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2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315017

ABSTRACT

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).

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296511

ABSTRACT

Background: Household overcrowding is associated with increased risk of infectious diseases across contexts and countries. Limited data exist linking household overcrowding and risk of COVID-19. We used data collected from the Virus Watch cohort to examine the association between overcrowded households and SARS-CoV-2. Methods: The Virus Watch study is a household community cohort of acute respiratory infections in England and Wales. We calculated overcrowding using the measure of persons per room for each household. We considered two primary outcomes: PCR-confirmed positive SARS-CoV-2 antigen tests and laboratory-confirmed SARS-CoV-2 antibodies. We used mixed-effects logistic regression models that accounted for household structure to estimate the association between household overcrowding and SARS-CoV-2 infection. Results: 26,367 participants were included in our analyses. The proportion of participants with a positive SARS-CoV-2 PCR result was highest in the overcrowded group (9.0%;99/1,100) and lowest in the under-occupied group (4.2%;980/23,196). In a mixed-effects logistic regression model, we found strong evidence of an increased odds of a positive PCR SARS-CoV-2 antigen result (odds ratio 2.45;95% CI:1.43–4.19;p-value=0.001) and increased odds of a positive SARS-CoV-2 antibody result in individuals living in overcrowded houses (3.32;95% CI:1.54–7.15;p-value<0.001) compared with people living in under-occupied houses. Conclusion: Public health interventions to prevent and stop the spread of SARS-CoV-2 should consider the risk of infection for people living in overcrowded households and pay greater attention to reducing household transmission.

4.
Clin Microbiol Infect ; 28(3): 371-374, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1509691

ABSTRACT

BACKGROUND: Most treatment guidelines for coronavirus disease 2019 (COVID-19) currently recommend tocilizumab in combination with dexamethasone in critically ill patients who are exhibiting rapid respiratory decompensation. AIMS: To produce a critical review and summary of the pathway which led to the repurposing of tocilizumab for COVID-19 treatment, from in vitro observations to guidelines recommendations. SOURCES: All studies evaluating the effectiveness of tocilizumab to treat COVID-19 disease published between July 2020 and July 2021. CONTENT: Two large and methodologically well conducted observational studies, the TESEO and the STOP COVID cohorts, showed a reduction in the risk of invasive mechanical ventilation or death in patients treated with tocilizumab as compared to standard of care in 2020. Concomitantly, and up to February 2021, a number of randomized trials (RCTs) with small sample sizes were showing discrepant results. These RCTs had a number of issues: small sample size, various designs and inclusion criteria, and different dosages of tocilizumab used. The confidence interval of the meta-analytic estimate for the RCT results was consistent with the hypothesis of no efficacy of tocilizumab. In our opinion, this was mainly because the meta-analysis included small and heterogeneous studies. These results led to a delay in the inclusion of tocilizumab in guidelines which occurred only in the summer of 2021. IMPLICATIONS: Although observational studies are unable to control for unmeasured confounding, they can be put together quickly during a pandemic and promptly provide important information. The large sample size allows us to investigate effect measure modifiers and to better target interventions. It is key that the effect size is somewhat large (RR > 2), all sources of bias are properly accounted for, and the direct evidence is weighted against these factors. It appears to us that for tocilizumab, not having dismissed the results of carefully designed and analysed observational studies in 2020 could have prevented many deaths over those months.


Subject(s)
COVID-19 , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Humans , SARS-CoV-2
5.
HIV Med ; 23(2): 121-133, 2022 02.
Article in English | MEDLINE | ID: covidwho-1434702

ABSTRACT

BACKGROUND: The contribution of HIV to COVID-19 outcomes in hospitalized inpatients remains unclear. 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 people living with HIV (PLWH) admitted from 1 February 2020 to 31 May 2020 up to a 3:1 ratio by the following: hospital site, SARS-CoV-2 test date ± 7 days, age ± 5 years, gender, and index of multiple deprivation decile ± 1. The primary objective was clinical improvement (two-point improvement or better on a seven-point ordinal scale) or hospital discharge by day 28, whichever was earlier. RESULTS: A total of 68 PLWH and 181 HIV-negative comparators were included. In unadjusted analyses, PLWH had a reduced hazard of achieving clinical improvement or discharge [adjusted hazard ratio (aHR) = 0.57, 95% confidence interval (CI): 0.39-0.85, p = 0.005], but this association was ameliorated (aHR = 0.70, 95% CI: 0.43-1.17, p = 0.18) after additional adjustment for ethnicity, frailty, baseline hypoxaemia, duration of symptoms prior to baseline, body mass index (BMI) categories and comorbidities. 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. The PLWH were more likely to be of black, Asian and minority ethnic background (75.0% vs 48.6%, p = 0.0002), higher median clinical frailty score [3 × interquartile range (IQR): 2-5 vs, 2 × IQR: 1-4, p = 0.0069), and to have a non-significantly higher proportion of active malignancy (14.4% vs 9.9%, p = 0.29). CONCLUSIONS: Adjusting for confounding comorbidities and demographics in a matched cohort ameliorated differences in outcomes of PLWH hospitalized with COVID-19, highlighting the importance of an appropriate comparison group when assessing outcomes of PLWH hospitalized with COVID-19.


Subject(s)
COVID-19 , HIV Infections , COVID-19/epidemiology , COVID-19/therapy , England/epidemiology , Female , HIV Infections/epidemiology , Hospitalization , Humans , Male , Pandemics , Retrospective Studies , Treatment Outcome
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