A retrospect of ozone formation mechanisms during the COVID-19 lockdown: The potential role of isoprene.

Wuhan took strict measures to prevent the spread of COVID-19 from January 26 to April 7 in 2020. The lockdown reduced the concentrations of atmospheric pollutants, except ozone (O3). To investigate the increase in O3 during the lockdown, trace gas pollutants were collected. The initial concentrations of volatile organic compounds (VOCs) were calculated based on a photochemical ratio method, and the ozone formation potential (OFP) was obtained using the initial and measured VOC concentrations. The O3 formation regime was NOX-limited based on the VOCs/NOX diurnal ratios during the lockdown period. The reduced nitric oxide (NO) concentrations and lower wind speed (WS) could explain the night-time O3 accumulation. The initial total VOCs (TVOCs) during the lockdown were 47.6 ± 2.9 ppbv, and alkenes contributed 48.1%. The photochemical loss amounts of alkenes were an order of magnitude higher than those of alkenes in the same period in 2019 and increased from 16.6 to 28.0 ppbv in the daytime. The higher initial alkene concentrations sustained higher OFP during the lockdown, reaching between 252.4 and 504.4 ppbv. The initial isoprene contributed approximately 35.0-55.0% to the total OFP and had a positive correlation with the increasing O3 concentrations. Approximately 75.5% of the temperatures were concentrated in the range of 5 and 20 °C, which were higher than those in 2019. In addition to stronger solar radiation, the higher temperatures induced higher isoprene emission rates, partially accounting for the higher isoprene concentrations. Lower isoprene-emitting trees should be considered for future urban vegetation to control O3 episodes.

The SARS-CoV-2 Transcriptome and the Dynamics of the S Gene Furin Cleavage Site in Primary Human Airway Epithelia.

The spike (S) polypeptide of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consists of the S1 and S2 subunits and is processed by cellular proteases at the S1/S2 boundary that contains a furin cleavage site (FCS), 682RRAR↓S686 Various deletions surrounding the FCS have been identified in patients. When SARS-CoV-2 propagated in Vero cells, it acquired deletions surrounding the FCS. We studied the viral transcriptome in Vero cell-derived SARS-CoV-2-infected primary human airway epithelia (HAE) cultured at an air-liquid interface (ALI) with an emphasis on the viral genome stability of the FCS. While we found overall the viral transcriptome is similar to that generated from infected Vero cells, we identified a high percentage of mutated viral genome and transcripts in HAE-ALI. Two highly frequent deletions were found at the FCS region: a 12 amino acid deletion (678TNSPRRAR↓SVAS689) that contains the underlined FCS and a 5 amino acid deletion (675QTQTN679) that is two amino acids upstream of the FCS. Further studies on the dynamics of the FCS deletions in apically released virions from 11 infected HAE-ALI cultures of both healthy and lung disease donors revealed that the selective pressure for the FCS maintains the FCS stably in 9 HAE-ALI cultures but with 2 exceptions, in which the FCS deletions are retained at a high rate of >40% after infection of ≥13 days. Our study presents evidence for the role of unique properties of human airway epithelia in the dynamics of the FCS region during infection of human airways, which is likely donor dependent.IMPORTANCE Polarized human airway epithelia at an air-liquid interface (HAE-ALI) are an in vitro model that supports efficient infection of SARS-CoV-2. The spike (S) protein of SARS-CoV-2 contains a furin cleavage site (FCS) at the boundary of the S1 and S2 domains which distinguishes it from SARS-CoV. However, FCS deletion mutants have been identified in patients and in vitro cell cultures, and how the airway epithelial cells maintain the unique FCS remains unknown. We found that HAE-ALI cultures were capable of suppressing two prevalent FCS deletion mutants (Δ678TNSPRRAR↓SVAS689 and Δ675QTQTN679) that were selected during propagation in Vero cells. While such suppression was observed in 9 out of 11 of the tested HAE-ALI cultures derived from independent donors, 2 exceptions that retained a high rate of FCS deletions were also found. Our results present evidence of the donor-dependent properties of human airway epithelia in the evolution of the FCS during infection.

Chinese Herbal Medicine Used With or Without Conventional Western Therapy for COVID-19: An Evidence Review of Clinical Studies.

Objective: To present the evidence of the therapeutic effects and safety of Chinese herbal medicine (CHM) used with or without conventional western therapy for COVID-19. Methods: Clinical studies on the therapeutic effects and safety of CHM for COVID-19 were included. We summarized the general characteristics of included studies, evaluated methodological quality of randomized controlled trials (RCTs) using the Cochrane risk of bias tool, analyzed the use of CHM, used Revman 5.4 software to present the risk ratio (RR) or mean difference (MD) and their 95% confidence interval (CI) to estimate the therapeutic effects and safety of CHM. Results: A total of 58 clinical studies were identified including RCTs (17.24%, 10), non-randomized controlled trials (1.72%, 1), retrospective studies with a control group (18.97%, 11), case-series (20.69%, 12) and case-reports (41.38%, 24). No RCTs of high methodological quality were identified. The most frequently tested oral Chinese patent medicine, Chinese herbal medicine injection or prescribed herbal decoction were: Lianhua Qingwen granule/capsule, Xuebijing injection and Maxing Shigan Tang. In terms of aggravation rate, pooled analyses showed that there were statistical differences between the intervention group and the comparator group (RR 0.42, 95% CI 0.21 to 0.82, six RCTs; RR 0.38, 95% CI 0.23 to 0.64, five retrospective studies with a control group), that is, CHM plus conventional western therapy appeared better than conventional western therapy alone in reducing aggravation rate. In addition, compared with conventional western therapy, CHM plus conventional western therapy had potential advantages in increasing the recovery rate and shortening the duration of fever, cough and fatigue, improving the negative conversion rate of nucleic acid test, and increasing the improvement rate of chest CT manifestations and shortening the time from receiving the treatment to the beginning of chest CT manifestations improvement. For adverse events, pooled data showed that there were no statistical differences between the CHM and the control groups. Conclusion: Current low certainty evidence suggests that there maybe a tendency that CHM plus conventional western therapy is superior to conventional western therapy alone. The use of CHM did not increase the risk of adverse events.

Characteristics of registered studies for Coronavirus disease 2019 (COVID-19): A systematic review.

BACKGROUND: The World Health Organization characterized the Coronavirus disease 2019 (COVID-19) as a pandemic on March 11th. Many clinical trials on COVID-19 have been registered, and we aim to review the study characteristics and provide guidance for future trials to avoid duplicated effort. METHODS: Studies on COVID-19 registered before March 3rd, 2020 on eight registry platforms worldwide were searched and the data of design, participants, interventions, and outcomes were extracted and analyzed. RESULTS: Three hundred and ninety-three studies were identified and 380 (96.7%) were from mainland China, while 3 in Japan, 3 in France, 2 in the US, and 3 were international collaborative studies. Two hundred and sixty-six (67.7%) aimed at therapeutic effect, others were for prevention, diagnosis, prognosis, etc. Two hundred and two studies (51.4%) were randomized controlled trials. Two third of therapeutic studies tested Western medicines including antiviral drugs (17.7%), stem cell and cord blood therapy (10.2%), chloroquine and derivatives (8.3%), 16 (6.0%) on Chinese medicines, and 73 (27.4%) on integrated therapy of Western and Chinese medicines. Thirty-one studies among 266 therapeutic studies (11.7%) used mortality as primary outcome, while the most designed secondary outcomes were symptoms and signs (47.0%). Half of the studies (45.5%) had not started recruiting till March 3rd. CONCLUSION: Inappropriate outcome setting, delayed recruitment and insufficient numbers of new cases in China implied many studies may fail to complete. Strategies and protocols of the studies with robust and rapid data sharing are warranted for emergency public health events, helping the timely evidence-based decision-making.