Background Scarce data are available on what variables affect the risk of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the development of symptomatic COVID-19, and, particularly, the relationship with viral load. We aimed to analyse data from linked index cases of COVID-19 and their contacts to explore factors associated with transmission of SARS-CoV-2. Methods In this cohort study, patients were recruited as part of a randomised controlled trial done between March 17 and April 28, 2020, that aimed to assess if hydroxychloroquine reduced transmission of SARS-CoV-2. Patients with COVID-19 and their contacts were identified by use of the electronic registry of the Epidemiological Surveillance Emergency Service of Catalonia (Spain). Patients with COVID-19 included in our analysis were aged 18 years or older, not hospitalised, had quantitative PCR results available at baseline, had mild symptom onset within 5 days before enrolment, and had no reported symptoms of SARS-CoV-2 infections in their accommodation or workplace within the 14 days before enrolment. Contacts included were adults with a recent history of exposure and absence of COVID-19-like symptoms within the 7 days preceding enrolment. Viral load of contacts, measured by quantitative PCR from a nasopharyngeal swab, was assessed at enrolment, at day 14, and whenever the participant reported COVID-19-like symptoms. We assessed risk of transmission and developing symptomatic disease and incubation dynamics using regression analysis. We assessed the relationship of viral load and characteristics of cases (age, sex, number of days from reported symptom onset, and presence or absence of fever, cough, dyspnoea, rhinitis, and anosmia) and associations between risk of transmission and characteristics of the index case and contacts. Findings We identified 314 patients with COVID-19, with 282 (90%) having at least one contact (753 contacts in total), resulting in 282 clusters. 90 (32%) of 282 clusters had at least one transmission event. The secondary attack rate was 17% (125 of 753 contacts), with a variation from 12% when the index case had a viral load lower than 1 × 10⁶ copies per mL to 24% when the index case had a viral load of 1 × 10¹⁰ copies per mL or higher (adjusted odds ratio per log 10 increase in viral load 1•3, 95% CI 1•1-1•5). Increased risk of transmission was also associated with household contact (3•0, 1•59-5•65) and age of the contact (per year: 1•02, 1•01-1•04). 449 contacts had a positive PCR result at baseline. 28 (6%) of 449 contacts had symptoms at the first visit. Of 421 contacts who were asymptomatic at the first visit, 181 (43%) developed symptomatic COVID-19, with a variation from approximately 38% in contacts with an initial viral load lower than 1 × 10⁷ copies per mL to greater than 66% for those with an initial viral load of 1 × 10¹⁰ copies per mL or higher (hazard ratio per log 10 increase in viral load 1•12, 95% CI 1•05-1•20; p=0•0006). Time to onset of symptomatic disease decreased from a median of 7 da...

Initiation of combined antiretroviral therapy within the first 12 weeks of life in vertically human immunodeficiency virus type 1-infected children favors the establishment of low-level proviral reservoirs. Nevertheless, treatment discontinuation in these patients may lead to rapid and irreversible expansion of reservoir size.

Background There remains limited data on what variables affect the risk of transmission of SARS-CoV-2 and developing symptomatic Covid-19 and in particular the relationship to viral load (VL). Methods We analysed data collected in a trial of hydroxychloroquine post-exposure prophylaxis. Covid-19 cases and their contacts were identified through the local epidemiological surveillance system. VL, estimated by quantitative PCR, was assessed at enrollment, at day 14, and whenever the participant reported Covid-19-like symptoms. Risk of transmission, risk of developing symptomatic disease and incubation dynamics were evaluated using random-effects regression analysis. Findings We identified 314 cases, 282 of which had at least one contact (753 contacts in total). Ninety (33%) of 282 clusters had at least one transmission event. The secondary attack rate was 16% (125/753), with a variation from 12% to 24% for VL of the index case of <106, and >109 copies/mL, respectively (OR per log10 increase in VL 1.3 95%CI 1.1 to 1.6). Increased risk of transmission was also associated with household contact (OR 2.7; 1.4 to 5.06) and age of the contact (OR 1.02; 1.01 to 1.04). The proportion of PCR positive contacts who developed symptomatic Covid-19 was 40.3% (181/449), with a variation from 25% to 60% for VL of the contact <107, and >109 copies/mL (HR log10 increase in VL 1.12; 95% CI 1.05 to 1.2). Time to onset of symptomatic disease decreased from a median of 7 days (IQR 5 to 10) for individuals with an initial viral load <107 to 6 days (4 to 8) and 5 days (3 to 8) for individuals with an initial viral load of 107 to 109 and >109, respectively. Interpretation We show that the viral load of the index case is a leading driver of SARS-CoV-2 transmission. The risk of symptomatic Covid-19 is strongly associated with viral load of the contact at baseline, which shortens the incubation time in a dose-dependent manner.

BackgroundMyeloid cells are key players in the recognition and response of the host against invading viruses. Paradoxically, upon HIV-1 infection, myeloid cells might also promote viral pathogenesis through trans-infection, a mechanism that promotes HIV-1 transmission to target cells via viral capture and storage. The receptor Siglec-1 (CD169) potently enhances HIV-1 trans-infection and is regulated by immune activating signals present throughout the course of HIV-1 infection, such as interferon α (IFNα).ResultsHere we show that IFNα-activated dendritic cells, monocytes and macrophages have an enhanced ability to capture and trans-infect HIV-1 via Siglec-1 recognition of viral membrane gangliosides. Monocytes from untreated HIV-1-infected individuals trans-infect HIV-1 via Siglec-1, but this capacity diminishes after effective antiretroviral treatment. Furthermore, Siglec-1 is expressed on myeloid cells residing in lymphoid tissues, where it can mediate viral trans-infection.ConclusionsSiglec-1 on myeloid cells could fuel novel CD4+ T-cell infections and contribute to HIV-1 dissemination in vivo.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-015-0160-x) contains supplementary material, which is available to authorized users.

Background The current standard for COVID-19 diagnosis, RT-qPCR, has important drawbacks for its use as a tool for epidemiological control, including the need of laboratory-processing, high cost, and long turnaround from sampling to results release. Antigen-based rapid diagnostic tests (Ag-RDT) provide a promising alternative for this purpose. Methods We assessed the analytical and clinical performance of the Ag-RDT Panbio COVID-19 Ag Test (Abbott), using RT-qPCR as a reference test. The clinical performance was assessed using nasopharyngeal swabs, collected in routine practice for case confirmation and contact tracing, and nasal mid-turbinate swabs, collected in preventive screenings of asymptomatic individuals. Fresh samples were analysed by RT-q-PCR, stored at -80 C, and analysed using the Ag-RDT according to the manufacturer instructions. Findings The Ag-RDT had a limit of detection of 6.5 *105 copies/reaction. The clinical performance was assessed on 1,406 frozen swabs with a PCR result available: 951 (67.7%) positive and 455 (32.4%) negative. The Ag-RDT identified the presence of SARS-CoV-2 in 872 of 951 PCR-positive samples (91.7%; 95% CI 89.8-93.4 and ruled out its presence in 450 of 455 PCR-negative samples (specificity 98.9%; 95% CI 97.5 - 99.6). Sensitivity increased in samples with lower Ct values (Ct <25, 98.2%; Ct<30, 94.9%) and was higher among symptomatic cases (92.6%) and their contacts (94.2%) than among asymptomatic individuals (79.5%). In the setting of asymptomatic screening, sensitivity also increased with lower Ct values (Ct <25, 100%; Ct<30, 98.6%). Assuming a pre-test probability of 5%, the negative and positive predictive values were 99.6% (99.5 - 99.6) and 81.5% (65.0 - 93.2), respectively. Interpretation The Panbio COVID-19 Ag-RDT has high sensitivity for detecting the presence of SARS-CoV-2 in nasal or nasopharyngeal swabs of both, symptomatic and asymptomatic individuals. The diagnostic performance of the test is particularly good in samples with viral loads associated with high risk of viral transmission (Ct <25), which show high positive and negative predictive values even when assuming a prevalence as low as 5%.

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Analytical and clinical performance of the panbio COVID-19 antigen-detecting rapid diagnostic test Dear Editor, Recent articles in this Journal have suggested the potential of antigen-based rapid diagnostic tests (Ag-RDT) as low-cost and ease-of-use tools for massive screening and epidemiological surveillance of SARS-CoV-2 spread. 1 , 2 Based on a pre-screening of four Ag-RDT on 40 frozen specimens from nasopharyngeal swabs with known PCR results (Table S1, Appendix), we selected the Panbio COVID-19 Ag Test (Abbott) for investigating its analytical and clinical performance. The analysis of serial dilutions of a SARS-CoV-2 isolate, propagated in Vero E6 cells, yielded a limit of detection (LoD) of 6.5 × 10 5 genome copies/reaction (Table S2). According to this value, the test would not detect SARS-CoV-2 infection in respiratory specimens with very low viral load. Still, the LoD was one logarithmic unit below the 10 6 copies/mL threshold necessary for successful virus isolate from respiratory samples. 3 The clinical performance was analysed on frozen swabs from 1406 individuals (mean age 40.4 years; SD 24.5) with an RT-qPCR result available: 951 (67.6%) positive and 455 (32.4%) negative. Overall, 446 (31.7%) and 473 (33.6%) samples were nasopharyngeal swabs from symptomatic individuals and contacts exposed to symptomatic cases, respectively, and 487 (34.6%) were nasal mid-turbinate swabs from asymptomatic individuals collected in screening campaigns. The cycle threshold (Ct) of PCR-positive samples was

Addition of maraviroc in early integrase inhibitor-based treatment of HIV-1 infection results in faster reduction of 2-LTR newly infected cells and recovery of CD4 T-cell counts, and a modest reduction in total reservoir size after 48 weeks of treatment. Paradoxically, CCR5 blockade also induced a slower decrease in plasma viremia and immune activation.