Spatially resolved single-cell atlas of the lung in fatal Covid19 in an African population reveals a distinct cellular signature and an interferon gamma dominated response (preprint)

Postmortem single-cell studies have transformed understanding of lower respiratory tract diseases (LRTD) including Covid19 but there is almost no data from African settings where HIV, malaria and other environmental exposures may affect disease pathobiology and treatment targets. We used histology and high-dimensional imaging to characterise fatal lung disease in Malawian adults with (n=9) and without (n=7) Covid19, and generated single-cell transcriptomics data from lung, blood and nasal cells. Data integration with other cohorts showed a conserved Covid19 histopathological signature, driven by contrasting immune and inflammatory mechanisms: in the Malawi cohort, by response to interferon-gamma (IFN-{gamma}) in lung-resident alveolar macrophages, in USA, European and Asian cohorts by type I/III interferon responses, particularly in blood-derived monocytes. HIV status had minimal impact on histology or immunopathology. Our study provides data resources and highlights the importance of studying the cellular mechanisms of disease in underrepresented populations, indicating shared and distinct targets for treatment.

Women’s reactions to the COVID-19 food system shock and insights for strategies supporting healthy purchasing and dietary behaviours: a qualitative study

BackgroundThe COVID-19 pandemic disrupted usual routines, including families’ food acquisition and consumption patterns. This pandemic could have lasting effects on consumer behaviour and implications for future strategies to improve population diet. The aim of this study was to gain in-depth understanding of families lived experiences by i) examining the impact of disruption resulting from the pandemic on the food purchasing and eating behaviours of young women, and ii) identifying the insights these experiences bring to designing future healthy eating interventions.MethodsA cross-sectional sample of 34 customers aged 18–45 years, from a UK discount supermarket chain completed semi-structured telephone interviews. Women were asked questions to understand their lived experiences of food shopping, cooking, and eating during the COVID-19 lockdown. Interviews were transcribed verbatim and analysed thematically using QSR NVIVO software. Six researchers were involved in developing the initial coding framework, double coding of eleven interview transcripts and refining the coding framework.ResultsParticipants’ median age was 35 years and 56% were in paid employment. Findings show that participants displayed emotional responses to COVID-19 pandemic disruptions of their food purchasing and dietary behaviours. Anxiety was common, with many feeling anxious about not acquiring enough or preferred foods for their families;contracting COVID-19 while food shopping;or needing to balance food costs, meal/snack variety and health. Frustration was also widespread, particularly about those who stockpiled;the poor availability of products which caused challenging situations at family mealtimes;shoppers who did not respect social distancing rules;and queues/one-way systems that made food shopping longer or less successful. These negative emotions were balanced against feelings of empathy, altruism, and pleasure. Many participants were understanding of government and supermarket restrictions or took the risk of shopping in-store to leave delivery slots for vulnerable customers or to help neighbours. Several women enjoyed leaving the house/family to go food shopping but missed being able to browse for meal ideas;others liked having more family meals and time to cook healthier dishes together.ConclusionStrategies to improve food purchasing and diet may be enhanced if positive emotions, like pleasure in families cooking and eating together, are targeted. As communicating the necessity for COVID-19 rules increased the public acceptance of these restrictions, a similar approach could be adopted for government policies to improve supermarket environments that may disrupt shoppers’ routines but are necessary to improve shopping patterns.

Clinical Outcomes of Patients With and Without HIV Hospitalised with COVID-19 in England During the Early Stages of the Pandemic: A Matched Retrospective Multicentre Analysis (RECEDE-C19 Study) (preprint)

Background: It is unclear from epidemiological data for COVID-19 infections, whether people living with HIV (PLWH) have a different outcomes compared to the general population. We conducted a multi-centre, retrospective matched cohort study of SARS-CoV-2 PCR-positive hospital inpatients analysed by HIV-status.Methods: HIV-negative patients were matched to PLWH admitted to hospital before 31 st May 2020, with a 3:1 ratio by: hospital site, SARS-CoV-2 test date +/- 7 days, age +/- 5 years, gender, and index of multiple deprivation decile (IMDD) +/- 1. The primary objective was clinical improvement (≥2-point improvement on a 7-point ordinal scale) or hospital discharge by day 28, whichever was earlier.Results: 68 PLWH and 181 HIV-negative comparators were included. After adjustment for ethnicity, frailty, baseline hypoxia, duration of symptoms prior to baseline, body mass index categories, and comorbidities (hypertension, chronic cardiac disease, chronic lung disease, active malignancy, diabetes, and chronic renal disease), the effect size of HIV status was not associated with time to clinical improvement or discharge from hospital (aHR 0.70, 95%CI 0.43, 1.17; p=0.18), despite unadjusted hazards of PLWH achieving the primary outcome being 43% lower (p=0.005). Baseline frailty (aHR=0.79; 95%CI 0.65, 0.95; p=0.011), malignancy (aHR=0.37; 95%CI 0.17, 0.82; p=0.014) remained associated with poorer outcomes. PLWH were more likely of black and minority ethnicities (75.0% vs 48.6%, p=0.0002), higher median clinical frailty score (3 IQR 2-5 vs 2 IQR 1-4, p=0.0069), higher proportion of active malignancy (14.4% vs 9.9%, p=0.29). Median body mass index (BMI) was lower amongst PLWH (27.7 IQR 23.9-32.3 vs 29.4 IQR 24.7-34.3, p=0.19). Median CD4 count of PLWH was 352cells/µL (IQR 235-619) and 95.7% had suppressed viral loads <200copies/mL, 63/68 (92.3%) were taking antiretroviral therapy.Conclusions: Differences in clinical outcomes of COVID-19 hospitalisations in PLWH may be due to other important factors including increased frailty and comorbidities such as malignancies, rather than HIV-status alone.Funding Statement: This study has not received any funding sources.Declaration of Interests: MJL has received grants and honoraria from Gilead Sciences and Viiv Healthcare not related to this work. SF has received research grants to her institution from NIH, MRC, BMGF. JT has received support for virtual conference registration from ViiV Healthcare and research grants from the Medical Research Council and the British HIV Association not related to this work. CvH has received educational grants, conference support and advisory board fees from ViiV Healthcare, Gilead Sciences, MSC not related to this work. MP reports grants and personal fees from Gilead Sciences and personal fees from QIAGEN, outside the submitted work. MP is supported by a NIHR Development and Skills Enhancement Award (NIHR301192) and in receipt of funding from UKRI / MRC (MR/V027549/1). He acknowledges the support from UKRI, the NIHR Leicester BRC and NIHR ARC East Midlands. No other competing interests, financial relationships with any organisations that might have an interest in the submitted work, or other relationships or activities that could appear to have influenced the submitted work have been reported by other authors.Ethics Approval Statement: Ethical approval was granted by the UK Health Research Authority (REC reference 20/HRA/2278).