SLIDE: Saliva-Based SARS-CoV-2 Self-Testing with RT-LAMP in a Mobile Device.

Regular, accurate, rapid, and inexpensive self-testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently needed to quell pandemic propagation. The existing at-home nucleic acid testing (NAT) test has high sensitivity and specificity, but it requires users to mail the sample to the central lab, which often takes 3-5 days to obtain the results. On the other hand, rapid antigen tests for the SARS-CoV-2 antigen provide a fast sample to answer the test (15 min). However, the sensitivity of antigen tests is 30 to 40% lower than nucleic acid testing, which could miss a significant portion of infected patients. Here, we developed a fully integrated SARS-CoV-2 reverse transcription loop-mediated isothermal amplification (RT-LAMP) device using a self-collected saliva sample. This platform can automatically handle the complexity and can perform the functions, including (1) virus particles' thermal lysis preparation, (2) sample dispensing, (3) target sequence RT-LAMP amplification, (4) real-time detection, and (5) result report and communication. With a turnaround time of less than 45 min, our device achieved the limit of detection (LoD) of 5 copies/µL of the saliva sample, which is comparable with the LoD (6 copies/µL) using FDA-approved quantitative real-time polymerase chain reaction (qRT-PCR) assays with the same heat-lysis saliva sample preparation method. With clinical samples, our platform showed a good agreement with the results from the gold-standard RT-PCR method. These results show that our platform can perform self-administrated SARS-CoV-2 nucleic acid testing by laypersons with noninvasive saliva samples. We believe that our self-testing platform will have an ongoing benefit for COVID-19 control and fighting future pandemics.

Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: a randomized, double-blind, placebo-controlled phase 2 trial.

Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95% CI -29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.

CRISPR-based detection of SARS-CoV-2: A review from sample to result.

The current pandemic of the 2019 novel coronavirus (COVID-19) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) has raised significant public health concern. Rapid, affordable, and accurate diagnostics of SARS-CoV-2 is essential for early treatment and control of the disease spread. In the past few years, CRISPR technology has shown great potential for highly sensitive and specific molecular diagnostics. Amid the ongoing COVID-19 pandemic, there is an increasing interest in implementing CRISPR-based diagnostic principles to develop fast and precise methods for detecting SARS-CoV-2. In this work, we reviewed and summarized these CRISPR-based diagnostic systems as well as their characteristics and challenges. We also provided future perspectives of CRISPR-based sensing towards point-of-care molecular diagnosis applications.