Dynamic and features of SARS-CoV-2 infection in Gabon.

In a context where SARS-CoV-2 population-wide testing is implemented, clinical features and antibody response in those infected have never been documented in Africa. Yet, the information provided by analyzing data from population-wide testing is critical to understand the infection dynamics and devise control strategies. We described clinical features and assessed antibody response in people screened for SARS-CoV-2 infection. We analyzed data from a cohort of 3464 people that we molecularly screened for SARS-CoV-2 infection in our routine activity. We recorded people SARS-CoV-2 diagnosis, age, gender, blood types, white blood cells (WBC), symptoms, chronic disease status and time to SARS-CoV-2 RT-PCR conversion from positive to negative. We calculated the age-based distribution of SARS-CoV-2 infection, analyzed the proportion and the spectrum of COVID-19 severity. Furthermore, in a nested sub-study, we screened 83 COVID-19 patients and 319 contact-cases for anti-SARS-CoV-2 antibodies. Males and females accounted for respectively 51% and 49% of people screened. The studied population median and mean age were both 39 years. 592 out of 3464 people (17.2%) were diagnosed with SARS-CoV-2 infection with males and females representing, respectively, 53% and 47%. The median and mean ages of SARS-CoV-2 infected subjects were 37 and 38 years respectively. The lowest rate of infection (8%) was observed in the elderly (aged > 60). The rate of SARS-Cov-2 infection in both young (18-35 years old) and middle-aged adults (36-60 years old) was around 20%. The analysis of SARS-CoV-2 infection age distribution showed that middle-aged adults accounted for 54.7% of SARS-CoV-2 positive persons, followed respectively by young adults (33.7%), children (7.7%) and elderly (3.8%). 68% (N = 402) of SARS-CoV-2 infected persons were asymptomatic, 26.3% (N = 156) had influenza-like symptoms, 2.7% (N = 16) had influenza-like symptoms associated with anosmia and ageusia, 2% (N = 11) had dyspnea and 1% (N = 7) had respiratory failure, which resulted in death. Data also showed that 12% of SARS-CoV-2 infected subjects, had chronic diseases. Hypertension, diabetes, and asthma were the top concurrent chronic diseases representing respectively 58%, 25% and 12% of recorded chronic diseases. Half of SARS-CoV-2 RT-PCR positive patients were cured within 14 days following the initiation of the anti-COVID-19 treatment protocol. 78.3% of COVID-19 patients and 55% of SARS-CoV-2 RT-PCR confirmed negative contact-cases were positive for anti-SARS-CoV-2 antibodies. Patients with severe-to-critical illness have higher leukocytes, higher neutrophils and lower lymphocyte counts contrarily to asymptomatic patients and patients with mild-to-moderate illness. Neutrophilic leukopenia was more prevalent in asymptomatic patients and patients with mild-to-moderate disease for 4 weeks after diagnosis (27.1-42.1%). In Patients with severe-to-critical illness, neutrophilic leukocytosis or neutrophilia (35.6-50%) and lymphocytopenia (20-40%) were more frequent. More than 60% of participants were blood type O. It is also important to note that infection rate was slightly higher among A and B blood types compared with type O. In this African setting, young and middle-aged adults are most likely driving community transmission of COVID-19. The rate of critical disease is relatively low. The high rate of anti-SARS-CoV-2 antibodies observed in SARS-CoV-2 RT-PCR negative contact cases suggests that subclinical infection may have been overlooked in our setting.

[Classical actions of vitamin D: insights from human genetics and from mouse models on calcium and phosphate homeostasis]. / Actions classiques de la vitamine D : apport de la génétique humaine et de modèles de souris génétiquement modifiées.

At the beginning of the 20th century, the discovery of vitamin D by Sir EV McCollum allowed a better comprehension of its origin and its role, and made it possible to cure rickets, a largely prevalent disease at that time. The main role of vitamin D3 is to maintain calcium and phosphate homeostasis through the action of 1,25-dihydroxyvitamin D3, its active form. This underlies physiological functions related to calcium and phosphate, such as bone mineralization or muscle function. Progress in basic research for the last 40 years led to the discovery of the main hydroxylation steps that produce and catabolize the active form of vitamin D. It also uncovered the molecular aspects of vitamin D action, from its nuclear receptor, VDR, to the various target genes of this hormone. Recent progress in human genetics pointed out mutations in genes involved in vitamin D metabolism and 1,25-dihydroxyvitamin D3 actions. It also helped to understand the role of the major actors that control vitamin D production and effects, through 1,25-dihydroxyvitamin D3 actions on phosphate and calcium homeostasis, and on bone biology. Genetical engineering targeting the whole animal or defined tissues or cell types have yielded many mouse models in the past decades. When targeted to tissues important for vitamin D metabolism and activity, these models allowed a more detailed comprehension of vitamin effects on calcium and phosphorus homeostasis.

Growth, calcium status and vitamin D receptor (VDR) promoter genotype in European children with normal or low calcium intake.

Calcium homeostasis and bone metabolism require the vitamin D receptor (VDR) to function properly, as evidenced in patients and transgenic mice with VDR mutations. We have shown that (A/G) polymorphism at the -1012 locus of the VDR promoter (rs4516035) is frequent in European populations, may influence VDR expression, is associated with height in French adolescent girls, and is associated with their lumbar spine mineral density in case of insufficient milk intake. Here, an association study was performed in a cohort of Moldovan children and adolescents, living at latitude similar to the first cohort but receiving a cereal-based diet with very low milk/dairy product intakes. Children and adolescents in this cohort had similar 25-(OH) D levels, but a short stature and low serum calcium levels, compared to the first cohort. Their height remained associated with the A-1012G VDRp genotype. In addition, their serum calcium levels were associated with VDRp polymorphism, excepted when their 25-(OH) D levels were low (below 33 nmol/L). In conclusion, the -1012 VDRp genotype appears to be associated with height in European children whatever their calcium/dairy product intakes, and may modulate their calcium homeostasis in conditions of low calcium/milk intakes when vitamin D status is sufficient.