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Cellular aging dynamics after acute malaria infection: A 12-month longitudinal study.

ABSTRACT: Accelerated cellular aging and reduced lifespan have recently been shown in birds chronically infected with malaria parasites. Whether malaria infection also affects cellular aging in humans has not been reported. Here, we assessed the effect of a single acute Plasmodium falciparum malaria infection on cellular aging dynamics in travelers prospectively followed over one year in Sweden. DNA and RNA were extracted from venous blood collected at the time of admission and repeatedly up to one year. Telomere length was measured using real-time quantitative PCR, while telomerase activity and CDKN2A expression were measured by reverse transcriptase (RT)-qPCR. Our results show that acute malaria infection affects cellular aging as reflected by elevated levels of CDKN2A expression, lower telomerase activity, and substantial telomere shortening during the first three months postinfection. After that CDKN2A expression declined, telomerase activity increased and telomere length was gradually restored over one year, reflecting that cellular aging was reversed. These findings demonstrate that malaria infection affects cellular aging and the underlying cellular mechanism by which pathogens can affect host cellular aging and longevity need to be elucidated. Our results urge the need to investigate whether repeated malaria infections have more pronounced and long-lasting effects on cellular aging and lifespan (similarly to what was observed in birds) in populations living in malaria endemic areas.

SUBMITTER: Asghar M

PROVIDER: S-EPMC5771395 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Cellular aging dynamics after acute malaria infection: A 12-month longitudinal study.

Asghar Muhammad M Yman Victor V Homann Manijeh Vafa MV Sondén Klara K Hammar Ulf U Hasselquist Dennis D Färnert Anna A

Aging cell 20171116 1

Accelerated cellular aging and reduced lifespan have recently been shown in birds chronically infected with malaria parasites. Whether malaria infection also affects cellular aging in humans has not been reported. Here, we assessed the effect of a single acute Plasmodium falciparum malaria infection on cellular aging dynamics in travelers prospectively followed over one year in Sweden. DNA and RNA were extracted from venous blood collected at the time of admission and repeatedly up to one year. ...[more]

PMID: 29143441

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Project description:The COVID-19 pandemic hit healthcare professionals (HCPs) hard, potentially leading to mental health deterioration. This longitudinal study investigated the 1-year evolution of psychological health of acute care HCPs during the COVID-19 pandemic and explored possible differences between high and low resilient HCPs. From April 2020 to April 2021, a convenience sample of 520 multinational HCPs completed an online survey every 3 months, up to five times. We used mixed linear models to examine the association between resilience and the variation of COVID-19-related anxiety, depressiveness, perceived vulnerability, and psychological trauma symptomatology. We demonstrated "u-shaped" trajectories for all mental health symptoms. We also explored differences in the abovementioned variables between front-line and second-line acute care HCPs. In contrast to HCP.s with lower levels of resilience (-1SD), those with higher levels of resilience (+1SD) showed increased COVID-19 anxiety and perceived vulnerability over time. Front-line and second-line HCPs differed in their depressiveness and psychological trauma variation during the 1-year analysis. High and average resilient second-line HCPs showed steeper depressiveness increases with time than high and average resilient front-line HCPs. Acute care HCPs reported their most elevated clinical symptoms of depressiveness (5-7%) and psychological trauma symptomatology (26-46%) in April 2020. During the first year of the COVID-19 pandemic, second-line HCPs with more resilience showed a steeper worsening of their depressiveness than more resilient front-line HCPs. HCPs with low resilience may benefit from interventions at the beginning of a pandemic, whereas HCPs with high resilience might benefit from resilience-enhancing interventions at later phases.Trial registrationThe study protocol was pre-registered with the International Standard Randomised Controlled Trial Number (ISRCTN13694948) published (Fuchs et al., 2020).

Project description:BackgroundSARS-CoV-2 remains a world-wide health issue. SARS-CoV-2-specific immunity is induced upon both infection and vaccination. However, defining the long-term immune trajectory, especially after infection, is limited. In this study, we aimed to further the understanding of long-term SARS-CoV-2-specific immune response after infection.ResultsWe conducted a longitudinal cohort study among 93 SARS-CoV-2 recovered individuals. Immune responses were continuously monitored for up to 20 months after infection. The humoral responses were quantified by Spike- and Nucleocapsid-specific IgG levels. T cell responses to Spike- and non-Spike epitopes were examined using both intercellular cytokine staining (ICS) assay and Activation-Induced marker (AIM) assay with quantification of antigen-specific IFNγ production. During the 20 months follow-up period, Nucleocapsid-specific antibody levels and non-Spike-specific CD4 + and CD8 + T cell frequencies decreased in the blood. However, a majority of participants maintained a durable immune responses 20 months after infection: 59% of the participants were seropositive for Nucleocapsid-specific IgG, and more than 70% had persisting non-Spike-specific T cells. The Spike-specific response initially decreased but as participants were vaccinated against COVID-19, Spike-specific IgG levels and T cell frequencies were boosted reaching similar or higher levels compared to 1 month post-infection. The trajectory of infection-induced SARS-CoV-2-specific immunity decreases, but for the majority of participants it persists beyond 20 months. The T cell response displays a greater durability. Vaccination boosts Spike-specific immune responses to similar or higher levels as seen after primary infection.ConclusionsFor most participants, the response persists 20 months after infection, and the cellular response appears to be more long-lived compared to the circulating antibody levels. Vaccination boosts the S-specific response but does not affect the non-S-specific response. Together, these findings support the understanding of immune contraction, and with studies showing the immune levels required for protection, adds to the knowledge of durability of protection against future SARS-CoV-2.

Dataset Information

Cellular aging dynamics after acute malaria infection: A 12-month longitudinal study.

Publications

Cellular aging dynamics after acute malaria infection: A 12-month longitudinal study.

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