Mass Drug Administration Interruption by COVID-19 reportedly increases lymphatic filarial attacks, pains, and perceived increased lymphatic filarial infection transmission in rural Ghana (preprint)

BackgroundLike all other diseases, the advent of the COVID-19 pandemic has been implicated to impact the elimination schedule and control of neglected tropical diseases such as human lymphatic filarial (LF) infections in endemic countries. However, it is unclear the extent to which delays in mass drug administration has affected people living with chronic lymphatic filarial pathology in rural Ghana as a result of the COVID-19 pandemic, and thus remain to be investigated. MethodTo address this, a cross-sectional study where 133 LF participants from 8 LF-endemic communities in the Ahanta West District of Ghana were recruited to assess the impact of MDA interruptions as a result of COVID-19 among individuals presenting with the filarial pathology. Here, the chi-square test of independence was used as a statistical tool to assess the dependency: 1) between MDA interruption and filarial attacks 2) between MDA interruption and filarial-related pains 3) between MDA interruption and a perceived increase in LF transmission.ResultsStudy participants were asked whether the MDA interruption has affected them in any way. Here, 81% of the patients indicated yes, it had. In addition, we sought to investigate whether MDA interruption has resulted in increased filarial attacks and pains. At this, 68% of the study respondents reported an increase in filarial attacks. Similarly, 65% reported an increase in filarial-related pains. The study further reported that filarial attacks (B=14.997, df=1, p-value <0.001) and pains (a=11.773, df=1, p-value <0.001)  are dependent on MDA interruption. Next, we further report that the perceived increase in LF transmission is dependent on MDA interruption (c=9.415, df=1, p-value=0.002).   ConclusionIn this study, MDA interruption is reported to increase filarial attacks, filarial-related pains, and a perceived LF transmission increase in the study communities. This study's findings are important and urgent, suggesting that sustained MDA interruption in LF-endemic communities could further worsen LF patients' plight as filarial attacks, pains, and transmission could increase. Therefore, the need to immediately identify alternative modes of MDA distribution in LF-endemic areas where mass treatment has been halted in the wake of COVID-19 to prevent an unwarranted surge in LF attacks, pains, and transmission.

Impact of the SARS-CoV-2 S-protein G476S mutation on the interaction with human ACE-2 receptor and neutralizing antibodies (preprint)

The G476S mutation of the SARS-CoV-2 S-protein occurs in the receptor binding domain (RBD), the region that binds to the human angiotensin-converting enzyme 2 (hACE-2) receptor and also the main target for neutralizing antibodies. The 476S variant was first reported in the USA. Emerging evidence show that the 476S variant resists neutralization by antibodies such as S2E12 and CC6.29. The impact of the mutation on the interactions with hACE-2 receptor and the dynamics of the S-protein, has not been not fully explored. Here, we provide insights into the structure dynamics of the 476S variant and investigate the impact of the mutation on interactions with hACE-2 and selected neutralizing antibodies. We report that the mutation induces a destabilization effect in the RBD and an increased flexibility for most of the receptor binding residues. The mutation, however, does not affect the interactions with the hACE-2 receptor. Both Gly-476 and Ser-476, although located within the hACE-2 interacting residue hotspot, do not contribute to the stabilization of the RBD-hACE-2 complex. Our findings suggest that both H014 and P2P-2F6 antibodies neutralize the 476G and 476S S-proteins with similar efficacy.

Transmission of SARS-CoV-2 in Northern Ghana; Insights from Whole Genome Sequencing (preprint)

In regions lacking genomic data, analysis of sequences from the early stages of an outbreak can provide important insights into the diversity of pathogens present. Following the detection of the first imported case of COVID-19 in the Northern sector of Ghana on 13th March 2020, we have now molecularly characterized and phylogenetically analysed sequences including three (3) complete genomes of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) isolated from nine (9) patients observed in Ghana. Eight (8) of these patients reported with a recent history of foreign travel and one (1) with no history of foreign travel. We performed high throughput sequencing for 9 samples following the determination of high concentration of viral RNA. In addition, we estimated the potential impact that long distance transportation of samples to testing centres may have on sequencing outcomes. Here, two samples that were closest in terms of viral RNA concentration but transported from sites which are over 400km apart were assessed. All sequences were compared to previous sequences from Ghana and representative sequences from regions where our patients had previously travelled. Complete genomes were obtained for three (3) sequences and with another near complete genome with a coverage of 95.6%. Sequences with coverage in excess of 80% were found to belong to three lineages namely A, B.1 and B.2. Our sequences clustered in two different clades with the majority falling within a clade composed of sequences from sub-Saharan Africa. Less RNA fragmentation was seen in sample KATH23 which was collected 9km compared with sample TTH6 which was collected and transported over a distance of 400km to the testing site. The clustering of several sequences from sub-Saharan Africa suggests regional circulation of the viruses in the subregion. Importantly, there may be the need to decentralize testing sites and build more capacity across Africa to boost the sequencing output of the subregion.