BACKGROUND No therapeutics have yet been proven effective for the treatment of mild-illness caused by SARS-CoV-2. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be more efficacious than no-treatment for outpatients with mild Covid-19. METHODS We conducted a multicenter, open label, randomized controlled trial in Catalonia (Spain) between March 17, and May 26, 2020. Eligible Covid-19 cases were non-hospitalized adult patients with recently confirmed SARS-CoV-2 infection and less than five days of symptoms. Patients were assigned to receive HCQ (800 mg on day 1, followed by 400 mg once daily for 6 days) or no antiviral treatment (not-placebo controlled). Study outcomes were the reduction of viral RNA load in nasopharyngeal swabs up to 7 days after treatment start, patient disease progression using the WHO scale up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days. RESULTS A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD 12.6), mean viral load at baseline was 7.90 (SD 1.82) Log10 copies/mL, and median time from symptom onset to randomization was 3 days. No significant differences were found in the mean reduction of viral load at day 3 (-1.41 vs. -1.41 Log10 copies/mL in the control and intervention arm, respectively; difference 0.01 [95% CI -0.28;0.29]) or at day 7 (-3.37 vs. -3.44; d –0.07 [-0.44;0.29]). This treatment regimen did not reduce risk of hospitalization (7.1%, control vs. 5.9%, intervention; RR 0.75 [0.32;1.77]) nor shortened the time to complete resolution of symptoms (12 days, control vs. 10 days, intervention; p = 0.38). No relevant treatment-related AEs were reported. CONCLUSIONS In patients with mild Covid-19, no benefit was observed with HCQ beyond the usual care.

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...

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.

Background Current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are limited to non-pharmacological interventions. Hydroxychloroquine (HCQ) has been proposed as a postexposure therapy to prevent Coronavirus disease 2019 (Covid-19) but definitive evidence is lacking. Methods We conducted an open-label, cluster-randomized trial including asymptomatic contacts exposed to a PCR-positive Covid-19 case in Catalonia, Spain. Clusters were randomized to receive no specific therapy (control arm) or HCQ 800mg once, followed by 400mg daily for 6 days (intervention arm). The primary outcome was PCR-confirmed symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, either symptomatically compatible or a PCR-positive result regardless of symptoms. Adverse events (AEs) were assessed up to 28 days. Results The analysis included 2,314 healthy contacts of 672 Covid-19 index cases identified between Mar 17 and Apr 28, 2020. A total of 1,198 were randomly allocated to usual care and 1,116 to HCQ therapy. There was no significant difference in the primary outcome of PCR-confirmed, symptomatic Covid-19 disease (6.2% usual care vs. 5.7% HCQ; risk ratio 0.89 [95% confidence interval 0.54-1.46]), nor evidence of beneficial effects on prevention of SARS-CoV-2 transmission (17.8% usual care vs. 18.7% HCQ). The incidence of AEs was higher in the intervention arm than in the control arm (5.9% usual care vs 51.6% HCQ), but no treatment-related serious AEs were reported. Conclusions Postexposure therapy with HCQ did not prevent SARS-CoV-2 disease and infection in healthy individuals exposed to a PCR-positive case. Our findings do not support HCQ as postexposure prophylaxis for Covid-19.

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%.