Changing patterns in the burden of paediatric injuries during the COVID-19 pandemic: a study in Mozambique’s central hospitals

Abstract Introduction There is a substantial body of knowledge on the effects of the COVID-19 pandemic on injuries showing frequent but inconsistent reductions in both volume and pattern. Yet, studies specifically addressing children are less common, not least from low- and middle-income countries. This study investigated whether changes in the pattern and outcome of paediatric injury admissions to Mozambique’s four regional referral hospitals during 2020. Methods Clinical charts of paediatric patients presenting to the targeted hospitals with acute injuries were reviewed using a set of child, injury, and outcome characteristics during each of two consecutive restriction periods in 2020 using as a comparator the same periods in 2019, the year before the pandemic. Differences between 2020 and 2019 proportions for any characteristic were examined using the t-test (significance level 0.05). Results During both restriction periods, compared with the previous year, reductions in the number of injuries were noticed in nearly all aspects investigated, albeit more remarkably during the first restriction period, in particular, greater proportions of injuries in the home setting and from burns (7.2% and 11.5% respectively) and a reduced one of discharged patients (by 2.5%). Conclusion During the restrictions implemented to contend the pandemic in Mozambique in 2020, although each restriction period saw a drop in the volume of injury admissions at central hospitals, the pattern of child, injury and outcome characteristics did not change much, except for an excess of home and burn injuries in the first, more restrictive period. Whether this reflects the nature of the restrictions only or, rather, other mechanisms that came into play, individual or health systems related, remains to be determined

An introduction to the microbiome and MS

The human microbiota is composed of diverse forms of microorganisms that live on or in us and plays a crucial role in the health and development. Commensal species that reside in the intestine particularly influence host physiology at local and systemic levels. Multiple sclerosis (MS) is a debilitating autoimmune disorder of the central nervous system for which there is currently no cure. While the cause of MS is unknown, there is a growing body of evidence suggesting that the microbiota can play both pathogenic and protective roles in disease progression. In this review, we provide a brief overview, based on both animal and clinical studies, of the current understanding by which the microbiota may influence MS and discuss opportunities for therapeutic intervention that may alleviate the symptoms associated with this debilitating neuroimmunological disease. </jats:p

Alpha-defensin 5 differentially modulates adenovirus vaccine vectors from different serotypes in vivo.

Adenoviral vectors have shown significant promise as vaccine delivery vectors due to their ability to elicit both innate and adaptive immune responses. α-defensins are effector molecules of the innate immune response and have been shown to modulate natural infection with adenoviruses, but the majority of α-defensin-adenovirus interactions studied to date have only been analyzed in vitro. In this study, we evaluated the role of α-defensin 5 (HD5) in modulating adenovirus vaccine immunogenicity using various serotype adenovirus vectors in mice. We screened a panel of human adenoviruses including Ad5 (species C), Ad26 (species D), Ad35 (species B), Ad48 (species D) and a chimeric Ad5HVR48 for HD5 sensitivity. HD5 inhibited transgene expression from Ad5 and Ad35 but augmented transgene expression from Ad26, Ad48, and Ad5HVR48. HD5 similarly suppressed antigen-specific IgG and CD8+ T cell responses elicited by Ad5 vectors in mice, but augmented IgG and CD8+ T cell responses and innate cytokine responses elicited by Ad26 vectors in mice. Moreover, HD5 suppressed the protective efficacy of Ad5 vectors but enhanced the protective efficacy of Ad26 vectors expressing SIINFEKL against a surrogate Listeria-OVA challenge in mice. These data demonstrate that HD5 differentially modulates adenovirus vaccine delivery vectors in a species-specific manner in vivo

Longitudinal analysis of Ad26-elicicted antigen-specific CD8⁺ T cell responses.

C57BL/6 mice (n = 5/group) were administered i.m. Ad26.SIINFEKL (108 - 107vp) pretreated with either PBS or 100 μM HD5. Mice were bled and SIINFEKL-specific CD8+ T cell responses were measured by H-2Kb tetramer staining at (A-F) weeks 1–8 post immunization. The data are representative of experiments performed two times. Mean ± SEM are shown. *** p p p < 0.05, Mann-Whitney U Test (compared to virus only control).</p

Vaccine-elicited antibody responses to Ad5 and Ad26 ± HD5 pretreatment.

C57BL/6 mice (n = 5/group) were pretreated with either PBS or a dose titration of 25 μM– 100 μM HD5 with (A) Ad5.SIVEnv (109 vp) or 100 μM HD5 with (B) Ad26.SIVEnv (108–107 vp) encoding SIV ENV. Env-specific IgG responses were determined in serum by ELISA at days 14 and 28 post immunization. Means and standard deviations of endpoint ELISA titers are shown. *** p p p 6 vp) with and without 100 μM HD5 on Day 14 and 28 post immunization. Groups (Ad26-HD5 compared to Ad26) were assessed for significance on day 14 or day 28 using a Fisher Exact Test to identify nonrandom associations between groups. The day 28 analysis resulted in a two-tailed Fisher Exact Test p value = 0.0017. The data are representative of experiments performed three times.</p

In vivo luciferase transgene expression by Ad5 and Ad26 ± HD5 pretreatment.

Animals were pretreated with a dose titration of 2.5 μM– 100 μM HD5, 100 μM mutant HD5 (linear peptide), or PBS ± 100 μM HD5 and immunized i.m. with (A) Ad5 (109 vp) or (B) 25 μM– 100 μM HD5 with Ad26 (109 vp) vectors encoding luciferase transgene cassettes. Representative day 3 IVIS images are shown for each experimental condition assayed. The Total Flux (photons/sec/cm2/radian) released by luciferase activity was averaged for (C) Ad5 and (D) Ad26 at each time-point. n = 5 animals per group. The data are representative of experiments performed two times. Mean ± SEM are shown. *** p p p < 0.05, one-way ANOVA test (compared to virus only control).</p

Analysis of Ad5HVR48 sensitivity to HD5 in A549 cells.

Ad5, Ad48, and Ad5HVR48 were incubated with 0.2 μM– 33 μM HD5 or 50 μM mutant HD5 (diagonal box) and assessed for % of cells expressing luciferase 24 h post infection. Experimental results are normalized to control infected with virus (100%) in the absence of peptide. Data is expressed as the mean (±SD) of three independent experiments. *** p p p < 0.05, one-way ANOVA test (compared to virus only control).</p

HD5 alters antigen-specific CD8⁺ T cell responses primed by Ad5 and Ad26 vectors in a recombinant <i>Listeria monocytogenes</i> challenge model in mice.

C57BL/6 mice (n = 5/group) were administered i.m. Ad5.SIINFEKL (108 vp) or Ad26.SIINFEKL (108 vp) pretreated with either PBS or 100 μM HD5. (A) On day 11 after immunization, mice were bled and SIINFEKL-specific CD8+ T cell responses were measured by H-2Kb tetramer staining. Following bleeding, animals were challenged with 1.0 X 105 CFU Lm-OVA. (B) The mean number of bacteria per spleen was determined 48 h after Listeria monocytogenes infection. The data are representative of experiments performed two times. Mean ± SEM are shown. ** p p < 0.05, Mann-Whitney U Test (compared to virus only control).</p