Seroprofiling of antibodies against endemic human coronaviruses and SARS-CoV-2 in an HIV cohort in Lesotho: correlates of antibody response and seropositivity.

BACKGROUND: Serological data on endemic human coronaviruses (HCoVs) and SARS-CoV-2 in southern Africa are scarce. Here, we report on i) endemic HCoV seasonality, ii) SARS-CoV-2 seroprevalence, and iii) predictive factors for SARS-CoV-2 seropositivity and strength of SARS-CoV-2 and HCoV serological response during a 17-month period at the start of the COVID-19 pandemic among adults living with HIV. METHODS: Plasma samples were collected from February 2020 to July 2021 within an outpatient HIV cohort in Lesotho. We used the ABCORA multiplex immunoassay to measure antibody responses to endemic HCoV (OC43, HKU1, NL63, and 229E) and SARS-CoV-2 antigens. RESULTS: Results of 3'173 samples from 1'403 adults were included. Serological responses against endemic HCoVs increased over time and peaked in winter/spring. SARS-CoV-2 seropositivity reached >35% among samples collected in early 2021 and was associated with female sex (p = 0.004), obesity (p < 0.001), working outside the home (p = 0.02), and recent tiredness (p = 0.005) or fever (p = 0.007). Positive correlations were observed between the strength of response to endemic HCoVs and to SARS-CoV-2, and between older age or obesity and the IgG response to SARS-CoV-2. CONCLUSIONS: These results add to our understanding of the impact of biological, clinical, and social/behavioural factors on serological responses to coronaviruses in southern Africa.

Antibody Response After Third Vaccination With mRNA-1273 or BNT162b2: Extension of a Randomized Controlled SARS-CoV-2 Noninferiority Vaccine Trial in Patients With Different Levels of Immunosuppression (COVERALL-2).

Extension of the COVERALL (COrona VaccinE tRiAL pLatform) randomized trial showed noninferiority in antibody response of the third dose of Moderna mRNA-1273 vaccine (95.3% [95% confidence interval {CI}, 91.9%-98.7%]) compared to Pfizer-BioNTech BNT162b2 vaccine (98.1% [95% CI, 95.9%-100.0%]) in individuals with different levels of immunosuppression (difference, -2.8% [95% CI, -6.8% to 1.3%]).

Triggers of change in sexual behavior among people with HIV: The Swiss U = U statement and Covid-19 compared.

We assessed changes in sexual behaviour among people with HIV (PWH) over 20 years. Condom use with stable partners steadily declined from over 90% to 29% since the Swiss U = U statement with similar trajectories between men who have sex with men (MSM) and heterosexuals. Occasional partnership remained higher among MSM compared to heterosexuals even during COVID-19 social distancing.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2022 Recommendations of the International Antiviral Society-USA Panel.

Importance: Recent advances in treatment and prevention of HIV warrant updated recommendations to guide optimal practice. Objective: Based on a critical evaluation of new data, to provide clinicians with recommendations on use of antiretroviral drugs for the treatment and prevention of HIV, laboratory monitoring, care of people aging with HIV, substance use disorder and HIV, and new challenges in people with HIV, including COVID-19 and monkeypox virus infection. Evidence Review: A panel of volunteer expert physician scientists were appointed to update the 2020 consensus recommendations. Relevant evidence in the literature (PubMed and Embase searches, which initially yielded 7891 unique citations, of which 834 were considered relevant) and studies presented at peer-reviewed scientific conferences between January 2020 and October 2022 were considered. Findings: Initiation of antiretroviral therapy (ART) is recommended as soon as possible after diagnosis of HIV. Barriers to care should be addressed, including ensuring access to ART and adherence support. Integrase strand transfer inhibitor-containing regimens remain the mainstay of initial therapy. For people who have achieved viral suppression with a daily oral regimen, long-acting injectable therapy with cabotegravir plus rilpivirine given as infrequently as every 2 months is now an option. Weight gain and metabolic complications have been linked to certain antiretroviral medications; novel strategies to ameliorate these complications are needed. Management of comorbidities throughout the life span is increasingly important, because people with HIV are living longer and confronting the health challenges of aging. In addition, management of substance use disorder in people with HIV requires an evidence-based, integrated approach. Options for preexposure prophylaxis include oral medications (tenofovir disoproxil fumarate or tenofovir alafenamide plus emtricitabine) and, for the first time, a long-acting injectable agent, cabotegravir. Recent global health emergencies, like the SARS-CoV-2 pandemic and monkeypox virus outbreak, continue to have a major effect on people with HIV and the delivery of services. To address these and other challenges, an equity-based approach is essential. Conclusions and Relevance: Advances in treatment and prevention of HIV continue to improve outcomes, but challenges and opportunities remain.

Developing and testing a Corona VaccinE tRiAL pLatform (COVERALL) to study Covid-19 vaccine response in immunocompromised patients.

BACKGROUND: The rapid course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic calls for fast implementation of clinical trials to assess the effects of new treatment and prophylactic interventions. Building trial platforms embedded in existing data infrastructures is an ideal way to address such questions within well-defined subpopulations. METHODS: We developed a trial platform building on the infrastructure of two established national cohort studies: the Swiss human immunodeficiency virus (HIV) Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS). In a pilot trial, termed Corona VaccinE tRiAL pLatform (COVERALL), we assessed the vaccine efficacy of the first two licensed SARS-CoV-2 vaccines in Switzerland and the functionality of the trial platform. RESULTS: Using Research Electronic Data Capture (REDCap), we developed a trial platform integrating the infrastructure of the SHCS and STCS. An algorithm identifying eligible patients, as well as baseline data transfer ensured a fast inclusion procedure for eligible patients. We implemented convenient re-directions between the different data entry systems to ensure intuitive data entry for the participating study personnel. The trial platform, including a randomization algorithm ensuring balance among different subgroups, was continuously adapted to changing guidelines concerning vaccination policies. We were able to randomize and vaccinate the first trial participant the same day we received ethics approval. Time to enroll and randomize our target sample size of 380 patients was 22 days. CONCLUSION: Taking the best of each system, we were able to flag eligible patients, transfer patient information automatically, randomize and enroll the patients in an easy workflow, decreasing the administrative burden usually associated with a trial of this size.

Antibodies from convalescent plasma promote SARS-CoV-2 clearance in individuals with and without endogenous antibody response.

BACKGROUNDNeutralizing antibodies are considered a key correlate of protection by current SARS-CoV-2 vaccines. The manner in which human infections respond to therapeutic SARS-CoV-2 antibodies, including convalescent plasma therapy, remains to be fully elucidated.METHODSWe conducted a proof-of-principle study of convalescent plasma therapy based on a phase I trial in 30 hospitalized COVID-19 patients with a median interval between onset of symptoms and first transfusion of 9 days (IQR, 7-11.8 days). Comprehensive longitudinal monitoring of the virological, serological, and disease status of recipients allowed deciphering of parameters on which plasma therapy efficacy depends.RESULTSIn this trial, convalescent plasma therapy was safe as evidenced by the absence of transfusion-related adverse events and low mortality (3.3%). Treatment with highly neutralizing plasma was significantly associated with faster virus clearance, as demonstrated by Kaplan-Meier analysis (P = 0.034) and confirmed in a parametric survival model including viral load and comorbidity (adjusted hazard ratio, 3.0; 95% CI, 1.1-8.1; P = 0.026). The onset of endogenous neutralization affected viral clearance, but even after adjustment for their pretransfusion endogenous neutralization status, recipients benefitted from plasma therapy with high neutralizing antibodies (hazard ratio, 3.5; 95% CI, 1.1-11; P = 0.034).CONCLUSIONOur data demonstrate a clear impact of exogenous antibody therapy on the rapid clearance of viremia before and after onset of the endogenous neutralizing response, and point beyond antibody-based interventions to critical laboratory parameters for improved evaluation of current and future SARS-CoV-2 therapies.TRIAL REGISTRATIONClinicalTrials.gov NCT04869072.FUNDINGThis study was funded via an Innovation Pool project by the University Hospital Zurich; the Swiss Red Cross Glückskette Corona Funding; Pandemiefonds of the UZH Foundation; and the Clinical Research Priority Program "Comprehensive Genomic Pathogen Detection" of the University of Zurich.

Canakinumab in patients with COVID-19 and type 2 diabetes - A multicentre, randomised, double-blind, placebo-controlled trial.

Background: Patients with type 2 diabetes and obesity have chronic activation of the innate immune system possibly contributing to the higher risk of hyperinflammatory response to SARS-CoV2 and severe COVID-19 observed in this population. We tested whether interleukin-1ß (IL-1ß) blockade using canakinumab improves clinical outcome. Methods: CanCovDia was a multicenter, randomised, double-blind, placebo-controlled trial to assess the efficacy of canakinumab plus standard-of-care compared with placebo plus standard-of-care in patients with type 2 diabetes and a BMI > 25 kg/m2 hospitalised with SARS-CoV2 infection in seven tertiary-hospitals in Switzerland. Patients were randomly assigned 1:1 to a single intravenous dose of canakinumab (body weight adapted dose of 450-750 mg) or placebo. Canakinumab and placebo were compared based on an unmatched win-ratio approach based on length of survival, ventilation, ICU stay and hospitalization at day 29. This study is registered with ClinicalTrials.gov, NCT04510493. Findings: Between October 17, 2020, and May 12, 2021, 116 patients were randomly assigned with 58 in each group. One participant dropped out in each group for the primary analysis. At the time of randomization, 85 patients (74·6 %) were treated with dexamethasone. The win-ratio of canakinumab vs placebo was 1·08 (95 % CI 0·69-1·69; p = 0·72). During four weeks, in the canakinumab vs placebo group 4 (7·0%) vs 7 (12·3%) participants died, 11 (20·0 %) vs 16 (28·1%) patients were on ICU, 12 (23·5 %) vs 11 (21·6%) were hospitalised for more than 3 weeks, respectively. Median ventilation time at four weeks in the canakinumab vs placebo group was 10 [IQR 6.0, 16.5] and 16 days [IQR 14.0, 23.0], respectively. There was no statistically significant difference in HbA1c after four weeks despite a lower number of anti-diabetes drug administered in patients treated with canakinumab. Finally, high-sensitive CRP and IL-6 was lowered by canakinumab. Serious adverse events were reported in 13 patients (11·4%) in each group. Interpretation: In patients with type 2 diabetes who were hospitalised with COVID-19, treatment with canakinumab in addition to standard-of-care did not result in a statistically significant improvement of the primary composite outcome. Patients treated with canakinumab required significantly less anti-diabetes drugs to achieve similar glycaemic control. Canakinumab was associated with a prolonged reduction of systemic inflammation. Funding: Swiss National Science Foundation grant #198415 and University of Basel. Novartis supplied study medication.

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone. DESIGN: Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multinational, multicenter trial. PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: Intravenous ensovibep, 600 mg, or placebo. MEASUREMENTS: Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90. RESULTS: An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR < 1 would favor ensovibep). LIMITATION: The trial was prematurely stopped because of futility, limiting power for the primary outcome. CONCLUSION: Compared with placebo, ensovibep did not improve clinical outcomes for hospitalized participants with COVID-19 receiving standard care, including remdesivir; no safety concerns were identified. PRIMARY FUNDING SOURCE: National Institutes of Health.

Determinants of antibody response to severe acute respiratory syndrome coronavirus 2 mRNA vaccines in people with HIV.

We identified determinants of SARS-CoV-2 mRNA vaccine antibody response in people with HIV (PWH). Antibody response was higher among PWH less than 60 years, with CD4+ cell count superior to 350 cells/µl and vaccinated with mRNA-1273 by Moderna compared with BNT162b2 by Pfizer-BioNTech. Preinfection with SARS-CoV-2 boosted the antibody response and smokers had an overall lower antibody response. Elderly PWH and those with low CD4+ cell count should be prioritized for booster vaccinations.

Developing and testing a Corona VaccinE tRiAL pLatform (COVERALL) to study Covid-19 vaccine response in immunocompromised patients

The rapid course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic calls for fast implementation of clinical trials to assess the effects of new treatment and prophylactic interventions. Building trial platforms embedded in existing data infrastructures is an ideal way to address such questions within well-defined subpopulations. We developed a trial platform building on the infrastructure of two established national cohort studies: the Swiss human immunodeficiency virus (HIV) Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS). In a pilot trial, termed Corona VaccinE tRiAL pLatform (COVERALL), we assessed the vaccine efficacy of the first two licensed SARS-CoV-2 vaccines in Switzerland and the functionality of the trial platform. Using Research Electronic Data Capture (REDCap), we developed a trial platform integrating the infrastructure of the SHCS and STCS. An algorithm identifying eligible patients, as well as baseline data transfer ensured a fast inclusion procedure for eligible patients. We implemented convenient re-directions between the different data entry systems to ensure intuitive data entry for the participating study personnel. The trial platform, including a randomization algorithm ensuring balance among different subgroups, was continuously adapted to changing guidelines concerning vaccination policies. We were able to randomize and vaccinate the first trial participant the same day we received ethics approval. Time to enroll and randomize our target sample size of 380 patients was 22 days. Taking the best of each system, we were able to flag eligible patients, transfer patient information automatically, randomize and enroll the patients in an easy workflow, decreasing the administrative burden usually associated with a trial of this size.

Antibody Response in Immunocompromised Patients After the Administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine BNT162b2 or mRNA-1273: A Randomized Controlled Trial.

BACKGROUND: BNT162b2 by Pfizer-BioNTech and mRNA-1273 by Moderna are the most commonly used vaccines to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Head-to-head comparison of the efficacy of these vaccines in immunocompromised patients is lacking. METHODS: Parallel, 2-arm (allocation 1:1), open-label, noninferiority randomized clinical trial nested into the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study. People living with human immunodeficiency virus (PLWH) or solid organ transplant recipients (SOTR; ie, lung and kidney) from these cohorts were randomized to mRNA-1273 or BNT162b2. The primary endpoint was antibody response to SARS-CoV-2 spike (S1) protein receptor binding domain (Elecsys Anti-SARS-CoV-2 immunoassay, Roche; cutoff ≥0.8 units/mL) 12 weeks after first vaccination (ie, 8 weeks after second vaccination). In addition, antibody response was measured with the Antibody Coronavirus Assay 2 (ABCORA 2). RESULTS: A total of 430 patients were randomized and 412 were included in the intention-to-treat analysis (341 PLWH and 71 SOTR). The percentage of patients showing an immune response was 92.1% (95% confidence interval [CI]: 88.4-95.8; 186/202) for mRNA-1273 and 94.3% (95% CI: 91.2-97.4; 198/210) for BNT162b2 (difference: -2.2%; 95% CI: -7.1 to 2.7), fulfilling noninferiority of mRNA-1273. With the ABCORA 2 test, 89.1% had an immune response to mRNA-1273 (95% CI: 84.8-93.4; 180/202) and 89.5% to BNT162b2 (95% CI: 85.4-93.7; 188/210). Based on the Elecsys test, all PLWH had an antibody response (100.0%; 341/341), whereas for SOTR, only 60.6% (95% CI: 49.2-71.9; 43/71) had titers above the cutoff level. CONCLUSIONS: In immunocompromised patients, the antibody response of mRNA-1273 was noninferior to BNT162b2. PLWH had in general an antibody response, whereas a high proportion of SOTR had no antibody response.

An Approach to Quantifying the Interaction between Behavioral and Transmission Clusters.

We hypothesize that patterns of sexual behavior play a role in the conformation of transmission networks, i.e., the way you behave might influence whom you have sex with. If that was the case, behavioral grouping might in turn correlate with, and potentially predict transmission networking, e.g., proximity in a viral phylogeny. We rigorously present an intuitive approach to address this hypothesis by quantifying mapped interactions between groups defined by similarities in sexual behavior along a virus phylogeny while discussing power and sample size considerations. Data from the Swiss HIV Cohort Study on condom use and hepatitis C virus (HCV) sequences served as proof-of-concept. In this case, a strict inclusion criteria contrasting with low HCV prevalence hindered our possibilities to identify significant relationships. This manuscript serves as guide for studies aimed at characterizing interactions between behavioral patterns and transmission networks. Large transmission networks such as those of HIV or COVID-19 are prime candidates for applying this methodological approach.

Multifactorial seroprofiling dissects the contribution of pre-existing human coronaviruses responses to SARS-CoV-2 immunity.

Determination of SARS-CoV-2 antibody responses in the context of pre-existing immunity to circulating human coronavirus (HCoV) is critical for understanding protective immunity. Here we perform a multifactorial analysis of SARS-CoV-2 and HCoV antibody responses in pre-pandemic (N = 825) and SARS-CoV-2-infected donors (N = 389) using a custom-designed multiplex ABCORA assay. ABCORA seroprofiling, when combined with computational modeling, enables accurate definition of SARS-CoV-2 seroconversion and prediction of neutralization activity, and reveals intriguing interrelations with HCoV immunity. Specifically, higher HCoV antibody levels in SARS-CoV-2-negative donors suggest that pre-existing HCoV immunity may provide protection against SARS-CoV-2 acquisition. In those infected, higher HCoV activity is associated with elevated SARS-CoV-2 responses, indicating cross-stimulation. Most importantly, HCoV immunity may impact disease severity, as patients with high HCoV reactivity are less likely to require hospitalization. Collectively, our results suggest that HCoV immunity may promote rapid development of SARS-CoV-2-specific immunity, thereby underscoring the importance of exploring cross-protective responses for comprehensive coronavirus prevention.

A trial platform to assess approved SARS-CoV-2 vaccines in immunocompromised patients: first sub-protocol for a pilot trial comparing the mRNA vaccines Comirnaty® and COVID-19 mRNA Vaccine Moderna®.

BACKGROUND: Late 2019, a new highly contagious coronavirus SARS-CoV-2 has emerged in Wuhan, China, causing within 2 months a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. The pandemic has highlighted that new and more flexible clinical trial approaches, such as trial platforms, are needed to assess the efficacy and safety of interventions in a timely manner. The two existing Swiss cohorts of immunocompromised patients (i.e., Swiss HIV Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS)) are an ideal foundation to set-up a trial platform in Switzerland leveraging routinely collected data. Within a newly founded trial platform, we plan to assess the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorization in Switzerland in the frame of a pilot randomized controlled trial (RCT) while at the same time assessing the functionality of the trial platform. METHODS: We will conduct a multicenter randomized controlled, open-label, 2-arm sub-study pilot trial of a platform trial nested into two Swiss cohorts. Patients included in the SHCS or the STCS will be eligible for randomization to either receiving the mRNA vaccine Comirnaty® (Pfizer/BioNTech) or the COVID-19 mRNA Vaccine Moderna®. The primary clinical outcome will be change in pan-lg antibody response (pan-Ig anti-S1-RBD; baseline vs. 3 months after first vaccination; binary outcome, considering ≥ 0.8 units/ml as a positive antibody response). The pilot study will also enable us to assess endpoints related to trial conduct feasibility (i.e., duration of RCT set-up; time of patient recruitment; patient consent rate; proportion of missing data). Assuming vaccine reactivity of 90% in both vaccine groups, we power our trial, using a non-inferiority margin such that a 95% two-sided confidence interval excludes a difference in favor of the reference group of more than 10%. A sample size of 380 (190 in each treatment arm) is required for a statistical power of 90% and a type I error of 0.025. The study is funded by the Swiss National Science Foundation (National Research Program NRP 78, "COVID-19"). DISCUSSION: This study will provide crucial information about the efficacy and safety of the mRNA SARS-CoV-2 vaccines in HIV patients and organ transplant recipients. Furthermore, this project has the potential to pave the way for further platform trials in Switzerland. TRIAL REGISTRATION: ClinicalTrials.gov NCT04805125 . Registered on March 18, 2021.

Reduced Relative Sensitivity of the Elecsys SARS-CoV-2 Antigen Assay in Saliva Compared to Nasopharyngeal Swabs.

Early identification and isolation of SARS-CoV-2-infected individuals is central to contain the COVID-19 pandemic. Nasopharyngeal swabs (NPS) serve as a specimen for detection by RT-PCR and rapid antigen screening tests. Saliva has been confirmed as a reliable alternative specimen for RT-PCR and has been shown to be valuable for diagnosing children and in repetitive mass testing due to its non-invasive collection. Combining the advantages of saliva with those of antigen tests would be highly attractive to further increase test capacities. Here, we evaluated the performance of the Elecsys SARS-CoV-2 Antigen assay (Roche) in RT-PCR-positive paired NPS and saliva samples (N = 87) and unpaired NPS (N = 100) with confirmed SARS-CoV-2 infection (Roche cobas SARS-CoV-2 IVD test). We observed a high positive percent agreement (PPA) of the antigen assay with RT-PCR in NPS, reaching 87.2% across the entire cohort, whereas the overall PPA for saliva was insufficient (40.2%). At Ct values ≤ 28, PPA were 100% and 91.2% for NPS and saliva, respectively. At lower viral loads, the sensitivity loss of the antigen assay in saliva was striking. At Ct values ≤ 35, the PPA for NPS remained satisfactory (91.5%), whereas the PPA for saliva dropped to 46.6%. In conclusion, saliva cannot be recommended as a reliable alternative to NPS for testing with the Elecsys Anti-SARS-CoV-2 Antigen assay. As saliva is successfully used broadly in combination with RT-PCR testing, it is critical to create awareness that suitability for RT-PCR cannot be translated to implementation in antigen assays without thorough evaluation of each individual test system.

High Efficacy of Saliva in Detecting SARS-CoV-2 by RT-PCR in Adults and Children.

Rising demands for repetitive SARS-CoV-2 screens and mass testing necessitate additional test strategies. Saliva may serve as an alternative to nasopharyngeal swab (NPS) as its collection is simple, non-invasive and amenable for mass- and home testing, but its rigorous validation, particularly in children, is missing. We conducted a large-scale head-to-head comparison of SARS-CoV-2 detection by RT-PCR in saliva and NPS of 1270 adults and children reporting to outpatient test centers and an emergency unit. In total, 273 individuals were tested positive for SARS-CoV-2 in either NPS or saliva. SARS-CoV-2 RT-PCR results in the two specimens showed a high agreement (overall percent agreement = 97.8%). Despite lower viral loads in the saliva of both adults and children, detection of SARS-CoV-2 in saliva fared well compared to NPS (positive percent agreement = 92.5%). Importantly, in children, SARS-CoV-2 infections were more often detected in saliva than NPS (positive predictive value = 84.8%), underlining that NPS sampling in children can be challenging. The comprehensive parallel analysis reported here establishes saliva as a generally reliable specimen for the detection of SARS-CoV-2, with particular advantages for testing children, that is readily applicable to increase and facilitate repetitive and mass testing in adults and children.

Do we cause false positives? An experimental series on droplet or airborne SARS-CoV-2 contamination of sampling tubes during swab collection in a test center.

The rapid spread of the coronavirus disease 2019 pandemic urged immense testing capacities as one cornerstone of infection control. Many institutions opened outpatient SARS-CoV-2 test centers to allow large number of tests in comparatively short time frames. With increasing positive test rates, concerns for a possible airborne or droplet contamination of specimens leading to false-positive results were raised. In our experimental series performed in a dedicated SARS-CoV-2 test center, 40 open collection tubes placed for defined time periods in proximity to individuals were found to be SARS-CoV-2 negative. These findings argue against false-positive SARS-CoV-2 results due to droplet or airborne contamination.

Assessing the potential impact of transmission during prolonged viral shedding on the effect of lockdown relaxation on COVID-19.

A key parameter in epidemiological modeling which characterizes the spread of an infectious disease is the generation time, or more generally the distribution of infectiousness as a function of time since infection. There is increasing evidence supporting a prolonged viral shedding window for COVID-19, but the transmissibility in this phase is unclear. Based on this, we develop a generalized Susceptible-Exposed-Infected-Resistant (SEIR) model including an additional compartment of chronically infected individuals who can stay infectious for a longer duration than the reported generation time, but with infectivity reduced to varying degrees. Using the incidence and fatality data from different countries, we first show that such an assumption also yields a plausible model in explaining the data observed prior to the easing of the lockdown measures (relaxation). We then test the predictive power of this model for different durations and levels of prolonged infectiousness using the incidence data after the introduction of relaxation in Switzerland, and compare it with a model without the chronically infected population to represent the models conventionally used. We show that in case of a gradual easing on the lockdown measures, the predictions of the model including the chronically infected population vary considerably from those obtained under a model in which prolonged infectiousness is not taken into account. Although the existence of a chronically infected population still remains largely hypothetical, we believe that our results provide tentative evidence to consider a chronically infected population as an alternative modeling approach to better interpret the transmission dynamics of COVID-19.

Diagnosis of latent tuberculosis infection is associated with reduced HIV viral load and lower risk for opportunistic infections in people living with HIV.

Approximately 28% of the human population have been exposed to Mycobacterium tuberculosis (MTB), with the overwhelming majority of infected individuals not developing disease (latent TB infection (LTBI)). While it is known that uncontrolled HIV infection is a major risk factor for the development of TB, the effect of underlying LTBI on HIV disease progression is less well characterized, in part because longitudinal data are lacking. We sorted all participants of the Swiss HIV Cohort Study (SHCS) with at least 1 documented MTB test into one of the 3 groups: MTB uninfected, LTBI, or active TB. To detect differences in the HIV set point viral load (SPVL), linear regression was used; the frequency of the most common opportunistic infections (OIs) in the SHCS between MTB uninfected patients, patients with LTBI, and patients with active TB were compared using logistic regression and time-to-event analyses. In adjusted models, we corrected for baseline demographic characteristics, i.e., HIV transmission risk group and gender, geographic region, year of HIV diagnosis, and CD4 nadir. A total of 13,943 SHCS patients had at least 1 MTB test documented, of whom 840 (6.0%) had LTBI and 770 (5.5%) developed active TB. Compared to MTB uninfected patients, LTBI was associated with a 0.24 decreased log HIV SPVL in the adjusted model (p < 0.0001). Patients with LTBI had lower odds of having candida stomatitis (adjusted odds ratio (OR) = 0.68, p = 0.0035) and oral hairy leukoplakia (adjusted OR = 0.67, p = 0.033) when compared to MTB uninfected patients. The association of LTBI with a reduced HIV set point virus load and fewer unrelated infections in HIV/TB coinfected patients suggests a more complex interaction between LTBI and HIV than previously assumed.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2020 Recommendations of the International Antiviral Society-USA Panel.

Importance: Data on the use of antiretroviral drugs, including new drugs and formulations, for the treatment and prevention of HIV infection continue to guide optimal practices. Objective: To evaluate new data and incorporate them into current recommendations for initiating HIV therapy, monitoring individuals starting on therapy, changing regimens, preventing HIV infection for those at risk, and special considerations for older people with HIV. Evidence Review: New evidence was collected since the previous International Antiviral (formerly AIDS) Society-USA recommendations in 2018, including data published or presented at peer-reviewed scientific conferences through August 22, 2020. A volunteer panel of 15 experts in HIV research and patient care considered these data and updated previous recommendations. Findings: From 5316 citations about antiretroviral drugs identified, 549 were included to form the evidence basis for these recommendations. Antiretroviral therapy is recommended as soon as possible for all individuals with HIV who have detectable viremia. Most patients can start with a 3-drug regimen or now a 2-drug regimen, which includes an integrase strand transfer inhibitor. Effective options are available for patients who may be pregnant, those who have specific clinical conditions, such as kidney, liver, or cardiovascular disease, those who have opportunistic diseases, or those who have health care access issues. Recommended for the first time, a long-acting antiretroviral regimen injected once every 4 weeks for treatment or every 8 weeks pending approval by regulatory bodies and availability. For individuals at risk for HIV, preexposure prophylaxis with an oral regimen is recommended or, pending approval by regulatory bodies and availability, with a long-acting injection given every 8 weeks. Monitoring before and during therapy for effectiveness and safety is recommended. Switching therapy for virological failure is relatively rare at this time, and the recommendations for switching therapies for convenience and for other reasons are included. With the survival benefits provided by therapy, recommendations are made for older individuals with HIV. The current coronavirus disease 2019 pandemic poses particular challenges for HIV research, care, and efforts to end the HIV epidemic. Conclusion and Relevance: Advances in HIV prevention and management with antiretroviral drugs continue to improve clinical care and outcomes among individuals at risk for and with HIV.