SARS-CoV-2 transmission via apical syncytia release from primary bronchial epithelia and infectivity restriction in children epithelia

The beta-coronavirus SARS-CoV-2 is at the origin of a persistent worldwide pandemic. SARS-CoV-2 infections initiate in the bronchi of the upper respiratory tract and are able to disseminate to the lower respiratory tract eventually causing acute severe respiratory syndrome with a high degree of mortality in the elderly. Here we use reconstituted primary bronchial epithelia from adult and children donors to follow the infection dynamic following infection with SARS-CoV-2. We show that in bronchial epithelia derived from adult donors, infections initiate in multi-ciliated cells. Then, infection rapidly spread within 24-48h throughout the whole epithelia. Within 3-4 days, large apical syncytia form between multi-ciliated cells and basal cells, which dissipate into the apical lumen. We show that these syncytia are a significant source of the released infectious dose. In stark contrast to these findings, bronchial epithelia reconstituted from children donors are intrinsically more resistant to virus infection and show active restriction of virus spread. This restriction is paired with accelerated release of IFN compared to adult donors. Taken together our findings reveal apical syncytia formation as an underappreciated source of infectious virus for either local dissemination or release into the environment. Furthermore, we provide direct evidence that children bronchial epithelia are more resistant to infection with SARS-CoV-2 providing experimental support for epidemiological observations that SARS-CoV-2 cases fatality is linked to age.

COVID-19 epidemic in Malaysia: Impact of lockdown on infection dynamics

COVID-19 epidemic in Malaysia started as a small wave of 22 cases in January 2020 through imported cases. It was followed by a bigger wave mainly from local transmissions resulting in 651 cases. The following wave saw unexpectedly three digit number of daily cases following a mass gathering urged the government to choose a more stringent measure. A limited lock-down approach called Movement Control Order (MCO) was immediately initiated to the whole country as a way to suppress the epidemic trajectory. The lock-down causes a major socio-economic disruption thus the ability to forecast the infection dynamic is urgently required to assist the government on timely decisions. Limited testing capacity and limited epidemiological data complicate the understanding of the future infection dynamic of the COVID-19 epidemic. Three different epidemic forecasting models was used to generate forecasts of COVID-19 cases in Malaysia using daily reported cumulative case data up until 1st April 2020 from the Malaysia Ministry of Health. The forecasts were generated using a Curve Fitting Model with Probability Density Function and Skewness Effect, the SIR Model, and a System Dynamic Model. Method one based on curve fitting with probability density function estimated that the peak will be on 19th April 2020 with an estimation of 5,637 infected persons. Method two based on SIR Model estimated that the peak will be on 20th - 31st May 2020 if Movement Contro (MCO) is in place with an estimation of 630,000 to 800,000 infected persons. Method three based on System Dynamic Model estimated that the peak will be on 17th May 2020 with an estimation of 22,421 infected persons. Forecasts from each of model suggested the epidemic may peak between middle of April to end of May 2020.

THE STUDY OF THE INNATE AND ACQUIRED CELLULAR IMMUNITY CHAINS INDICATORS IN THE PERIPHERAL BLOOD OF PATIENTS WITH HIV INFECTION

In this study was made an attempt to reveal additional laboratory markers of white blood for preliminary estimation level of HIV-infection development. Essentially such markers these are in progress without complex equipment and expensive reagent. It was studied alterations of basic values cells of innate and acquired immunity of peripheral blood HIV-infected individuals with and without antiretroviral treatment (ART) during infection. It was estimate value leukocytes, neutrophils, monocytes, lymhpocytes, T-lymhpocytes, CD4+, CD8+ T-cells, CD4/CD8 index. It was used the first analysis in the time of registration for regular medical check-up and the intermediate derived during 2017-2018 years. Patients without ART and with ART before and after treatment had rates of leukocytes, lymhpocytes, T-lymhpocytes, monocytes and neutrophils within the normal guideline. Essential changes were observed in basic conventional laboratory parameters evaluation of HIV-infection dynamic (parameters of CD4+and CD8+ cells, CD4/CD8 index). Thereby it was impossible to reveal supplementary immunological markers of HIV-infection.

Developmental competence and antigen switch frequency can be uncoupled in Trypanosoma brucei

African trypanosomes use an extreme form of antigenic variation to evade host immunity, involving the switching of expressed variant surface glycoproteins by a stochastic and parasite-intrinsic process. Parasite development in the mammalian host is another feature of the infection dynamic, with trypanosomes undergoing quorum sensing (QS)-dependent differentiation between proliferative slender forms and arrested, transmissible, stumpy forms. Longstanding experimental studies have suggested that the frequency of antigenic variation and transmissibility may be linked, antigen switching being higher in developmentally competent, fly-transmissible, parasites (“pleomorphs”) than in serially passaged “monomorphic” lines that cannot transmit through flies. Here, we have directly tested this tenet of the infection dynamic by using 2 experimental systems to reduce pleomorphism. Firstly, lines were generated that inducibly lose developmental capacity through RNAi-mediated silencing of the QS signaling machinery (“inducible monomorphs”). Secondly, de novo lines were derived that have lost the capacity for stumpy formation by serial passage (“selected monomorphs”) and analyzed for their antigenic variation in comparison to isogenic preselected populations. Analysis of both inducible and selected monomorphs has established that antigen switch frequency and developmental capacity are independently selected traits. This generates the potential for diverse infection dynamics in different parasite populations where the rate of antigenic switching and transmission competence are uncoupled. Further, this may support the evolution, maintenance, and spread of important trypanosome variants such as Trypanosoma brucei evansi that exploit mechanical transmission.

Modeling Inhibitory Effect on the Growth of Uninfected T Cells Caused by Infected T Cells: Stability and Hopf Bifurcation

We consider a class of viral infection dynamic models with inhibitory effect on the growth of uninfected T cells caused by infected T cells and logistic target cell growth. The basic reproduction number R0 is derived. It is shown that the uninfected equilibrium is globally asymptotically stable if R0<1. Sufficient conditions for the existence of Hopf bifurcation at the infected equilibrium are investigated by analyzing the distribution of eigenvalues. Furthermore, the properties of Hopf bifurcation are determined by the normal form theory and the center manifold. Numerical simulations are carried out to support the theoretical analysis.