Persistent SARS-CoV-2 infection and intra-host evolution in association with advanced HIV infection

Karim, Farina; Moosa, Mohamed Y. S.; Gosnell, B. I.; Cele, Sandile; Giandhari, Jennifer; Pillay, Sureshnee; Tegally, Houriiyah; Wilkinson, Eduan; San, JE; Msomi, Nokukhanya; Mlisana, Koleka; Khan, Khadija; Bernstein, Mallory; Manickchund, Nithendra; Singh, Lakhveer; Ramphal, Upasana; Hanekom, Willem A.; Lessells, Richard J; Sigal, Alex; Oliveira, Túlio de

doi:10.1101/2021.06.03.21258228

Cited by 92 publications

(115 citation statements)

References 43 publications

(45 reference statements)

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“…Our cohort and interim analysis does not represent the entire spectrum of immune dysfunction, which we will continue to probe through ongoing recruitment to test these relationships more rigorously. This would be highly relevant in the context of emergence of specific SARS-CoV-2 variants associated with immunosuppression described in the UK 78 , and in parts of the world with high HIV prevalence and suboptimal HIV suppression levels 79 as evidenced by a recent report of in host SARS-CoV-2 evolution in viremic HIV infection 80 .…”

Section: Discussionmentioning

confidence: 99%

Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV

et al. 2021

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There is an urgent need to understand the nature of immune responses against SARS-CoV-2, to inform risk-mitigation strategies for people living with HIV (PLWH). Here we show that the majority of PLWH with ART suppressed HIV viral load, mount a detectable adaptive immune response to SARS-CoV-2. Humoral and SARS-CoV-2-specific T cell responses are comparable between HIV-positive and negative subjects and persist 5-7 months following predominately mild COVID-19 disease. T cell responses against Spike, Membrane and Nucleoprotein are the most prominent, with SARS-CoV-2-specific CD4 T cells outnumbering CD8 T cells. We further show that the overall magnitude of SARS-CoV-2-specific T cell responses relates to the size of the naive CD4 T cell pool and the CD4:CD8 ratio in PLWH. These findings suggest that inadequate immune reconstitution on ART, could hinder immune responses to SARS-CoV-2 with implications for the individual management and vaccine effectiveness in PLWH.

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Section: Discussionmentioning

confidence: 99%

Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV

et al. 2021

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“…Based on the results obtained in this study, a coverage of 500× allowed to detect LFV until an AF of 5% with perfect sensitivity and would therefore be less suited to detect LFV at lower AFs. Lythgoe et al (2021) recommended a depth of at least 100 reads with an AF of at least 3% to detect the LFV in diagnostic samples with high viral loads (50,000 uniquely mapped reads), while Siqueira et al (2021) used an AF threshold of 2% and a minimal depth coverage of 500 reads and Karim et al (2021) adopted an AF of 1% and a minimal depth coverage of 10×. Based on the results in this study, these recommendations appear not sufficiently strict, since we observed that an AF of 1, 2, and 3%, requires at least a sequencing coverage of 10,000, 2500, and 1500× to detect all LFV or 3500, 1000, and 500× to detect 90% of LFV, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…In-depth genome analysis, including recombination, rearrangement, haplotype reconstruction and large insertions and deletions (indel) detection, should be investigated using long-read sequencing technologies with a recommended read length of minimally 1000 bp and a sequencing coverage of 500× across more than 95% of the genome ( ECDC, 2021 ). A few studies evaluated quasispecies in diagnostic samples by only evaluating positions with a minimum depth of 100× ( Lythgoe et al, 2021 ), by employing a minimum AF of 2% and a minimum depth of 500× ( Siqueira et al, 2021 ) or by using Lofreq with a false discovery rate cut-off of 1%, minimum coverage of 10×, dynamic Bonferroni correction for variant quality and strand bias filtering ( Karim et al, 2021 ). Due to the high cost of sequencing large quantities of samples from individual patients, samples that tested positive for a selection of mutations related to VOCs using RT-qPCR and have a sufficiently high viral load are typically sequenced.…”

Section: Introductionmentioning

confidence: 99%

Strategy and Performance Evaluation of Low-Frequency Variant Calling for SARS-CoV-2 Using Targeted Deep Illumina Sequencing

et al. 2021

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The ongoing COVID-19 pandemic, caused by SARS-CoV-2, constitutes a tremendous global health issue. Continuous monitoring of the virus has become a cornerstone to make rational decisions on implementing societal and sanitary measures to curtail the virus spread. Additionally, emerging SARS-CoV-2 variants have increased the need for genomic surveillance to detect particular strains because of their potentially increased transmissibility, pathogenicity and immune escape. Targeted SARS-CoV-2 sequencing of diagnostic and wastewater samples has been explored as an epidemiological surveillance method for the competent authorities. Currently, only the consensus genome sequence of the most abundant strain is taken into consideration for analysis, but multiple variant strains are now circulating in the population. Consequently, in diagnostic samples, potential co-infection(s) by several different variants can occur or quasispecies can develop during an infection in an individual. In wastewater samples, multiple variant strains will often be simultaneously present. Currently, quality criteria are mainly available for constructing the consensus genome sequence, and some guidelines exist for the detection of co-infections and quasispecies in diagnostic samples. The performance of detection and quantification of low-frequency variants using whole genome sequencing (WGS) of SARS-CoV-2 remains largely unknown. Here, we evaluated the detection and quantification of mutations present at low abundances using the mutations defining the SARS-CoV-2 lineage B.1.1.7 (alpha variant) as a case study. Real sequencing data were in silico modified by introducing mutations of interest into raw wild-type sequencing data, or by mixing wild-type and mutant raw sequencing data, to construct mixed samples subjected to WGS using a tiling amplicon-based targeted metagenomics approach and Illumina sequencing. As anticipated, higher variation and lower sensitivity were observed at lower coverages and allelic frequencies. We found that detection of all low-frequency variants at an abundance of 10, 5, 3, and 1%, requires at least a sequencing coverage of 250, 500, 1500, and 10,000×, respectively. Although increasing variability of estimated allelic frequencies at decreasing coverages and lower allelic frequencies was observed, its impact on reliable quantification was limited. This study provides a highly sensitive low-frequency variant detection approach, which is publicly available at https://galaxy.sciensano.be, and specific recommendations for minimum sequencing coverages to detect clade-defining mutations at certain allelic frequencies. This approach will be useful to detect and quantify low-frequency variants in both diagnostic (e.g., co-infections and quasispecies) and wastewater [e.g., multiple variants of concern (VOCs)] samples.

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“…What is known though is that being infected with HIV-1 is a risk factor for developing severe COVID-19 ( 79 ) and for COVID-19 related mortality ( 33 – 35 ). Furthermore, a recent case report in South Africa revealed the development of over ten new SARS-CoV-2 variants in one individual who presented with untreated HIV-1 infection and had been co-infected with SARS-CoV-2 ( 80 ). The authors proposed that untreated HIV-1 infection might provide a fertile environment that favours intra-host mutation of SARS-CoV-2 ( 80 ).…”

Section: Covid-19 In Hiv-1-infected Individualsmentioning

confidence: 99%

SARS-CoV-2 and HIV-1: Should HIV-1-Infected Individuals in Sub-Saharan Africa Be Considered a Priority Group for the COVID-19 Vaccines?

Mandala

Liu

2021

Front. Immunol.

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Since its emergence in 2019 SARS-CoV-2 has proven to have a higher level of morbidity and mortality compared to the other prevailing coronaviruses. Although initially most African countries were spared from the devastating effect of SARS-CoV-2, at present almost every country has been affected. Although no association has been established between being HIV-1-infected and being more vulnerable to contracting COVID-19, HIV-1-infected individuals have a greater risk of developing severe COVID-19 and of COVID-19 related mortality. The rapid development of the various types of COVID-19 vaccines has gone a long way in mitigating the devastating effects of the virus and has controlled its spread. However, global vaccine deployment has been uneven particularly in Africa. The emergence of SARS-CoV-2 variants, such as Beta and Delta, which seem to show some subtle resistance to the existing vaccines, suggests COVID-19 will still be a high-risk infection for years. In this review we report on the current impact of COVID-19 on HIV-1-infected individuals from an immunological perspective and attempt to make a case for prioritising COVID-19 vaccination for those living with HIV-1 in Sub-Saharan Africa (SSA) countries like Malawi as one way of minimising the impact of COVID-19 in these countries.

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Persistent SARS-CoV-2 infection and intra-host evolution in association with advanced HIV infection

Cited by 92 publications

References 43 publications

Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV

Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV

Strategy and Performance Evaluation of Low-Frequency Variant Calling for SARS-CoV-2 Using Targeted Deep Illumina Sequencing

SARS-CoV-2 and HIV-1: Should HIV-1-Infected Individuals in Sub-Saharan Africa Be Considered a Priority Group for the COVID-19 Vaccines?

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