Browsing by Subject "rhinovirus"

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  • Hemilä, Harri; Chalker, Elizabeth (2021)
    In this individual patient data meta-analysis we examined datasets of two randomized placebo-controlled trials which investigated the effect of nasal carrageenan separately on children and adults. In both trials, iota-carrageenan was administered nasally three times per day for 7 days for patients with the common cold and follow-up lasted for 21 days. We used Cox regression to estimate the effect of carrageenan on recovery rate. We also used quantile regression to calculate the effect of carrageenan on colds of differing lengths. Nasal carrageenan increased the recovery rate from all colds by 54% (95% CI 15%-105%; p = .003). The increase in recovery rate was 139% for coronavirus infections, 119% for influenza A infections, and 70% for rhinovirus infections. The mean duration of all colds in the placebo groups of the first four quintiles were 4.0, 6.8, 8.8, and 13.7 days, respectively. The fifth quintile contained patients with censored data. The 13.7-day colds were shortened by 3.8 days (28% reduction), and 8.8-day colds by 1.3 days (15% reduction). Carrageenan had no meaningful effect on shorter colds. In the placebo group, 21 patients had colds lasting over 20 days, compared with six patients in the carrageenan group, which corresponds to a 71% (p = .003) reduction in the risk of longer colds. Given that carrageenan has an effect on diverse virus groups, and effects at the clinical level on two old coronaviruses, it seems plausible that carrageenan may have an effect on COVID-19. Further research on nasal iota-carrageenan is warranted.
  • Hemilä, Harri; Chalker, Elizabeth (2021)
    A Commentary on: The Long History of Vitamin C: From Prevention of the Common Cold to Potential Aid in the Treatment of COVID-19. A review of the effects of vitamin C on the immune system and respiratory tract infections was recently published (1). We are the authors of a review of vitamin C and the common cold (2), which was cited in the article. We consider that some of the authors’ statements are inaccurate and here we describe the issues on which we disagree.
  • DIABIMMUNE Study Grp; Ruohtula, Terhi; Kondrashova, Anita; Lehtonen, Jussi; Oikarinen, Sami; Hämäläinen, Anu-Maaria; Niemelä, Onni; Peet, Aleksandr; Tillmann, Vallo; Nieminen, Janne K.; Ilonen, Jorma; Knip, Mikael; Vaarala, Outi; Hyöty, Heikki (2021)
    Early childhood infections have been implicated in the development of immune-mediated diseases, such as allergies, asthma, and type 1 diabetes. We set out to investigate the immunomodulatory effects of early viral infections experienced before the age of one year on the peripheral regulatory T cell population (Treg) and circulating cytokines in a birth-cohort study of Estonian and Finnish infants. We show here a temporal association of virus infection with the expression of FOXP3 in regulatory T cells. Infants with rhinovirus infection during the preceding 30 days had a higher FOXP3 expression in Treg cells and decreased levels of several cytokines related to Th1 and Th2 responses in comparison to the children without infections. In contrast, FOXP3 expression was significantly decreased in highly activated (CD4+CD127-/loCD25+FOXP3high) regulatory T cells (TregFOXP3high) in the infants who had enterovirus infection during the preceding 30 or 60 days. After enterovirus infections, the cytokine profile showed an upregulation of Th1- and Th17-related cytokines and a decreased activation of CCL22, which is a chemokine derived from dendritic cells and associated with Th2 deviation. Our results reveal that immunoregulatory mechanisms are up-regulated after rhinovirus infections, while enterovirus infections are associated with activation of proinflammatory pathways and decreased immune regulation.
  • Saarinen, Niila V. V.; Lehtonen, Jussi; Veijola, Riitta; Lempainen, Johanna; Knip, Mikael; Hyöty, Heikki; Laitinen, Olli H.; Hytönen, Vesa P. (2020)
    Immunological assays detecting antibodies against enteroviruses typically use a single enterovirus serotype as antigen. This limits the ability of such assays to detect antibodies against different enterovirus types and to detect possible type-specific variation in antibody responses. We set out to develop a multiplexed assay for simultaneous detection of antibodies against multiple enterovirus and rhinovirus types encompassing all human infecting species. Seven recombinant VP1 proteins from enteroviruses EV-A to EV-D and rhinoviruses RV-A to RV-C species were produced. Using Meso Scale Diagnostics U-PLEX platform we were able to study antibody reactions against these proteins as well as non-structural enterovirus proteins in a single well with 140 human serum samples. Adults had on average 33-fold stronger antibody responses to these antigens (p<10(-11)) compared to children, but children had less cross-reactivity between different enterovirus types. The results suggest that this new high-throughput assay offers clear benefits in the evaluation of humoral enterovirus immunity in children, giving more exact information than assays that are based on a single enterovirus type as antigen.
  • Seppälä, Alma (Helsingin yliopisto, 2021)
    Rhinovirus infections cause the common cold, for which there is no cure. The consequences of the disease are mainly seen as absence from school or work, as the disease is usually mild, self-limiting and symptoms disappear in a few days, but infections can also lead to severe asthma exacerbations and hospitalization. This research is based on earlier findings of benzene sulfonamide derivative compounds that inhibited a broad range of enteroviruses by binding to a newly identified capsid pocket. Here, four promising compounds were tested against four different rhinoviruses belonging to Rhinovirus A and B species in a cell-based inhibition assay. After identification of a potential inhibitory compound against rhinovirus A9 and rhinovirus B14, a rhinovirus A9 homology model was generated, and then the binding was predicted with computational analysis using the rhinovirus A9 homology model and the published structure for rhinovirus B14. As the same compound has previously been shown to bind and inhibit coxsackievirus B4, this virus was used a control. Thermal stability testing of rhinovirus A9 revealed that the virus survives heat treatment up to at least 58°C, in contrast to previously published results. An efficient rhinovirus A9 purification protocol was established and high- quality cryo electron microscopy data were collected for structure determination of rhinovirus A9, which resulted in a 3.1 Å resolution map. The map was used for building the first atomic model of rhinovirus A9. The atomic model revealed that rhinovirus A9 has the expected T=1, pseudo T=3 capsid structure composed primarily of the three β-barrel proteins VP1, VP2 and VP3, with VP4 between the inside of the capsid and the RNA genome. The model confirmed the presence of the interprotomer pocket and VP1 pocket, although density for lipid factor was not detected. The final atomic model was compared to the homology model and used for comparative docking of the inhibitory compound to the pocket. The results revealed that empirical structure determination is still more accurate for large macromolecule complexes than modelling and that empirical data of the binding is required for reliable computational work.
  • Hemilä, Harri (1996)
    In 1971, Linus Pauling carried out a meta-analysis of four placebo-controlled trials and concluded that it was highly unlikely that the decrease in the "integrated morbidity of the common cold" in vitamin C groups was caused by chance alone (P < 0.00003). Studies carried out since then have consistently found that vitamin C (> or = 1 g/d) alleviates common cold symptoms, indicating that the vitamin does indeed have physiologic effects on colds. However, widespread conviction that the vitamin has no proven effects on the common cold still remains. Three of the most influential reviews drawing this conclusion are considered in the present article. Two of them are cited in the current edition of the RDA nutritional recommendations as evidence that vitamin C is ineffective against colds. In this article, these three reviews are shown to contain serious inaccuracies and shortcomings, making them unreliable sources on the topic. The second purpose is to suggest possible conceptual reasons for the persistent resistance to the notion that vitamin C might have effects on colds. Although placebo-controlled trials have shown that vitamin C does alleviate common cold symptoms, important questions still remain.