Corrigendum: Elevated IFNA1 and suppressed IL12p40 associated with persistent hyperinflammation in COVID-19 pneumonia.

[This corrects the article DOI: 10.3389/fimmu.2023.1101808.].

Elevated IFNA1 and suppressed IL12p40 associated with persistent hyperinflammation in COVID-19 pneumonia.

Introduction: Despite of massive endeavors to characterize inflammation in COVID-19 patients, the core network of inflammatory mediators responsible for severe pneumonia stillremain remains elusive. Methods: Here, we performed quantitative and kinetic analysis of 191 inflammatory factors in 955 plasma samples from 80 normal controls (sample n = 80) and 347 confirmed COVID-19 pneumonia patients (sample n = 875), including 8 deceased patients. Results: Differential expression analysis showed that 76% of plasmaproteins (145 factors) were upregulated in severe COVID-19 patients comparedwith moderate patients, confirming overt inflammatory responses in severe COVID-19 pneumonia patients. Global correlation analysis of the plasma factorsrevealed two core inflammatory modules, core I and II, comprising mainly myeloid cell and lymphoid cell compartments, respectively, with enhanced impact in a severity-dependent manner. We observed elevated IFNA1 and suppressed IL12p40, presenting a robust inverse correlation in severe patients, which was strongly associated with persistent hyperinflammation in 8.3% of moderate pneumonia patients and 59.4% of severe patients. Discussion: Aberrant persistence of pulmonary and systemic inflammation might be associated with long COVID-19 sequelae. Our comprehensive analysis of inflammatory mediators in plasmarevealed the complexity of pneumonic inflammation in COVID-19 patients anddefined critical modules responsible for severe pneumonic progression.

Evaluation of shields and ventilation as a countermeasure to protect bus drivers from infection.

We evaluated the deposition of droplets and droplet nuclei-generated by simulated coughing and talking from three points in a bus-on the driver's face and on surfaces around the driver (e.g., the steering wheel), based on whether countermeasures were taken, and assuming that an infected passenger was talking to the driver. When a shield, such as acrylic boards or polyvinyl chloride (PVC) sheets, was used as the countermeasure, the deposition of artificial droplets (>4 µm), emitted from beside or behind the driver, on his eyes, mouth, and cheeks reduced by two to three orders of magnitude or more. Deposition on the surfaces around the driver was also reduced following the use of shields. For artificial droplet nuclei (1.3 µm of polystyrene latex (PSL)) emitted from atomizers beside the driver, the operation of the ventilation fan (VF) and air conditioner (AC), and defroster (DEF) greatly reduced the driver's exposure, while the use of the shield did not. The infection risk of the driver was estimated through exposure to the virus via transfer to the mucosa via hands or surface-to-finger, direct adhesion on the mucosa, and direct inhalation of droplets and droplet nuclei. This is under the assumption that the droplets and droplet nuclei measured in this study are 40% the diameter of those after immediately leaving the mouth of the infected person and are constant regardless of particle size. When using the shield, total infection risk via droplet, airborne, and contact transmission was decreased by 75.0-99.8%. When the shield was not installed, the infection risk decreased by 9.74-48.7% with the operation of the VF, AC, and/or DEF.

FDA-Approved Trifluoromethyl Group-Containing Drugs: A Review of 20 Years

As people around the world regard 2020 as the year of COVID-19, the medical community considers this year to be the second-best year, shared with the year 1996, with respect to the number of drug molecules approved by the US Food and Drug Administration (FDA). Both years, 2020 and 1996, had a record of 53 new drug molecules approved by the FDA. In the year 2020, 53 new chemical entities and 13 biological medicines were approved, including 10 monoclonal antibodies, 2 antibody-drug conjugates, 3 peptides, and 2 oligonucleotides. Among them, most of the compounds were found to have fluorine or fluorine-containing functional groups exhibiting numerous pharmacological activities. Herein, we summarized the trifluoromethyl (TFM, -CF3)-group-containing FDA-approved drugs for the last 20 years. This article specially features and details the previous 20-year literature data, covering CF3-incorporated potential drug molecules, including their syntheses and uses for various diseases and disorders. The review covers the detailed chemistry of 19 FDA-approved drugs in the past 20 years, which contains the TFM group as one of the pharmacophores.

Experience of emergency medical services provider training using online training of trainers during COVID-19: official development assistance project in Tashkent, Uzbekistan.

OBJECTIVE: Since onsite education is difficult due to the COVID-19 pandemic, official development assistance (ODA) projects have implemented online training of trainers (ToT) for emergency medical experts and staff. This study aims to share and discuss the ToT experience and its results in Uzbekistan. METHODS: We trained emergency medical advanced course instructors through online ToT among emergency medical service experts in Uzbekistan as a part of an ODA project. After the ToT, instructors were selected based on written tests, video monitoring of practice, and simulation performance. They operated the emergency medical course including lectures, practices, and simulations for 5 days. We tested the trainees through written tests before and after the course. They were surveyed regarding the course contents, its relevance, and their satisfaction with the course. RESULTS: Six instructors were selected after the online ToT program. They educated 68 emergency medical workers through the three training courses. The total score of the pretest was 129.2±34.8, and the posttest score was 170.8±31.2, which was significantly higher (P<0.05). The satisfaction calculated by adding the values of survey items for this curriculum was 28.0 (interquartile range, 26.0-30.0), and there was no statistical difference regarding trainee satisfaction between the three courses (P=0.148). CONCLUSION: Instructors trained by online ToT programs could provide an in-person emergency medical advanced course.

Air exchange rates and advection-diffusion of CO2 and aerosols in a route bus for evaluation of infection risk.

As COVID-19 continues to spread, infection risk on public transport is concerning. Air exchange rates (ACH) and advection-diffusion of CO2 and particles were determined in a route bus to evaluate the infection risk. ACH increased with bus speed whether windows were open or closed, and ACH were greater when more windows were open. With two open windows, ACH was greater when a front and rear window were open than when two rear windows were open. With both front and rear ventilation fans set to exhaust, ACH was more than double that when both were set to supply. With air conditioning (AC) off, CO2 and particles spread proportionally at the same rate from a source, whereas with the AC on, the spread rate of particles was about half that of CO2 , because particles might be trapped by a prefilter on the AC unit. Infection risk can be reduced by equipping AC unit with an appropriate filter. Calculations with a modified Wells-Riley equation showed that average infection risk was reduced by 92% in the moving bus with windows open comparing to with windows closed. When the bus was moving with windows closed, exhaust fan operation reduced the average risk by 35%.

Study of Aerosol Movement and countermeasures in public transportation

Public transportation is required to have effective measures against the new corona infection. In this study, the authors investigated the actual condition of ventilation, which is said to be the infection route of the virus, and examined the countermeasures in addition, the behavior of the particles when they were diffused into the route bus was measured. PSL and artificial saliva were used as the particles. PSL tends to be deposited easily, so the particle concentration is too low. It may lead to evaluation. Also, the particle collection ability of the aerosol filter was evaluated. From this result, it was found that it has the same effect as window opening ventilation.

Intracerebral Hemorrhage due to Thrombosis with Thrombocytopenia Syndrome after Vaccination against COVID-19: the First Fatal Case in Korea.

Vaccination with an adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in the rare development of thrombosis with thrombocytopenia mediated by platelet-activating antibodies against platelet factor 4 (PF4). This is a life-threating condition that may be accompanied by bleeding due to thrombocytopenia with thrombosis of the cerebral venous sinus or splanchnic vein. Herein, we describe the first fatal case of thrombosis with thrombocytopenia syndrome in Korea, presenting with intracranial hemorrhage caused by cerebral venous sinus thrombosis. A 33-year-old Korean man received the first dose of the ChAdOx1 nCoV-19 vaccination. He developed severe headache with vomiting 9 days after the vaccination. Twelve days after vaccination, he was admitted to the hospital with neurological symptoms and was diagnosed with cerebral venous sinus thrombosis, which was accompanied by intracranial hemorrhage. Thrombocytopenia and D-dimer elevation were observed, and the result of the PF4 enzyme-linked immunosorbent assay antibody test was reported to be strongly positive. Despite intensive treatment, including intravenous immunoglobulin injection and endovascular mechanical thrombectomy, the patient died 19 days after vaccination. Physicians need to be aware of thrombosis with thrombocytopenia syndrome (TTS) in adenoviral vector-vaccinated patients. Endovascular mechanical thrombectomy might be a useful therapeutic option for the treatment of TTS with cerebral venous sinus thrombosis.

Survey of air exchange rates and evaluation of airborne infection risk of COVID-19 on commuter trains.

To identify potential countermeasures for coronavirus disease (COVID-19), we determined the air exchange rates in stationary and moving train cars under various conditions in July, August, and December 2020 in Japan. When the doors were closed, the air exchange rates in both stationary and moving trains increased with increasing area of window-opening (0.23-0.78/h at 0 m2, windows closed to 2.1-10/h at 2.86 m2, fully open). The air exchange rates were one order of magnitude higher when doors were open than when closed. With doors closed, the air exchange rates were higher when the centralized air conditioning (AC) and crossflow fan systems (fan) were on than when off. The air exchange rates in moving trains increased as train speed increased, from 10/h at 20 km/h to 42/h at 57 km/h. Air exchange rates did not differ significantly between empty cars and those filled with 230 mannequins representing commuters. The air exchange rates were lower during aboveground operation than during underground. Assuming that 30-300 passengers travel in a train car for 7-60 min and that the community infection rate is 0.0050-0.30%, we estimated that commuters' infection risk on trains was reduced by 91-94% when all 12 windows were opened (to a height of 10 cm) and the AC/fan was on compared with that when windows were closed and the AC/fan was off.

Environmental factors involved in SARS-CoV-2 transmission: effect and role of indoor environmental quality in the strategy for COVID-19 infection control.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new zoonotic agent that emerged in December 2019, causes coronavirus disease 2019 (COVID-19). This infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. SARS-CoV-2 spreads primarily via respiratory droplets during close person-to-person contact in a closed space, especially a building. This article summarizes the environmental factors involved in SARS-CoV-2 transmission, including a strategy to prevent SARS-CoV-2 transmission in a building environment. SARS-CoV-2 can persist on surfaces of fomites for at least 3 days depending on the conditions. If SARS-CoV-2 is aerosolized intentionally, it is stable for at least several hours. SARS-CoV-2 is inactivated rapidly on surfaces with sunlight. Close-contact aerosol transmission through smaller aerosolized particles is likely to be combined with respiratory droplets and contact transmission in a confined, crowded, and poorly ventilated indoor environment, as suggested by some cluster cases. Although evidence of the effect of aerosol transmission is limited and uncertainty remains, adequate preventive measures to control indoor environmental quality are required, based on a precautionary approach, because COVID-19 has caused serious global damages to public health, community, and the social economy. The expert panel for COVID-19 in Japan has focused on the "3 Cs," namely, "closed spaces with poor ventilation," "crowded spaces with many people," and "close contact." In addition, the Ministry of Health, Labour and Welfare of Japan has been recommending adequate ventilation in all closed spaces in accordance with the existing standards of the Law for Maintenance of Sanitation in Buildings as one of the initial political actions to prevent the spread of COVID-19. However, specific standards for indoor environmental quality control have not been recommended and many scientific uncertainties remain regarding the infection dynamics and mode of SARS-CoV-2 transmission in closed indoor spaces. Further research and evaluation are required regarding the effect and role of indoor environmental quality control, especially ventilation.

Measures against COVID-19 concerning Summer Indoor Environment in Japan

Information on air-conditioning and ventilation has been continuously disseminated in response to the Japanese Government's announcement of the need for appropriate ventilation measures against the new coronavirus disease (COVID-19), and the issuing of an emergency presidential discourse by the presidents of Engineering Societies. In this paper, we add to the information the latest knowledge on the behavior of SARS-CoV-2 in air, describe its diffusion characteristics in the built environment, and summarize the effects of temperature and humidity on the virus. Then we recommend varying approaches of air-conditioning control for facility type.

Impact of climate and ambient air pollution on the epidemic growth during COVID-19 outbreak in Japan.

Coronavirus disease 2019 (COVID-19) rapidly spread worldwide in the first quarter of 2020 and resulted in a global crisis. Investigation of the potential association of the spread of the COVID-19 infection with climate or ambient air pollution could lead to the development of preventive strategies for disease control. To examine this association, we conducted a longitudinal cohort study of 28 geographical areas of Japan with documented outbreaks of COVID-19. We analyzed data obtained from March 13 to April 6, 2020, before the Japanese government declared a state of emergency. The results revealed that the epidemic growth of COVID-19 was significantly associated with increase in daily temperature or sunshine hours. This suggests that an increase in person-to-person contact due to increased outing activities on a warm and/or sunny day might promote the transmission of COVID-19. Our results also suggested that short-term exposure to suspended particles might influence respiratory infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Further research by well-designed or well-controlled study models is required to ascertain this effect. Our findings suggest that weather has an indirect role in the transmission of COVID-19 and that daily adequate preventive behavior decreases the transmission.