Immunogenicity and safety of a recombinant fusion protein vaccine (V-01) against coronavirus disease 2019 in healthy adults: a randomized, double-blind, placebo-controlled, phase II trial.

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 µg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 µg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 µg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 µg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 µg V-01 two-dose group, and 50 µg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 µg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).

An observation approach in evaluation of ozone production to precursor changes during the COVID-19 lockdown.

The increase of surface ozone during the Corona Virus Disease 2019 (COVID-19) lockdown in China has aroused great concern. In this study, we combine 1.5 years of measurements for ozone, volatile organic compounds (VOCs), and nitrogen oxide (NOX) at four sites to investigate the effect of COVID-19 lockdown on surface ozone in Dongguan, an industrial city in southern China. We show that the average concentrations of NOX and VOCs decreased by 70%-77% and 54%-68% during the lockdown compared to pre-lockdown, respectively. Based on the source apportionment of VOCs, the contribution of industrial solvent use reduced significantly (86%-94%) during the lockdown, and climbed back slowly along with the re-opening of the industry after lockdown. A slight increase in mean ozone concentration (3%-14%) was observed during the lockdown. The rise of ozone was the combined effect of substantial increase at night (58%-91%) and small reduction in the daytime (1%-17%). These conflicting observations in ozone response between day and night to emission change call for a more detailed approach to diagnostic ozone production response with precursor changes, rather than directly comparing absolute concentrations. We propose that the ratio of daily Ox (i.e. ozone + NO2) enhancement to solar radiation can provide a diagnostic parameter for ozone production response during the lockdown period. Smaller ratio of daily OX (ozone + NO2) enhancement to solar radiation during the lockdown were observed from the long-term measurements in Dongguan, suggesting significantly weakened photochemistry during the lockdown successfully reduces local ozone production. Our proposed approach can provide an evaluation of ozone production response to precursor changes from restrictions of social activities during COVID-19 epidemic and also other regional air quality abatement measures (e.g. public mega-events) around the globe.

Communication on the prevention and treatment of COVID-19 epidemic between Anhui Province of China and federal districts along the Volga river in Russia

The ongoing coronavirus infection (COVID19) pandemic is associated with high rates of morbidity and mortality. Russia, as a transport hub between Europe and Asia, has been hit hard by COVID19. The aim of this publication is to present the materials of a teleconference held between experts from Anhui province in China and experts from the federal districts of Russia. Material and methods. Discussion of methods of prevention and treatment of the new coronavirus infection COVID19, as well as issues affecting the immune aspects of the disease, complications and possible longterm followup for patients after a new coronavirus infection. Results and discussion. The situation was especially difficult for the federal district along the Volga River, so we shared and discussed questions on the prevention and treatment of the COVID19 epidemic, which were asked by the experts of the region. Conclusion. The presented article is the result of an online meeting of the doctors from the Volga region of Russia with experts from Anhui province in China.

Impact of COVID-19 lockdown on ambient levels and sources of volatile organic compounds (VOCs) in Nanjing, China.

A lot of restrictive measures were implemented in China during January-February 2020 to control rapid spread of COVID-19. Many studies reported impact of COVID-19 lockdown on air quality, but little research focused on ambient volatile organic compounds (VOCs) till now, which play important roles in production of ozone and secondary organic aerosol. In this study, impact of COVID-19 lockdown on VOCs mixing ratios and sources were assessed based on online measurements of VOCs in Nanjing during December 20, 2019-Feburary 15, 2020 (P1-P2) and April 15-May 13, 2020 (P3). Average VOCs levels during COVID-19 lockdown period (P2) was 26.9 ppb, about half of value for pre-lockdown period (P1). Chemical composition of VOCs also showed significant changes. Aromatics contribution during decreased from 13% during P1 to 9% during P2, whereas alkanes contribution increased from 64% to 68%. Positive matrix factorization (PMF) was then applied for non-methane hydrocarbons (NMHCs) sources apportionment. Five sources were identified, including a source related to transport and background air masses, three sources related to petrochemical industry or chemical industry (petrochemical industry#1-propene/ethene, petrochemical industry#2-C7-C9 aromatics, and chemical industry-benzene), and a source attributed to gasoline evaporation and vehicular emission. During P2, NMHCs levels from petrochemical industry#2-C7-C9 aromatics showed the largest relative decline of 94%, followed by petrochemical industry#1-propene/ethene (67%), and gasoline evaporation and vehicular emission (67%). Furthermore, ratios of OH reactivity of NMHCs versus NO2 level (ROH,NMHCs/NO2) and total oxidant production rate (P (OX)) were calculated to assess potential influences of COVID-19 lockdown on O3 formation.

Discovery of rhodomyrtone as a broad-spectrum antiviral inhibitor with anti-SARS-CoV-2 activity (preprint)

The outbreak of new viruses, such as serve acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as the emerging of drug-resistance viruses highlight the urgent need for the development of broad-spectrum antiviral drugs. Herein, we report the discovery of a plant-derived small molecule, 6,8-dihydroxy-9-isobutyl-2,2,4,4-tetramethyl-7-(3-methylbutanoyl)-4,9-dihydro-1H- xanthene-1,3(2H)-dione (rhodomyrtone, RDT), which exhibited potent broad-spectrum antiviral activities against several RNA and DNA viruses, including SARS-CoV-2, respiratory syncytial virus (RSV), herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and Kaposi's sarcoma-associated herpesvirus (KSHV). RDT can significantly suppress viral gene expression and show the low possibility to elicit drug-resistant variants. Mechanistic study implied that RDT inhibited viral infection by disturbing the cellular factors that essential for viral gene expression. Our results suggested that RDT might be a promising lead compound for the development of broad-spectrum antiviral drugs.