Long-term symptoms after SARS-CoV-2 infection in a cohort of people living with HIV (PLWH): a real-life study (preprint)

Background Our Hospital in Northern Italy assists 3817 people living with HIV (PLWH) and has faced the impact of COVID-19. Little is known about the impact of HIV infection on the risk of post-COVID-19 conditions (PCCs) onset. We aim to assess the incidence of PCC in PLWH and the factors associated with its occurrence.Methods We performed a retrospective, observational study including all PLWH > 18 years registered in the Brescia Health Protection Agency database, assessing SARS-CoV-2 burden, vaccination status, socio-demographic, and viro-immunological parameters from February 2020 until May 2022. Persistence of self-reported symptoms (clustered into gastrointestinal, respiratory, osteo-muscular, and neuro-behavioral symptoms) was evaluated after 3 months by a telephone-administered questionnaire. We estimated the associations between all variables and outcomes through univariate and multivariable logistic models.Results In the study period, 653 PLWH were diagnosed with SARS-CoV-2 infection (17.1%). We observed 19 (2.9%) reinfections, 71 (10.9%) hospitalizations, and 3 (0.5%) deaths. We interviewed 510/653 PLWH (78%), and 178 (PCCs prevalence 34.9%; CI95% 30.7–39.2) reported persistent symptoms. Asthenia/fatigue was the most reported symptom (60/178), followed by muscular pain (54/178). In the multivariate regression model, male sex was protective (adjusted OR = 0.64; CI95% 0.99–3.66), while hospitalization during acute infection was associated with an increased the risk of PCCs (adjusted OR = 1.9; CI95% 0.99–3.66). Notably, no viro-immunological variable modified the PCCs risk onset.Conclusions Our study highlights a substantial prevalence of PCCs among PLWH, three months post-SARS-CoV-2 infection, independent of viro-immunological features or vaccination status.

A Structured Telephone Interview for collecting Geriatric health domains in Older People with HIV during COVID era (preprint)

Background Elderly people living with HIV show a significant prevalence of multimorbidity, polypharmacy and frailty that increase the risk of disability. Telehealth has been suggested as a new tool to monitor people living with HIV in the COVID era, but its effectiveness in elderly is unknown. The aim of this study was two-fold: to explore feasibility of a telephone interview and its capability to collect relevant geriatric outcomes. Methods Assessed health domains included comorbidities, falls, urinary incontinence, antiretroviral drugs exposure and comedications (polypharmacy), and the following patient reported outcomes: quality of life, intrinsic capacity, and resilience. Results 214 (70.6%) answered and completed the interview. During confinement period, 57 (26.7%) of people switched antiretroviral therapy : 119 (55.4%) to dual therapy regimens and 95 (44.6%) to triple regimens. Prevalence of geriatric syndromes were falls in 31 cases (14.7%), urinary incontinence in 48 cases (22.7%) and polypharmacy 122 cases (57.2%). Mean Health-related Quality of Life score was mildly impaired (0,88%) with good concordance of Helath-related Quality of Life self-perception in a visual analogue scale (8/10) (r=+0.348; p <0.01). Intrinsic capacity depicted impaired functional ability in multiple domains (0.737 ) and Resilience (CD-RISC) was suboptimal (0.6). Conclusions A structured telephone call was feasible in elderly people living with HIV and allowed to collect clinically meaningful geriatric health domains when face-to-face visits are not needed or discouraged.

Development and Validation of SCOPE Score: A Clinical Score to Predict Progression to Severe Respiratory Failure in Hospitalized Patients With COVID-19 Pneumonia (preprint)

Most patients infected with SARS-CoV-2 (COVID-19) experience mild, non-specific symptoms, but several develop severe symptoms associated with an excessive inflammatory response. Elevated plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) provide early warning of progression to severe respiratory failure (SRF) or death, but access to suPAR testing may be limited. The Severe COvid Prediction Estimate (SCOPE) score, derived from C-reactive protein, D-dimer, interleukin-6, and ferritin circulating concentrations at hospitalization during the SAVE-MORE study, offers comparable predictive accuracy for progression to SRF or death within 14 days as suPAR ≥6 ng/ml (area under receiver operator characteristic curve, 0.81 for both). SCOPE score was validated against an independent dataset from the SAVE study. The SCOPE score is an alternative to suPAR for predicting progression to SRF or death within 14 days of hospital admission for pneumonia, and it can be used to guide treatment decisions.Funding: The study was funded in part by the Hellenic Institute for the Study of Sepsis and by Swedish Orphan Biovitrum. The Hellenic Institute for the Study of Sepsis is the Sponsor of the SAVE and SAVE-MORE studies.Declaration of Interests:E. J. Giamarellos-Bourboulis has received honoraria from Abbott CH, bioMérieux, Brahms GmbH, GSK, InflaRx GmbH, Sobi and XBiotech Inc; independent educational grants from Abbott CH, AxisShield, bioMérieux Inc, InflaRx GmbH, Johnson & Johnson, MSD, Sobi and XBiotech Inc.; and funding from the Horizon2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), and the Horizon 2020 European Grants ImmunoSep and RISKinCOVID (granted to the Hellenic Institute for the Study of Sepsis). G. Poulakou has received independent educational grants from Pfizer, MSD, Angelini, and Biorad. H. Milionis reports receiving honoraria, consulting fees and non-financial support from healthcare companies, including Amgen, Angelini, Bayer, Mylan, MSD, Pfizer, and Servier. L. Dagna had received consultation honoraria from SOBI. M. Bassetti has received funds for research grants and/or advisor/consultant and/or speaker/chairman from Angelini, Astellas, Bayer, Biomerieux, Cidara, Cipla, Gilead, Menarini, MSD, Pfizer, Roche, Shionogi and Nabriva. P. Panagopoulos has received honoraria from GILEAD Sciences, Janssen, and MSD. G. N. Dalekos is an advisor or lecturer for Ipsen, Pfizer, Genkyotex, Novartis, Sobi, received research grants from Abbvie, Gilead and has served as PI in studies for Abbvie, Novartis, Gilead, Novo Nordisk, Genkyotex, Regulus Therapeutics Inc, Tiziana Life Sciences, Bayer, Astellas, Pfizer, Amyndas Pharmaceuticals, CymaBay Therapeutics Inc., Sobi and Intercept Pharmaceuticals. M. G. Netea is supported by an ERC Advanced Grant (#833247) and a Spinoza grant of the Netherlands Organization for Scientific Research. Hes is a scientific founder of TTxD and he has received independent educational grants from TTxD, GSK, Ono Pharma and ViiV HealthCare. The other authors do not have any competing interest to declare.Ethics Approval Statement: The SAVE protocol was approved by the National Ethics Committee of Greece (approval 38/20) and National Organization for Medicines approval (ISO 28/20). The SAVE-MORE protocol was approved by the National Ethics Committee of Greece (approval 161/20) and by the Ethics Committee of the National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, in Rome (1 February 2021).Trial Registration: The SAVE study was prospectively registered prior to enrolling the first patient (EudraCT number 2020-001466-11; ClinicalTrials.gov identifier NCT04357366). The SAVE-MORE study was prospectively registered (EudraCT no. 2020-005828-11; ClinicalTrials.gov identifier NCT04680949). Written informed consent was provided by all patients prior to enrollment.

Psychological and Emotional Impact Of COVID-19 Pandemic on People Living with Chronic Disease: HIV and Cancer (preprint)

People living with chronic disease (PLWCD) are the frailest category, both for the risk of severe COVID-19 illness and for the impact on the care continuum. Aim of this study was to analyze coping strategies and resilience in people living with HIV (PLWH) compared to people living with oncological diseases (PLWOD) during COVID-19 pandemic. We administrated an anonymous questionnaire, which explored the emotional experience, the demographic factors linked to a COVID-19-related stress syndrome, the patient’s perception about the adequacy of clinical undertaking from the hospital and the resilience. We analyzed 324 questionnaires. There were no significant differences in prevalence of psychological distress among the whole cohort; however, PLWOD were calmer, less troubled, and more serene than PLWH. Moreover, PLWH smoked more, ate more and gained more weight than PLWOD. Most patients didn’t feel lonely and continued to take pleasure from their activities. No differences in resilience were found between the groups. In the whole cohort lower levels of resilience were found in patients that were unemployed, with history of psychological disorders and in those who experienced more feelings of anger, anxiety and concern. PLWCD had high level of resilience, preserved their well-being, and activated adaptive coping during the pandemic.

Explorative Study Regarding Influenza Vaccine Hesitancy Among HIV-infected Patients (preprint)

There are scarce data regarding flu vaccination among people with HIV infection (PWHIV). The goal of this explorative study is to assess hesitancy toward influenza vaccination in a group of PWHIV during the pandemic. A questionnaire was administered to 219 patients vaccinated at our clinic during the 2020-2021 campaign. It evaluated subjects’ adherence over the last 3 seasonal vaccination campaigns, vaccine confidence, complacency and convenience, and the effect of the pandemic on the choice to vaccinate. The population was divided into two groups: fully adherent (all 3 campaigns, 117 patients) and non-fully adherent (1 or 2 campaigns, 102 patients). Adherence increased in non-fully adherent group in 2020-2021, but the pandemic did not affect the choice. Misbelieves emerged: influenza vaccine was considered protective SARS-CoV-2 (22.8% of total population); almost half of all patients thought influenza vaccine could improve their CD4+ cell level (57.3% in fully adherent, 40.2% in non-fully adherent, p<0.05). A quarter of the non-fully adherent group would not have vaccinated in a location other than our clinic (24.5% vs 11.9% in fully adherent group, p<0.05). Conclusively, offering a secure and private space for vaccination seems to encourage vaccination; healthcare professionals should improve counselling to increase adherence and correct misbeliefs.

The clinical spectrum of encephalitis in COVID-19 disease: the ENCOVID multicentre study (preprint)

Background: Several preclinical and clinical investigations have argued for nervous system involvement in SARS-CoV-2 infection. Some sparse case reports have described various forms of encephalitis in COVID-19 disease, but very few data have focused on clinical presentations, clinical course, response to treatment and outcomes yet. Objective: to describe the clinical phenotype, laboratory and neuroimaging findings of encephalitis associated with SARS-CoV-2 infection, their relationship with respiratory function and inflammatory parameters and their clinical course and response to treatment. Design: The ENCOVID multicentre study was carried out in 13 centres in northern Italy between February 20th and May 31st, 2020. Only patients with altered mental status and at least two supportive criteria for encephalitis with full infectious screening, CSF, EEG, MRI data and a confirmed diagnosis of SARS-CoV-2 infection were included. Clinical presentation and laboratory markers, severity of COVID-19 disease, response to treatment and outcomes were recorded. Results: Out of 45 cases screened, twenty-five cases of encephalitis positive for SARS-CoV-2 infection with full available data were included. The most common symptoms at onset were delirium (68%), aphasia/dysarthria (24%) and seizures (24%). CSF showed hyperproteinorrachia and/or pleocytosis in 68% of cases whereas SARS-CoV-2 RNA by RT-PCR resulted negative. Based on MRI, cases were classified as ADEM (n=3), limbic encephalitis (LE, n=2), encephalitis with normal imaging (n=13) and encephalitis with MRI alterations (n=7). ADEM and LE cases showed a delayed onset compared to the other encephalitis (p=0.001) and were associated with previous more severe COVID-19 respiratory involvement. Patients with MRI alterations exhibited worse response to treatment and final outcomes compared to other encephalitis. Conclusions and relevance: We found a wide clinical spectrum of encephalitis associated with COVID19 infection, underlying different pathophysiological mechanisms. Response to treatment and final outcome strongly depended on specific CNS-manifestations.

Steroid-responsive severe encephalopathy in SARS-CoV-2 infection (preprint)

SARS-CoV-2 infection has the potential for targeting central nervous system and several neurological symptoms have been described in patients with severe respiratory distress. Here we described the case of an otherwise healthy 60-year old subject with SARS-CoV-2 infection but only mild respiratory abnormalities who developed severe progressive encephalopathy associated with mild pleocytosis and hyperproteinorrachia. MRI was negative whereas EEG showed theta waves on the anterior brain regions. Serum and CSF analyses excluded other known infectious or autoimmune disorders. The patient dramatically improved after high-doses steroid treatment suggesting an inflammatory-mediated brain involvement related to SARS-CoV-2 infection