Modeling and Analyzing Transmission of Infectious Diseases Using Generalized Stochastic Petri Nets

Some infectious diseases such as COVID-19 have the characteristics of long incubation period, high infectivity during the incubation period, and carriers with mild or no symptoms which are more likely to cause negligence. Global researchers are working to find out more about the transmission of infectious diseases. Modeling plays a crucial role in understanding the transmission of the new virus and helps show the evolution of the epidemic in stages. In this paper, we propose a new general transmission model of infectious diseases based on the generalized stochastic Petri net (GSPN). First, we qualitatively analyze the transmission mode of each stage of infectious diseases such as COVID-19 and explain the factors that affect the spread of the epidemic. Second, the GSPN model is built to simulate the evolution of the epidemic. Based on this model’s isomorphic Markov chain, the equilibrium state of the system and its changing laws under different influencing factors are analyzed. Our paper demonstrates that the proposed GSPN model is a compelling tool for representing and analyzing the transmission of infectious diseases from system-level understanding, and thus contributes to providing decision support for effective surveillance and response to epidemic development.

Occupants’ satisfaction with LEED- and non-LEED-certified apartments using social media data

Leadership in Energy and Environmental Design (LEED) certified buildings aim to offer a sustainable and healthy building environment. Previous studies have shown mixed and inconsistent results on whether occupants in LEED-certified buildings are more satisfied than in non-LEED-certified counterparts. Those studies are usually based on surveys or questionnaires for commercial buildings and were limited by sample size and pre-defined question structures. Since most people would spend more time at home after experiencing the COVID-19 pandemic due to the flexibility to work remotely, assessing the satisfaction with residential buildings benefits future environmental design and certification system development. In this work, we propose a natural language processing-based approach for such assessment. The study collected 16,761 online reviews of 232 LEED-certified and 129 non-LEED-certified apartment buildings from social media, then applied topic modeling and sentiment analysis to evaluate occupants’ satisfaction. Based on topic modeling, we categorized online comments into three topics, 1) location and transportation, 2) running cost, and 3) health and wellbeing. The subsequent sentiment analysis has shown a statistically significant but small or negligible enhancement in the satisfaction occurring in LEED-certified apartments compared to non-LEED-certified ones concerning all three topics. The “significant but small or negligible uptick” has also been found in online star rating and indoor environmental satisfaction. The only exception with a large effect size is lighting which is found to be significantly more satisfying in LEED-certified apartments. Nevertheless, the statistical significance in online star rating disappears when normalized by rent price and property house value.

Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant (preprint)

We report the first local transmission of the SARS-CoV-2 Delta variant in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of the quarantined subjects indicated that the viral loads of Delta infections, when they first become PCR+, were on average ~1000 times greater compared to A/B lineage infections during initial epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. We performed high-quality sequencing on samples from 126 individuals. Reliable epidemiological data meant that, for 111 transmission events, the donor and recipient cases were known. The estimated transmission bottleneck size was 1-3 virions with most minor intra-host single nucleotide variants (iSNVs) failing to transmit to the recipients. However, transmission heterogeneity of SARS-CoV-2 was also observed. The transmission of minor iSNVs resulted in at least 4 of the 30 substitutions identified in the outbreak, highlighting the contribution of intra-host variants to population level viral diversity during rapid spread. Disease control activities, such as the frequency of population testing, quarantine during pre-symptomatic infection, and level of virus genomic surveillance should be adjusted in order to account for the increasing prevalence of the Delta variant worldwide.

Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant (preprint)

Summary We report the first local transmission of the SARS-CoV-2 Delta variant in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of the quarantined subjects indicated that the viral loads of Delta infections, when they first become PCR+, were on average ∼1000 times greater compared to A/B lineage infections during initial epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. We performed high-quality sequencing on samples from 126 individuals. Reliable epidemiological data meant that, for 111 transmission events, the donor and recipient cases were known. The estimated transmission bottleneck size was 1-3 virions with most minor intra-host single nucleotide variants (iSNVs) failing to transmit to the recipients. However, transmission heterogeneity of SARS-CoV-2 was also observed. The transmission of minor iSNVs resulted in at least 4 of the 30 substitutions identified in the outbreak, highlighting the contribution of intra-host variants to population level viral diversity during rapid spread. Disease control activities, such as the frequency of population testing, quarantine during pre-symptomatic infection, and level of virus genomic surveillance should be adjusted in order to account for the increasing prevalence of the Delta variant worldwide.

Air pollution and soiling implications for solar photovoltaic power generation: A comprehensive review

Solar photovoltaic (PV) is a promising and highly cost-competitive technology for sustainable power supply, enjoying a continuous global installation growth supported by the encouraging policies and commercial markets. However, air pollution and soiling of PV modules prevail worldwide, potentially casting a shadow on solar PV power generation. This study presents a comprehensive review of the documented impact of air pollution and PV soiling on solar resources and techno-economic performances of PV systems. Both air pollution attenuation and soiling could significantly reduce the solar PV power generation globally, and soiling losses contribute to most of the total power reduction in most regions except in high-polluted areas. In addition, considering the natural soiling processes, the influencing parameters of soiling such as environmental and configurational factors and their correlation to dust deposition on PV surface are discussed. Furthermore, this study introduces the impact of air pollution elimination on surface solar radiation and solar PV power generation. Given the current novel coronavirus disease 2019 (COVID-19) pandemic, studies related to its effects on the solar PV sector are discussed in the present review. The reported soiling mitigation approaches and technologies are systematically compared. Finally, the current research challenges are stated, and suggestions for future works in improving the penetration of solar PV applications are provided to help promote solar power generation towards carbon neutrality all over the world.

Clinical, Immunological and Virological Characterization of COVID-19 Patients that Test Re-Positive for SARS-CoV-2 by RT-PCR (preprint)

Background: COVID-19 pandemic is underway. Some COVID-19 cases re-tested positive for SARS-CoV-2 RNA after discharge raising the public concern on their infectivity. Characterization of re-positive cases are urgently needed for designing intervention strategies. Methods: Clinical data were obtained through Guangdong COVID-19 surveillance network. Neutralization antibody titre was determined using a microneutralization assay. Potential infectivity of clinical samples was evaluated after the cell inoculation. SARS-CoV-2 RNA was detected using three different RT-PCR kits and multiplex PCR with nanopore sequencing. Findings: Among 619 discharged COVID-19 cases, 87 were re-tested as SARS-CoV-2 positive in circumstance of social isolation. All re-positive cases had mild or moderate symptoms in initial diagnosis and a younger age distribution (mean, 30·4). Re-positive cases (n=59) exhibited similar neutralization antibodies (NAbs) titre distributions to other COVID-19 cases (n=150) parallel-tested in this study. No infective viral strain could be obtained by culture and none full-length viral genomes could be sequenced for all re-positive cases. Interpretation: Re-positive SARS-CoV-2 was not caused by the secondary infection and was identified in around 14% of discharged cases. A robust Nabs response and a potential virus genome degradation were detected from nearly all re-positive cases suggesting a lower transmission risk, especially through a respiratory route. Funding: This work was supported by grants from Guangdong Provincial Novel Coronavirus Scientific and Technological Project (2020111107001), Science and Technology Planning Project of Guangdong(2018B020207006), National Science and Technology Project(2020YFC0846800).Declaration of Interests: All authors: No reported conflicts of interest.Ethics Approval Statement: This study was reviewed and approved by the Medical Ethical Committee of Guangdong Provincial Center for Disease Control and Prevention. Data collection and analysis of cases were determined by the Health Commission of Guangdong province to be part of a continuing public health outbreak investigation during the emergency response and were thus considered exempt from institutional review board approval.

Clinical, immunological and virological characterization of COVID-19 patients that test re-positive for SARS-CoV-2 by RT-PCR (preprint)

BackgroundCOVID-19 pandemic is underway. Some COVID-19 cases re-tested positive for SARS-CoV-2 RNA after discharge raising the public concern on their infectivity. Characterization of re-positive cases are urgently needed for designing intervention strategies. MethodsClinical data were obtained through Guangdong COVID-19 surveillance network. Neutralization antibody titre was determined using a microneutralization assay. Potential infectivity of clinical samples was evaluated after the cell inoculation. SARS-CoV-2 RNA was detected using three different RT-PCR kits and multiplex PCR with nanopore sequencing. ResultsAmong 619 discharged COVID-19 cases, 87 were re-tested as SARS-CoV-2 positive in circumstance of social isolation. All re-positive cases had mild or moderate symptoms in initial diagnosis and a younger age distribution (mean, 30.4). Re-positive cases (n=59) exhibited similar neutralization antibodies (NAbs) titre distributions to other COVID-19 cases (n=150) parallel-tested in this study. No infective viral strain could be obtained by culture and none full-length viral genomes could be sequenced for all re-positive cases. ConclusionsRe-positive SARS-CoV-2 was not caused by the secondary infection and was identified in around 14% of discharged cases. A robust Nabs response and a potential virus genome degradation were detected from nearly all re-positive cases suggesting a lower transmission risk, especially through a respiratory route.

Organizing Pneumonia of COVID-19: Time-dependent Evolution and Outcome in CT Findings (preprint)

Objective: As a pandemic, a most-common pattern resembled organizing pneumonia (OP) has been identified by CT findings in novel coronavirus disease (COVID-19). We aimed to delineate the evolution of CT findings and outcome in OP of COVID-19. Materials and Methods: 106 COVID-19 patients with OP based on CT findings were retrospectively included and categorized into non-severe (mild/common) and severe (severe/critical) groups. CT features including lobar distribution, presence of ground glass opacities (GGO), consolidation, linear opacities and total severity CT score were evaluated at three time intervals from symptom-onset to CT scan (day 0-7, day 8-14, day>14). Discharge or adverse outcome (admission to ICU or death), and pulmonary sequelae (complete absorption or lesion residuals) on CT after discharge were analyzed based on the CT features at different time interval. Results: 79(74.5%) patients were non-severe and 103(97.2%) were discharged at median day 25 (range, day 8-50) after symptom-onset. Of 67 patients with revisit CT at 2-4 weeks after discharge, 20(29.9%) had complete absorption of lesions at median day 38 (range, day 30-53) after symptom-onset. Significant differences between complete absorption and residuals groups were found in percentages of consolidation (1.5% vs. 13.8%, P=0.010), number of involved lobe >3 (40.0% vs. 72.5%, P=0.030), CT score >4 (20.0% vs. 65.0%, P=0.010) at day 8-14. Conclusions: Most OP cases had good prognosis. Approximately one-third of cases had complete absorption of lesions during 1-2 months after symptom-onset while those with increased frequency of consolidation, number of involved lobe>3, and CT score >4 at week 2 after symptom-onset may indicate lesion residuals on CT.

Differences of clinical and imaging findings in multiple generations of secondary COVID-19 infection in Xi'an, China (preprint)

PURPOSE: In the global presence of secondary infections with the coronavirus disease 2019 (COVID-19), little is known about the transmission characteristics of COVID-19 outside Wuhan, China. We evaluated differences in clinic and radiologic findings of multiple generations of COVID-19 infection in Xi'an (Shaanxi, China) to provide more clues for the correct estimate of the disease. METHODS: All COVID-19 infected patients reported in Xi'an up to 10 February 2020 were included for this analysis. Among these cases, clinical and chest CT data of 62 cases were obtained from three hospital in Xi'an. With this information, patients were grouped on basis of exposure history and transmission chains as first-generation, second-generation and third-generation patients. We described clinical characteristics and evaluated CT score/patterns in these COVID-19 cases. RESULTS: There was a clear age differences in multiple generations with COVID-19 infection. Above two thirds of the second-generation (75.0%) and third-generation patients (77.8%) were aged [≥]45 years while 40.0% of first-generation cases at this age (p=0.001). More than half of second-generation patients (52.8%) and third-generation patients (55.6%) have comorbidities and is predominantly hypertensive (22.8% of second-generation vs. 27.8% of third-generation infections). The main exposure of second- and third-generation patients in Xi'an is family exposure (35.2%). For evaluation of CT findings of pulmonary involvement, the total CT score were 4.22{+/-}3.00 in first-generation group, 4.35{+/-}3.03 in second-generation group and 7.62{+/-}3.56 in third-generation group (p<0.001). In all of three generations, the predominant pattern of abnormality observed was organizing pneumonia (65.5% in first-generation group, 61.5% in second-generation group and 71.4% in third-generation group). The average courses of the disease in third-generation infections has obviously extension (22.93{+/-}7.22 days of first-generation, 21.53{+/-}8.31 days of second-generation vs. 31.00{+/-}8.12 days of third-generation group, p=0.004). There were no significant differences of the pulmonary sequelae among three generation patients. CONCLUSION: There is more serious pulmonary infection of COVID-19 pneumonia in second- and third-generation patients, which might be attribute to the elder age and comorbidity of these patients.

A pattern categorization of CT findings to predict outcome of COVID-19 pneumonia (preprint)

AbstractsO_ST_ABSPurposeC_ST_ABSAs global healthcare system is overwhelmed by novel coronavirus disease (COVID-19), early identification of risks of adverse outcomes becomes the key to optimize management and improve survival. This study aimed to provide a CT-based pattern categorization to predict outcome of COVID-19 pneumonia. Methods165 patients with COVID-19 (91 men, 4-89 years) underwent chest CT were retrospectively enrolled. CT findings were categorized as Pattern0 (negative), Pattern1 (bronchopneumonia), Pattern2 (organizing pneumonia), Pattern3 (progressive organizing pneumonia) and Pattern4 (diffuse alveolar damage). Clinical findings were compared across different categories. Time-dependent progression of CT patterns and correlations with clinical outcomes, i.e. discharge or adverse outcome (admission to ICU, requiring mechanical ventilation, or death), with pulmonary sequelae (complete absorption or residuals) on CT after discharge were analyzed. ResultsOf 94 patients with outcome, 81(86.2%) were discharged, 3(3.2%) were admitted to ICU, 4(4.3%) required mechanical ventilation, 6(6.4%) died. 31(38.3%) had complete absorption at median day 37 after symptom-onset. Significant differences between pattern-categories were found in age, disease-severity, comorbidity and laboratory results (all P<0.05). Remarkable evolution was observed in Pattern0-2 and Pattern3-4 within 3 and 2 weeks after symptom-onset, respectively; most of patterns remained thereafter. After controlling for age, CT pattern significantly correlated with adverse outcomes (Pattern4 vs. Pattern0-3 [reference]; hazard-ratio[95%CI], 18.90[1.91-186.60], P=0.012). CT pattern (Pattern3-4 vs. Pattern0-2 [reference]; 0.26[0.08-0.88], P=0.030) and C-reactive protein (>10 vs. [≤]10mg/L [reference]; 0.31[0.13-0.72], P=0.006) were risk-factors associated with pulmonary residuals. ConclusionCT pattern categorization allied with clinical characteristics within 2 weeks after symptom-onset would facilitate early prognostic stratification in COVID-19 pneumonia.

Genomic epidemiology of SARS-CoV-2 in Guangdong Province, China (preprint)

Highlights: 1) 1.6 million molecular diagnostic tests identified 1,388 SARS-CoV-2 infections in Guangdong Province, China, by 19th March 2020; 2) Virus genomes can be recovered using a variety of sequencing approaches from a range of patient samples. 3) Genomic analyses reveal multiple virus importations into Guangdong Province, resulting in genetically distinct clusters that require careful interpretation. 4) Large-scale epidemiological surveillance and intervention measures were effective in interrupting community transmission in Guangdong Summary: COVID-19 is caused by the SARS-CoV-2 coronavirus and was first reported in central China in December 2019. Extensive molecular surveillance in Guangdong, China's most populous province, during early 2020 resulted in 1,388 reported RNA positive cases from 1.6 million tests. In order to understand the molecular epidemiology and genetic diversity of SARS-CoV-2 in China we generated 53 genomes from infected individuals in Guangdong using a combination of metagenomic sequencing and tiling amplicon approaches. Combined epidemiological and phylogenetic analyses indicate multiple independent introductions to Guangdong, although phylogenetic clustering is uncertain due to low virus genetic variation early in the pandemic. Our results illustrate how the timing, size and duration of putative local transmission chains were constrained by national travel restrictions and by the province's large-scale intensive surveillance and intervention measures. Despite these successes, COVID-19 surveillance in Guangdong is still required as the number of cases imported from other countries is increasing.

Identification of a common deletion in the spike protein of SARS-CoV-2 (preprint)

Two notable features have been identified in the SARS-CoV-2 genome: (1) the receptor binding domain of SARS-CoV-2; (2) a unique insertion of twelve nucleotide or four amino acids (PRRA) at the S1 and S2 boundary. For the first feature, the similar RBD identified in SARs-like virus from pangolin suggests the RBD in SARS-CoV-2 may already exist in animal host(s) before it transmitted into human. The left puzzle is the history and function of the insertion at S1/S2 boundary, which is uniquely identified in SARS-CoV-2. In this study, we identified two variants from the first Guangdong SARS-CoV-2 cell strain, with deletion mutations on polybasic cleavage site (PRRAR) and its flank sites. More extensive screening indicates the deletion at the flank sites of PRRAR could be detected in 3 of 68 clinical samples and half of 22 in vitro isolated viral strains. These data indicate (1) the deletion of QTQTN, at the flank of polybasic cleavage site, is likely benefit the SARS-CoV-2 replication or infection in vitro but under strong purification selection in vivo since it is rarely identified in clinical samples; (2) there could be a very efficient mechanism for deleting this region from viral genome as the variants losing 23585-23599 is commonly detected after two rounds of cell passage. The mechanistic explanation for this in vitro adaptation and in vivo purification processes (or reverse) that led to such genomic changes in SARS-CoV-2 requires further work. Nonetheless, this study has provided valuable clues to aid further investigation of spike protein function and virus evolution. The deletion mutation identified in vitro isolation should be also noted for current vaccine development.

The Reversed Halo Sign in COVID-19 Pneumonia (preprint)

ObjectivesTo evaluate the frequency and time course of RHS on CT in patient with COVID-19 pneumonia.Materials and methodsA total of 147 patients with COVID-19 pneumonia were divided into mild, moderate, severe and critical categories. The number, location, shape, wall appearance of RHS on CT were analyzed. Other parenchymal abnormalities include GGO, consolidation and linear opacity were also recorded.ResultsRHS was observed in 37 (25.2%) of 147 patients and it was more common in patients with moderate disease than severe or critical disease (31.3% vs. 13.0%, P = 0.019). Time from symptom onset to appearance of RHS was 9 ± 5 days in moderate patients and 14 ± 8 days in severe/critical patients. A total of 64 RHS lesions were identified and the majority of lesions were located in peripheral aspect of lungs (55, 85.9%) and lower lobes (52, 81.2%). All lesions with RHS were round or oval-shaped. The rim of RHS were smooth in 54 (84.4%) and irregular in 10 (15.6%). Follow-up CT scans of 27 patients (50 lesions) showed 43(86%) lesions gradually resolved or developed into GGO and linear opacities and 7(14%) lesions remained unchanged appearance.ConclusionsRHS occurred sooner after symptom onset and with higher frequency in patients with moderate compared to those with severe or critical disease. RHS may represent a favorable prognostic sign in COVID-19 pneumonia.Key Points• 37 (25.2%) of 147 patients with COVID-19 pneumonia had RHS on at least one CT• RHS was more prevalent in patients with moderate disease than those with severe or critical disease• RHSs (78.4%) mostly occurred within 2 weeks after symptom onset

Role of the Eye in Transmitting Human Coronavirus: What We Know and What We Do Not Know (preprint)

The outbreak of recently identified 2019 novel coronavirus (2019-nCOV) infection has become a world-wide health threat. Currently, more information is needed for further understanding the transmission, clinical characteristics, and infection control procedures of 2019-nCOV. Recently, the role of the eye in transmitting 2019-nCOV has been intensively discussed. Previous investigations about other high infectious human COVs, that is, severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), may provide helpful information. In this review, we describe the genomics and morphology of human CoVs, the epidemiology, systemic and ophthalmic manifestations, mechanisms of human CoVs infection, and infection control procedures. The role of the eye in the transmission of SARS-CoV and 2019-nCOV is discussed. Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of ocular surface and upper respiratory tract is connected by nasolacrimal duct and share same entry receptors for some respiratory viruses. The eye is rarely involved in human CoVs infection, conjunctivitis is quite rare in patients with SARS-CoV and 2019-nCoV infection, and COV RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with SARS-CoV and 2019-nCoV infection is also very low, which imply that the eye is neither a preferred organ of human COVs infection, nor is a preferred gateway of entry for human COVs to infect respiratory tract. However, pathogens exposed to the ocular surface might be transported to nasal and nasopharyngeal mucosa by constant tear rinsing through lacrimal duct, and then cause respiratory tract infection. Considering close doctor-patient contact is quite common in ophthalmic practice which are apt to transmit human COVs by droplets and fomites, hand hygiene and personal protection are still highly recommended for health care workers to avoid hospital-related viral transmission during ophthalmic practice.

Evolution of CT Findings in Patients with COVID-19 Pneumonia (preprint)

Objectives To delineate the evolution of CT findings in patients with mild COVID-19 pneumonia outside of Wuhan.Methods CT images and medical records of 88 patients with confirmed mild COVID-19 pneumonia outside of Wuhan, a baseline and at least one follow-up CT were retrospectively reviewed. CT features including lobar distribution and presence of ground glass opacities (GGO), consolidation, and linear opacities, were analyzed on per patient basis during each of five time intervals spanning the three weeks after disease onset. Total severity scores were calculated.Results 85.2 % of patients had travel history to Wuhan or known contact with infected individuals. The most common symptoms were fever (84.1%) and cough (56.8%). The baseline CT was obtained on average 5 days from symptom onset. Four patients (4.5%) had negative initial CT. Significant differences were found among the time intervals in the proportion of pulmonary lesions that are 1) pure GGO, 2) mixed attenuation, 3) mixed attenuation with linear opacities, 4) consolidation with linear opacities, and 5) pure consolidation. The majority of patients had involvement of ≥ 3 lobes. Bilateral involvement was more prevalent than unilateral involvement. The proportions of patients observed to have pure GGO or GGO and consolidation decreased over time while proportion of patients with GGO and linear opacities increased. Total severity score showed an increasing trend in the first two weeks. Conclusions While bilateral GGO are predominant features, CT findings changed during different time intervals in the three weeks after symptom onset in patients with COVID-19.

Human-to-human transmission of 2019-novel coronavirus (2019-nCoV) (preprint)

Background: On December 31, 2019, an outbreak of COVID-19 in humans was reported in Wuhan, and then spread fast to other provinces, China. We analyzed data from field investigations and genetic sequencing to describe the evidence and characteristics of human-to-human transmission in Guangdong Province. Methods: A confirmed COVID-19 case was defined if a suspected case was verified with positive of SARS-CoV-2 in throat swabs, nasal swabs, bronchoalveolar lavage fluid (BALF), or endotracheal aspirates by real-time reverse transcriptase polymerase chain reaction assay (RT-PCR) or genetic sequencing. Field investigations were conducted for each confirmed case. Clinical and demographic data of confirmed cases were collected from medical records. Exposure and travel history were obtained by interview. Results: A total of 1,151 confirmed cases were identified as of February 10, 2020 in Guangdong Province, China. Of them, 697 (60.1%) cases were from 234 cluster infections. Two hundred and fourteen (18.6%) were secondary cases, in which 144 cases were from family cluster infections. With the epidemic continuing, although familial cluster events were dominated, community cluster events increased with a nosocomial event. The whole genomes within the same family cluster infections were identical, and presented a few unique single nucleotide variants (SNVs) compared with SARS-CoV-2 identified on December 2019 in Wuhan. Conclusions: We observed evident human-to-human transmissions of SARS-CoV-2 in Guangdong, China. Although most of them were from family cluster infections, community and nosocomial infections were increasing. Our findings indicate that human-to-human transmission risks are transferring from family to community in Guangdong Province.