Baricitinib as a novel treatment for bullous pemphigoid: a case series report (preprint)

Bullous pemphigoid (BP) is an autoimmune blistering disorder occurring mostly in the elderly. The standard treatment of BP patients with systemic corticosteroid have some potential serious side effects. Up till now, there is still lack of novel treatment for BP patients. Baricitinib, a selective Janus kinase (JAK) 1 and 2 inhibitor, has been used to treat rheumatoid arthritis, alopecia areata, and COVID-19. Successful treatment of refractory BP by JAK inhibitors has been reported in sporadic cases. In this study, we reported 8 BP patients treated with baricitinib. The patients after treatment were followed up for 3-24 months, with an average of 9.1 months. All 8 cases achieved disease control and the mean disease control period was 3 weeks (1-6 weeks). The bullous pemphigoid disease area index total (21.2 ± 13.0 to 2.5 ± 4.3, p<0.01), erosion/blister (6.0 ± 7.7 to 0.2 ± 0.5, p<0.05), urticaria/erythema (10.2 ± 11.9 to 0.0 ± 0.0, p=0.06), mucosal erosion/blister (10.0 ± 6.4 to 4.5 ± 5.1, n=4, p=0.25) and itching NRS (3.6 ± 3.5 to 0.0 ± 0.0, p=0.06) scores were all reduced after 2 months’ treatment. Seven of 8 patients achieved complete remission during tapering at month 3 and did not experience relapse during the follow-up period. The serum levels of anti-BP180 autoantibodies (IgG) were reduced significantly (77.1 ± 47.8U/mL to 40.1 ± 37.1U/mL, n=6, p<0.05) after 3 months’ treatment. During the follow-up period, only one patient experienced mild elevation of serum creatinine level after 3 months’ treatment of baricitinib, which returned to normal through discontinuation of the medication. In conclusion, this study demonstrated that low-dose, short-term administration of baricitinib is effective and safe for treating BP patients.

Lianhua Qingwen prescription for Coronavirus disease 2019 (COVID-19) treatment: Advances and prospects.

BACKGROUND: An outbreak of Coronavirus Disease 2019 (COVID-19) which was infected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is still spreading and has led to unprecedented health emergency over the world. Though no specific drug has been developed so far, emerging agents have been confirmed effective or potentially beneficial to restrain it. Lianhua Qingwen (LHQW) is a commonly used Chinese medical preparation to treat viral influenza, including in the fight against SARS in 2002-2003 in China. Recent data also showed that LHQW played a vigorous role in COVID-19 treatment. PURPOSE: This review will elucidate the pre-clinical and clinical evidence of LHQW in lung protection and antiviral activities, and provide timely data delivery for the exploration of effective treatment strategies in the therapy of COVID-19. STUDY DESIGN AND METHOD: The research data were obtained from the academic databases (up to August 8, 2020) including Pubmed, CNKI and Web of Science, on ethnobotany and ethno medicines. The search keywords for screening the literature information were "virus", "COVID-19", or "SARS-CoV-2", and "Lianhua Qingwen". The documents were filtered and summarized for final evaluation. RESULTS: The collected evidence demonstrated that LHQW exhibited benefits against COVID-19. Impressively, LHQW in conjunction with conventional treatment could significantly improve COVID-19 patients as a synergetic strategy. The mechanisms were mainly involved the antiviral activity, and regulation of inflammation response as well as immune function. CONCLUSION: Although the data were far from adequate, the latest advances had shown the benefits of LHQW in COVID-19, especially in combination with other antiviral drugs. This review provides comprehensive evidence of LHQW as a complementary strategy for treating COVID-19. Nevertheless, imperious researches should be conducted to clarify the unconfirmed effects, regulatory mechanisms and adverse reactions of LHQW in treating COVID-19 by means of well designed randomized controlled trials.

Transmission Dynamics of Coronavirus Disease 2019 (COVID-19) in the World: The Roles of Intervention and Seasonality (preprint)

The coronavirus disease 2019 (COVID-19) is spreading rapidly all over the world. The transmission dynamics of the COVID-19 pandemic is still unclear, but developing strategies for mitigating the severity of the pandemic is yet a top priority for global public health. In this study, we developed a novel compartmental model, SEIR-CV(susceptible-exposed-infectious-removed with control variables), which not only considers the key characteristics of asymptomatic infection and the effects of seasonal variations, but also incorporates different control measures for multiple transmission routes, so as to accurately predict and effectively control the spread of COVID-19. Based on SEIR-CV, we predicted the COVID-19 epidemic situation in China out of Hubei province and proposed corresponding control strategies. The results showed that the prediction results are highly consistent with the outbreak surveillance data, which proved that the proposed control strategies have achieved sound consequent in the actual epidemic control. Subsequently, we have conducted a rolling prediction for the United States, Brazil, India, five European countries (the United Kingdom, Italy, Spain, Germany, and France), southern hemisphere, northern hemisphere, and the world out of China. The results indicate that control measures and seasonal variations have a great impact on the progress of the COVID-19 pandemic. Our prediction results show that the COVID-19 pandemic is developing more rapidly due to the impact of the cold season in the southern hemisphere countries such as Brazil. While the development of the pandemic should have gradually weakened in the northern hemisphere countries with the arrival of the warm season, instead of still developing rapidly due to the relative loose control measures such as the United States and India. Furthermore, the prediction results illustrate that if keeping the current control measures in the main COVID-19 epidemic countries, the pandemic will not be contained and the situation may eventually turn to group immunization, which would lead to the extremely severe disaster of about 5 billion infections and 300 million deaths globally. However, if China's super stringent control measures were implemented from 15 July, 15 August or 15 September 2020, the total infections would be contained about 15 million, 32 million or 370 million respectively, which indicates that the stringent and timely control measures is critical, and the best window period is before September for eventually overcoming COVID-19.

Evidence for probable aerosol transmission of SARS-CoV-2 in a poorly ventilated restaurant (preprint)

Background: The role of aerosols in the transmission of SARS-CoV-2 remains debated. We analysed an outbreak involving three non-associated families in Restaurant X in Guangzhou, China, and assessed the possibility of aerosol transmission of SARS-CoV-2 and characterize the associated environmental conditions. Methods: We collected epidemiological data, obtained a video record and a patron seating-arrangement from the restaurant, and measured the dispersion of a warm tracer gas as a surrogate for exhaled droplets from the suspected index patient. Computer simulations were performed to simulate the spread of fine exhaled droplets. We compared the in-room location of subsequently infected cases and spread of the simulated virus-laden aerosol tracer. The ventilation rate was measured using the tracer decay method. Results: Three families (A, B, C), 10 members of which were subsequently found to have been infected with SARS-CoV-2 at this time, or previously, ate lunch at Restaurant X on Chinese New Year's Eve (January 24, 2020) at three neighboring tables. Subsequently, three members of family B and two members of family C became infected with SARS-CoV-2, whereas none of the waiters or 68 patrons at the remaining 15 tables became infected. During this occasion, the ventilation rate was 0.75-1.04 L/s per person. No close contact or fomite contact was observed, aside from back-to-back sitting by some patrons. Our results show that the infection distribution is consistent with a spread pattern representative of exhaled virus-laden aerosols. Conclusions: Aerosol transmission of SARS-CoV-2 due to poor ventilation may explain the community spread of COVID-19.

Transmission routes of Covid-19 virus in the Diamond Princess Cruise ship (preprint)

Background: An outbreak of COVID-19 occurred on the Diamond Princess cruise ship in January and February 2020. We analysed information about cases to infer transmission dynamics and potential modes of transmission. Methods: We collected the daily number of 197 symptomatic cases, and that of the 146 passenger cases in two categories, i.e. those who stayed and did not stay in the same stateroom. We retrieved the quarantine details and the ship's 14-day itinerary. We searched the websites of national/local health authority along the cruise routes and local news using Google for locally confirmed cases associated with the ship. We obtained the design of air conditioning and sewage treatment of the ship from literature. We back-calculated the dates of infection from the epidemic curve and compared with the start of on-board quarantine. Results: Major infections started on Jan 28 and completed by Feb 6 for passengers except those who stayed in the same stateroom with infected individual(s). No other confirmed cases were identified among the disembarked people in Hong Kong except an 80 years old passenger. No confirmed cases were reported in three other stopovers between Jan 27-31 associated with disembarked passengers or visitors from the ship, however two Okinawa taxi drivers became confirmed cases in association with driving the ship passengers. Infection among passengers after Feb 6 was limited to those who stayed in the same stateroom with an infected passenger. Infections in crew members peaked on Feb 7, suggesting significant transmission among crew members after quarantine on Feb 5. Conclusions: We infer that the ship central air conditioning system did not play a role, i.e. the long-range airborne route was absent in the outbreak. Most transmission appears to have occurred through close contact and fomites.

Toilets dominate environmental detection of SARS-CoV-2 virus in a hospital (preprint)

Background: Respiratory and faecal aerosols play a suspected role in transmitting the SARS-CoV-2 virus. We performed extensive environmental sampling in a dedicated hospital building for Covid-19 patients in both toilet and non-toilet environments, and analysed the associated environmental factors. Methods: We collected data of the Covid-19 patients. 107 surface samples, 46 air samples, two exhaled condensate samples, and two expired air samples were collected were collected within and beyond the four three-bed isolation rooms. We reviewed the environmental design of the building and the cleaning routines. We conducted field measurement of airflow and CO2 concentrations. Findings: The 107 surface samples comprised 37 from toilets, 34 from other surfaces in isolation rooms (ventilated at 30-60 L/s), and 36 from other surfaces outside isolation rooms in the hospital. Four of these samples were positive, namely two ward door-handles, one bathroom toilet-seat cover and one bathroom door-handle; and three were weakly positive, namely one bathroom toilet seat, one bathroom washbasin tap lever and one bathroom ceiling-exhaust louvre. One of the 46 air samples was weakly positive, and this was a corridor air sample. The two exhaled condensate samples and the two expired air samples were negative. Interpretation: The faecal-derived aerosols in patients' toilets contained most of the detected SARS-CoV-2 virus in the hospital, highlighting the importance of surface and hand hygiene for intervention.

Indoor transmission of SARS-CoV-2 (preprint)

Background: By early April 2020, the COVID-19 pandemic had infected nearly one million people and had spread to nearly all countries worldwide. It is essential to understand where and how SARS-CoV-2 is transmitted. Methods: Case reports were extracted from the local Municipal Health Commissions of 320 prefectural cities (municipalities) in China, not including Hubei province, between 4 January and 11 February 2020. We identified all outbreaks involving three or more cases and reviewed the major characteristics of the enclosed spaces in which the outbreaks were reported and associated indoor environmental issues. Results: Three hundred and eighteen outbreaks with three or more cases were identified, involving 1245 confirmed cases in 120 prefectural cities. We divided the venues in which the outbreaks occurred into six categories: homes, transport, food, entertainment, shopping, and miscellaneous. Among the identified outbreaks, 53.8% involved three cases, 26.4% involved four cases, and only 1.6% involved ten or more cases. Home outbreaks were the dominant category (254 of 318 outbreaks; 79.9%), followed by transport (108; 34.0%; note that many outbreaks involved more than one venue category). Most home outbreaks involved three to five cases. We identified only a single outbreak in an outdoor environment, which involved two cases. Conclusions: All identified outbreaks of three or more cases occurred in an indoor environment, which confirms that sharing indoor space is a major SARS-CoV-2 infection risk.