Influence Disease Severity Research Articles

Risk Factors Associated With COVID-19 Symptoms and Potential Vertical Transmission During Pregnancy: A Retrospective Cohort Study.

ObjectiveThe COVID-19 pandemic is of special concern for pregnant women. A growing body of evidence suggests the virus can have a deleterious impact upon outcomes related to birth and newborn health. There is a paucity of published research demonstrating the factors that influence disease severity among those who are pregnant, while a growing body of evidence demonstrates that vertical transmission occurs. Our study investigated the impact of maternal characteristics upon COVID-19 outcomes, as well as whether disease severity impacted pregnancy outcomes.MethodsWe conducted a retrospective cohort study of pregnant women with COVID-19 who were admitted to two public hospitals in our state between April-August, 2020. Pregnancy outcomes and clinical, laboratory, and placental data were collected.ResultsThirty-four pregnant women tested positive for SARS-CoV-2. Among them, 55% (19/34) were symptomatic. Of those who were symptomatic, 68% (13/19) presented with fever and cough. Those with symptoms had a statistically significant higher pregestational mean body mass index (BMI) compared with asymptomatic women (35.7±7.9 vs 26.7±6.9, P=0.004). Screening of biochemical records demonstrated that symptomatic women had lower potassium levels compared with those who were asymptomatic (median: 3.70 mEq/L vs 4.30 mEq/L, P=0.009). The lowest potassium level (3.0 mEq/L) and one of the highest BMIs (42.4 kg/m2) was observed in the only case of postpartum mortality among the symptomatic women. We did not observe any influence of maternal COVID-19 severity on placental histopathology/infant health or evidence of vertical transmission.ConclusionHigh pregestational BMI and lower potassium levels were associated with the presence of COVID-19 symptoms among pregnant women.

Functional Single-Nucleotide Polymorphisms in the MBL2 and TLR3 Genes Influence Disease Severity in Influenza A (H1N1)pdm09 Virus-Infected Patients from Maharashtra, India.

The clinical outcome in influenza A (H1N1)pdm09 virus-infected subjects is determined by several factors, including host genetics. In the present study, single-nucleotide polymorphisms (SNPs) in the IFITM, MBL2, TLR3, TLR8, DDX58, IFIH1, CD55, and FCGR2, genes were investigated in influenza A (H1N1)pdm09 virus-infected subjects to find out their association with disease severity. Influenza A (H1N1)pdm09 virus-infected subjects with severe disease (n = 86) and mild disease (n = 293) from western India were included in the study. The SNPs were investigated by PCR-based methods. The results revealed a higher frequency of TLR3 rs5743313 T/T genotype [odds ratio (OR) with 95% confidence interval (CI) 2.55 (1.08-6.04) p = 0.039] and TLR3 two-locus haplotype rs3775291-rs3775290 T-A [OR with 95% CI 7.94 (2.05-30.68)] in severe cases. Lower frequency of the mutant allele of MBL2 rs1800450 [OR with 95% CI 0.51 (0.27-0.87), p = 0.01] and TLR3 two-locus haplotype rs3775291-rs3775290 T-G [OR with 95% CI 0.48 (0.27-0.85)] was observed in severe cases compared with cases with mild disease. Higher frequency of TLR3 two-locus haplotype rs3775291-rs3775290 T-A was observed in severe cases [OR with 95% CI 7.9 (2.0-30.7)]. The allele and genotype frequencies of other SNPs were not different between the study categories. The results suggest that the functional SNPs in MBL2 and TLR3 are associated with severe disease in influenza A (H1N1)pdm09 virus-infected subjects.

Impact of agronomic practices onFusarium mycotoxin accumulation in maize grain

In the Great Lakes region of North America,Gibberella ear rot (GER), caused byFusarium graminearum, affects grain quality due to the accumulation of mycotoxins. GER severity is strongly influenced by environmental conditions; however, agronomic practices can also influence disease severity and mycotoxin accumulation. In this study, three separate small-plot experiments were conducted at Ridgetown, ON, Canada during 2019 and 2020 under an inoculated-misted system to determineFusarium mycotoxin accumulation as affected by: (1) plant population density; (2) in-row-plant developmental variability; and (3) the effect of integrated Bt refuge genetics. In this study, DON concentrations were at least 49% higher in maize at 113,600 plants/ha compared to 79,000 plants/ha. Moreover, mycotoxin accumulation was higher in plants that were delayed developmentally in the crop row; total DON concentrations were at least 310% higher in late silked plants adjacent to early silked plants. Results of the plant population density and in-row-plant developmental variability suggest that the main driver for mycotoxin accumulation was stress induced by plant competition rather than environmental conditions; this highlights the importance of avoiding plant competitive stress as a strategy to reduce the risks of mycotoxin accumulation. In this study, there was no statistical difference in DON accumulation between the Bt component and the non-Bt component in each of the four hybrids tested; however, there was evidence that hybrids varied in susceptibility, including the Bt and non-Bt components that were paired commercially in a bag of seed maize. Reducing mycotoxins in maize requires integrated management, which includes agronomic considerations. These results indicate that mycotoxins are favoured with high plant populations and plant-to-plant variability in the row, especially in susceptible hybrids.

Gut bacterial dysbiosis and instability is associated with the onset of complications and mortality in COVID-19

ABSTRACT There is a growing debate about the involvement of the gut microbiome in COVID-19, although it is not conclusively understood whether the microbiome has an impact on COVID-19, or vice versa, especially as analysis of amplicon data in hospitalized patients requires sophisticated cohort recruitment and integration of clinical parameters. Here, we analyzed fecal and saliva samples from SARS-CoV-2 infected and post COVID-19 patients and controls considering multiple influencing factors during hospitalization. 16S rRNA gene sequencing was performed on fecal and saliva samples from 108 COVID-19 and 22 post COVID-19 patients, 20 pneumonia controls and 26 asymptomatic controls. Patients were recruited over the first and second corona wave in Germany and detailed clinical parameters were considered. Serial samples per individual allowed intra-individual analysis. We found the gut and oral microbiota to be altered depending on number and type of COVID-19-associated complications and disease severity. The occurrence of individual complications was correlated with low-risk (e.g., Faecalibacterium prausznitzii) and high-risk bacteria (e.g., Parabacteroides ssp.). We demonstrated that a stable gut bacterial composition was associated with a favorable disease progression. Based on gut microbial profiles, we identified a model to estimate mortality in COVID-19. Gut microbiota are associated with the occurrence of complications in COVID-19 and may thereby influencing disease severity. A stable gut microbial composition may contribute to a favorable disease progression and using bacterial signatures to estimate mortality could contribute to diagnostic approaches. Importantly, we highlight challenges in the analysis of microbial data in the context of hospitalization.

Phenotyping Mediterranean Durum Wheat Landraces for Resistance to Zymoseptoria tritici in Tunisia.

Durum wheat landraces have huge potential for the identification of genetic factors valuable for improving resistance to biotic stresses. Tunisia is known as a hot spot for Septoria tritici blotch disease (STB), caused by the fungus Zymoseptoria tritici (Z. tritici). In this context, a collection of 3166 Mediterranean durum wheat landraces were evaluated at the seedling and adult stages for STB resistance in the 2016–2017 cropping season under field conditions in Kodia (Tunisia). Unadapted/susceptible accessions were eliminated to reach the final set of 1059 accessions; this was termed the Med-collection, which comprised accessions from 13 countries and was also screened in the 2018–2019 cropping season. The Med-collection showed high frequency of resistance reactions, among which over 50% showed an immune reaction (HR) at both seedling and adult growth stages. Interestingly, 92% of HR and R accessions maintained their resistance levels across the two years, confirming the highly significant correlation found between seedling- and adult-stage reactions. Plant Height was found to have a negative significant effect on adult-stage resistance, suggesting that either this trait can influence disease severity, or that it can be due to environmental/epidemiological factors. Accessions from Italy showed the highest variability, while those from Portugal, Spain and Tunisia showed the highest levels of resistance at both growth stages, suggesting that the latter accessions may harbor novel QTLs effective for STB resistance.

Hereditary Spastic Paraplegia in Koreans: Clinical Characteristics and Factors Influencing the Disease Severity.

Hereditary spastic paraplegia (HSP) progresses over time and is associated with locomotive dysfunction. Understanding the factors affecting disease severity and locomotive function is important in HSP. This study investigated the factors influencing disease severity and ambulation status of HSP.We consecutively enrolled 109 Korean patients (64 males, and 45 females)from 84 families with a clinical diagnosis of HSP. HSP was primarily diagnosed based on clinical criteria including clinical findings, family history, and supported by genetic studies. Epidemiological and clinical features of the patients were analyzed, and the Spastic Paraplegia Rating Scale (SPRS) score and ambulatory status were used to evaluate disease severity.Ninety-two (84.4%) patients had pure HSP, and 55 (50.4%) had a dominant family history. Thirty-one (28.4%) patients required a mobility aid for locomotion. A Kaplan-Meier analysis showed that HSP patients lost their independent gait ability after a median disease duration of 34 years. Those with an age at onset of ≤18 years had a longer median independent walking time. Pure HSP is characterized by predominant bilateral lower extremity weakness and spasticity, whereas complicated HSP presents more complex neurological findings such as ocular and bulbar symptoms, ataxia, and cognitive impairment. Complicated HSP was significantly correlated with the SPRS mobility score (β=3.70, 95% confidence interval=0.45-6.94). The age at onset and disease duration were significantly correlated with disease severity, and they were significant predictors of the use of a mobility aid (p<0.05).These findings suggest that a later age at onset and longer disease duration are significant factors affecting the disease severity and ambulatory function in patients with HSP. These findings can help clinicians to identify subjects at risk of locomotive impairment.

Intravenous vitamin C use and risk of severity and mortality in COVID-19: A systematic review and meta-analysis.

The administration of intravenous vitamin C (IV‐VC) in treating patients with coronavirus disease 2019 (COVID‐19) is still highly controversial. There have been no previous studies on the effect of IV‐VC on the severity and mortality of COVID‐19. Hence, we conducted a systematic review and meta‐analysis to compare the disease severity and mortality in patients with COVID‐19 who promptly received IV‐VC treatment vs those who did not.We performed a comprehensive systematic search of seven health science databases, including PubMed, Embase, Cochrane Library, MEDLINE, Web of Science, China National Knowledge Infrastructure, and Wanfang Data, up to June 23, 2021. We identified a total of seven related articles, which were included in this study.This meta‐analysis showed that IV‐VC treatment did not affect disease severity compared with placebo treatment or usual care (odds ratio [OR], 0.70; 95% CI, 0.45 to 1.07; P = 0.10). In addition, no statistically significant difference in mortality was observed between patients who received IV‐VC treatment and those who did not (OR, 0.64; 95% CI, 0.41 to 1.00; P = 0.05). Moreover, the adjusted meta‐analysis revealed that the use of IV‐VC did not influence disease severity (OR, 0.67; 95% CI, 0.34 to 1.31; P = 0.242) or mortality (OR, 1.02; 95% CI, 0.75 to 1.40; P = 0.877) in comparison with a control group.The results of this meta‐analysis demonstrated that short‐term IV‐VC treatment did not reduce the risk of severity and mortality in patients with COVID‐19.

Markers of Coagulation Dysfunction and Inflammation in Diabetic and Non Diabetic COVID-19 Patients- A Retrospective Study

Introduction: Since the end of 2019, a novel Coronavirus Disease 2019 (COVID-19), declared a pandemic by World Health Organization (WHO) has ravaged the world. Diabetic patients have been reported to be more susceptible to intensive care admissions, and deaths due to COVID-19. Diabetes Mellitus (DM) and COVID-19, both associated with chronic and acute inflammation respectively can impact each other in terms of clinical progression and outcome. Given the novelty of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pathogen, there is need to update and increase the limited evidence on the probability of DM acting as a risk factor and influencing disease severity and progression. Aim: To compare the markers of inflammation and coagulation dysfunction between COVID-19 patients with and without DM as co-morbidity and thereby to study the effect DM has on the prognosis of COVID-19. Materials and Methods: This was a retrospective, observational, single-centre study, conducted Department of Biochemistry at Gauhati Medical College and Hospital, Guwahati, Assam, India, from January 2021 to June 2021. Clinical and laboratory data of 500 laboratory confirmed COVID-19 patients were reviewed in this study. The patients were grouped as diabetic case group and non diabetic control group. Data was presented as percentages for categorical variables and median (interquartile range) for continuous variables. Chi-square test was used to see the association of different qualitative information and MannWhitney U test was used to see the association of quantitative data and all p-values were given for justification. A p-value &lt;0.05 was considered statistically significant. Results: The sample included 300 diabetic and 200 non diabetic COVID-19 patients. The mean age non diabetic patients (47.5 years) was significantly less as compared to the diabetic group (54.5 years), p-value &lt;0.001. The serum level of inflammatory biomarkers, C-Reactive Protein (CRP), ferritin, and markers of hypercoagulable state, D-dimer, was found to be significantly high (p-value &lt;0.001) in diabetic patients as compared to non diabetic patients. Diabetics had a poor prognosis with 231 (77%) receiving oxygen as compared to 51 (25.5%) of non diabetic patients. Total 173 (57.7%) of diabetic COVID-19 patients had to be shifted to ICU, 201 (67%) suffered from post COVID-19 complications and the mortality rate was higher at 18% in diabetics as compared to 1.5% in non diabetic subjects. Conclusion: Diabetic patients are at higher risk of uncontrolled inflammation and hypercoagulable state which eventually leads to deterioration of COVID-19 infection status.

Hereditary Spastic Paraplegia in Koreans: Clinical Characteristics and Factors Influencing the Disease Severity.

Background and PurposeHereditary spastic paraplegia (HSP) progresses over time and is associated with locomotive dysfunction. Understanding the factors affecting disease severity and locomotive function is important in HSP. This study investigated the factors influencing disease severity and ambulation status of HSP.MethodsWe consecutively enrolled 109 Korean patients (64 males, and 45 females)from 84 families with a clinical diagnosis of HSP. HSP was primarily diagnosed based on clinical criteria including clinical findings, family history, and supported by genetic studies. Epidemiological and clinical features of the patients were analyzed, and the Spastic Paraplegia Rating Scale (SPRS) score and ambulatory status were used to evaluate disease severity.ResultsNinety-two (84.4%) patients had pure HSP, and 55 (50.4%) had a dominant family history. Thirty-one (28.4%) patients required a mobility aid for locomotion. A Kaplan-Meier analysis showed that HSP patients lost their independent gait ability after a median disease duration of 34 years. Those with an age at onset of ≤18 years had a longer median independent walking time. Pure HSP is characterized by predominant bilateral lower extremity weakness and spasticity, whereas complicated HSP presents more complex neurological findings such as ocular and bulbar symptoms, ataxia, and cognitive impairment. Complicated HSP was significantly correlated with the SPRS mobility score (β=3.70, 95% confidence interval=0.45–6.94). The age at onset and disease duration were significantly correlated with disease severity, and they were significant predictors of the use of a mobility aid (p<0.05).ConclusionsThese findings suggest that a later age at onset and longer disease duration are significant factors affecting the disease severity and ambulatory function in patients with HSP. These findings can help clinicians to identify subjects at risk of locomotive impairment.

Impact of Coinfection With SARS-CoV-2 and Influenza on Disease Severity: A Systematic Review and Meta-Analysis.

Background: Although coinfection with influenza in COVID-19 patients has drawn considerable attention, it is still not completely understood whether simultaneously infected with these two viruses influences disease severity. We therefore aimed to estimate the impact of coinfected with SARS-CoV-2 and influenza on the disease outcomes compared with the single infection of SARS-CoV-2.Materials and Methods: We searched the PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure Database (CNKI) to identify relevant articles up to July 9, 2021. Studies that assessed the effect of SARS-CoV-2 and influenza coinfection on disease outcomes or those with sufficient data to calculate risk factors were included. Risk effects were pooled using fixed or random effects model.Results: We ultimately identified 12 studies with 9,498 patients to evaluate the risk effects of SARS-CoV-2 and influenza coinfection on disease severity. Results indicated that coinfection was not significantly associated with mortality (OR = 0.85, 95%CI: 0.51, 1.43; p = 0.55, I2 = 76.00%). However, mortality was found significantly decreased in the studies from China (OR = 0.51, 95%CI: 0.39, 0.68; I2 = 26.50%), while significantly increased outside China (OR = 1.56, 95%CI: 1.12, 2.19; I2 = 1.00%). Moreover, a lower risk for critical outcomes was detected among coinfection patients (OR = 0.64, 95%CI: 0.43, 0.97; p = 0.04, I2 = 0.00%). Additionally, coinfection patients presented different laboratory indexes compared with the single SARS-CoV-2 infection, including lymphocyte counts and APTT.Conclusion: Our study revealed that coinfection with SARS-CoV-2 and influenza had no effect on overall mortality. However, risk for critical outcomes was lower in coinfection patients and different associations were detected in the studies from different regions and specific laboratory indexes. Further studies on influenza strains and the order of infection were warranted. Systematic testing for influenza coinfection in COVID-19 patients and influenza vaccination should be recommended.

TNFA and IL10 Polymorphisms and IL-6 and IL-10 Levels Influence Disease Severity in Influenza A(H1N1)pdm09 Virus Infected Patients

Cytokines are key modulators of immune response, and dysregulated production of proinflammatory and anti-inflammatory cytokines contributes to the pathogenesis of influenza A(H1N1)pdm09 virus infection. Cytokine production is impacted by single nucleotide polymorphisms (SNPs) in the genes coding for them. In the present study, SNPs in the IL6, TNFA, IFNG, IL17A, IL10, and TGFB were investigated for their association with disease severity and fatality in influenza A(H1N1)pdm09-affected patients with mild disease (n = 293) and severe disease (n = 86). Among those with severe disease, 41 patients had fatal outcomes. In a subset of the patients, levels of IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17 were assayed in the plasma for their association with severe disease. The frequency of TNFA rs1800629 G/A allele was significantly higher in severe cases and survived severe cases group compared to that of those with mild infection (OR with 95% for mild vs. severe cases 2.95 (1.52–5.73); mild vs. survived severe cases 4.02 (1.84–8.82)). IL10 rs1800896-rs1800872 G-C haplotype was significantly lower (OR with 95% 0.34 (0.12–0.95)), while IL10 rs1800896-rs1800872 G-A haplotype was significantly higher (OR with 95% 12.11 (2.23–76.96)) in fatal cases group compared to that of the mild group. IL-6 and IL-10 levels were significantly higher in fatal cases compared to that of survived severe cases. IL-6 levels had greater discriminatory power than IL-10 to predict progression to fatal outcome in influenza A(H1N1)pdm09 virus-infected patients. To conclude, the present study reports the association of TNFA and IL10 SNPs with severe disease in Influenza A(H1N1)pdm09 virus-infected subjects. Furthermore, IL-6 levels can be a potential biomarker for predicting fatal outcomes in Influenza A(H1N1)pdm09 virus infected subjects.

COVID-19 severity determinants inferred through ecological and epidemiological modeling

Understanding variations in the severity of infectious diseases is essential for planning proper mitigation strategies. Determinants of COVID-19 clinical severity are commonly assessed by transverse or longitudinal studies of the fatality counts. However, the fatality counts depend both on disease clinical severity and transmissibility, as more infected also lead to more deaths. Instead, we use epidemiological modeling to propose a disease severity measure that accounts for the underlying disease dynamics. The measure corresponds to the ratio of population-averaged mortality and recovery rates (m/r), is independent of the disease transmission dynamics (i.e., the basic reproduction number), and has a direct mechanistic interpretation. We use this measure to assess demographic, medical, meteorological, and environmental factors associated with the disease severity. For this, we employ an ecological regression study design and analyze different US states during the first disease outbreak. Principal Component Analysis, followed by univariate, and multivariate analyses based on machine learning techniques, is used for selecting important predictors. The usefulness of the introduced severity measure and the validity of the approach are confirmed by the fact that, without using prior knowledge from clinical studies, we recover the main significant predictors known to influence disease severity, in particular age, chronic diseases, and racial factors. Additionally, we identify long-term pollution exposure and population density as not widely recognized (though for the pollution previously hypothesized) significant predictors. The proposed measure is applicable for inferring severity determinants not only of COVID-19 but also of other infectious diseases, and the obtained results may aid a better understanding of the present and future epidemics. Our holistic, systematic investigation of disease severity at the human-environment intersection by epidemiological dynamical modeling and machine learning ecological regressions is aligned with the One Health approach. The obtained results emphasize a syndemic nature of COVID-19 risks.

A large animal model of RDH5-associated retinopathy recapitulates important features of the human phenotype.

Pathogenic variants in retinol dehydrogenase 5 (RDH5) attenuate supply of 11-cis-retinal to photoreceptors leading to a range of clinical phenotypes including night blindness because of markedly slowed rod dark adaptation and in some patients, macular atrophy. Current animal models (such as Rdh5-/- mice) fail to recapitulate the functional or degenerative phenotype. Addressing this need for a relevant animal model we present a new domestic cat model with a loss-of-function missense mutation in RDH5 (c.542G > T; p.Gly181Val). As with patients, affected cats have a marked delay in recovery of dark adaptation. In addition, the cats develop a degeneration of the area centralis (equivalent to the human macula). This recapitulates the development of macular atrophy that is reported in a subset of patients with RDH5 mutations and is shown in this paper in seven patients with biallelic RDH5 mutations. There is notable variability in the age at onset of the area centralis changes in the cat, with most developing changes as juveniles but some not showing changes over the first few years of age. There is similar variability in development of macular atrophy in patients and while age is a risk factor, it is hypothesized that genetic modifying loci influence disease severity, and we suspect the same is true in the cat model. This novel cat model provides opportunities to improve molecular understanding of macular atrophy and test therapeutic interventions for RDH5-associated retinopathies.

Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease.

AimsPatients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system (RAAS) were suspected to influence disease severity.Methods and resultsWe analyzed 1946 consecutive patients with cardiovascular comorbidities or hypertension enrolled in one of the largest European COVID-19 registries, the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. Here, we show that angiotensin II receptor blocker intake is associated with decreased mortality in patients with COVID-19 [OR 0.75 (95% CI 0,59–0.96; p = 0.013)]. This effect was mainly driven by patients, who presented in an early phase of COVID-19 at baseline [OR 0,64 (95% CI 0,43–0,96; p = 0.029)]. Kaplan-Meier analysis revealed a significantly lower incidence of death in patients on an angiotensin receptor blocker (ARB) (n = 33/318;10,4%) compared to patients using an angiotensin-converting enzyme inhibitor (ACEi) (n = 60/348;17,2%) or patients who received neither an ACE-inhibitor nor an ARB at baseline in the uncomplicated phase (n = 90/466; 19,3%; p<0.034). Patients taking an ARB were significantly less frequently reaching the mortality predicting threshold for leukocytes (p<0.001), neutrophils (p = 0.002) and the inflammatory markers CRP (p = 0.021), procalcitonin (p = 0.001) and IL-6 (p = 0.049). ACE2 expression levels in human lung samples were not altered in patients taking RAAS modulators.ConclusionThese data suggest a beneficial effect of ARBs on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity.

Microbiome Profiling Using Shotgun Metagenomic Sequencing Identified Unique Microorganisms in COVID-19 Patients With Altered Gut Microbiota

COVID-19 is mainly associated with respiratory distress syndrome, but a subset of patients often present gastrointestinal (GI) symptoms. Imbalances of gut microbiota have been previously linked to respiratory virus infection. Understanding how the gut–lung axis affects the progression of COVID-19 can provide a novel framework for therapies and management. In this study, we examined the gut microbiota of patients with COVID-19 (n = 47) and compared it to healthy controls (n = 19). Using shotgun metagenomic sequencing, we have identified four microorganisms unique in COVID-19 patients, namely Streptococcus thermophilus, Bacteroides oleiciplenus, Fusobacterium ulcerans, and Prevotella bivia. The abundances of Bacteroides stercoris, B. vulgatus, B. massiliensis, Bifidobacterium longum, Streptococcus thermophilus, Lachnospiraceae bacterium 5163FAA, Prevotella bivia, Erysipelotrichaceae bacterium 6145, and Erysipelotrichaceae bacterium 2244A were enriched in COVID-19 patients, whereas the abundances of Clostridium nexile, Streptococcus salivarius, Coprococcus catus, Eubacterium hallii, Enterobacter aerogenes, and Adlercreutzia equolifaciens were decreased (p < 0.05). The relative abundance of butyrate-producing Roseburia inulinivorans is evidently depleted in COVID-19 patients, while the relative abundances of Paraprevotella sp. and the probiotic Streptococcus thermophilus were increased. We further identified 30 KEGG orthology (KO) modules overrepresented, with 7 increasing and 23 decreasing modules. Notably, 15 optimal microbial markers were identified using the random forest model to have strong diagnostic potential in distinguishing COVID-19. Based on Spearman’s correlation, eight species were associated with eight clinical indices. Moreover, the increased abundance of Bacteroidetes and decreased abundance of Firmicutes were also found across clinical types of COVID-19. Our findings suggest that the alterations of gut microbiota in patients with COVID-19 may influence disease severity. Our COVID-19 classifier, which was cross-regionally verified, provides a proof of concept that a set of microbial species markers can distinguish the presence of COVID-19.

Cytokine response in cerebrospinal fluid of meningitis patients and outcome associated with pneumococcal serotype

Streptococcus pneumoniae causes life-threatening meningitis. Its capsular polysaccharide determines the serotype and influences disease severity but the mechanism is largely unknown. Due to evidence of elevated cytokines levels in the meningeal inflammatory response, we measured 41 cytokines/chemokines and growth factors in cerebrospinal fluid (CSF) samples from 57 South African meningitis patients (collected in the period 2018–2019), with confirmed S. pneumoniae serotypes, using a multiplexed bead-based immunoassay. Based on multivariable Bayesian regression, using serotype 10A as a reference and after adjusting for HIV and age, we found IL-6 concentrations significantly lower in patients infected with serotypes 6D (undetectable) and 23A (1601 pg/ml), IL-8 concentrations significantly higher in those infected with 22A (40,459 pg/ml), 7F (32,400 pg/ml) and 15B/C (6845 pg/ml), and TNFα concentration significantly higher in those infected with serotype 18A (33,097 pg/ml). Although a relatively small number of clinical samples were available for this study and 28% of samples could not be assigned to a definitive serotype, our data suggests 15B/C worthy of monitoring during surveillance as it is associated with in-hospital case fatality and not included in the 13-valent polysaccharide conjugate vaccine, PCV13. Our data provides average CSF concentrations of a range of cytokines and growth factors for 18 different serotypes (14, 19F, 3, 6A, 7F, 19A, 8, 9N, 10A, 12F, 15B/C, 22F, 16F, 23A, 31, 18A, 6D, 22A) to serve as a basis for future studies investigating host–pathogen interaction during pneumococcal meningitis. We note that differences in induction of IL-8 between serotypes may be particularly worthy of future study.

Гастроезофагеальна рефлюксна хвороба в педіатричній практиці: сучасні проблемні питання

Останнім часом багато уваги приділяється захворюванням верхніх відділів травного тракту в дітей, зокрема гастроезофагеальній рефлюксній хворобі як причині, що призводить до порушення якості життя вже в дітей шкільного віку, а в подальшому — і в осіб молодого віку. У зв’язку з цим існують пошуки оптимізації раннього виявлення, нових методів неінвазивної діагностики, скринінгу цієї патології серед дитячого населення з метою визначення осіб із факторами ризику та запобігання розвитку захворювання та ускладненого перебігу, а також пошуки формування алгоритму профілактичних заходів. Вчені дійшли консенсусу, що всі обстеження, які використовуються в педіатричній практиці, повинні бути максимально доступними, простими та неінвазивними, наскільки це дозволяє стан дитини. Залишається відкритим питання про доцільність проведення фіброезофагогастродуоденоскопії всім пацієнтам зі скаргами на печію та іншими симптомами гастроезофагеальної рефлюксної хвороби, питання щодо застосування ультразвукової діагностики стравоходу в дітей як додаткового методу обстеження, використання опитувальників у педіатричній практиці, формування алгоритмів прогнозування перебігу захворювання та визначення профілактичних заходів індивідуально для кожного пацієнта. Щоб мати змогу обґрунтувати їх призначення, необхідно добре розуміти механізми розвит-ку цієї патології та враховувати індивідуальні фактори ризику, що можуть вплинути на тяжкість захворювання та прогнозування перебігу, які виникають у дітей в різні періоди життя. Отже, метою цієї роботи було подати огляд сучасної літератури з проблемних питань щодо клінічних проявів, факторів ризику, діагностики, прогнозування перебігу гастроезофагеальної рефлюксної хвороби в дітей різного віку (із питань основних етіологічних та патогенетичних факторів, клінічних проявів (стравохідних та позастравохідних), методів діагностики та сучасних підходів до лікування гастроезофагеальної рефлюксної хвороби).

Effects of mechanical thinning on botrytis bunch rot on Sauvignon blanc wine grapes

Mechanical fruit thinning could be a practical and cost-effective alternative to hand thinning of Sauvignon blanc grapes to increase quality by reducing yield. Botrytis bunch rot, caused by the fungus Botrytis cinerea, is the main seasonal disease risk for grapes grown in New Zealand but it is unknown if this disease is exacerbated by mechanical rather than manual thinning of the vines. It was hypothesised that the damage caused by mechanical thinning would result in more disease or increase disease pressure than hand thinning or no thinning. Botrytis bunch rot was determined in the field at harvest following mechanical thinning in the 2009, 2010 and 2011 seasons compared with an un-thinned control. In the 2011 season, possible mechanisms that may have influenced disease severity were investigated. The parameters investigated were: bunch openness; berry susceptibility to infection; and percentage of bunch debris infected with Botrytis cinerea. Mechanical thinning resulted in the same or lower observed disease severity compared with the un-thinned control in the 2009, 2010 and 2011 seasons while reducing yield as desired. In all seasons, both heavy and light machine thinning treatments reduced incidence of botrytis compared to the un-thinned control and the heavy machine treatment always reduced disease severity compared to the un-thinned control. Berry susceptibility to Botrytis cinerea was a complex interaction between various factors. Heavy machine thinned berries without wounding and inoculation were significantly less susceptible than the un-thinned control. Further investigation will be required to determine if the significant differences observed in berry susceptibility to infection and total infected bunch debris per bunch can be correlated with observed field disease levels.

Serum levels of small HDL particles are negatively correlated with death or lung transplantation in an observational study of idiopathic pulmonary fibrosis.

Serum lipoproteins, such as high-density lipoproteins (HDL), may influence disease severity in idiopathic pulmonary fibrosis (IPF). Here, we investigated associations between serum lipids and lipoproteins and clinical end-points in IPF. Clinical data and serum lipids were analysed from a discovery cohort (59 IPF subjects, 56 healthy volunteers) and validated using an independent, multicentre cohort (207 IPF subjects) from the Pulmonary Fibrosis Foundation registry. Associations between lipids and clinical end-points (forced vital capacity, 6-min walk distance, gender age physiology (GAP) index, death or lung transplantation) were examined using Pearson's correlation and multivariable analyses. Serum concentrations of small HDL particles measured using nuclear magnetic resonance spectroscopy (S-HDLPNMR) correlated negatively with the GAP index in the discovery cohort of IPF subjects. The negative correlation of S-HDLPNMR with GAP index was confirmed in the validation cohort of IPF subjects. Higher levels of S-HDLPNMR were associated with lower odds of death or its competing outcome, lung transplantation (OR 0.9 for each 1-μmol·L-1 increase in S-HDLPNMR, p<0.05), at 1, 2 and 3 years from study entry in a combined cohort of all IPF subjects. Higher serum levels of S-HDLPNMR are negatively correlated with the GAP index, as well as with lower observed mortality or lung transplantation in IPF subjects. These findings support the hypothesis that S-HDLPNMR may modify mortality risk in patients with IPF.

Exploring the influence of smoking and alcohol consumption on clinical severity in patients with facioscapulohumeral muscular dystrophy

Despite the growing knowledge on the (epi)genetic background of facioscapulohumeral muscular dystrophy (FSHD), the substantial variability in disease severity that exists between FSHD patients is not fully understood. We hypothesized that smoking and alcohol consumption are disease modifiers in FSHD and contribute to the variability in disease severity, because they are both associated with higher levels of oxidative stress in muscle tissue. Oxidative stress is known to influence FSHD muscle tissue. One hundred and ninety-eight genetically confirmed FSHD patients completed a questionnaire from which the number of packyears of smoking and the lifetime cumulative alcohol units consumed were calculated. Disease severity was determined by the FSDH evaluation score. Multiple linear regression analyses showed that both the number of packyears and the amount of alcohol consumption did not influence disease severity (respectively B = 0.025, ΔR2=0.006, p = 0.231; and B = 0.000, ΔR2=0.004, p = 0.406). Although smoking and excessive alcohol consumption are unhealthy habits which should be discouraged, these results show that smoking and alcohol consumption have no clinically meaningful modifying effect on disease severity in FSHD patients. However, prospective data should show whether alcohol consumption and smoking influence disease progression rate.