I) at day 53
The genomic and clinical data suggest that virus evolution may have been driven by selective pressure from an impaired neutralizing antibody response due to advanced HIV disease.
Disruptions to HIV programs as a result of COVID-19 could potentially increase the burden of advanced HIV45. These findings highlight the importance of maintaining essential health services in high HIV prevalence settings, and accelerating progress towards 90-90-90 targets.
If persistent SARS-CoV-2 infection and evolution of virus does occur more frequently in the context of HIV, it may provide justification for prioritising people living with HIV for COVID-19 vaccination.
Real teamwork with @farinakarim @sigallab @rjlessells @AHRI_News @krisp_news and the clinical team of the Infectious Diseases Department of UKZN!

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More from @Tuliodna

14 May
A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa…
By 5 May 2021, 14,504 SARS-CoV-2 genomes had been submitted to the GISAID database from 38 African countries and two overseas territories (Mayotte and Réunion) (Fig. 1A). Overall, this corresponds to approximately one sequence per ~300 reported cases.
Overall, the number of sequences correlates closely with the number of reported cases per country. lmost half of the sequences were from South Africa, consistent with it being responsible for almost half of the reported cases in Africa.
Read 21 tweets
13 May
Confirmed Detection of eight (8) more genomes B.1.617.2 and two (2) community transmission of B.1.1.7 in South Africa, By Network for Genomic Surveillance in South Africa (NGS-SA), 13 May 2021
The eight new cases of B.1.617.2 variant have been detected from KwaZulu-Natal province. More specifically, these were cases in crew members of a commercial vessel that arrived in Durban Port from India.
The cases were isolated on the vessel, and other crew members have been quarantined according to national COVID-19 case management guidelines. The individuals who tested positive for COVID-19 did not disembark in South Africa, with exception of one that was admitted to hospital
Read 9 tweets
9 May
Confirmed Detection of B.1.617.2 and B.1.1.7 in South Africa by NGS-SA

This report was sent to our Health Minister @DrZweliMkhize yesterday.

In this Twitter thread, we highlight the details and repercussion of the discovery to South Africa
In response to the continued emergence and spread of new variants around the world, the Network for Genomic Surveillance in South Africa (NGS-SA) recently intensified the monitoring of confirmed COVID-19 cases in recent arrivals to the country.
We can now confirm that today we detected four cases of the B.1.617.2 variant. The four cases have been detected from Gauteng (n=2) and KwaZulu-Natal (n=2) provinces and all have a history of recent arrivals from India.
Read 17 tweets
4 May
First genomic surveillance results from a traveler to India in South Africa. A patient at Tygerberg Hospital who tested positive for SARS-CoV-2 about 3 days after traveling to SA from India. This first genome is a 501Y.V2 (B.1.351) and not the B.1.617 described in India.
The 501Y.V2 (B.1.351) is the 3rd most common variant in India after the B.1.617 and the B.1.1.7. Below a graph from @trvrb showing the spread of the variants in India.
The 501Y.V2 (B.1.351) was firstly identified in South Africa by the network for genomic surveillance in South Africa (NGS-SA). It shows how variants can be introduced back and forth between countries.
Read 8 tweets
29 Mar
Today paper on neutralization of 501Y.V2 (B.1.351) - Show effective neutralization of other SARS-CoV-2 lineages by 501Y.V2 @nature…

All start with a good cohort... We obtained convalescent plasma & sequenced the matching infecting virus of 1st & 2nd wave
A first wave variant lacking the 501Y.V2 RBD and NTD mutations (B.1.1.177) was outgrown from one participant infected in the first South African infection wave, and 501Y.V2 was outgrown from a participant at the beginning of the second wave.
A focus forming live virus neutralization assay (LVNA) was used to quantify neutralization.
Read 14 tweets
25 Mar
We just submitted a pre-print 'A novel variant of interest (VOI) of SARS-CoV-2 with multiple spike mutations detected through travel surveillance in Africa.'

This VOI has 31 amino acids mutations. In Spike has 11 mutations and three deletions in the N-terminal domain Image
It has some key mutations, including the E484K, R346K and P681H. The R346K is the associated with resistance to class 3 RBD NAbs recently described by @jbloom_lab
There are also 5 substitutions and 3 deletions in the NTD antigenic supersite (Y144Δ, R246M, SYL247-249Δ and W258L)
It the most diverse A lineage sequencers ever described. It also worry us as it was found in three travelers from Tanzania in Angola. There is almost no data from COVID-19 in Tanzania. Image
Read 8 tweets

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