Control measure implications of COVID-19 infection in healthcare facilities reconsidered from human physiological and engineering aspects.

The Wells-Riley model invokes human physiological and engineering parameters to successfully treat airborne transmission of infectious diseases. Applications of this model would have high potentiality on evaluating policy actions and interventions intended to improve public safety efforts on preventing the spread of COVID-19 in an enclosed space. Here, we constructed the interaction relationships among basic reproduction number (R0) - exposure time - indoor population number by using the Wells-Riley model to provide a robust means to assist in planning containment efforts. We quantified SARS-CoV-2 changes in a case study of two Wuhan (Fangcang and Renmin) hospitals. We conducted similar approach to develop control measures in various hospital functional units by taking all accountable factors. We showed that inhalation rates of individuals proved crucial for influencing the transmissibility of SARS-CoV-2, followed by air supply rate and exposure time. We suggest a minimum air change per hour (ACH) of 7 h-1 would be at least appropriate with current room volume requirements in healthcare buildings when indoor population number is < 10 and exposure time is < 1 h with one infector and low activity levels being considered. However, higher ACH (> 16 h-1) with optimal arranged-exposure time/people and high-efficiency air filters would be suggested if more infectors or higher activity levels are presented. Our models lay out a practical metric for evaluating the efficacy of control measures on COVID-19 infection in built environments. Our case studies further indicate that the Wells-Riley model provides a predictive and mechanistic basis for empirical COVID-19 impact reduction planning and gives a framework to treat highly transmissible but mechanically heterogeneous airborne SARS-CoV-2.

Assessing regional emissions of vehicle-based tire wear particle from macro-to micro/nano-scales with pandemic lockdowns and electromobility scenarios implications.

Despite increasing the public awareness of ubiquity of microplastics (MPs) in air, the issue on particular source of tire wear particles (TWPs) emission into atmosphere and their exposure-associated human health has not received the attention it deserves. Here we linked vehicle kilometers traveled (VKT) estimates covering demography, socio-environmental, and transportation features and emission factors to predict regional emission patterns of TWP-derived atmospheric MPs. A data-driven probabilistic approach was developed to consider variability across the datasets and uncertainty of model parameters in terms of country-level and vehicle-type emissions. We showed that country-specific VKT from billion to trillion vehicle-kilometer resulted in 103-105 metric tons of airborne TWP-derived atmospheric MPs annually in the period 2015-2019, with the highest emissions from passenger cars and heavy-duty vehicles. On average, we found that airborne TWP emissions from passenger cars by country had substantial decreased (up to ∼33%) during COVID-19 lockdowns in 2020 and pronounced increased (by a factor ∼1.9) from vehicle electrification by the next three decades. We conclude that the stunning mass of airborne TWP is a predominant source of atmospheric MP. We underscore the necessity of TWP emissions control among the United States, China, and India. Our findings can be of great use to environmental transportation planners for devising vehicle/tire-oriented decision support tools. Our data offer information to enhance TWP-exposure estimates, to examine long-term exposure trends, and subsequently to improve health risk assessment during pandemic outbreak and future electrification.

Characterization of Virus Replication, Pathogenesis, and Cytokine Responses in Syrian Hamsters Inoculated with SARS-CoV-2.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus which caused a global respiratory disease pandemic beginning in December 2019. Understanding the pathogenesis of infection and the immune responses in a SARS-CoV-2-infected animal model is urgently needed for vaccine development. METHODS: Syrian hamsters (Mesocricetus auratus) were intranasally inoculated with 105, 5×105, and 106 TCID50 of SARS-CoV-2 per animal and studied for up to 14 days. Body weight, viral load and real-time PCR amplification of the SARS-CoV-2 N gene were measured. On days 3, 6 and 9, lung, blood, liver, pancreas, heart, kidney, and bone marrow were harvested and processed for pathology, viral load, and cytokine expression. RESULTS: Body weight loss, increased viral load, immune cell infiltration, upregulated cytokine expression, viral RNA, SARS-CoV-2 nucleoprotein, and mucus were detected in the lungs, particularly on day 3 post-infection. Extremely high expression of the pro-inflammatory cytokines MIP-1 and RANTES was detected in lung tissue, as was high expression of IL-1ß, IL-6, IL-12, and PD-L1. The glutamic oxalacetic transaminase/glutamic pyruvic transaminase (GOT/GPT) ratio in blood was significantly increased at 6 days post-infection, and plasma amylase and lipase levels were also elevated in infected hamsters. CONCLUSION: Our results provide new information on immunological cytokines and biological parameters related to the pathogenesis and immune response profile in the Syrian hamster model of SARS-CoV-2 infection.

An unusual COVID-19 case with over four months of viral shedding in the presence of low neutralizing antibodies: a case report.

The ongoing coronavirus disease 2019 (COVID-19) pandemic is a global public health crisis, causing social and economic disasters in many countries. In China, two-consecutive negative results of nucleic acid tests for SARS-CoV-2 from the respiratory samples are required to end the quarantine of COVID-19 patients. However, clinicians face a dilemma in case of patients with long-term viral shedding. This report described an unusual COVID-19 case who had persistent viral RNA positivity for more than 4 months after initial illness in the presence of low neutralizing antibodies, but without prolonged clinical symptoms. Multiple anti-viral drug treatments had no impact and there was no evidence of re-infection. When the patient was self-quarantined at home, no infection occurred to the three family members living with her for 15 to 19 days. Sputum viral culture in BSL-3 laboratory on the 102 nd day after symptom onset was negative. From the 129 th day on, 8 continuous nucleic acid tests of sputum samples showed negative results. The patient was discharged on 137 th days since symptom onset. In conclusion, viral RNA shedding in the sputum of the COVID-19 patient may last over 4 months. As no evidence shows the existence of infectious virus, two-consecutive negative nucleic acid tests may not be the prerequisite for ending quarantine of COVID-19 patients with prolonged viral shedding.

Clinical Use of Short-Course and Low-Dose Corticosteroids in Patients With Non-severe COVID-19 During Pneumonia Progression.

Background: The emerging coronavirus disease 2019 (COVID-19) has become a serious public health concern with a high number of fatalities. It is unclear whether corticosteroids could be a candidate for an early intervention strategy for patients with COVID-19. Methods: In this retrospective cohort study, we analyzed data from 28 corticosteroid-treated patients with non-severe but advanced COVID-19, in which short-course and low-dose corticosteroids were administered because of unremitting or worsening clinical conditions during hospitalization. To compare the effect of corticosteroids on viral clearance, 44 corticosteroid-untreated patients were included as controls. Results: At the time of admission, corticosteroid-treated patients (n = 28) had a more advanced baseline illness compared with corticosteroid-untreated patients (n = 44), as reflected by poorer blood laboratory parameters (lymphocytes, C-reactive protein, and lactate dehydrogenase) and more extensive chest computed tomography (CT) abnormalities. Corticosteroids were given because of radiological evidence of pneumonia progression (26/28) and/or unremitting fever (22/28) after admission. The median time from illness onset to corticosteroid treatment was 9 days (IQR, 7-10). The median duration and accumulated dose of corticosteroid treatment were 4.5 days [interquartile range (IQR), 3-5] and 140 mg of methylprednisolone (IQR, 120-200). Intravenous immunoglobulin (20 g per day for 3-5 days) was co-administered with corticosteroids. With the corticosteroid treatment, all patients achieved an abatement of fever within 1 day, and 78.6% (22/28) of the patients achieved radiological remission when evaluated about 3 days later. Only one (3.6%) patient progressed to severe COVID-19, and all patients recovered and were discharged without any sequela. The median time from illness onset to viral clearance was similar, as compared with 44 corticosteroid-untreated patients with relatively milder disease [18 (IQR 14.3-23.5) days vs. 17 (IQR, 12-20) days, p = 0.252]. When adjusted for age, sex, underlying comorbidities, baseline blood laboratory parameters, viral load, and chest radiological findings, the causal hazard ratio of corticosteroid treatment for the viral clearance was 0.79 (95%CI, 0.48-1.30, p = 0.34). Conclusion: Short-course and low-dose applications of corticosteroids, when co-administered with intravenous immunoglobulin, in non-severe COVID-19 patients during the stage of clinical deterioration may possibly prevent disease progression, while having a negligible impact on the viral clearance.

Quantifying the clinical characteristics of coronavirus disease 2019 (COVID-19) of different age segments based on 60 patients (preprint)

Background: Novel coronavirus disease 2019 (COVID-19) has spread around the world; therefore, more attention should be paid to the clinical features of COVID-19, with the aim of improving the diagnosis and treatment of patients. Methods: By 15 February 2020, 60 patients diagnosed with COVID-19 had been admitted to Nanjing Second Hospital. We analyzed the clinical features of different age segments infected with COVID-19 prospectively, including epidemiological, clinical, laboratory, and radiological characteristics; treatment, clinical outcomes, and prognosis of this cohort of patients. Results: The cohort comprised 29 male and 31 female patients (median age = 46.18 years old (range: 18–97). Fifty-five (91.7%) patients had a clear epidemiological contact history. The average incubation period was 7.92 days. The most common clinical manifestations were fever (85%) and cough (75%). Peripheral white blood cell counts were mostly normal at admission, 7 days, and 14 days, with no differences among patients of different ages. The lymphocyte counts of all patients were in the normal range on admission, and after 7 days and 14 days of treatment; however, the lymphocyte count in > 65-year-old patients was less than that in the < 40 and 40–65-year-old groups after 7 and 14 days of treatment (P < 0.05, respectively). At admission, the CD4 T lymphocyte count was within the normal range; however, the CD4 T lymphocyte count in >65-year-old group was less than that in the < 40 and 40–65-years-old groups after 14 days of treatment. The CD4 T lymphocyte counts were 723.46 ± 243.82/ml (< 40), 640.00 ± 242.30/ml (40–65), and 399.88 ± 256.16/ml (> 65) (P =0.0075). The > 65-years-old group had higher levels of lactate dehydrogenase (269.83 ± 73.36 vs. 208.52 ± 35.67 and 243.83 ± 76.66) after 14 days (P = 0.0496). Imaging revealed more lesions in the 40–65 and > 65-year-old groups (P < 0.0001). The days after the nucleic acid detection turned negative in the three age groups were: 9.19 ± 3.93 (< 40), 10.04 ± 4.10 (40–65), and 13.57 ± 2.76 (> 65) (P = 0.0373). After antiviral treatment, together with anti-infection regimen if the patient with lung infection and continuous oxygen inhalation if the patient is hypoxic, all patients achieved total recovery and were discharged with follow-up. Conclusion: Patients with COVID-19 pneumonia generally had an epidemiological history. Older patients showed more extensive lesions upon admission, more severe illness, slower recovery of immune function, the longer viral nucleic acid persistence.