Exposure to nature during the COVID-19 pandemic and the associated effect on mental health: a systematic review with meta-analysis

BACKGROUND: The COVID-19 pandemic and measures such as lockdowns to control its transmission generated unique effects on psychological health and well-being. In these circumstances, access to nature and outdoor spaces became a potentially important coping strategy, but the evidence exploring the mental health benefits of nature exposure during different stages of the pandemic is mixed and poorly understood. We systematically synthesised the evidence to examine larger trends in associations between nature exposure and mental health during the COVID-19 pandemic.

Identification of a microbiome signature predicting immune checkpoint inhibitor outcomes across multiple cancer types in the MITRE study

Background: The gut microbiome is implicated as a biomarker of response to immune checkpoint inhibitors (ICIs), based on preclinical mouse models and preliminary observations in limited patient series. Furthermore, early reports suggest faecal microbial transfer may have therapeutic potential, converting ICI nonresponders to responders. So far, identification of specific responsible bacterial taxa has been inconsistent between published studies, which limits future application. By culturing and metagenomic sequencing of stool sample bacteria, our group has identified a unique microbiome signature, which appears to be predictive of response to ICIs across all key published series as well as our own melanoma patient series (Robinson M et al, J Immunother Cancer 2020;8(suppl 3):A404). Because the patient numbers in all published series remain low, we are now further exploring and validating this microbiome signature in a larger scale study across several different cancer types. Methods: MITRE (Microbiome Immunotherapy Toxicity and Response Evaluation) is a UK NIHR portfolio multi-centre prospective study funded jointly by Cancer Research UK and Microbiotica (NCT04107168) Up to 1800 patients receiving ICIs will be recruited over a 5-year period. In the first stage 1: anti-PD1 monotherapy, cohort 2: antiPD1+anti-CTLA-4 combination), renal cancer (cohort 3: anti-PD(L)1+kinase inhibitor, cohort 4: anti-PD1+anti-CTLA-4 combination) and nonsmall cell lung cancer (cohort 5: anti-PD(L)1 monotherapy, cohort 6: antiPD(L)1+chemotherapy+anti-angiogenic) are being recruited, 50 patients to each cohort. A cohort-specific, simulation-based power calculation will then be performed, guiding subsequent recruitment. Stool and blood are collected prior to treatment, at 3, 6 and 12 months, or disease progression (whichever is sooner), as well as after any grade >3 immunerelated adverse events. Patients collect and freeze their own stool samples which are cultured and subjected to shotgun metagenomic sequencing. Plasma, whole blood buffy coat, RNA and PBMCs are being stored for correlative studies. Any tumour, or organ biopsies, taken prior to and during treatment are also being collected. Clinical data collection includes treatment, disease response (using RECIST criteria) and toxicity. The primary outcome measure is 1 year progression-free survival. Patients are also asked to invite a household member to be part of the study control group. Recruitment started in July 2020 The Covid-19 pandemic hindered recruitment last year, but the protocol was amended to incorporate a Covid-19 substudy (to document testing, infection and vaccination) and adapt processes for remote trial delivery as much as possible. As of February 2021, 7 sites have opened, 17 patients and 5 household controls have been recruited.