Tracing the origin of large respiratory droplets by their deposition characteristics inside the respiratory tract during speech

Origin of differently sized respiratory droplets is fundamental for clarifying their viral loads and the sequential transmission mechanism of SARS-CoV-2 in indoor environments. Transient talking activities characterized by low (0.2 L/s), medium (0.9 L/s), and high (1.6 L/s) airflow rates of monosyllabic and successive syllabic vocalizations were investigated by computational fluid dynamics (CFD) simulations based on a real human airway model. SST k−ω model was chosen to predict the airflow field, and the discrete phase model (DPM) was used to calculate the trajectories of droplets within the respiratory tract. The results showed that flow field in the respiratory tract during speech is characterized by a significant laryngeal jet, and bronchi, larynx, and pharynx-larynx junction were main deposition sites for droplets released from the lower respiratory tract or around the vocal cords, and among which, over 90% of droplets over 5 µm released from vocal cords deposited at the larynx and pharynx-larynx junction. Generally, droplets' deposition fraction increased with their size, and the maximum size of droplets that were able to escape into external environment decreased with the airflow rate. This threshold size for droplets released from the vocal folds was 10–20 µm, while that for droplets released from the bronchi was 5–20 µm under various airflow rates. Besides, successive syllables pronounced at low airflow rates promoted the escape of small droplets, but do not significantly affect the droplet threshold diameter. This study indicates that droplets larger than 20 µm may entirely originate from the oral cavity, where viral loads are lower;it provides a reference for evaluating the relative importance of large-droplet spray and airborne transmission route of COVID-19 and other respiratory infections.

Tracing the origin of large respiratory droplets by their deposition characteristics inside the respiratory tract during speech.

Origin of differently sized respiratory droplets is fundamental for clarifying their viral loads and the sequential transmission mechanism of SARS-CoV-2 in indoor environments. Transient talking activities characterized by low (0.2 L/s), medium (0.9 L/s), and high (1.6 L/s) airflow rates of monosyllabic and successive syllabic vocalizations were investigated by computational fluid dynamics (CFD) simulations based on a real human airway model. SST k-ω model was chosen to predict the airflow field, and the discrete phase model (DPM) was used to calculate the trajectories of droplets within the respiratory tract. The results showed that flow field in the respiratory tract during speech is characterized by a significant laryngeal jet, and bronchi, larynx, and pharynx-larynx junction were main deposition sites for droplets released from the lower respiratory tract or around the vocal cords, and among which, over 90% of droplets over 5 µm released from vocal cords deposited at the larynx and pharynx-larynx junction. Generally, droplets' deposition fraction increased with their size, and the maximum size of droplets that were able to escape into external environment decreased with the airflow rate. This threshold size for droplets released from the vocal folds was 10-20 µm, while that for droplets released from the bronchi was 5-20 µm under various airflow rates. Besides, successive syllables pronounced at low airflow rates promoted the escape of small droplets, but do not significantly affect the droplet threshold diameter. This study indicates that droplets larger than 20 µm may entirely originate from the oral cavity, where viral loads are lower; it provides a reference for evaluating the relative importance of large-droplet spray and airborne transmission route of COVID-19 and other respiratory infections.

Efficacy and safety of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies in COVID-19 patients: a meta-analysis.

OBJECTIVE: This study aims to determine the efficacy and safety of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies in COVID-19 patients. METHODS: We searched Cochrane Library, PubMed, Embase, and ClinicalTrials.gov databases until July 27, 2022. Both randomized control trials (RCTs) and cohort studies were included and analyzed separately. The outcomes included mortality, incidence of invasive mechanical ventilation (IMV), ventilation improvement rate (need oxygen therapy to without oxygen therapy), secondary infection, and adverse events (AEs). The odds ratio (OR) with a 95% confidence interval (CI) was calculated by a random-effects meta-analysis model. RESULTS: Five RCTs and 2 cohort studies with 1726 COVID-19 patients were recruited (n = 866 in the GM-CSF antibody group and n = 891 in the control group). GM-CSF antibodies treatment reduced the incidence of IMV, which was supported by two cohort studies (OR 0.16; 95% CI 0.03, 0.74) and three RCTs (OR 0.62; 95% CI 0.41, 0.94). GM-CSF antibodies resulted in slight but not significant reductions in mortality (based on two cohort studies and five RCTs) and ventilation improvement (based on one cohort study and two RCTs). The sensitive analysis further showed the results of mortality and ventilation improvement rate became statistically significant when one included study was removed. Besides, GM-CSF antibodies did not increase the risks of the second infection (based on one cohort study and five RCTs) and AEs (based on five RCTs). CONCLUSION: GM-CSF antibody treatments may be an efficacious and well-tolerant way for the treatment of COVID-19. Further clinical evidence is still warranted.

Monocytic HLA-DR Expression in Immune Responses of Acute Pancreatitis and COVID-19.

Acute pancreatitis is a common gastrointestinal disease with increasing incidence worldwide. COVID-19 is a potentially life-threatening contagious disease spread throughout the world, caused by severe acute respiratory syndrome coronavirus 2. More severe forms of both diseases exhibit commonalities with dysregulated immune responses resulting in amplified inflammation and susceptibility to infection. Human leucocyte antigen (HLA)-DR, expressed on antigen-presenting cells, acts as an indicator of immune function. Research advances have highlighted the predictive values of monocytic HLA-DR (mHLA-DR) expression for disease severity and infectious complications in both acute pancreatitis and COVID-19 patients. While the regulatory mechanism of altered mHLA-DR expression remains unclear, HLA-DR-/low monocytic myeloid-derived suppressor cells are potent drivers of immunosuppression and poor outcomes in these diseases. Future studies with mHLA-DR-guided enrollment or targeted immunotherapy are warranted in more severe cases of patients with acute pancreatitis and COVID-19.

Effects of occupant behavior and ventilation on exposure to respiratory droplets in the indoor environment

To quantify the risk of the transmission of respiratory infections in indoor environments, we systematically assessed exposure to talking- and breathing-generated respiratory droplets in a generic indoor environment using computational fluid dynamic (CFD) simulations. The flow field in the indoor environment was obtained with SST k-ω model and Lagrangian method was used to predict droplet trajectories, where droplet evaporation was considered. Droplets can be categorized into small droplets (initial size ≤30 μm or ≤10 μm as droplet nuclei), medium droplets (30–80 μm) and large droplets (>100 μm) according to the exposure characteristics. Droplets up to 100 μm, particular the small ones, can contribute to both short-range and long-range airborne routes. For the face-to-face talking scenario, the intake fraction and deposition fractions of droplets on the face and facial mucosa of the susceptible were up to 4.96%, 2.14%, and 0.12%, respectively, indicating inhalation is the dominant route. The exposure risk from a talking infector decreases monotonically with the interpersonal distance, while that of nasal-breathing generated droplets maintains a relatively stable level within 1.0 m. Keeping an angle of 15° or above with the expiratory flow is efficient to reduce intake fractions to <0.37% for small droplets. Adjusting the orientation from face-to-face to face-to-back can reduce exposure to small droplets by approximately 88.0% during talking and 66.2% during breathing. A higher ventilation rate can reduce the risk of exposure to small droplets but may increase the risk of transmission via medium droplets by enhancing their evaporation rate. This study would serve as a fundamental research for epidemiologist, healthcare workers and the public in the purpose of infection control.

Efficacy and safety of granulocyte–macrophage colony-stimulating factor (GM-CSF) antibodies in COVID-19 patients: a meta-analysis

Objective This study aims to determine the efficacy and safety of granulocyte–macrophage colony-stimulating factor (GM-CSF) antibodies in COVID-19 patients. Methods We searched Cochrane Library, PubMed, Embase, and ClinicalTrials.gov databases until July 27, 2022. Both randomized control trials (RCTs) and cohort studies were included and analyzed separately. The outcomes included mortality, incidence of invasive mechanical ventilation (IMV), ventilation improvement rate (need oxygen therapy to without oxygen therapy), secondary infection, and adverse events (AEs). The odds ratio (OR) with a 95% confidence interval (CI) was calculated by a random-effects meta-analysis model. Results Five RCTs and 2 cohort studies with 1726 COVID-19 patients were recruited (n = 866 in the GM-CSF antibody group and n = 891 in the control group). GM-CSF antibodies treatment reduced the incidence of IMV, which was supported by two cohort studies (OR 0.16;95% CI 0.03, 0.74) and three RCTs (OR 0.62;95% CI 0.41, 0.94). GM-CSF antibodies resulted in slight but not significant reductions in mortality (based on two cohort studies and five RCTs) and ventilation improvement (based on one cohort study and two RCTs). The sensitive analysis further showed the results of mortality and ventilation improvement rate became statistically significant when one included study was removed. Besides, GM-CSF antibodies did not increase the risks of the second infection (based on one cohort study and five RCTs) and AEs (based on five RCTs). Conclusion GM-CSF antibody treatments may be an efficacious and well-tolerant way for the treatment of COVID-19. Further clinical evidence is still warranted. Supplementary Information The online version contains supplementary material available at 10.1007/s10787-022-01105-9.

Comparison of chest CT features between progressive and nonprogressive patients with COVID-19 pneumonia: A meta-analysis.

OBJECTIVE: The aim of this study was to compare the radiographic features of patients with progressive and nonprogressive coronavirus disease 2019 (COVID-19) pneumonia. METHODS: PubMed, Embase, and Cochrane Library databases were searched from January 1, 2020, to February 28, 2022, by using the keywords: "COVID-19", "novel Coronavirus", "2019-novel coronavirus", "CT", "radiology" and "imaging". We summarized the computed tomography manifestations of progressive and nonprogressive COVID-19 pneumonia. The meta-analysis was performed using the Stata statistical software version 16.0. RESULTS: A total of 10 studies with 1092 patients were included in this analysis. The findings of this meta-analysis indicated that the dominating computed tomography characteristics of progressive patients were a crazy-paving pattern (odds ratio [OR] = 2.10) and patchy shadowing (OR = 1.64). The dominating lesions distribution of progressive patients were bilateral (OR = 11.62), central mixed subpleural (OR = 1.37), and central (OR = 1.36). The other dominating lesions of progressive patients were pleura thickening (OR = 2.13), lymphadenopathy (OR = 1.74), vascular enlargement (OR = 1.39), air bronchogram (OR = 1.29), and pleural effusion (OR = 1.29). Two patterns of lesions showed significant links with the progression of disease: nodule (P = .001) and crazy-paving pattern (P = .023). Four lesions distribution showed significant links with the progression of disease: bilateral (P = .004), right upper lobe (P = .003), right middle lobe (P = .001), and left upper lobe (P = .018). CONCLUSION: Nodules, crazy-paving pattern, and/or new lesions in bilateral, upper and middle lobe of right lung, and lower lobe of left lung may indicate disease deterioration. Clinicians should formulate or modify treatment strategies in time according to these specific conditions.

S100A4 exerts robust mucosal adjuvant activity for co-administered antigens in mice.

The lack of clinically applicable mucosal adjuvants is a major hurdle in designing effective mucosal vaccines. We hereby report that the calcium-binding protein S100A4, which regulates a wide range of biological functions, is a potent mucosal adjuvant in mice for co-administered antigens, including the SARS-CoV-2 spike protein, with comparable or even superior efficacy as cholera toxin but without causing any adverse reactions. Intranasal immunization with recombinant S100A4 elicited antigen-specific antibody and pulmonary cytotoxic T cell responses, and these responses were remarkably sustained for longer than 6 months. As a self-protein, S100A4 did not stimulate antibody responses against itself, a quality desired of adjuvants. S100A4 prolonged nasal residence of intranasally delivered antigens and promoted migration of antigen-presenting cells. S100A4-pulsed dendritic cells potently activated cognate T cells. Furthermore, S100A4 induced strong germinal center responses revealed by both microscopy and mass spectrometry, a novel label-free technique for measuring germinal center activity. Importantly, S100A4 did not induce olfactory bulb inflammation after nasal delivery, which is often a safety concern for nasal vaccination. In conclusion, S100A4 may be a promising adjuvant in formulating mucosal vaccines, including vaccines against pathogens that infect via the respiratory tract, such as SARS-CoV-2.

Numerical investigation of airborne transmission of respiratory infections on the subway platform

Underground subway platforms are among the world’s busiest public transportation systems, but the airborne transmission mechanism of respiratory infections on these platforms has been rarely studied. Here, computational fluid dynamics (CFD) modeling is used to investigate the airflow patterns and infection risks in an island platform under two common ventilation modes: Mode 1- both sides have air inlets and outlets;Mode 2- air inlets are present at the two sides and outlets are present in the middle. Under the investigated scenario, airflow structure is characterized by the ventilation jet and human thermal plumes. Their interaction with the infector’s breathing jet imposes the front passenger under the highest exposure risk by short-range airborne route, with intake fractions up to 2.57% (oral breathing) or 0.63% (nasal breathing) under Mode 1;oral breathing of the infector may impose higher risks for the front passenger compared with nasal breathing. Pathogen are efficiently diluted as they travel further, in particular to adjacent crowds. The maximum and median value of intake fractions of passengers in adjacent crowds are respectively 0.093% and 0.016% (oral breathing), and 0.073% and 0.014% (nasal breathing) under Mode 1. Compared with Mode 1, the 2nd mode minimizes the interaction of ventilation jet and breathing jet, where the maximum intake fraction is only 0.34%, and the median value in the same crowd and other crowds are reduced by 23-63%. Combining published quanta generation rate data of COVID-19 and influenza infectors, the predicted maximum and median infection risks for passengers in the same crowds are respectively 1.46%−40.23% and 0.038%−1.67% during the 3−10 min waiting period, which are more sensitive to ventilation rate and exposure time compared with return air. This study can provide practical guidance for the prevention of respiratory infections in subway platforms.

A meta-analysis of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody treatment for COVID-19 patients.

OBJECTIVE: This meta-analysis aims to assess the efficacy and safety of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies on COVID-19. METHODS: Relevant literatures about GM-CSF antibody treatment in COVID-19 patients were searched from the PubMed, Cochrane Library, Embase, Google scholar, and Baiduscholar databases from the COVID-19 outbreak in December 2019 until 1 January 2021. The primary outcomes included the death, intensive care unit (ICU) admission risk, ventilation requirement, and secondary infection. RESULTS: A total of 12 eligible literature involving 8979 COVID-19 patients were recruited, and they were divided into experimental group (n = 2673) and control group (n = 6306). Using a random-effect model, it is found that the GM-CSF antibody treatment was associated with a 23% decline of the risk of death [odd's ratio (OR): 0.34, 95% confidence interval (CI): 0.21-0.56, p < 0.0001] and a 20% enhancement of ventilation (OR: 1.47, 95% CI: 1.19, 1.80, p = 0.0002). GM-CSF antibody treatment did not have a significant correlation to secondary infection and increased risk of ICU admission in COVID-19 patients, which may be attributed to the older age and the length of stay. CONCLUSIONS: Severe COVID-19 patients can benefit from GM-CSF antibodies.

Cold atmospheric plasma: A non-negligible strategy for viral RNA inactivation to prevent SARS-CoV-2 environmental transmission.

Cold atmospheric plasma (CAP), regarded as a powerful physics technology, displays antimicrobial, antitumor, and even antiviral properties, but the underlying mechanism is rarely studied. In this study, four CAP exposure doses (30, 60, 120, and 240 s) were applied to inactivate a severe acute respiratory syndrome coronavirus 2 like pseudovirus on a stainless steel disk, which comprised spike protein on its membrane and can express a green fluorescent protein. In order to unravel the potential effects of CAP irradiation on pseudovirus, infection assay, optical emission spectra analysis, transmission electron microscopy (TEM), sodium dodecyl sulfate polyacrylamide gel electrophoresis, ELISA, and qPCR experiments were carried out. As a result, our study indicated that CAP irradiation can significantly decrease the infectivity of pseudovirus in a dose dependent manner through destroying the cell membrane and further damaging viral RNA, with the molecular weight and conformation of spike receptor binding domain protein unchanged.

Asian-Pacific perspective on the psychological well-being of healthcare workers during the evolution of the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to significant strain on front-line healthcare workers. AIMS: In this multicentre study, we compared the psychological outcomes during the COVID-19 pandemic in various countries in the Asia-Pacific region and identified factors associated with adverse psychological outcomes. METHOD: From 29 April to 4 June 2020, the study recruited healthcare workers from major healthcare institutions in five countries in the Asia-Pacific region. A self-administrated survey that collected information on prior medical conditions, presence of symptoms, and scores on the Depression Anxiety Stress Scales and the Impact of Events Scale-Revised were used. The prevalence of depression, anxiety, stress and post-traumatic stress disorder (PTSD) relating to COVID-19 was compared, and multivariable logistic regression identified independent factors associated with adverse psychological outcomes within each country. RESULTS: A total of 1146 participants from India, Indonesia, Singapore, Malaysia and Vietnam were studied. Despite having the lowest volume of cases, Vietnam displayed the highest prevalence of PTSD. In contrast, Singapore reported the highest case volume, but had a lower prevalence of depression and anxiety. In the multivariable analysis, we found that non-medically trained personnel, the presence of physical symptoms and presence of prior medical conditions were independent predictors across the participating countries. CONCLUSIONS: This study highlights that the varied prevalence of psychological adversity among healthcare workers is independent of the burden of COVID-19 cases within each country. Early psychological interventions may be beneficial for the vulnerable groups of healthcare workers with presence of physical symptoms, prior medical conditions and those who are not medically trained.

Multi-route transmission potential of SARS-CoV-2 in healthcare facilities.

Understanding the transmission mechanism of SARS-CoV-2 is a prerequisite to effective control measures. To investigate the potential modes of SARS-CoV-2 transmission, 21 COVID-19 patients from 12-47 days after symptom onset were recruited. We monitored the release of SARS-CoV-2 from the patients' exhaled breath and systematically investigated environmental contamination of air, public surfaces, personal necessities, and the drainage system. SARS-CoV-2 RNA was detected in 0 of 9 exhaled breath samples, 2 of 8 exhaled breath condensate samples, 1 of 12 bedside air samples, 4 of 132 samples from private surfaces, 0 of 70 samples from frequently touched public surfaces in isolation rooms, and 7 of 23 feces-related air/surface/water samples. The maximum viral RNA concentrations were 1857 copies/m3 in the air, 38 copies/cm2 in sampled surfaces and 3092 copies/mL in sewage/wastewater samples. Our results suggest that nosocomial transmission of SARS-CoV-2 can occur via multiple routes. However, the low detection frequency and limited quantity of viral RNA from the breath and environmental specimens may be related to the reduced viral load of the COVID-19 patients on later days after symptom onset. These findings suggest that the transmission dynamics of SARS-CoV-2 differ from those of SARS-CoV in healthcare settings.

[Pharmacovigilance study on drug-induced cardiac injury during treatment of COVID-19].

Because coronavirus disease 2019(COVID-19) is highly contagious and serious, it has posed a major threat to public health worldwide. The curative effects of integrated traditional Chinese medicine and Western medicine in the treatment of COVID-19 have been widely recognized and confirmed. However, medical workers shall pay attention to drug-induced heart injury in clinical application. Based on the guideline from the Diagnosis and Treatment Plans for COVID-19(trial seventh edition), taking the recommended drugs as examples, by Western medicine, traditional Chinese medicine, Chinese herbal injection and integrated traditional Chinese and Western medicine, the study analyzed the basic characteristics of recommended drugs for cardiac injury by means of literature review and bioinformatics methods, and summarized cardiac adverse reactions, toxicity mechanisms, combined pharmacotherapy, special population and drug monitoring, focusing on the clinical manifestations, toxic components, targets and regulatory mechanisms of drug-induced cardiac injury. The findings suggested being vigilant to drug-induced cardiac injury during the treatment of COVID-19, playing the advantages of clinical pharmacists and clinical Chinese pharmacists, improving the knowledge reserve of pharmacovigilance, strengthening the prescription review, medication notification and medication monitoring, promoting rational drug use and paying attention to special populations and high-risk groups. The study aims to provide suggestions and reference for pharmacovigilance and pharmaceutical care for front-line doctors and pharmacists against COVID-19, in order to avoid the occurrence of drug-induced heart injury for patients with COVID-19.

The clinical benefits of Chinese patent medicines against COVID-19 based on current evidence.

The outbreak of emerging infectious pneumonia caused by 2019 Novel Coronavirus (2019-nCoV) has posed an enormous threat to public health, and traditional Chinese medicine (TCM) have made vast contribution to the prevention, treatment and rehabilitation of coronavirus disease 19 (COVID-19) among Chinese population. As an indispensable part of TCM, Chinese patent medicines (CPMs) are highly valued and critically acclaimed in their campaign to contain and tackle the epidemic, they can achieve considerable effects for both suspected cases under medical observation period, and confirmed individuals with serious underlying diseases or critical conditions. Given this, based on the Guideline on Diagnosis and Treatment of Coronavirus Disease 2019 in China, the present review summarized the basic information, clinical evidence and published literatures of recommended CPMs against COVID-19. The details were thoroughly introduced involving compositions, therapeutic effects, clinical indications, medication history of CPMs and the profiles of corresponding research. With regard to infected patients with different stages and syndrome, the preferable potentials and therapeutic mechanism of CPMs were addressed through the comprehensive collection of relevant literatures and on-going clinical trials. This study could provide an insight into clinical application and underlying mechanism of recommended CPMs against COVID-19, with the aim to share the Chinese experience in clinical practice and facilitate scientific development of TCM, especially CPMs in the fierce battle of COVID-19.

A multinational, multicentre study on the psychological outcomes and associated physical symptoms amongst healthcare workers during COVID-19 outbreak.

OBJECTIVE: Since the declaration of the coronavirus 2019 (COVID-19) outbreak as pandemic, there are reports on the increased prevalence of physical symptoms observed in the general population. We investigated the association between psychological outcomes and physical symptoms among healthcare workers. METHODS: Healthcare workers from 5 major hospitals, involved in the care for COVID-19 patients, in Singapore and India were invited to participate in a study by performing a self-administered questionnaire within the period of February 19 to April 17, 2020. Healthcare workers included doctors, nurses, allied healthcare workers, administrators, clerical staff and maintenance workers. This questionnaire collected information on demographics, medical history, symptom prevalence in the past month, Depression Anxiety Stress Scales (DASS-21) and the Impact of Events Scale-Revised (IES-R) instrument. The prevalence of physical symptoms displayed by healthcare workers and the associations between physical symptoms and psychological outcomes of depression, anxiety, stress, and post-traumatic stress disorder (PTSD) were evaluated. RESULTS: Out of the 906 healthcare workers who participated in the survey, 48 (5.3%) screened positive for moderate to very-severe depression, 79 (8.7%) for moderate to extremely-severe anxiety, 20 (2.2%) for moderate to extremely-severe stress, and 34 (3.8%) for moderate to severe levels of psychological distress. The commonest reported symptom was headache (32.3%), with a large number of participants (33.4%) reporting more than four symptoms. Participants who had experienced symptoms in the preceding month were more likely to be older, have pre-existing comorbidities and a positive screen for depression, anxiety, stress, and PTSD. After adjusting for age, gender and comorbidities, it was found that depression (OR 2.79, 95% CI 1.54-5.07, p = 0.001), anxiety (OR 2.18, 95% CI 1.36-3.48, p = 0.001), stress (OR 3.06, 95% CI 1.27-7.41, p = 0.13), and PTSD (OR 2.20, 95% CI 1.12-4.35, p = 0.023) remained significantly associated with the presence of physical symptoms experienced in the preceding month. Linear regression revealed that the presence of physical symptoms was associated with higher mean scores in the IES-R, DASS Anxiety, Stress and Depression subscales. CONCLUSIONS: Our study demonstrates a significant association between the prevalence of physical symptoms and psychological outcomes among healthcare workers during the COVID-19 outbreak. We postulate that this association may be bi-directional, and that timely psychological interventions for healthcare workers with physical symptoms should be considered once an infection has been excluded.