Assessment of thermal and temporal stability of SARS-CoV-2 samples using real-time qRT-PCR.

BACKGROUND: As per the guidelines of the Indian Council of Medical Research, nasopharyngeal and oropharyngeal swabs in viral transport medium (VTM) are to be stored at 4 °C for less than 5 days and for more than 5 days at -70 °C. Samples are not transported or stored as per prescribed conditions because of the limitations, resulting in an apprehensive diagnosis. The aim of the study was to test the stability of the SARS-CoV-2 sample stored in VTM at different temperatures. METHODS: In this study, the stability of 21 positive and 9 negative samples for SARS-CoV-2 was evaluated in commercial VTM at different temperatures (-80 °C, -20 °C, 4 °C, and 25 to 30 °C). Stability was checked for up to 50 days in the above storage conditions at different intervals. PathoDetect™ and Hi-PCR® kits were used for the detection of the four genes of SARS-CoV-2. The Cycle Threshold (Ct) value for determining the positivity of samples for PathoDetect™ was < 40 and for Hi-PCR® was < 38. RESULTS: The SARS-CoV-2 confirmatory genes (RdRp and E genes) and the internal housekeeping gene remained detectable even on the 50th day of the study. The Ct of the RdRp and E genes were found to increase with storage duration, but all positive samples remained positive till the end of the study, or the Ct value remained below the cut-off level. The negative samples gave consistent results until the end of the study. When the differences in Ct values were compared between the days in a set of experiments, they were not significantly different except in a few samples. CONCLUSION: The SARS-CoV-2 genetic materials in commercial VTM were stable at room temperature to -80 °C for 50 days.

Assessment of Neuroendocrine Changes and Hypothalamo-Pituitary Autoimmunity in Patients with COVID-19.

SARS-CoV-2 may affect the hypothalamic-pituitary axis and pituitary dysfunction may occur. Therefore, we investigated neuroendocrine changes, in particular, secondary adrenal insufficiency, using a dynamic test and the role of autoimmunity in pituitary dysfunction in patients with COVID-19. The single-center, prospective, case-control study included patients with polymerase chain reaction (PCR)-confirmed COVID-19 and healthy controls. Basal hormone levels were measured, and the adrenocorticotropic hormone (ACTH) stimulation test was performed. Antipituitary (APA) and antihypothalamic antibodies (AHA) were also determined. We examined a total of 49 patients with COVID-19 and 28 healthy controls. The frequency of adrenal insufficiency in patients with COVID-19 was found as 8.2%. Patients with COVID-19 had lower free T3, IGF-1, and total testosterone levels, and higher cortisol and prolactin levels when compared with controls. We also demonstrated the presence of APA in three and AHA in one of four patients with adrenal insufficiency. In conclusion, COVID-19 may result in adrenal insufficiency, thus routine screening of adrenal functions in these patients is needed. Endocrine disturbances in COVID-19 are similar to those seen in acute stressful conditions or infections. Pituitary or hypothalamic autoimmunity may play a role in neuroendocrine abnormalities in COVID-19.

COVID-19, Green Deal and recovery plan permanently change emissions and prices in EU ETS Phase IV.

The EU emissions trading system's (ETS) invalidation rule implies that shocks and overlapping policies can change cumulative carbon emissions. This paper explains these mechanisms and simulates the effect of COVID-19, the European Green Deal, and the recovery stimulus package on cumulative EU ETS emissions and allowance prices. Our results indicate that the negative demand shock of the pandemic should have a limited effect on allowance prices and rather translates into lower cumulative carbon emissions. Aligning EU ETS with the 2030 reduction target of -55% might increase allowance prices to 45-94 €/ton CO2 today and reduce cumulative carbon emissions to 14.2-18.3 GtCO2 compared to 23.5-33.1 GtCO2 under a -40% 2030 reduction target. Our results crucially depend on when the waterbed will be sealed again, which is an endogenous market outcome, driven by the EU ETS design, shocks and overlapping climate policies such as the recovery plan.

Impacts of the COVID-19 pandemic on food prices: Evidence from storable and perishable commodities in India.

The supply chain disruptions caused by the COVID-19 outbreak have led to changes in food prices globally. The impact of COVID-19 on the price of essential and perishable food items in developing and emerging economies has been lacking. Using a recent phone survey by the World Bank, this study examines the impact of the COVID-19 pandemic on the prices of the three essential food items in India. The results indicate that price of basic food items such as atta (wheat flour) and rice increased significantly during the pandemic compared to the pre-pandemic period. In contrast, during the same period, the price of onions declined significantly. The findings may suggest panic-buying, hoarding, and storability of food items. The results further reveal that remittance income and cash transfers from the government negatively affected commodity prices. Thus, this study's findings suggest that families may have shifted the demand away from essential foods during the pandemic.

Genomic epidemiology of SARS-CoV-2 under an elimination strategy in Hong Kong.

Hong Kong employed a strategy of intermittent public health and social measures alongside increasingly stringent travel regulations to eliminate domestic SARS-CoV-2 transmission. By analyzing 1899 genome sequences (>18% of confirmed cases) from 23-January-2020 to 26-January-2021, we reveal the effects of fluctuating control measures on the evolution and epidemiology of SARS-CoV-2 lineages in Hong Kong. Despite numerous importations, only three introductions were responsible for 90% of locally-acquired cases. Community outbreaks were caused by novel introductions rather than a resurgence of circulating strains. Thus, local outbreak prevention requires strong border control and community surveillance, especially during periods of less stringent social restriction. Non-adherence to prolonged preventative measures may explain sustained local transmission observed during wave four in late 2020 and early 2021. We also found that, due to a tight transmission bottleneck, transmission of low-frequency single nucleotide variants between hosts is rare.

Perceptions of risk of SARS-CoV-2 transmission in social and educational activities by infectious diseases and general pediatric healthcare providers, a pre-vaccine risk perception cross-sectional survey.

BACKGROUND: The perception of the transmission risks of SARS-CoV-2 in social and educational settings by US healthcare providers have not been previously quantified. METHODS: Respondents completed an online survey between September and October 2020 to estimate the risk of SARS-CoV-2 transmission on a scale of 0-10 for different social and educational activities prior to the availability of the SARS-CoV-2 vaccines. Demographic information and experiences during the pandemic were also collected. The risk assessment was emailed to three listservs of healthcare providers, including national listservs of pediatric (PID) and adult infectious diseases (AID) providers, and a listserv of general pediatric practitioners in the St Louis, USA metropolitan area. RESULTS: Respondents identified the highest risk of SARS-CoV-2 transmission in spending time in a bar, eating at a restaurant, and attending an indoor sporting event. In the school setting, lower risk was identified in elementary and daycare students compared to high school or university-level students. Comparatively, the risk of transmission to students and teachers was lower than the identified high-risk social activities. Factors increasing risk perception in social activities included the absence of children in the respondent's household and female gender. For the school setting, AID providers perceived greater risk compared to PID providers or pediatric practitioners. CONCLUSIONS: Respondents identified high risk activities that were associated with a high density of participants in an indoor space where masks are removed for eating and drinking. Differences were apparent in the school setting where pediatric providers perceived lower risks when compared to adult providers.

Sensitivity of SARS-CoV-2 Life Cycle to IFN Effects and ACE2 Binding Unveiled with a Stochastic Model.

Mathematical modelling of infection processes in cells is of fundamental interest. It helps to understand the SARS-CoV-2 dynamics in detail and can be useful to define the vulnerability steps targeted by antiviral treatments. We previously developed a deterministic mathematical model of the SARS-CoV-2 life cycle in a single cell. Despite answering many questions, it certainly cannot accurately account for the stochastic nature of an infection process caused by natural fluctuation in reaction kinetics and the small abundance of participating components in a single cell. In the present work, this deterministic model is transformed into a stochastic one based on a Markov Chain Monte Carlo (MCMC) method. This model is employed to compute statistical characteristics of the SARS-CoV-2 life cycle including the probability for a non-degenerate infection process. Varying parameters of the model enables us to unveil the inhibitory effects of IFN and the effects of the ACE2 binding affinity. The simulation results show that the type I IFN response has a very strong effect on inhibition of the total viral progeny whereas the effect of a 10-fold variation of the binding rate to ACE2 turns out to be negligible for the probability of infection and viral production.

Structural assessment of HLA-A2-restricted SARS-CoV-2 spike epitopes recognized by public and private T-cell receptors.

T cells play a vital role in combatting SARS-CoV-2 and forming long-term memory responses. Whereas extensive structural information is available on neutralizing antibodies against SARS-CoV-2, such information on SARS-CoV-2-specific T-cell receptors (TCRs) bound to their peptide-MHC targets is lacking. Here we determine the structures of a public and a private TCR from COVID-19 convalescent patients in complex with HLA-A2 and two SARS-CoV-2 spike protein epitopes (YLQ and RLQ). The structures reveal the basis for selection of particular TRAV and TRBV germline genes by the public but not the private TCR, and for the ability of the TCRs to recognize natural variants of RLQ but not YLQ. Neither TCR recognizes homologous epitopes from human seasonal coronaviruses. By elucidating the mechanism for TCR recognition of an immunodominant yet variable epitope (YLQ) and a conserved but less commonly targeted epitope (RLQ), this study can inform prospective efforts to design vaccines to elicit pan-coronavirus immunity.

Development and evaluation of a low cost IgG ELISA test based in RBD protein for COVID-19.

Serology tests for SARS-CoV-2 have proven to be important tools to fight against the COVID-19 pandemic. These serological tests can be used in low-income and remote areas for patient contact tracing, epidemiologic studies and vaccine efficacy evaluations. In this study, we used a semi-stable mammalian episomal expression system to produce high quantities of the receptor-binding domain-RBD of SARS-CoV-2 in a simple and very economical way. The recombinant antigen was tested in an in-house IgG ELISA for COVID-19 with a panel of human sera. A performance comparison of this serology test with a commercial test based on the full-length spike protein showed 100% of concordance between tests. Thus, this serological test can be an attractive and inexpensive option in scenarios of limited resources to face the COVID-19 pandemic.

Quality comparability assessment of a SARS-CoV-2-neutralizing antibody across transient, mini-pool-derived and single-clone CHO cells.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a serious public health crisis worldwide, and considering the novelty of the disease, preventative and therapeutic measures alike are urgently needed. To accelerate such efforts, the development of JS016, a neutralizing monoclonal antibody directed against the SARS-CoV-2 spike protein, was expedited from a typical 12- to 18-month period to a 4-month period. During this process, transient Chinese hamster ovary cell lines are used to support preclinical, investigational new drug-enabling toxicology research, and early Chemistry, Manufacturing and Controls development; mini-pool materials to supply Phase 1 clinical trials; and a single-clone working cell bank for late-stage and pivotal clinical trials were successively adopted. Moreover, key process performance and product quality investigations using a series of orthogonal and state-of-the-art techniques were conducted to demonstrate the comparability of products manufactured using these three processes, and the results indicated that, despite observed variations in process performance, the primary and high-order structures, purity and impurity profiles, biological and immunological functions, and degradation behaviors under stress conditions were largely comparable. The study suggests that, in particular situations, this strategy can be adopted to accelerate the development of therapeutic biopharmaceuticals and their access to patients.

Community versus individual risk of SARS-CoV-2 infection in two municipalities of Louisiana, USA: An assessment of Area Deprivation Index (ADI) paired with seroprevalence data over time.

OBJECTIVE: Determine whether an individual is at greater risk of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) infection because of their community or their individual risk factors. STUDY DESIGN AND SETTING: 4,752 records from two large prevalence studies in New Orleans and Baton Rouge, Louisiana were used to assess whether zip code tabulation areas (ZCTA)-level area deprivation index (ADI) or individual factors accounted for risk of infection. Logistic regression models assessed associations of individual-level demographic and socioeconomic factors and the zip code-level ADI with SARS-CoV-2 infection. RESULTS: In the unadjusted model, there were increased odds of infection among participants residing in high versus low ADI (both cities) and high versus mid-level ADI (Baton Rouge only) zip codes. When individual-level covariates were included, the odds of infection remained higher only among Baton Rouge participants who resided in high versus mid-level ADI ZCTAs. Several individual factors contributed to infection risk. After adjustment for ADI, race and age (Baton Rouge) and race, marital status, household size, and comorbidities (New Orleans) were significant. CONCLUSIONS: While higher ADI was associated with higher risk of SARS-CoV-2 infection, individual-level participant characteristics accounted for a significant proportion of this association. Additionally, stage of the pandemic may affect individual risk factors for infection.

Rapid assessment of SARS-CoV-2-evolved variants using virus-like particles.

Efforts to determine why new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants demonstrate improved fitness have been limited to analyzing mutations in the spike (S) protein with the use of S-pseudotyped particles. In this study, we show that SARS-CoV-2 virus-like particles (SC2-VLPs) can package and deliver exogenous transcripts, enabling analysis of mutations within all structural proteins and at multiple steps in the viral life cycle. In SC2-VLPs, four nucleocapsid (N) mutations found universally in more-transmissible variants independently increased messenger RNA delivery and expression ~10-fold, and in a reverse genetics model, the serine-202→arginine (S202R) and arginine-203→methionine (R203M) mutations each produced >50 times as much virus. SC2-VLPs provide a platform for rapid testing of viral variants outside of a biosafety level 3 setting and demonstrate N mutations and particle assembly to be mechanisms that could explain the increased spread of variants, including B.1.617.2 (Delta, which contains the R203M mutation).

Risk of infections in psoriasis: assessment and challenges in daily management.

INTRODUCTION: In daily practice management of psoriasis, evaluation of risk factors for infections is having a growing influence. Indeed, in psoriatic patients, risk of infections may be due to psoriasis itself, immunomodulatory therapy, and comorbidities that may increase this risk and patient hospitalization. AREAS COVERED: Given the greater understanding of psoriasis pathogenesis and the increasing number of treatment options, it is particularly important to customize therapy according to each, single patient; psoriasis features and comorbidities are also essential to tailor treatment goals. EXPERT OPINION: In this perspective, the current knowledge on the infectious risk in psoriatic patient, related to comorbidities, such as diabetes mellitus, cardiovascular disease, and chronic obstructive pulmonary, to 'special populations,' to chronic infections, such as latent tuberculosis, chronic hepatitis B and C, and HIV, and to the most recent Covid-19 pandemic scenario, is reviewed and discussed in order to suggest the most appropriate approach and achieve the best available therapeutic option.

How did Covid-19 impact US household foods? an analysis six months in.

Using a nationwide survey of primary grocery shoppers conducted in August 2020, we examine household food spending when the economy had partially reopened and consumers had different spending opportunities in comparison to when the Covid-19 lockdown began. We estimate the impact of Covid-19 on household spending using interval and Order Probit regressions. Income levels, age, access to grocery stores and farmers markets, household demographic information, along with other independent variables are controlled in the model. Findings show that middle-class households (with income below $50,000, or with income between $50,000 and $99,999) are less likely to increase their grocery expenditures during the pandemic. Households with children or elderlies that usually require higher food quality and nutrition intakes had a higher probability of increasing their spending during Covid-19 than before. Furthermore, consumers' spending behaviors were also significantly affected by their safe handing levels and the Covid-19 severity and food accessibility in their residences.

Resilience against the pandemic: The impact of COVID-19 on migration and household welfare in Tajikistan.

The COVID-19 pandemic is likely to have adverse effects on the economy through damage to migration and remittances. We use a unique monthly household panel dataset that covers the period both before and after the outbreak to examine the impacts of COVID-19 on a variety of household welfare outcomes in Tajikistan, where remittance inflows in recent years have exceeded a quarter of annual GDP. We provide several findings. First, after April 2020, the adverse effects of the pandemic on household welfare were significantly observed and were particularly pronounced in the second quarter of 2020. Second, in contrast to expectation, the pandemic had a sharp but only transitory effect on the stock of migrants working abroad in the spring. Some expected migrants were forced to remain in their home country during the border closures, while some incumbent migrants expecting to return were unable to do so and remained employed in their destination countries. Both departures and returns started to increase again from summer. Employment and remittances of the migrants quickly recovered to levels seen in previous years after a sharp decline in April and May. Third, regression analyses reveal that both migration and remittances have helped to mitigate the adverse economic outcomes at home during the "with-COVID-19" period, suggesting that they served as a form of insurance. Overall, the unfavorable effects of the COVID-19 pandemic were severe and temporary right after the outbreak, but households with migrants were more resilient against the pandemic.

A critical assessment of the potential vertical transmission hypotheses: Implications for research on the early-life infection with COVID-19.

The risk of potential vertical transmission in SARS-CoV-2 infected pregnant women is currently a topic of debate. To explore the correlation between the two, we searched PubMed, Embase®, and Web of Science for studies on vertical transmission of COVID-19. The quality of the studies was evaluated by the Cochrane risk of bias tool. Detailed information of each included case including methods of delivery, protection measures for mothers and neonates at birth, types of specimens, inspection time, results of testing and feeding patterns was collected to assess the possibility of vertical transmission. The results showed that of the 390 neonates reported in 36 studies, 23 were infected with SARS-CoV-2 by potential vertical transmission. From the perspective of virology and pathology, vertical transmission of SARS-CoV-2 was possible via uterus or breastmilk. Some reported potential vertically transmitted neonates could be attributed to horizontal transmission. It is extremely vital to fully elucidate the potential routes of transmission of SARS-CoV-2, implicating clinical practice and nursing to reduce the risk of not only horizontal transmission but also vertical transmission, thus protecting neonates from COVID-19 infection.

Effective vaccine allocation strategies, balancing economy with infection control against COVID-19 in Japan.

Due to COVID-19, many countries including Japan have implemented a suspension of economic activities for infection control. It has contributed to reduce the transmission of COVID-19 but caused severe economic losses. Today, several promising vaccines have been developed and are already being distributed in some countries. Therefore, we evaluated various vaccine and intensive countermeasure strategies with constraint of economic loss using SEIR model to obtain knowledge of how to balance economy with infection control in Japan. Our main results were that the vaccination strategy that prioritized younger generation was better in terms of deaths when a linear relationship between lockdown intensity and acceptable economic loss was assumed. On the other hand, when a non-linearity relationship was introduced, implying that the strong lockdown with small economic loss was possible, the old first strategies were best in the settings of small basic reproduction number. These results indicated a high potential of remote work when prioritizing vaccination for the old generation. When focusing on only the old first strategies as the Japanese government has decided to do, the strategy vaccinating the young next to the old was superior to the others when a non-linear relationship was assumed due to sufficient reduction of contact with small economic loss.

Application of telemedicine in the COVID-19 epidemic: An analysis of Gansu Province in China.

This paper analyzes the application of various telemedicine services in Gansu Province, China during the COVID-19 epidemic, and summarizes the experiences with these services. In addition, the satisfaction levels of patients and doctors with the application of telemedicine in COVID-19 were investigated, the deficiencies of telemedicine in Gansu were determined, and recommendations for modification were proposed. Coronavirus Disease 2019 (COVID-19) has broken out in China, and Gansu Province in Northwest of China has not been spared. To date, there are 91 local COVID-19 cases and 42 imported cases. 109 hospitals were selected as designated hospitals during the COVID-19 outbreak, and most of them were secondary hospitals. However, it was unsatisfactory that the ability of medical services is relatively low in most of secondary hospitals and primary hospitals. Therefore, we helped the secondary hospitals cope with COVID-19 by means of remote consultation, long-distance education, telemedicine question and answer (Q&A). Our practical experience shows that telemedicine can be widely used during the COVID-19 epidemic, especially in developing countries and areas with lagging medical standards.