The Intersection Between HIV and COVID-19: Findings From the WHO Global Clinical Platform (preprint)

Background: Evidence on the association between HIV infection and the risk of poor clinical outcomes in people with COVID-19 remains inconclusive. The World Health Organization (WHO) has established a Global Clinical Platform aimed to assess clinical features and risk factors for severe/fatal COVID-19 among individuals hospitalized with suspected or confirmed SARS-CoV-2 infection.Methods: Between January 2020-June 2021 anonymized individual-level clinical data from 338,566 patients hospitalized in 38 countries were reported to the WHO Clinical Platform using a standardized set of variables including demographics, vital signs, underlying conditions, laboratory values, therapeutics and medical care received, and clinical outcomes. Descriptive and regression analyses whether HIV status was a risk factor for severity at admission and in-hospital mortality among people hospitalized for COVID-19.Findings: Of 197,479 patients reporting HIV status, 8.6% (16,955) were living with HIV (PLHIV), and 94.6% (16,283) were from Africa. Among those, 37.1% were male, mean age was 45.5 years, 38.3% were admitted with severe or critical illness and 24.7% died in-hospital. Among 10,166 individuals with information about antiretroviral therapy (ART) status, 91.5% were on ART. When compared to those without HIV, PLHIV had 15% increased odds of severe/critical presentation (aOR=1.15, 95%CI 1.10–1.20) and 38% more likely to die in-hospital (aHR=1.38, 95%CI 1.34-1.41). Among PLHIV, being male, age 45-75 years, having chronic cardiac disease or hypertension increased the odds of severe/critical COVID-19; male sex, age>18 years, having diabetes, hypertension, malignancy, TB, or chronic kidney disease increased the risk of in-hospital mortality.Interpretation: In this sample of hospitalized people contributing data to the WHO Global Clinical Platform for COVID-19, HIV was a significant independent risk factor for both severe/critical COVID-19 at admission and in-hospital mortality. These findings have informed the WHO COVID-19 Clinical Management Guidelines and SAGE recommendations around COVID-19 vaccination prioritization among vulnerable groups.Funding Information: None.Declaration of Interests: R.H. received funding from the Wellcome Trust, CIHR UKRI/MRC and ICODA. None of the other authors have any conflicts of interest to disclose.Ethics Approval Statement: The analysis plan25 was submitted to the WHO Ethical Review Committee which granted a waiver from ethical review clearance as this was passive, anonymized clinical surveillance. Ethical clearance was obtained, where necessary, by relevant institutional or national bodies.

RNA Extraction Alternative Method for SARS-CoV-2 Molecular Diagnosis (preprint)

Background: the devastating outbreak of COVID-19 poses serious challenges for the diagnostics laboratories, which are often facing global shortage of reagents and equipment. With the aim of increasing the diagnostic throughput for SARS-CoV-2 molecular test, the purpose of this study was to validate an additional RNA extraction method respect to those already recommended by WHO and the US Centers for Disease Control and Prevention (CDC). Methods: a new protocol for RNA extraction from nasopharyngeal swab was set up, adapting the Qiagen RNeasy 96 plate and validated on a set of 100 clinical samples analyzed in parallel by Roche-Magnapure method (already recommended by CDC guidelines). Results: the internal control and target genes analysis showed a good agreement between the two extraction methods indicating that the two methods can be considered equivalent and that the RNeasy-adapted method can be applied for the SARS-CoV-2 diagnostics. The addition of this new extraction method resulted in a throughput increase for SARS-CoV-2 molecular test of about 2000 samples/month during the initial months of the pandemic emergency in which the lack of reagents for the extraction led to an insufficient sample processing throughput of the analysis of the swabs.

Recommendations from the Brazilian Society of Nephrology for approaching Covid-19 Diagnostic Testing in Dialysis Units

ABSTRACT The Covid-19 pandemic brought several challenges to the healthcare system: diagnosis, treatment and measures to prevent the spread of the disease. With the greater availability and variety of diagnostic tests, it is essential to properly interpret them. This paper intends to help dialysis units concerning the use of clinical criteria and diagnostic tests for decision making regarding the discontinuation of isolation of patients with suspected or confirmed Covid-19, as well as the return to work activities for employees with suspected or confirmed Covid-19. RESUMO A pandemia da Covid-19 trouxe desafios ao sistema de saúde em diversas esferas: diagnóstico, tratamento e medidas para evitar a disseminação da doença. Com a maior disponibilização e variedades de testes diagnósticos, torna-se fundamental sua adequada interpretação. Este posicionamento pretende orientar unidades de diálise em relação ao uso de critérios clínicos e testes diagnósticos para a tomada de decisão referente à descontinuação do isolamento de pacientes com suspeita ou confirmação de Covid-19, assim como para o retorno às atividades laborais de colaboradores com suspeita ou confirmação de Covid-19.

Sensitivity, specificity and predictive values of molecular and serological tests for COVID-19. A longitudinal study in emergency room. (preprint)

Accuracy of diagnostic tests is essential for suspected cases of Coronavirus Disease 2019 (COVID-19). This study aimed to assess the sensitivity, specificity and positive and negative predictive value (PPV and NPV) of molecular and serological tests for the diagnosis of SARS-CoV-2 infection. A total of 346 consenting, adult patients were enrolled at the emergency room of IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy. We evaluated three RT-PCR methods including six different gene targets; five serologic rapid diagnostic tests (RDT); one ELISA test. The final classification of infected/not infected patients was performed using Latent Class Analysis in combination with clinical re-assessment of incongruous cases and was the basis for the main analysis of accuracy. Of 346 patients consecutively enrolled, 85 (24.6%) were classified as infected. The molecular test with the highest sensitivity, specificity, PPV and NPV was RQ-SARS-nCoV-2 with 91.8% (C.I. 83.8-96.6), 100% (C.I. 98.6-100.0), 100.0% (C.I. 95.4-100.0) and 97.4% (C.I. 94.7-98.9) respectively, followed by CDC 2019-nCoV with 76.2% (C.I. 65.7-84.8), 99.6% (C.I. 97.9-100.0), 98.5% (C.I. 91.7-100.0) and 92.9% (C.I. 89.2-95.6) and by in-house test targeting E-RdRp with 61.2% (C.I. 50.0-71.6), 99.6% (C.I. 97.9-100.0), 98.1% (C.I. 89.9-100.0) and 88.7% (C.I. 84.6-92.1). The analyses on single gene targets found the highest sensitivity for S and RdRp of the RQ-SARS-nCoV-2 (both with sensitivity 94.1%, C.I. 86.8-98.1). The in-house RdRp had the lowest sensitivity (62.4%, C.I. 51.2-72.6). The specificity ranged from 99.2% (C.I. 97.3-99.9) for in-house RdRp and N2 to 95.0% (C.I. 91.6-97.3) for E. The PPV ranged from 97.1% (C.I. 89.8-99.6) of N2 to 85.4% (C.I. 76.3-92.00) of E, and the NPV from 98.1% (C.I. 95.5-99.4) of gene S to 89.0% (C.I. 84.8-92.4) of in-house RdRp. All serological tests had <50% sensitivity and low PPV and NPV. One RDT (VivaDiag IgM) had high specificity (98.5%, with PPV 84.0%), but poor sensitivity (24.7%). Molecular tests for SARS-CoV-2 infection showed excellent specificity, but significant differences in sensitivity. As expected, serological tests have limited utility in a clinical context.