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Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

D. Saikia et al.

J. Virtanen et al.

Ż. Zajączkowska et al.

C. Botto-Mahan et al.

AbstractBackgroundCerebral malaria (CM) is a rare, but severe and frequently fatal outcome of infections with Plasmodium falciparum. Pathogenetic mechanisms include endothelial activation and sequestration of parasitized erythrocytes in the cerebral microvessels. Increased concentrations of glycosaminoglycans in urine and plasma of malaria patients have been described, suggesting involvement of endothelial glycocalyx.MethodsWe used lectin histochemistry on postmortem samples to compare the distribution of multiple sugar epitopes on cerebral capillaries in children who died from CM and from non-malarial comas.ResultsN-acetyl glucosamine residues detected by tomato lectin are generally reduced in children with CM compared to controls. We used the vascular expression of intercellular adhesion molecule-1 and mannose residues on brain capillaries of CM as evidence of local vascular inflammation, and both were expressed more highly in CM patients than controls. Sialic acid residues were found to be significantly reduced in patients with CM. By contrast, the levels of other sugar epitopes regularly detected on the cerebral vasculature were unchanged, and this suggests specific remodeling of cerebral microvessels in CM patients.ConclusionsOur findings support and expand upon earlier reports of disruptions of the endothelial glycocalyx in children with severe malaria.

AbstractBackgroundWaning antibody levels post-vaccination and the emergence of variants of concern (VOCs) capable of evading protective immunity has raised the need for booster vaccinations. However, which combination of COVID-19 vaccines offers the strongest immune response against Omicron variant is unknown.MethodsThis randomized, subject-blinded, controlled trial assessed the reactogenicity and immunogenicity of different COVID-19 vaccine booster combinations. 100 BNT162b2-vaccinated individuals were enrolled and randomized 1: 1 to either homologous (BNT162b2 + BNT162b2 + BNT162b2; ‘BBB’) or heterologous mRNA booster vaccine (BNT162b2 + BNT162b2 + mRNA-1273; ‘BBM’). Primary endpoint was the level of neutralizing antibodies against SARS-CoV-2 wild-type and VOCs at Day 28.Results51 participants were allocated to BBB and 49 to BBM; 50 and 48 respectively were analyzed for safety and immunogenicity outcomes. At Day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBB (22,382  IU/mL 95% CI, 18,210 to 27,517) vs BBM (29,751  IU/mL 95% CI, 25,281 to 35,011, p = 0.034) as was the median level of neutralizing antibodies: BBB 99.0% (IQR 97.9 to 99.3%) vs BBM 99.3% (IQR 98.8 to 99.5%, p = 0.021). On sub-group analysis, significant differences in mean spike antibody titer and live Omicron neutralization titer was only observed in older adults. Median surrogate neutralizing antibody level against all VOCs was also significantly higher with BBM in older adults, and against Omicron was BBB 72.8% (IQR 54.0 to 84.7%) vs BBM 84.3% (IQR 78.1 to 88.7%, p = 0.0073). Both vaccines were well tolerated.ConclusionsHeterologous mRNA-1273 booster vaccination induced a stronger neutralizing response against the Omicron variant in older individuals compared with homologous BNT123b2.

Several errors appeared in supplementary data for the corrected proof publication of this article (de Castilhos J, Zamir E, Hippchen T, et al. Severe Dysbiosis and Specific Haemophilus and Neisseria Signatures as Hallmarks of the Oropharyngeal Microbiome in Critically Ill Coronavirus Disease 2019 [COVID-19] Patients. Clin Infect Dis; https://doi.org/10.1093/cid/ciab902).

AbstractA positive follow-up blood culture for methicillin-resistant Staphylococcus aureus (MRSA) while on seemingly appropriate therapy is a common and ominous development. However, the definition and management of persistent MRSA bacteremia is unstandardized. In this Opinion Paper we identify the presence of bacteremia for > 1 calendar day as a ‘worry point’ that should trigger an intensive diagnostic evaluation to identify metastatic infection sites. Next, we define the duration of MRSA bacteremia that likely constitutes ‘antibiotic failure’, and outline a proposed management algorithm for such patients. Finally, we propose pragmatic clinical trial designs to test treatment strategies for persistent MRSA bacteremia.

AbstractStaphylococcus aureus bacteremia (SAB) causes considerable morbidity and mortality and requires comprehensive assessment for metastatic infection. The roles of routine imaging beyond echocardiography in SAB, including 18F-FDG-PET/CT, remain contentious. We performed a literature review of studies reporting impact of 18F-FDG-PET/CT on the clinical management or outcomes of SAB published through 3/1/2022. We identified seven observational studies, in which 18F-FDG-PET/CT frequently identified metastatic foci of infection, revealed foci undetected by prior investigations, led to additional source control procedures, and was associated with fewer infection relapses and lower mortality. Calculated numbers needed to treat (NNTs) for receipt of 18F-FDG-PET/CT were 7-9 to change antimicrobial therapy, 10-27 to lead to an additional source control procedure, and 4-8 to prevent death. These data are comparable to the evidence for clinical impact of other diagnostic modalities accepted as standard of care in SAB, and form a compelling basis for advocacy to expand access to 18F-FDG-PET/CT.

AbstractGlobal access to COVID vaccines has been extraordinarily unequal and remains an ongoing source of global health insecurities due to the evolution of viral variants in the bodies of the unvaccinated. There have nevertheless been at least three significant alternatives developed to this disastrous bioethical failure. These alternatives are reviewed in this article in the terms of ‘vaccine diplomacy’, ‘vaccine charity’, and ‘vaccine liberty’. Vaccine diplomacy includes the diverse bilateral deliveries of vaccines organized by the geopolitical considerations of countries strategically seeking various kinds of global and regional advantages in international relations. Vaccine charity centrally involves the humanitarian work of the global health agencies and donor governments that have organized the COVAX program as an antidote to unequal access. Despite their many promises, however, both vaccine diplomacy and vaccine charity have failed to deliver the doses needed to overcome the global vaccination gap. Instead, they have unfortunately served to immunize the global vaccine supply system from more radical demands for a ‘People’s Vaccine’, technological transfer and compulsory licensing of vaccine intellectual property (IP). These more radical demands represent the third alternative to vaccine access inequalities. As a mix of NGO-led and politician-led social justice demands, they are diverse and multifaceted, but together they have been articulated as calls for vaccine liberty. After first describing the realities of vaccine access inequalities, this article compares and contrasts the effectiveness thus far of the three alternatives. In doing so, it also provides a critical bioethical framework for reflecting on how the alternatives have come to compete with one another in the context of the vaccine property norms and market structures entrenched in global IP law. The uneven and limited successes of vaccine diplomacy and vaccine charity in delivering vaccines in underserved countries can be re-considered in this way as compromised successes that not only compete with one another, but which have also worked together to undermine the promise of universal access through vaccine liberty.

AbstractOn February 2022, samples collected in Northwest France showed discordant molecular results. After virological and epidemiological investigations, 17 cases of Deltacron XD recombinant SARS-CoV-2 were confirmed by sequencing or suspected due to epidemiological links, showing evidence of an extended transmission event and circulation of this form, with low clinical severity.

AbstractBackgroundSARS-CoV-2 infection has been associated with adverse maternal and neonatal outcomes, yet uptake of SARS-CoV-2 vaccines during pregnancy and lactation has been slow. As a result, millions of pregnant and lactating women and their infants remain susceptible to the virus.MethodsWe measured Spike-specific immunoglobulin G (anti-S IgG) and A (anti-S IgA) in serum and breastmilk (BM) samples from 3 prospective mother-infant cohorts recruited in two academic medical centers. The primary aim was to determine the impact of maternal SARS-CoV-2 immunization vs infection and their timing on systemic and mucosal immunity.ResultsThe study included 28 mothers infected with SARS-CoV-2 in late pregnancy (INF), 11 uninfected mothers who received 2 doses of the BNT162b2 vaccine in the latter half of pregnancy (VAX-P) and 12 uninfected mothers who received 2 doses of BNT162b2 during lactation (VAX-L). VAX dyads had significantly higher serum anti-S IgG compared to INF dyads (p < .0001), while INF mothers had higher BM: serum anti-S IgA ratios compared to VAX mothers (p = .0001). Median IgG placental transfer ratios were significantly higher in VAX-P compared to INF mothers (p < 0.0001). There was a significant positive correlation between maternal and neonatal serum anti-S IgG after vaccination (r = 0.68, p = 0.013), but not infection.ConclusionsBNT161b2 vaccination in late pregnancy or lactation enhances systemic immunity through serum anti-S Ig, while SARS-CoV-2 infection induces mucosal over systemic immunity more efficiently through BM Ig production. Next generation vaccines boosting mucosal immunity could provide additional protection to the mother-infant dyad. Future studies should focus on identifying the optimal timing of primary and/or booster maternal vaccination for maximal benefit.

Infection can trigger thrombotic events. After respiratory and other infections, people have a 3–6-fold increased risk of arterial thrombosis, such as myocardial infarction and ischaemic stroke, and a 2–3-fold increased risk of venous thromboses, such as deep vein thrombosis of the legs and pulmonary embolism.1,2 The risk declines in the weeks after infection, although a higher risk can persist for a year or longer, particularly for venous thromboses.2…

Risks of venous thromboembolism and arterial thromboembolism were up to 1% among COVID-19 cases, and increased with age, among males, and in those who were hospitalised. Their occurrence was associated with excess mortality, underlying the importance of developing effective treatment strategies that reduce their frequency.

Bifidobacteria are among the earliest and most abundant bacterial colonizers of the neonatal gut in many mammals, where they elicit purported host health benefits. While early life-associated dynamics and diversity, as well as the metabolic and beneficial activities, of Bifidobacterium species have been well studied, functional contributions of bifidobacteria to health and well-being of adults remain less explored. In this opinion piece, we discuss the current knowledge regarding the relevance of endogenous Bifidobacterium species associated with adulthood.

Abstract

Purpose

Assess the impact of viral load estimated by cycle threshold (Ct) of reverse transcription real time-polymerase chain reaction (rRT-PCR) and the days from symptoms onset on mortality in hospitalized patients with COVID19.

Methods

Retrospective observational study of 782 patients with a positive rRT-PCR from a nasopharyngeal swab was performed within the first 24 h from admission. Demographic data, clinical manifestations and laboratory parameters were collected. Uni- and multivariate analyses were performed to identify factors associated with mortality at 60 days.

Results

Ct was divided into three groups and the mortality rate decreased from 27.3 to 20.7% and 9.8% for Ct values of ≤ 20, 21–25 and > 25, respectively (P = 0.0001). The multivariate analysis identified as predictors of mortality, a Ct value < 20 (OR 3.13, CI 95% 1.38–7.10), between 21–25 (OR 2.47, CI 95% 1.32–4.64) with respect to a Ct value > 25. Days from symptoms onset is a variable associated with mortality as well (DSOA) ≤ 6 (OR 1.86, CI 95% 1.00–3.46), among other factors. Patients requiring hospital admission within 6 DSOA with a Ct value ≤ 25 had the highest mortality rate (28%).

Conclusions

The inclusion of Ct values and DSOA in the characterization of study populations could be a useful tool to evaluate the efficacy of antivirals.

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Abstract

Background

Weather fluctuation affects the incidence of malaria through a network of causuative pathays. Globally, human activities have ultered weather conditions over time, and consequently the number of malaria cases. This study aimed at determining the influence of humidity, temperature and rainfall on malaria incidence in an inland (Muyuka) and a coastal (Tiko) settings for a period of seven years (2011–2017) as well as predict the number of malaria cases two years after (2018 and 2019).

Methods

Malaria data for Muyuka Health District (MHD) and Tiko Health District (THD) were obtained from the Regional Delegation of Public Health and Tiko District Health service respectively. Climate data for MHD was obtained from the Regional Delegation of Transport while that of THD was gotten from Cameroon Development Coorporation. Spearman rank correlation was used to investigate the relationship between number of malaria cases and the weather variables and the simple seasonal model was used to forecast the number of malaria cases for 2018 and 2019.

Results

The mean monthly rainfall, temperature and relative humidity for MHD were 200.38 mm, 27.050C, 82.35% and THD were 207.36 mm, 27.57 °C and 84.32% respectively, with a total number of malaria cases of 56,745 and 40,160. In MHD, mean yearly humidity strongly correlated negatively with number of malaria cases (r = − 0.811, p = 0.027) but in THD, a moderate negative yearly correlation was observed (r = − 0.595, p = 0.159). In THD, the mean seasonal temperature moderately correlated (r = 0.599, p = 0.024) positively with the number of malaria cases, whereas MHD had a very weak negative correlation (r = − 0.174, p = 0.551). Likewise mean seasonal rainfall in THD moderately correlated (r = − 0.559, p = 0.038) negatively with malaria cases, contrary to MHD which showed a very weak positive correlation (r = 0.425, p = 0.130). The simple seasonal model predicted 6,842 malaria cases in Muyuka, for 2018 and same number for 2019, while 3167 cases were observed in 2018 and 2848 in 2019. Also 6,738 cases of malaria were predicted for MHD in 2018 likewise 2019, but 7327 cases were observed in 2018 and 21,735 cases in 2019.

Conclusion

Humidity is the principal climatic variable that negatively influences malaria cases in MHD, while higher seasonal temperatures and lower seasonal rain fall significantly increase malaria cases in THD.

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Abstract

Background

Most non-clinic based HIV pre-exposure prophylaxis (PrEP) programs require fingersticks to self-collect blood specimens for laboratory monitoring, a technique that often results in inadequate blood volume for quantitative syphilis and HIV serological testing. We evaluated the acceptability and feasibility of using the Tasso OnDemand™ device as a self-sampling method for PrEP monitoring tests and compared results from samples obtained using the Tasso device to clinician-collected blood samples.

Methods

We enrolled study subjects online and in a sexual health clinic and HIV clinic in Seattle, WA, USA to assess the acceptability of blood self-sampling and preferences for home-based PrEP monitoring. We compared HIV antigen/antibody, quantitative rapid plasma reagin and creatinine results in paired self-collected and clinical specimens collected from a subset of participants.

Results

Of 141 participants, 124 (88%) were interested in collecting samples for PrEP monitoring at home. Among 48 who completed blood collections, 94% found the Tasso device easy to use and 95% felt they could perform self-sampling at home. Of 27 participants who used two devices, 100% collected sufficient blood to perform up to two tests while 33% collected sufficient serum for three tests. Agreement in test results between paired samples was high.

Conclusions

These pilot data suggest that using the Tasso self-collection device is acceptable and could feasibly be used to obtain serum specimens sufficient for guideline-recommended PrEP monitoring, though use of a larger volume device may be preferable.

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Abstract

Background

Prospective observational data show that infected persons with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain polymerase chain reaction (PCR) positive for a prolonged duration, and that detectable antibodies develop slowly with time. We aimed to analyze how these effects can bias key epidemiological metrics used to track and monitor SARS-CoV-2 epidemics.

Methods

An age-structured mathematical model was constructed to simulate progression of SARS-CoV-2 epidemics in populations. PCR testing to diagnose infection and cross-sectional surveys to measure seroprevalence were also simulated. Analyses were conducted on simulated outcomes assuming a natural epidemic time course and an epidemic in presence of interventions.

Results

The prolonged PCR positivity biased the epidemiological measures. There was a lag of 10 days between the true epidemic peak and the actually-observed peak. Prior to epidemic peak, PCR positivity rate was twofold higher than that based only on current active infection, and half of those tested positive by PCR were in the prolonged PCR positivity stage after infection clearance. Post epidemic peak, PCR positivity rate poorly predicted true trend in active infection. Meanwhile, the prolonged PCR positivity did not appreciably bias estimation of the basic reproduction number R0. The time delay in development of detectable antibodies biased measured seroprevalence. The actually-observed seroprevalence substantially underestimated true prevalence of ever infection, with the underestimation being most pronounced around epidemic peak.

Conclusions

Caution is warranted in interpreting PCR and serological testing data, and any drawn inferences need to factor the effects of the investigated biases for an accurate assessment of epidemic dynamics.

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Abstract

Background

Patients with COVID-19 infection are commonly reported to have an increased risk of venous thrombosis. The choice of anti-thrombotic agents and doses are currently being studied in randomized controlled trials and retrospective studies. There exists a need for individualized risk stratification of venous thromboembolism (VTE) to assist clinicians in decision-making on anticoagulation. We sought to identify the risk factors of VTE in COVID-19 patients, which could help physicians in the prevention, early identification, and management of VTE in hospitalized COVID-19 patients and improve clinical outcomes in these patients.

Method

This is a multicenter, retrospective database of four main health systems in Southeast Michigan, United States. We compiled comprehensive data for adult COVID-19 patients who were admitted between 1st March 2020 and 31st December 2020. Four models, including the random forest, multiple logistic regression, multilinear regression, and decision trees, were built on the primary outcome of in-hospital acute deep vein thrombosis (DVT) and pulmonary embolism (PE) and tested for performance. The study also reported hospital length of stay (LOS) and intensive care unit (ICU) LOS in the VTE and the non-VTE patients. Four models were assessed using the area under the receiver operating characteristic curve and confusion matrix.

Results

The cohort included 3531 admissions, 3526 had discharge diagnoses, and 6.68% of patients developed acute VTE (N = 236). VTE group had a longer hospital and ICU LOS than the non-VTE group (hospital LOS 12.2 days vs. 8.8 days, p < 0.001; ICU LOS 3.8 days vs. 1.9 days, p < 0.001). 9.8% of patients in the VTE group required more advanced oxygen support, compared to 2.7% of patients in the non-VTE group (p < 0.001). Among all four models, the random forest model had the best performance. The model suggested that blood pressure, electrolytes, renal function, hepatic enzymes, and inflammatory markers were predictors for in-hospital VTE in COVID-19 patients.

Conclusions

Patients with COVID-19 have a high risk for VTE, and patients who developed VTE had a prolonged hospital and ICU stay. This random forest prediction model for VTE in COVID-19 patients identifies predictors which could aid physicians in making a clinical judgment on empirical dosages of anticoagulation.

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Abstract

Background

With the decline in local malaria transmission in Vietnam as a result of the National Malaria Control Program (NMCP) elimination activities, a greater focus on the importation and potential reintroduction of transmission are essential to support malaria elimination objectives.

Methods

We conducted a multi-method assessment of the demographics, epidemiology, and clinical characteristics of imported malaria among international laborers returning from African or Southeast Asian countries to Vietnam. Firstly, we conducted a retrospective review of hospital records of patients from January 2014 to December 2016. Secondly, we conducted a mixed-methods prospective study for malaria patients admitted to the study sites from January 2017 to May 2018 using a structured survey with blood sample collection for PCR analysis and in-depth interviews. Data triangulation of the qualitative and quantitative data was used during analysis.

Results

International laborers were young (median age 33.0 years IQR 28.0–39.5 years), predominantly male (92%) adults returning mostly from the African continent (84%) who stayed abroad for prolonged periods (median time 13.5 months; IQR 6.0–331.5 months) and were involved in occupations that exposed them to a higher risk of malaria infection. Epidemiological trends were also similar amongst study strands and included the importation of Plasmodium falciparum primarily from African countries and P. vivax from Southeast Asian countries. Of 11 P. malariae and P. ovale infections across two study strands, 10 were imported from the African continent. Participants in the qualitative arm demonstrated limited knowledge about malaria prior to travelling abroad, but reported knowledge transformation through personal or co-worker’s experience while abroad. Interestingly, those who had a greater understanding of the severity of malaria presented to the hospital for treatment sooner than those who did not; median of 3 days (IQR 2.0–7.0 days) versus 5 days (IQR 4.0–9.5 days) respectively.

Conclusion

To address the challenges to malaria elimination raised by a growing Vietnamese international labor force, consideration should be given to appropriately targeted interventions and malaria prevention strategies that cover key stages of migration including pre-departure education and awareness, in-country prevention and prophylaxis, and malaria screening upon return.

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Science Advances, <a href='https://www.science.org/toc/sciadv/8/19'>Volume 8, Issue 19</a>, May 2022. …

Science Advances, <a href='https://www.science.org/toc/sciadv/8/19'>Volume 8, Issue 19</a>, May 2022. …

Y. Huang et al.

V. Potdar et al.

Y. Yan et al.

S. Herrero-Cófreces et al.

Z. O. Allehebi et al.

A. Hoefer et al.