DMC1 attenuates RAD51-mediated recombination in Arabidopsis.

Ensuring balanced distribution of chromosomes in gametes, meiotic recombination is essential for fertility in most sexually reproducing organisms. The repair of the programmed DNA double strand breaks that initiate meiotic recombination requires two DNA strand-exchange proteins, RAD51 and DMC1, to search for and invade an intact DNA molecule on the homologous chromosome. DMC1 is meiosis-specific, while RAD51 is essential for both mitotic and meiotic homologous recombination. DMC1 is the main catalytically active strand-exchange protein during meiosis, while this activity of RAD51 is downregulated. RAD51 is however an essential cofactor in meiosis, supporting the function of DMC1. This work presents a study of the mechanism(s) involved in this and our results point to DMC1 being, at least, a major actor in the meiotic suppression of the RAD51 strand-exchange activity in plants. Ectopic expression of DMC1 in somatic cells renders plants hypersensitive to DNA damage and specifically impairs RAD51-dependent homologous recombination. DNA damage-induced RAD51 focus formation in somatic cells is not however suppressed by ectopic expression of DMC1. Interestingly, DMC1 also forms damage-induced foci in these cells and we further show that the ability of DMC1 to prevent RAD51-mediated recombination is associated with local assembly of DMC1 at DNA breaks. In support of our hypothesis, expression of a dominant negative DMC1 protein in meiosis impairs RAD51-mediated DSB repair. We propose that DMC1 acts to prevent RAD51-mediated recombination in Arabidopsis and that this down-regulation requires local assembly of DMC1 nucleofilaments.

The plant-specific DDR factor SOG1 increases chromatin mobility in response to DNA damage.

Homologous recombination (HR) is a conservative DNA repair pathway in which intact homologous sequences are used as a template for repair. How the homology search happens in the crowded space of the cell nucleus is, however, still poorly understood. Here, we measure chromosome and double-strand break (DSB) site mobility in Arabidopsis thaliana, using lacO/LacI lines and two GFP-tagged HR reporters. We observe an increase in chromatin mobility upon the induction of DNA damage, specifically at the S/G2 phases of the cell cycle. This increase in mobility is lost in the sog1-1 mutant, a central transcription factor of the DNA damage response in plants. Also, DSB sites show particularly high mobility levels and their enhanced mobility requires the HR factor RAD54. Our data suggest that repair mechanisms promote chromatin mobility upon DNA damage, implying a role of this process in the early steps of the DNA damage response.

RAD54 is essential for RAD51-mediated repair of meiotic DSB in Arabidopsis.

An essential component of the homologous recombination machinery in eukaryotes, the RAD54 protein is a member of the SWI2/SNF2 family of helicases with dsDNA-dependent ATPase, DNA translocase, DNA supercoiling and chromatin remodelling activities. It is a motor protein that translocates along dsDNA and performs multiple functions in homologous recombination. In particular, RAD54 is an essential cofactor for regulating RAD51 activity. It stabilizes the RAD51 nucleofilament, remodels nucleosomes, and stimulates the homology search and strand invasion activities of RAD51. Accordingly, deletion of RAD54 has dramatic consequences on DNA damage repair in mitotic cells. In contrast, its role in meiotic recombination is less clear. RAD54 is essential for meiotic recombination in Drosophila and C. elegans, but plays minor roles in yeast and mammals. We present here characterization of the roles of RAD54 in meiotic recombination in the model plant Arabidopsis thaliana. Absence of RAD54 has no detectable effect on meiotic recombination in otherwise wild-type plants but RAD54 becomes essential for meiotic DSB repair in absence of DMC1. In Arabidopsis, dmc1 mutants have an achiasmate meiosis, in which RAD51 repairs meiotic DSBs. Lack of RAD54 leads to meiotic chromosomal fragmentation in absence of DMC1. The action of RAD54 in meiotic RAD51 activity is thus mainly downstream of the role of RAD51 in supporting the activity of DMC1. Equivalent analyses show no effect on meiosis of combining dmc1 with the mutants of the RAD51-mediators RAD51B, RAD51D and XRCC2. RAD54 is thus required for repair of meiotic DSBs by RAD51 and the absence of meiotic phenotype in rad54 plants is a consequence of RAD51 playing a RAD54-independent supporting role to DMC1 in meiotic recombination.

Centromere Associations in Meiotic Chromosome Pairing.

Production of gametes of halved ploidy for sexual reproduction requires a specialized cell division called meiosis. The fusion of two gametes restores the original ploidy in the new generation, and meiosis thus stabilizes ploidy across generations. To ensure balanced distribution of chromosomes, pairs of homologous chromosomes (homologs) must recognize each other and pair in the first meiotic division. Recombination plays a key role in this in most studied species, but it is not the only actor and particular chromosomal regions are known to facilitate the meiotic pairing of homologs. In this review, we focus on the roles of centromeres and in particular on the clustering and pairwise associations of nonhomologous centromeres that precede stable pairing between homologs. Although details vary from species to species, it is becoming increasingly clear that these associations play active roles in the meiotic chromosome pairing process, analogous to those of the telomere bouquet.

SPO11.2 is essential for programmed double-strand break formation during meiosis in bread wheat (Triticum aestivum L.).

Meiotic recombination is initiated by formation of DNA double-strand breaks (DSBs). This involves a protein complex that includes in plants the two similar proteins, SPO11-1 and SPO11-2. We analysed the sequences of SPO11-2 in hexaploid bread wheat (Triticum aestivum), as well as in its diploid and tetraploid progenitors. We investigated its role during meiosis using single, double and triple mutants. The three homoeologous SPO11-2 copies of hexaploid wheat exhibit high nucleotide and amino acid similarities with those of the diploids, tetraploids and Arabidopsis. Interestingly, however, two nucleotides deleted in exon-2 of the A copy lead to a premature stop codon and suggest that it encodes a non-functional protein. Remarkably, the mutation was absent from the diploid A-relative Triticum urartu, but present in the tetraploid Triticum dicoccoides and in different wheat cultivars indicating that the mutation occurred after the first polyploidy event and has since been conserved. We further show that triple mutants with all three copies (A, B, D) inactivated are sterile. Cytological analyses of these mutants show synapsis defects, accompanied by severe reductions in bivalent formation and numbers of DMC1 foci, thus confirming the essential role of TaSPO11-2 in meiotic recombination in wheat. In accordance with its 2-nucleotide deletion in exon-2, double mutants for which only the A copy remained are also sterile. Notwithstanding, some DMC1 foci remain visible in this mutant, suggesting a residual activity of the A copy, albeit not sufficient to restore fertility.

Bread wheat TaSPO11-1 exhibits evolutionarily conserved function in meiotic recombination across distant plant species.

The manipulation of meiotic recombination in crops is essential to develop new plant varieties rapidly, helping to produce more cultivars in a sustainable manner. One option is to control the formation and repair of the meiosis-specific DNA double-strand breaks (DSBs) that initiate recombination between the homologous chromosomes and ultimately lead to crossovers. These DSBs are introduced by the evolutionarily conserved topoisomerase-like protein SPO11 and associated proteins. Here, we characterized the homoeologous copies of the SPO11-1 protein in hexaploid bread wheat (Triticum aestivum). The genome contains three SPO11-1 gene copies that exhibit 93-95% identity at the nucleotide level, and clearly the A and D copies originated from the diploid ancestors Triticum urartu and Aegilops tauschii, respectively. Furthermore, phylogenetic analysis of 105 plant genomes revealed a clear partitioning between monocots and dicots, with the seven main motifs being almost fully conserved, even between clades. The functional similarity of the proteins among monocots was confirmed through complementation analysis of the Oryza sativa (rice) spo11-1 mutant by the wheat TaSPO11-1-5D coding sequence. Also, remarkably, although the wheat and Arabidopsis SPO11-1 proteins share only 55% identity and the partner proteins also differ, the TaSPO11-1-5D cDNA significantly restored the fertility of the Arabidopsis spo11-1 mutant, indicating a robust functional conservation of the SPO11-1 protein activity across distant plants. These successful heterologous complementation assays, using both Arabidopsis and rice hosts, are good surrogates to validate the functionality of candidate genes and cDNA, as well as variant constructs, when the transformation and mutant production in wheat is much longer and more tedious.

The Linker Histone GH1-HMGA1 Is Involved in Telomere Stability and DNA Damage Repair.

Despite intensive searches, few proteins involved in telomere homeostasis have been identified in plants. Here, we used pull-down assays to identify potential telomeric interactors in the model plant species Arabidopsis (Arabidopsis thaliana). We identified the candidate protein GH1-HMGA1 (also known as HON4), an uncharacterized linker histone protein of the High Mobility Group Protein A (HMGA) family in plants. HMGAs are architectural transcription factors and have been suggested to function in DNA damage repair, but their precise biological roles remain unclear. Here, we show that GH1-HMGA1 is required for efficient DNA damage repair and telomere integrity in Arabidopsis. GH1-HMGA1 mutants exhibit developmental and growth defects, accompanied by ploidy defects, increased telomere dysfunction-induced foci, mitotic anaphase bridges, and degraded telomeres. Furthermore, mutants have a higher sensitivity to genotoxic agents such as mitomycin C and γ-irradiation. Our work also suggests that GH1-HMGA1 is involved directly in the repair process by allowing the completion of homologous recombination.

The Structure-Specific Endonucleases MUS81 and SEND1 Are Essential for Telomere Stability in Arabidopsis.

Structure-specific endonucleases act to repair potentially toxic structures produced by recombination and DNA replication, ensuring proper segregation of the genetic material to daughter cells during mitosis and meiosis. Arabidopsis thaliana has two putative homologs of the resolvase (structure-specific endonuclease): GEN1/Yen1. Knockout of resolvase genes GEN1 and SEND1, individually or together, has no detectable effect on growth, fertility, or sensitivity to DNA damage. However, combined absence of the endonucleases MUS81 and SEND1 results in severe developmental defects, spontaneous cell death, and genome instability. A similar effect is not seen in mus81 gen1 plants, which develop normally and are fertile. Absence of RAD51 does not rescue mus81 send1, pointing to roles of these proteins in DNA replication rather than DNA break repair. The enrichment of S-phase histone γ-H2AX foci and a striking loss of telomeric DNA in mus81 send1 further support this interpretation. SEND1 has at most a minor role in resolution of the Holliday junction but acts as an essential backup to MUS81 for resolution of toxic replication structures to ensure genome stability and to maintain telomere integrity.

Augmented reality in gynecologic surgery: evaluation of potential benefits for myomectomy in an experimental uterine model.

BACKGROUND: Augmented Reality (AR) is a technology that can allow a surgeon to see subsurface structures. This works by overlaying information from another modality, such as MRI and fusing it in real time with the endoscopic images. AR has never been developed for a very mobile organ like the uterus and has never been performed for gynecology. Myomas are not always easy to localize in laparoscopic surgery when they do not significantly change the surface of the uterus, or are at multiple locations. OBJECTIVE: To study the accuracy of myoma localization using a new AR system compared to MRI-only localization. METHODS: Ten residents were asked to localize six myomas (on a uterine model into a laparoscopic box) when either using AR or in conditions that simulate a standard method (only the MRI was available). Myomas were randomly divided in two groups: the control group (MRI only, AR not activated) and the AR group (AR activated). Software was used to automatically measure the distance between the point of contact on the uterine surface and the myoma. We compared these distances to the true shortest distance to obtain accuracy measures. The time taken to perform the task was measured, and an assessment of the complexity was performed. RESULTS: The mean accuracy in the control group was 16.80 mm [0.1-52.2] versus 0.64 mm [0.01-4.71] with AR. In the control group, the mean time to perform the task was 18.68 [6.4-47.1] s compared to 19.6 [3.9-77.5] s with AR. The mean score of difficulty (evaluated for each myoma) was 2.36 [1-4] versus 0.87 [0-4], respectively, for the control and the AR group. DISCUSSION: We developed an AR system for a very mobile organ. This is the first user study to quantitatively evaluate an AR system for improving a surgical task. In our model, AR improves localization accuracy.

Regulation of Arabidopsis leaf hydraulics involves light-dependent phosphorylation of aquaporins in veins.

The water status of plant leaves depends on the efficiency of the water supply, from the vasculature to inner tissues. This process is under hormonal and environmental regulation and involves aquaporin water channels. In Arabidopsis thaliana, the rosette hydraulic conductivity (Kros) is higher in darkness than it is during the day. Knockout plants showed that three plasma membrane intrinsic proteins (PIPs) sharing expression in veins (PIP1;2, PIP2;1, and PIP2;6) contribute to rosette water transport, and PIP2;1 can fully account for Kros responsiveness to darkness. Directed expression of PIP2;1 in veins of a pip2;1 mutant was sufficient to restore Kros. In addition, a positive correlation, in both wild-type and PIP2;1-overexpressing plants, was found between Kros and the osmotic water permeability of protoplasts from the veins but not from the mesophyll. Thus, living cells in veins form a major hydraulic resistance in leaves. Quantitative proteomic analyses showed that light-dependent regulation of Kros is linked to diphosphorylation of PIP2;1 at Ser-280 and Ser-283. Expression in pip2;1 of phosphomimetic and phosphorylation-deficient forms of PIP2;1 demonstrated that phosphorylation at these two sites is necessary for Kros enhancement under darkness. These findings establish how regulation of a single aquaporin isoform in leaf veins critically determines leaf hydraulics.

Roles of XRCC2, RAD51B and RAD51D in RAD51-independent SSA recombination.

The repair of DNA double-strand breaks by recombination is key to the maintenance of genome integrity in all living organisms. Recombination can however generate mutations and chromosomal rearrangements, making the regulation and the choice of specific pathways of great importance. In addition to end-joining through non-homologous recombination pathways, DNA breaks are repaired by two homology-dependent pathways that can be distinguished by their dependence or not on strand invasion catalysed by the RAD51 recombinase. Working with the plant Arabidopsis thaliana, we present here an unexpected role in recombination for the Arabidopsis RAD51 paralogues XRCC2, RAD51B and RAD51D in the RAD51-independent single-strand annealing pathway. The roles of these proteins are seen in spontaneous and in DSB-induced recombination at a tandem direct repeat recombination tester locus, both of which are unaffected by the absence of RAD51. Individual roles of these proteins are suggested by the strikingly different severities of the phenotypes of the individual mutants, with the xrcc2 mutant being the most affected, and this is confirmed by epistasis analyses using multiple knockouts. Notwithstanding their clearly established importance for RAD51-dependent homologous recombination, XRCC2, RAD51B and RAD51D thus also participate in Single-Strand Annealing recombination.

Meiotic recombination in Arabidopsis is catalysed by DMC1, with RAD51 playing a supporting role.

Recombination establishes the chiasmata that physically link pairs of homologous chromosomes in meiosis, ensuring their balanced segregation at the first meiotic division and generating genetic variation. The visible manifestation of genetic crossing-overs, chiasmata are the result of an intricate and tightly regulated process involving induction of DNA double-strand breaks and their repair through invasion of a homologous template DNA duplex, catalysed by RAD51 and DMC1 in most eukaryotes. We describe here a RAD51-GFP fusion protein that retains the ability to assemble at DNA breaks but has lost its DNA break repair capacity. This protein fully complements the meiotic chromosomal fragmentation and sterility of Arabidopsis rad51, but not rad51 dmc1 mutants. Even though DMC1 is the only active meiotic strand transfer protein in the absence of RAD51 catalytic activity, no effect on genetic map distance was observed in complemented rad51 plants. The presence of inactive RAD51 nucleofilaments is thus able to fully support meiotic DSB repair and normal levels of crossing-over by DMC1. Our data demonstrate that RAD51 plays a supporting role for DMC1 in meiotic recombination in the flowering plant, Arabidopsis.

Differing requirements for RAD51 and DMC1 in meiotic pairing of centromeres and chromosome arms in Arabidopsis thaliana.

During meiosis homologous chromosomes pair, recombine, and synapse, thus ensuring accurate chromosome segregation and the halving of ploidy necessary for gametogenesis. The processes permitting a chromosome to pair only with its homologue are not fully understood, but successful pairing of homologous chromosomes is tightly linked to recombination. In Arabidopsis thaliana, meiotic prophase of rad51, xrcc3, and rad51C mutants appears normal up to the zygotene/pachytene stage, after which the genome fragments, leading to sterility. To better understand the relationship between recombination and chromosome pairing, we have analysed meiotic chromosome pairing in these and in dmc1 mutant lines. Our data show a differing requirement for these proteins in pairing of centromeric regions and chromosome arms. No homologous pairing of mid-arm or distal regions was observed in rad51, xrcc3, and rad51C mutants. However, homologous centromeres do pair in these mutants and we show that this does depend upon recombination, principally on DMC1. This centromere pairing extends well beyond the heterochromatic centromere region and, surprisingly, does not require XRCC3 and RAD51C. In addition to clarifying and bringing the roles of centromeres in meiotic synapsis to the fore, this analysis thus separates the roles in meiotic synapsis of DMC1 and RAD51 and the meiotic RAD51 paralogs, XRCC3 and RAD51C, with respect to different chromosome domains.

Effects of XRCC2 and RAD51B mutations on somatic and meiotic recombination in Arabidopsis thaliana.

Homologous recombination is key to the maintenance of genome integrity and the creation of genetic diversity. At the mechanistic level, recombination involves the invasion of a homologous DNA template by broken DNA ends, repair of the break and exchange of genetic information between the two DNA molecules. Invasion of the template in eukaryotic cells is catalysed by the RAD51 and DMC1 recombinases, assisted by a number of accessory proteins, including the RAD51 paralogues. Eukaryotic genomes encode a variable number of RAD51 paralogues, ranging from two in yeast to five in animals and plants. The RAD51 paralogues form at least two distinct protein complexes, believed to play roles in the assembly and stabilization of the RAD51-DNA nucleofilament. Somatic recombination assays and immunocytology confirm that the three 'non-meiotic' paralogues of Arabidopsis, RAD51B, RAD51D and XRCC2, are involved in somatic homologous recombination, and that they are not required for the formation of radioinduced RAD51 foci. Given the presence of all five proteins in meiotic cells, the apparent absence of a meiotic role for RAD51B, RAD51D and XRCC2 is surprising, and perhaps simply the result of a more subtle meiotic phenotype in the mutants. Analysis of meiotic recombination confirms this, showing that the absence of XRCC2, and to a lesser extent RAD51B, but not RAD51D, increases rates of meiotic crossing over. The roles of RAD51B and XRCC2 in recombination are thus not limited to mitotic cells.

Diffusion-weighted magnetic resonance imaging in ileocolonic Crohn's disease: validation of quantitative index of activity.

OBJECTIVES: Magnetic resonance imaging (MRI) allows accurate assessment of Crohn's disease (CD), but requires gadolinium injection. Diffusion-weighted (DW)-MRI yields comparable performances in small bowel CD. We compared the accuracy of DW-MR enterocolonography (MREC) and the magnetic resonance index of activity (MaRIA), and performed an external validation of the Clermont score in assessing inflammation in CD. METHODS: This was an observational prospective study of a single-center cohort. A total of 130 CD patients underwent consecutively MREC with gadolinium injection and DWI sequences between July 2011 and December 2012. RESULTS: Of the 848 evaluated segments (small bowel=352, colon/rectum=496), 175 (20.6%) were active (small bowel=111, colon/rectum=64) defined as MaRIA ≥7. Using a receiver operating characteristic (ROC) curve, we determined an apparent coefficient of diffusion (ADC) threshold of 1.9 × 10(-3) mm(2)/s that yielded a sensitivity and a specificity in discriminating active from nonactive CD of 96.9% and 98.1%, respectively, for the colon/rectum, and 85.9% and 81.6%, respectively, for the ileum. ADC was better correlated to MaRIA ≥7 than related contrast enhancement obtained with injected sequences (P<0.001). The Clermont score (=1.646 × bowel thickness-1.321 × ADC+5.613 × edema+8.306 × ulceration+5.039) was highly correlated with the MaRIA (rho=0.99) in ileal CD but not in colonic CD (rho <0.80). Interobserver agreement was high with regard to ADC measurement (correlation >0.9, P<0.001, and concordance >0.9, P<0001). CONCLUSIONS: DW-MREC is a reliable tool to assess inflammation in colonic (ADC) and ileal (Clermont score) CD and its use in daily practice would avoid gadolinium injection.

Resection of pancreatic ductal adenocarcinoma with synchronous distant metastasis: is it worthwhile?

BACKGROUND: The purpose of this study is to report prolonged survival in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) managed by chemotherapy and surgery. METHODS: Between January 2009 and August 2013, 284 patients with metastatic PDAC were managed in our oncologic department. Among them, three (1%) with a single metastasis (liver in two cases and interaorticaval in one case) underwent one- or two-stage surgical resection of the metastasis and the main tumor. Perioperative data were recorded retrospectively, including disease-free and overall survival. RESULTS: The three patients had chemotherapy (FOLFOX or FOLFIRINOX regimen) with objective response or stable disease prior to surgery. Median time between chemotherapy and surgery was 9 (8 to 15) months. Resection consisted in pancreaticoduodenectomy in the three cases. None of the patients had grade III/IV postoperative complications, and median hospital stay was 12 (12 to 22) days. All the patients had postoperative chemotherapy. Only one patient experienced recurrence 11 months after surgery and died after 32.5 months. The two other patients were alive with no recurrence 26.3 and 24.7 months after initial treatment. CONCLUSION: Radical resection of PDAC with single distant metastases can offer prolonged survival with low morbidity after accurate selection by neoadjuvant chemotherapy.

DNA-binding site II is required for RAD51 recombinogenic activity in Arabidopsis thaliana.

Homologous recombination is a major pathway for the repair of DNA double strand breaks, essential both to maintain genomic integrity and to generate genetic diversity. Mechanistically, homologous recombination involves the use of a homologous DNA molecule as a template to repair the break. In eukaryotes, the search for and invasion of the homologous DNA molecule is carried out by two recombinases, RAD51 in somatic cells and RAD51 and DMC1 in meiotic cells. During recombination, the recombinases bind overhanging single-stranded DNA ends to form a nucleoprotein filament, which is the active species in promoting DNA invasion and strand exchange. RAD51 and DMC1 carry two major DNA-binding sites-essential for nucleofilament formation and DNA strand exchange, respectively. Here, we show that the function of RAD51 DNA-binding site II is conserved in the plant, Arabidopsis. Mutation of three key amino acids in site II does not affect RAD51 nucleofilament formation but inhibits its recombinogenic activity, analogous to results from studies of the yeast and human proteins. We further confirm that recombinogenic function of RAD51 DNA-binding site II is not required for meiotic double-strand break repair when DMC1 is present. The Arabidopsis AtRAD51-II3A separation of function mutant shows a dominant negative phenotype, pointing to distinct biochemical properties of eukaryotic RAD51 proteins.

Abdominal complications following neutropenia and haematopoietic stem cell transplantation: CT findings.

In haematology units, acute abdominal symptoms are common and often challenging for the clinician in charge. Two haematological conditions that may induce specific diagnoses are of particular concern: neutropenia and haematopoietic stem cell transplantation. Clinical and biological manifestations, including abdominal pain, fever, diarrhoea, hepatic cytolysis, or cholestasis are often non-specific. Computed tomography is often the primary imaging screening technique performed in such patients, as it is widely available, performs well for this indication, and may demonstrate evocative findings. The aim of this review is to provide the spectrum of specific diagnoses encountered and the corresponding key CT features in patients presenting with acute abdominal disorders following neutropenia and/or haematopoietic stem cell transplantation.

Fibrous tumours of the ovary: aetiologies and MRI features.

The ovaries can be affected by a vast variety of tumours, which may be benign or malignant, solid or cystic. Although ultrasonography is often the first examination performed in the evaluation of gynaecological conditions, magnetic resonance imaging is nowadays the most accurate imaging technique in the characterization of ovarian masses. Once the ovarian origin of a pelvic mass has been determined, the detection of any fibrous component within the lesion significantly reduces the spectrum of aetiologies that should be considered. Fibrotic tissue usually displays marked low-signal intensity on T2-weighted sequences at MRI, and enhancement is mostly moderate after intravenous administration of gadolinium chelates. This review aims to provide the main diagnoses to consider at MRI whenever an ovarian tumour, both purely solid or solid and cystic, contains a fibrous component, even if minimally abundant. The corresponding key imaging features are provided.

Acceptability and feasibility of home and hospital follow-up in Burkina Faso and Guinea: A mixed-method study among patients of the COVID-19 Coverage-Africa clinical trial.

Patient experiences and perspectives on trial participation and follow-up may influence their compliance with research procedures or negatively impact their well-being. We aimed to explore the acceptability and feasibility of home-based and hospital-based follow-up modalities among COVID-19 patients enrolled in the ANTICOV ANRS COV33 Coverage-Africa trial in Burkina Faso and Guinea. The trial (2021-2022) evaluated the efficacy of treatments to prevent clinical worsening among COVID-19 patients with mild to moderate symptoms. Patients were either based at home or hospitalized, as per national recommendations, and followed-up through face-to-face visits and phone calls. We conducted a mixed-methods sub-study administering a questionnaire to all consenting participants and individually interviewing purposively selected participants. We performed descriptive analyses of Likert scale questions for the questionnaires and thematic analysis for the interviews. We conducted framework analysis and interpretation. Of the 400 trial patients, 220 completed the questionnaire (n = 182 in Burkina Faso, n = 38 in Guinea) and 24 were interviewed (n = 16 and n = 8, respectively). Participants were mostly followed-up at home in Burkina Faso; all patients from Guinea were first hospitalized, then followed-up at home. Over 90% of participants were satisfied with follow-up. Home follow-up was considered acceptable if (i) participants perceived they were not severely ill, (ii) it was combined with telemedicine, and (iii) the risk of stigma could be avoided. Hospital-based follow-up was viewed as a way to prevent contamination of family members, but could be badly experienced when mandatory and conflicting with family responsibilities and commitments. Phone calls were seen as reassuring and as a way to ensure continuity of care. These overall positive findings support the development of home-based follow-up for mildly ill patients in West-Africa, provided that both emotional and cognitive factors at individual, familial/inter-relational, healthcare and national levels be addressed when planning the implementation of a trial, or developing any public health strategy.