ABSTRACT
BackgroundSARS-CoV-2 viral entry may disrupt angiotensin II (Ang II) homeostasis in part via ACE2 downregulation, potentially contributing to COVID-19 induced lung injury. Preclinical models of viral pneumonias that utilize ACE2 demonstrate Ang II type 1 receptor (AT1R) blockade mitigates lung injury, though observational COVID-19 data addressing the effect of AT1R blockade remain mixed. MethodsMulticenter, blinded, placebo-controlled randomized trial of losartan (50 mg PO twice daily for 10 days) versus placebo. Hospitalized patients with COVID-19 and a respiratory sequential organ failure assessment score of at least 1 and not already taking a renin-angiotensin-aldosterone system (RAAS) inhibitor were eligible. The primary outcome was the imputed partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio at 7 days. Secondary outcomes included ordinal COVID-19 severity, oxygen, ventilator, and vasopressor-free days, and mortality. Losartan pharmacokinetics (PK) and RAAS components [Ang II, angiotensin-(1-7) (Ang-(1-7)), ACE, ACE2] were measured in a subgroup of participants. FindingsFrom April 2020 - February 2021, 205 participants were randomized, 101 to losartan and 104 to placebo. Compared to placebo, losartan did not significantly affect PaO2/FiO2 ratio at 7 days [difference of -24.8 (95% -55.6 to 6.1; p=0.12)]. Losartan did not improve any secondary clinical outcome, but worsened vasopressor-free days. PK data were consistent with appropriate steady-state concentrations, but we observed no significant effect of losartan on RAAS components. InterpretationInitiation of orally administered losartan to hospitalized patients with COVID-19 and acute lung injury does not improve PaO2 / FiO2 ratio at 7 days. These data may have implications for ongoing clinical trials. Trial RegistrationLosartan for Patients With COVID-19 Requiring Hospitalization (NCT04312009), https://clinicaltrials.gov/ct2/show/NCT04312009
ABSTRACT
BackgroundAlthough nasopharyngeal (NP) samples have been considered the gold standard for COVID-19 testing, variability in viral load across different anatomical sites could theoretically cause NP samples to be less sensitive than saliva or nasal samples in certain cases. Self-collected samples also have logistical advantages over NP samples, making them amenable to population-scale screening. MethodsTo evaluate sampling alternatives for population screening, we collected NP, saliva, and nasal samples from two cohorts with varied levels and types of symptoms. ResultsIn a mixed cohort of 60 symptomatic and asymptomatic participants, we found that saliva had 88% concordance with NP when tested in the same testing lab (n = 41), and 68% concordance when tested in different testing labs (n = 19). In a second cohort of 20 participants hospitalized for COVID-19, saliva had 74% concordance with NP tested in the same testing lab, but detected virus in two participants that tested negative with NP on the same day. Medical record review showed that the saliva-based testing sensitivity was related to the timing of symptom onset and disease stage. ConclusionsWe find that no sample site will be perfectly sensitive for COVID-19 testing in all situations, and the significance of negative results will always need to be determined in the context of clinical signs and symptoms. Saliva retained high clinical sensitivity while allowing easier collection, minimizing the exposure of healthcare workers and need for personal protective equipment, and making it a viable option for population-scale testing.
ABSTRACT
The COVID-19 global pandemic is an unprecedented health emergency. Insufficient access to testing has hampered effective public health interventions and patient care management in a number of countries. Furthermore, the availability of regulatory-cleared reagents has challenged widespread implementation of testing. We rapidly developed a qRT-PCR SARS-CoV-2 detection assay using a 384-well format and tested its analytic performance across multiple nucleic acid extraction kits. Our data shows robust analytic accuracy on residual clinical biospecimens. Limit of detection sensitivity and specificity was confirmed with currently available commercial reagents. Our methods and results provide valuable information for other high-complexity laboratories seeking to develop effective, local, laboratory-developed procedures with high-throughput capability to detect SARS-CoV-2.
