The origins of COVID-19 pandemic: A brief overview.

The novel coronavirus disease (COVID-19) outbreak that emerged at the end of 2019 has now swept the world for more than 2 years, causing immeasurable damage to the lives and economies of the world. It has drawn so much attention to discovering how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated and entered the human body. The current argument revolves around two contradictory theories: a scenario of laboratory spillover events and human contact with zoonotic diseases. Here, we reviewed the transmission, pathogenesis, possible hosts, as well as the genome and protein structure of SARS-CoV-2, which play key roles in the COVID-19 pandemic. We believe the coronavirus was originally transmitted to human by animals rather than by a laboratory leak. However, there still needs more investigations to determine the source of the pandemic. Understanding how COVID-19 emerged is vital to developing global strategies for mitigating future outbreaks.

Using Chinese Coal Gangue as an Ecological Aggregate and Its Modification: A Review.

Coal gangue is a kind of industrial solid waste with serious ecological and environmental implications. Producing concrete with coal gangue aggregate is one of the green sustainable development requirements. This paper reviews the properties and preparation methods of Chinese gangue aggregate, studies the influence of gangue aggregate on concrete properties and the prediction model of gangue concrete, and summarizes the influence of modified materials on gangue concrete. The studies analyzed in this review show that different treatments influence the performance of coal gangue aggregate concrete. With the increase in the replacement ratio of coal gangue aggregate in concrete, the concrete workability and mechanical performance are reduced. Furthermore, the pore structure changes lead to decreased porosity, greatly affecting the durability. Coal gangue is not recommended for producing high-grade concretes. Nevertheless, pore structure can be improved by adding mineral admixtures, fibers, and admixtures to the coal gangue concrete. Hence, the working properties, mechanical properties, and durability of the concrete can be improved effectively, ensuring that coal gangue concrete meets engineering design requirements. Adding modified materials to coal gangue concrete is a viable future development direction.

Measurements of SARS-CoV-2 antibody dissociation rate constant by chaotrope-free biolayer interferometry in serum of COVID-19 convalescent patients.

Kinetics measurements of antigen-antibody binding interactions are critical to understanding the functional efficiency of SARS-CoV-2 antibodies. Previously reported chaotrope-based avidity assays that rely on artificial disruption of binding do not reflect the natural binding kinetics. This study developed a chaotrope- and label-free biolayer interferometry (BLI) assay for the real-time monitoring of receptor binding domain (RBD) binding kinetics with SARS-CoV-2 spike protein in convalescent COVID-19 patients. An improved conjugation biosensor probe coated with streptavidin-polysaccharide (SA-PS) led to a six-fold increase of signal intensities and two-fold reduction of non-specific binding (NSB) compared to streptavidin only probe. Furthermore, by utilizing a separate reference probe and biotin-human serum albumin (B-HSA) blocking process to subtracted NSB signal in serum, this BLI biosensor can measure a wide range of the dissociation rate constant (koff), which can be measured without knowledge of the specific antibody concentrations. The clinical utility of this improved BLI kinetics assay was demonstrated by analyzing the koff values in sera of 24 pediatric (≤18 years old) and 63 adult (>18 years old) COVID-19 convalescent patients. Lower koff values for SARS-CoV-2 serum antibodies binding to RBD were measured in samples from children. This rapid, easy to operate and chaotrope-free BLI assay is suitable for clinical use and can be readily adapted to characterize SARS-CoV-2 antibodies developed by COVID-19 patients and vaccines.

COVID-19 Pandemic Impacts on Children with Developmental Disabilities: Service Disruption, Transition to Telehealth, and Child Wellbeing.

The COVID-19 pandemic has resulted in substantial service disruption and transition from in-person services to telehealth for children with developmental disabilities. However, there is limited knowledge about the specific dimensions and consequences of the disruption and transition. This study aims to examine the extent of service disruption and transition, the experiences of client children and their caregivers with telehealth vis-à-vis in-person services, and the impacts of the disruption and transition on child wellbeing. The cross-sectional study collected data from parents of children with developmental disabilities using an online survey. McNemar's tests were used to compare service changes before and after the pandemic outbreak, and multivariate analyses were used to examine how service changes were associated with child wellbeing. Results show that more than two-thirds of the children experienced reduction in service amount, and one-third lost services for more than two months in about five months into the pandemic. While telehealth had comparable features relative to in-person services, it had lower ratings with respect to diagnostic accuracy, treatment effectiveness, and rapport building. Service disruption/transition and social isolation were associated with behavioral and emotional deterioration in children. However, child and family stress may have confounded these adverse effects. We concluded that the magnitude of service disruption and transition was large in the first half year after the pandemic outbreak, and the amount and duration of service loss varied substantially across clients. Diagnostic accuracy, treatment efficacy, and rapport building were areas in which parents had major concerns toward telehealth relative to in-person services. However, such drawbacks may partially be due to the limited logistics in telehealth implementation during the pandemic. Service disruption and transition seemed to contribute to family stress, which played a direct role in eroding child wellbeing. Implications of these findings for future research and practices are discussed.

The Evolution of Telepractice Use during the COVID-19 Pandemic: Perspectives of Pediatric Speech-Language Pathologists.

The study investigated how pediatric speech-language pathologists (SLPs) applied telepractice to compensate for the loss of in-person services and the dynamics of telepractice use during the COVID-19 pandemic in a rural state. We conducted interviews with 10 SLPs and then a statewide survey in which 51 SLPs participated. The qualitative interviews revealed themes including changes in service environment due to the pandemic (e.g., transition to telepractice, losing clients), challenges in the transition to telepractice (e.g., limited training, difficulty engaging clients), worsening wellbeing of clinicians and clients, and SLPs' perspectives and suggestions towards telepractice in the future. Survey results showed service disruptions and transition dynamics during the pandemic. SLPs' weekly caseloads reduced from an average of 42.3 clients prior to the pandemic to 25.9 and 23.4 from March to May and from June to September 2020, respectively, and then recovered to 37.2 clients from October to December 2020. In contrast, the number of telepractice caseloads sharply increased from 0.2 clients per week prior to the pandemic to 14.8 from March to May 2020. The weekly telepractice caseloads then declined to 5.5 clients from June to September and 7.9 clients from October to December 2020. In the months right after the pandemic outbreak (i.e., March to May), client children struggled with treatment gains and behavioral wellbeing. However, their outcomes gradually improved by October to December and approached pre-pandemic levels. About one-third of the SLPs reported that they would be more likely or much more likely to use telepractice in the future regardless of the pandemic. However, only about a quarter perceived telepractice as comparable to in-person services. We concluded that the transition from in-person services to telepractice substantially mitigated service disruptions right after the pandemic outbreak and that telepractice's substitute role evolved over time.

Rapid, robust, and sustainable antibody responses to mRNA COVID-19 vaccine in convalescent COVID-19 individuals.

Longitudinal studies are needed to evaluate the SARS-CoV-2 mRNA vaccine antibody response under real-world conditions. This longitudinal study investigated the quantity and quality of SARS-CoV-2 antibody response in 846 specimens from 350 patients, comparing BNT162b2-vaccinated individuals (19 previously diagnosed with COVID-19, termed RecoVax; and 49 never diagnosed, termed NaiveVax) with 122 hospitalized unvaccinated (HospNoVax) and 160 outpatient unvaccinated (OutPtNoVax) COVID-19 patients. NaiveVax experienced delay in generating SARS-CoV-2 total antibodies (TAb) and surrogate neutralizing antibodies (SNAb) after the first vaccine dose (D1) but rapid increase in antibody levels after the second dose (D2). However, these never reached RecoVax's robust levels. In fact, NaiveVax TAb and SNAb levels decreased 4 weeks after D2. For the most part, RecoVax TAb persisted, after reaching maximal levels 2 weeks after D2, but SNAb decreased significantly about 6 months after D1. Although NaiveVax avidity lagged behind that of RecoVax for most of the follow-up periods, NaiveVax did reach similar avidity by about 6 months after D1. These data suggest that 1 vaccine dose elicits maximal antibody response in RecoVax and may be sufficient. Also, despite decreasing levels in TAb and SNAb over time, long-term avidity may be a measure worth evaluating and possibly correlating to vaccine efficacy.

Adherence to dosing schedule of denosumab therapy for osteoporosis during COVID-19 lockdown: an electronic medical record and pharmacy claims database study from Asia.

COVID-19 lockdowns have impacted management of chronic diseases such as osteoporosis. Adherence to the 6-monthly dosing schedule of denosumab, the parenteral anti-osteoporosis medication most often used in Singapore, was significantly reduced during the lockdown period compared to that during pre-COVID-19 times. Patients managed by endocrinologists were more likely to be adherent. PURPOSE: No study thus far has quantified actual adherence rates to anti-osteoporosis therapy with denosumab during COVID-19 or explored factors associated with it. We aimed to estimate the adherence rates to denosumab in Singaporean men and women during COVID-19 lockdown and to compare it with those during the pre-COVID-19 period. METHOD: We conducted this retrospective, electronic medical records, and pharmacy claims database study at Singapore General Hospital, the largest hospital in the country. Patients initiated on subcutaneous denosumab between August 2019 and December 2019 and were thus scheduled to receive the second dose during the COVID-19 first-wave period from February 2020 to June 2020 (lockdown group) were analyzed, as were patients initiated anytime on denosumab between September 2011 and December 2018 (pre-COVID-19 group). Data extracted from the hospital's electronic prescription platform and patients' pharmacy purchase records were matched. Adherence was defined as being punctual (with an allowable delay of up to 4 weeks) with the second dose scheduled 6 months from the 1st dose. A sensitivity analysis with an allowable delay up to 8 weeks was also performed. We compared the adherence rates between the two periods and explored factors associated with adherence. RESULTS: A total of 768 and 1458 patients respectively during the lockdown and pre-COVID-19 periods were analyzed. The mean adherence rate during lockdown was 63.9%. The odds of being adherent during lockdown were higher if patients were managed by endocrinologists as opposed to those by other specialists [OR 2.516 (95% CI: 1.836-3.448); p < 0.001]. Adherence rates during the pre-COVID-19 period was 75.4%. Overall, the odds of being adherent to denosumab was significantly lower during lockdown than that during the pre-COVID-19 period [OR 0.525 (95% CI 0.430-0.640); p < 0.001], and odds of being adherent were higher if patients were managed by endocrinologists than if they were managed by other specialists (OR 1.765 (95% CI: 1.444-2.158; p < 0.001). CONCLUSION: Adherence to denosumab was significantly lower during COVID-19 lockdown than the pre-COVID-19 period. The odds of being adherent were higher in patients managed by endocrinologists. Whether healthcare providers from certain specialties spend more time counselling and educating patients about the importance of adherence to osteoporosis medications needs to be explored further.

Health-seeking behaviour of foreign workers in Singapore: Insights from emergency department visits.

INTRODUCTION: Foreign workers (FWs) on work permit face unique health challenges and potential barriers to healthcare. We aimed to examine the epidemiology, attendance patterns, disposition, and adherence to follow-up, by FWs on work permit to two emergency departments (EDs) in Singapore. METHODS: In this retrospective observational study, we included consecutive FWs on work permit who registered at the EDs of two public restructured hospitals from 1 May 2016 to 31 October 2016. Data obtained from electronic medical records included patient demographics, triage acuity, disposition, ED diagnoses and bill information. RESULTS: There were 6,429 individual FWs on work permit who contributed to 7,157 ED visits over the 6-month study period, with male predominance (72.7%, 4672/6429), and median age of 31 (interquartile range 26 to 38) years. A high proportion of these FWs were triaged to low-acuity status compared to the general ED population (66.9% versus 45.9%, P<0.001). Trauma-related injuries contributed to 34.4% of their visits, and were more likely to result in admission compared to non-trauma-related conditions (18.7% vs 15.2%, P<0.001). FWs engaged in shipyard, construction and process industries were more likely to be discharged "against medical advice" (14.8% vs 3.2%, P<0.001), and default their specialist outpatient follow-up (50.1% vs 34.2%, P<0.001) for non-trauma-related conditions compared to trauma-related injuries. CONCLUSION: In Singapore, the EDs of public restructured hospitals provide healthcare safety nets to FWs on work permit. These workers made more low-acuity visits compared to the general population during the study period and may face potential barriers to admission and follow-up.

TOP-Plus Is a Versatile Biosensor Platform for Monitoring SARS-CoV-2 Antibody Durability.

BACKGROUND: Low initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers dropping to undetectable levels within months after infection have raised concerns about long-term immunity. Both the antibody levels and the avidity of the antibody-antigen interaction should be examined to understand the quality of the antibody response. METHODS: A testing-on-a-probe "plus" panel (TOP-Plus) was developed to include a newly developed avidity assay built into the previously described SARS-CoV-2 TOP assays that measured total antibody (TAb), surrogate neutralizing antibody (SNAb), IgM, and IgG on a versatile biosensor platform. TAb and SNAb levels were compared with avidity in previously infected individuals at 1.3 and 6.2 months after infection in paired samples from 80 patients with coronavirus disease 2019 (COVID-19). Sera from individuals vaccinated for SARS-CoV-2 were also evaluated for antibody avidity. RESULTS: The newly designed avidity assay in this TOP panel correlated well with a reference Bio-Layer Interferometry avidity assay (r = 0.88). The imprecision of the TOP avidity assay was <10%. Although TAb and neutralization activity (by SNAb) decreased between 1.3 and 6.2 months after infection, the antibody avidity increased significantly (P < 0.0001). Antibody avidity in 10 SARS-CoV-2 vaccinated individuals (median: 28 days after vaccination) was comparable to the measured antibody avidity in infected individuals (median: 26 days after infection). CONCLUSIONS: This highly precise and versatile TOP-Plus panel with the ability to measure SARS-CoV-2 TAb, SNAb, IgG, and IgM antibody levels and avidity of individual sera on one sensor can become a valuable asset in monitoring not only patients infected with SARS-CoV-2 but also the status of individuals' COVID-19 vaccination response.

Clinical Characteristics of 107 Patients with COVID-19 in Ningbo, China: Single Center Experience Outside Hubei (preprint)

Background Since December 2019, there has be an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China. Nowadays, it rapidly spread across the country and then the worldwide. We aimed to investigate the clinical characteristics of patients with COVID-19.Methods The patients with confirmed COVID-19 admitted between January 25 and February 10, 2020, were enrolled. Epidemiological, demographic, clinical, laboratory, radiological data, and antivirus therapies, were retrospectively collected and analyzed. The 90-day follow-up of these patients was also performed.Results A total of 107 patients were included. The median age was 55.0 years (range from 18.0 to 85.0 years), and 72 (67.3%) were female. Ninety-three (86.9%) of the patients had a history of contacting with residents from Wuhan (n=31), or contacting with confirmed COVID-19 patients (n=62) within 2 weeks. Fifty-eight (54.2%) had a family cluster onset. Fever and cough were the most common symptoms. Only two patients had diarrhea. The most common underlying disease was hypertension. Lymphopenia was observed in 26 patients. Fifty-two patients with an elevated level of IL-6. On admission, bilateral patchy shadowing and ground-glass opacity were the typical radiological findings on chest computed tomography. Six patients had an intensive care unit (ICU) stay. Antivirus therapy was performed to all patients. 105 patients discharged with an improved condition, and no death was occurred during our 90-day follow-up for these patients.Conclusions Patients with COVID-19 in our hospital had relatively mild symptoms, and good prognosis. This study also highlights the importance of human-to-human transmission in COVID-19.

Atypical presentation of SARS-CoV-2 infection: A case report.

BACKGROUND: The first case of pneumonia subsequently attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, Hubei Province on December 8, 2019. The symptoms included fever, coughing, and breathing difficulties. A few patients with this infection may only have atypical symptoms, which could lead to a misdiagnosis and subsequently further facilitate the spread of the virus. CASE SUMMARY: A 74-year-old female patient complained of severe diarrhea. She did not have fever, coughing, or breathing difficulties. A physical examination revealed no obvious positive signs. The patient had been hypertensive for more than 10 years. Her blood pressure was well controlled. On January 9, 2020, the patient's son visited a colleague who was later confirmed positive for SARS-CoV-2 and his first close contact with our patient was on January 17. The patient was first diagnosed with gastrointestinal dysfunction. However, considering her indirect contact with a SARS-CoV-2-infected individual, we suggested that an atypical pneumonia virus infection should be ruled out. A computed tomography scan was performed on January 26, and showed ground-glass nodules scattered along the two lungs, suggestive of viral pneumonia. Given the clinical characteristics, epidemiological history, and examination, the patient was diagnosed with coronavirus disease-2019 (COVID-19). CONCLUSION: Our patient had atypical symptoms of COVID-19. Careful acquisition of an epidemiological history is necessary to make a correct diagnosis and strategize a treatment plan.