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Jennifer R. Hamilton, Elizabeth C. Stahl, Connor A. Tsuchida, Enrique Lin-Shiao, C. Kimberly Tsui, Kathleen Pestal, Holly K. Gildea, Lea B. Witkowsky, Erica A. Moehle, Shana L. McDevitt, et al.
Published: 11 January 2021
Abstract:
Saliva is an attractive specimen type for asymptomatic surveillance of COVID-19 in large populations due to its ease of collection and its demonstrated utility for detecting RNA from SARS-CoV-2. Multiple saliva-based viral detection protocols use a direct-to-RT-qPCR approach that eliminates nucleic acid extraction but can reduce viral RNA detection sensitivity. To improve test sensitivity while maintaining speed, we developed a robotic nucleic acid extraction method for detecting SARS-CoV-2 RNA in saliva samples with high throughput. Using this assay, the Free Asymptomatic Saliva Testing (IGI-FAST) research study on the UC Berkeley campus conducted 11,971 tests on supervised self-collected saliva samples and identified rare positive specimens containing SARS-CoV-2 RNA during a time of low infection prevalence. In an attempt to increase testing capacity, we further adapted our robotic extraction assay to process pooled saliva samples. We also benchmarked our assay against the gold standard, nasopharyngeal swab specimens. Finally, we designed and validated a RT-qPCR test suitable for saliva self-collection. These results establish a robotic extraction-based procedure for rapid PCR-based saliva testing that is suitable for samples from both symptomatic and asymptomatic individuals.
, , Nathan D. Grubaugh, Tara Alpert, Isabel M. Ott, Mallery I. Breban, Richard A. Martinello, Cindy Smith, Matthew W. Davis, Dayna Mcmanus, et al.
Published: 30 December 2021
Transplant Infectious Disease, Volume 24; https://doi.org/10.1111/tid.13782

The publisher has not yet granted permission to display this abstract.
Patricia González-Donapetry, Paloma García-Clemente, Iván Bloise, Consuelo García-Sánchez, Miguel Ángel Sánchez Castellano, María Pilar Romero, Almudena Gutiérrez Arroyo, Jesús Mingorance, María De Ceano-Vivas La Calle, Julio García-Rodriguez, et al.
Published: 17 February 2021
Abstract:
Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is the reference laboratory method to diagnose SARS-CoV-2 infection then requires equipment and is time-consuming. There is a crucial demand for rapid techniques such as antigen detection test. Considering the different diagnostic accuracy of tests with other respiratory viruses in adults and children, SARS-CoV-2 antigen test must be evaluated specifically in children. The purpose of this study was to evaluate the performance of Panbio COVID-19 Ag Rapid Test Device (Abbott) as a point-of-care test for diagnosis of SARS-CoV-2 in comparison to RT-qPCR in a pediatric population. Four hundred forty nasopharyngeal swabs were tested. Amongst the 18 positive RT-qPCR samples, 14 were detected by the rapid antigen test, given an overall sensitivity of 77.7%. All the samples detected positive with the antigen rapid test were also positive with RT-qPCR. The sensitivity of Panbio COVID-19 Ag Rapid Test Device is lower in children than in adults. Nevertheless, considering the good values of specificity, negative and positive predictive values this test could be used as a frontline test to obtain quick results, although the negative values with COVID-19 high clinical suspicion should be confirmed using RT-qPCR.
, , , Yamrot M. Amha, Mitchel Bartolo, Richard Danielson, Yeggie Dearborn, George Di Giovanni, Christobel Ferguson, Stephanie Fevig, et al.
Environmental Science: Water Research & Technology, Volume 7, pp 504-520; https://doi.org/10.1039/d0ew00946f

Abstract:
In response to COVID-19, the international water community rapidly developed methods to quantify the SARS-CoV-2 genetic signal in untreated wastewater. Wastewater surveillance using such methods has the potential to complement clinical testing in assessing community health. This interlaboratory assessment evaluated the reproducibility and sensitivity of 36 standard operating procedures (SOPs), divided into eight method groups based on sample concentration approach and whether solids were removed. Two raw wastewater samples were collected in August 2020, amended with a matrix spike (betacoronavirus OC43), and distributed to 32 laboratories across the U.S. Replicate samples analyzed in accordance with the project's quality assurance plan showed high reproducibility across the 36 SOPs: 80% of the recovery-corrected results fell within a band of ±1.15 log10 genome copies per L with higher reproducibility observed within a single SOP (standard deviation of 0.13 log10). The inclusion of a solids removal step and the selection of a concentration method did not show a clear, systematic impact on the recovery-corrected results. Other methodological variations (e.g., pasteurization, primer set selection, and use of RT-qPCR or RT-dPCR platforms) generally resulted in small differences compared to other sources of variability. These findings suggest that a variety of methods are capable of producing reproducible results, though the same SOP or laboratory should be selected to track SARS-CoV-2 trends at a given facility. The methods showed a 7 log10 range of recovery efficiency and limit of detection highlighting the importance of recovery correction and the need to consider method sensitivity when selecting methods for wastewater surveillance.
Published: 4 May 2021
Abstract:
Objective Reports of cerebral sinus and venous thrombosis (CVT) after ChAdOx1 vaccination against SARS-CoV-2 have raised safety concerns. We aimed to estimate the incidence of CVT within one month from first dose administration and the frequency of vaccine-induced immune thrombotic thrombocytopenia (VITT) as the underlying mechanism after vaccination with BNT162b2, ChAdOx1, and mRNA-1273, in Germany. Methods A web-based questionnaire was e-mailed to all Departments of Neurology. We asked to report cases of CVT within one month of a COVID-19 vaccination. Other cerebral events could also be reported. Incidence rates of CVT were calculated by using official statistics of nine German States. Results A total of 45 CVT cases were reported. In addition, 9 primary ischemic strokes, 4 primary intracerebral hemorrhages, and 4 other neurological events were recorded. Of the CVT patients, 35 (77.8%) were female, and 36 (80.0%) were below the age of 60 years. Fifty-three events were observed after vaccination with ChAdOx1 (85.5%), 9 after BNT162b2 (14.5%), and none after mRNA-1273 vaccination. After 7,126,434 first vaccine doses, the incidence rate of CVT within one month from first dose administration was 6.5 (95% CI, 4.4-9.2) per 100,000 person-years for all vaccines and 17.9 (11.8-26.1) for ChAdOx1 (after 2,320,535 ChAdOx1 first doses). The adjusted incidence rate ratio was 9.68 (3.46-34.98) for ChAdOx1 compared to mRNA-based vaccines and 3.14 (1.22-10.65) for women compared to non-women. In 26/45 patients with CVT (57.8%), VITT was graded highly probable. Conclusions Given an incidence of 0.22–1.75 per 100,000 person-years for CVT in the general population, these findings point towards a higher risk for CVT after ChAdOx1 vaccination, especially for women.
, Francesco Violante, Paolo Durando, Giuseppe De Palma, Enrico Pira, Luigi Vimercati, Alfonso Cristaudo, Giancarlo Icardi, Emma Sala, Maurizio Coggiola, et al.
Published: 30 July 2020
Abstract:
Healthcare workers (HCW) are at increased risk of being infected with SARS-CoV-2, yet limited information is available on risk factors of infection. We pooled data on occupational surveillance of 10,654 HCW who were tested for SARS-CoV-2 infection in six Italian centers. Information was available on demographics, job title, department of employment, source of exposure, use of personal protective equipment (PPE), and COVID-19-related symptoms. We fitted multivariable logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI). The prevalence of infection varied across centers and ranged from 3.0% to 22.0%, being strongly correlated with that of the respective areas. Women were at lower risk of infection compared to men. Fever, cough, dyspnea and malaise were the symptoms most strongly associated with infection, together with anosmia and ageusia. No differences in the risk of infection were detected between job titles, or working in a COVID-19 designated department. Reported contact with a patient inside or outside the workplace was a risk factor. Use of a mask was strongly protective against risk of infection as was use of gloves. The use of a mask by the source of exposure (patient or colleague) had an independent effect in reducing infection risk.
, Estela Cordero-Laurent, Adriana Godínez, Melany Calderón-Osorno, Hebleen Brenes, Claudio Soto-Garita, Cristian Pérez-Corrales, Jan Felix Drexler, Andres Moreira-Soto, Eugenia Corrales-Aguilar, et al.
Published: 22 December 2020
Abstract:
Genome sequencing is a key strategy in the surveillance of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Latin America is the hardest hit region of the world, accumulating almost 20% of COVID-19 cases worldwide. Costa Rica was first exemplary for the region in its pandemic control, declaring a swift state of emergency on March 16th that led to a low quantity of cases, until measures were lifted in early May. From the first detected case in March 6th to December 31st almost 170 000 cases have been reported in Costa Rica, 99.5% of them from May onwards. We analyzed the genomic variability during the SARS-CoV-2 pandemic in Costa Rica using 185 sequences, 52 from the first months of the pandemic, and 133 from the current wave.Three GISAID clades (G, GH, and GR) and three PANGOLIN lineages (B.1, B.1.1, and B.1.291) are predominant, with phylogenetic relationships that are in line with the results of other Latin American countries, suggesting introduction and multiple re-introductions from other regions of the world. The whole-genome variant calling analysis identified a total of 283 distinct nucleotide variants. These correspond mostly to non-synonymous mutations (51.6%, 146) but 45.6% (129) corresponded to synonymous mutations. The 283 variants showed an expected power-law distribution: 190 single nucleotide mutations were identified in single sequences, only 16 single nucleotide mutations were found in >5% sequences, and only two mutations in >50% genomes. These mutations were distributed through the whole genome. However, 63.6% were present in ORF1ab, 11.7% in Spike gene and 10.6% in the Nucleocapsid gene. Additionally, the prevalence of worldwide-found variant D614G in the Spike (98.9% in Costa Rica), ORF8 L84S (1.1%) is similar to what is found elsewhere. Interestingly, the frequency of mutation T1117I in the Spike has increased during the current pandemic wave beginning in May 2020 in Costa Rica, reaching 29.2% detection in the full genome analyses in November 2020. This variant has been observed in less than 1% of the GISAID reported sequences worldwide in all the 2020. Structural modeling of the Spike protein with the T1117I mutation suggest a potential effect on the viral oligomerization needed for cell infection, but no differences with other genomes on transmissibility, severity nor vaccine effectiveness are predicted. Nevertheless, in-vitro experiments are required to support these in-silico findings. In conclusion, genome analyses of the SARS-CoV-2 sequences over the course of COVID-19 pandemic in Costa Rica suggest introduction of lineages from other countries as travel bans and measures were lifted, similar to results found in other studies, as well as an increase in the Spike-T1117I variant that needs to be monitored and studied in further analyses as part of the surveillance program during the pandemic.
, , Ns Trovão, S Duarte, H Cortes-Martins, H Martiniano, I Gordo, R Leite, L Vieira, Portuguese network for SARS-CoV-2 genomics (Consortium), et al.
Published: 23 February 2021
Abstract:
Background Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. This unprecedented collaborative effort culminated in the generation of 1275 SARS-CoV-2 genome sequences, which represent 15.5% of all confirmed cases in March 2020, making Portugal one of the countries generating the highest volumes of SARS-CoV-2 genomic data during early COVID-19 pandemic. Methods We reconstructed and characterized the spatio-temporal dynamics of SARS-CoV-2 introductions and early dissemination in Portugal using recent phylodynamic models that allow integration of individual-based travel history, in order to obtain a more realistic reconstruction of the viral dynamics. Results We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy and Switzerland), which was broadly consistent with the available travel history data, as well as with the countries with most frequent connectivity and/or with the highest number of Portuguese immigrants. Although most introductions were estimated to have occurred during the last week of February and the first week of March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal several weeks before the first confirmed local cases on March 2, 2020. Discussion and Conclusion While the implemented preventive and early control measures seem to have been successful in mitigating community transmission from most independent introductions, our results suggest that their earlier implementation could have largely minimized the number of introductions and subsequent virus expansion. Here we lay the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlight the need for systematic, continuous and geographically-representative genomic surveillance to guide national and international public health authorities toward the characterization and control of SARS-CoV-2 circulating diversity.
, Lise Estcourt, Heli Harvala, David Roberts, David K. Menon, On behalf of the United Kingdom SARS-CoV-2 Convalescent Plasma Evaluation (SCoPE) Consortium
Published: 20 July 2020
Critical Care, Volume 24, pp 1-5; https://doi.org/10.1186/s13054-020-03163-3

, Robin Marwal, Vs Radhakrishnan, Kalaiarasan Ponnusamy, Bani Jolly, Rahul C. Bhoyar, Saman Fatihi, Meena Datta, Priyanka Singh, Uma Sharma, et al.
Published: 3 June 2021
Abstract:
Delhi, the national capital of India, has experienced multiple SARS-CoV-2 outbreaks in 2020 and reached a population seropositivity of over 50% by 2021. During April 2021, the city became overwhelmed by COVID-19 cases and fatalities, as a new variant B.1.617.2 (Delta) replaced B.1.1.7 (Alpha). A Bayesian model explains the growth advantage of Delta through a combination of increased transmissibility and partial reduction of immunity elicited by prior infection (median estimates; ×1.5-fold, 20% reduction). Seropositivity of an employee and family cohort increased from 42% to 86% between March and July 2021, with 27% reinfections, as judged by increased antibody concentration after previous decline. The likely high transmissibility and partial evasion of immunity by the Delta variant contributed to an overwhelming surge in Delhi. One-Sentence Summary Delhi experienced an overwhelming surge of COVID-19 cases and fatalities peaking in May 2021 as the highly transmissible and immune evasive Delta variant replaced the Alpha variant.
, Robin Marwal, Radhakrishnan Vs, Kalaiarasan Ponnusamy, Bani Jolly, Rahul C. Bhoyar, Viren Sardana, Salwa Naushin, Mercy Rophina, , et al.
Science, Volume 374, pp 995-999; https://doi.org/10.1126/science.abj9932

Abstract:
Deadly surge in Delhi: In the spring of 2021, Delhi, India experienced a wave of coronavirus cases that overwhelmed healthcare services despite the population showing a high level of immune positivity. Dhar et al . collated a mixture of serosurveillance, quantitative polymerase chain reaction, and genomic data, finding that waves of variants had passed through the Delhi population during 2020 and 2021. The alpha (B.1.1.7) variant dominated in March 2021 and was rapidly replaced by the delta (B.1.617.2) variant in April and May 2021. The delta variant outcompeted its predecessors by mutations that enhanced replication, immune evasion, and host receptor avidity, thus increasing transmissibility, reinfection, and vaccination breakthrough. —CA
, Audrey Duval, Jean Ralph Zahar, Lulla Opatowski, Laura Temime, Niels Hendrickx, Kévin Jean, Sofía Jijón, Ajmal Oodally, George Shirreff, et al.
Published: 11 January 2022
Nature Communications, Volume 13, pp 1-10; https://doi.org/10.1038/s41467-021-27845-w

Abstract:
Healthcare facilities are vulnerable to SARS-CoV-2 introductions and subsequent nosocomial outbreaks. Antigen rapid diagnostic testing (Ag-RDT) is widely used for population screening, but its health and economic benefits as a reactive response to local surges in outbreak risk are unclear. We simulate SARS-CoV-2 transmission in a long-term care hospital with varying COVID-19 containment measures in place (social distancing, face masks, vaccination). Across scenarios, nosocomial incidence is reduced by up to 40-47% (range of means) with routine symptomatic RT-PCR testing, 59-63% with the addition of a timely round of Ag-RDT screening, and 69-75% with well-timed two-round screening. For the latter, a delay of 4-5 days between the two screening rounds is optimal for transmission prevention. Screening efficacy varies depending on test sensitivity, test type, subpopulations targeted, and community incidence. Efficiency, however, varies primarily depending on underlying outbreak risk, with health-economic benefits scaling by orders of magnitude depending on the COVID-19 containment measures in place.
, Isabelle Malet, Valentin Leducq, Karen Zafilaza, Delphine Sterlin, Delphine Planas, Adélie Gothland, , , , et al.
Published: 8 February 2021
Nature Communications, Volume 12, pp 1-7; https://doi.org/10.1038/s41467-021-21111-9

Abstract:
There are only few data concerning persistence of neutralizing antibodies (NAbs) among SARS-CoV-2-infected healthcare workers (HCW). These individuals are particularly exposed to SARS-CoV-2 infection and at potential risk of reinfection. We followed 26 HCW with mild COVID-19 three weeks (D21), two months (M2) and three months (M3) after the onset of symptoms. All the HCW had anti-receptor binding domain (RBD) IgA at D21, decreasing to 38.5% at M3 (p< 0.0001). Concomitantly a significant decrease in NAb titers was observed between D21 and M2 (p = 0.03) and between D21 and M3 (p< 0.0001). Here, we report that SARS-CoV-2 can elicit a NAb response correlated with anti-RBD antibody levels. However, this neutralizing activity declines, and may even be lost, in association with a decrease in systemic IgA antibody levels, from two months after disease onset. This short-lasting humoral protection supports strong recommendations to maintain infection prevention and control measures in HCW, and suggests that periodic boosts of SARS-CoV-2 vaccination may be required.
Andrea Lo Vecchio, Silvia Garazzino, Andrea Smarrazzo, Elisabetta Venturini, Marco Poeta, Paola Berlese, Marco Denina, Antonella Meini, Samantha Bosis, Luisa Galli, et al.
Abstract:
The gastrointestinal (GI) tract is one of the target organs affected by SARS-CoV-2. The colocalization of angiotensin-converting enzyme 2 and the proteaselike transmembrane serine protease 2, essential receptors for SARS-CoV-2 cell binding and internalization, has been noted in the human GI tract.1,2 The presence of isolated GI symptoms in some patients with SARS-CoV-2 infection, as well as the prolonged fecal shedding reported in neonates and children, supports the hypothesis of a fecal-oral transmission of SARS-CoV-2.3
, Chantal B. F. Vogels, Inci Yildirim, Jessica E. Rothman, , Valter Monteiro, Jeff R. Gehlhausen, Melissa Campbell, , Alexandra Tabachnikova, et al.
Published: 11 October 2021
Nature, Volume 600, pp 523-529; https://doi.org/10.1038/s41586-021-04085-y

The publisher has not yet granted permission to display this abstract.
Orna Mor, Michal Mandelboim, Shay Fleishon, Efrat Bucris, Dana Bar-Ilan, Michal Linial, Yaniv Lustig, Israel National Consortium for SARS-CoV-2 sequencing, Ella Mendelson,
Published: 7 July 2021
Abstract:
Emerging SARS-CoV-2 variants may threaten global vaccination efforts and awaited reduction in outbreak burden. In this study, we report a novel variant carrying the L452R mutation that emerged from a local B.1.362 lineage, B.1.362+L452R. The L452R mutation is associated with the Delta and Epsilon variants and was shown to cause increased infection and reduction in neutralization in pseudoviruses. Indeed, the B.1.362+L452R variant demonstrated a X4-fold reduction in neutralization capacity of sera from BNT162b2-vaccinated individuals compared to a wild-type strain. The variant infected 270 individuals in Israel between December 2020 and March 2021, until diminishing due to the gain in dominance of the Alpha variant in February 2021. This study demonstrates an independent, local emergence of a variant carrying a critical mutation, L452R, which may have the potential of becoming a variant of concern and emphasizes the importance of routine surveillance and detection of novel variants among efforts undertaken to prevent further disease spread.
Petra Mlcochova, Steven Kemp, Mahesh Shanker Dhar, Guido Papa, Bo Meng, Swapnil Mishra, Charlie Whittaker, Thomas Mellan, Isabella Ferreira, Rawlings Datir, et al.
Published: 22 June 2021
Abstract:
The SARS-CoV-2 B.1.617.2 (Delta) variant was first identified in the state of Maharashtra in late 2020 and has spread throughout India, displacing the B.1.1.7 (Alpha) variant and other pre-existing lineages. Mathematical modelling indicates that the growth advantage is most likely explained by a combination of increased transmissibility and immune evasion. Indeed in vitro, the delta variant is less sensitive to neutralising antibodies in sera from recovered individuals, with higher replication efficiency as compared to the Alpha variant. In an analysis of vaccine breakthrough in over 100 healthcare workers across three centres in India, the Delta variant not only dominates vaccine-breakthrough infections with higher respiratory viral loads compared to non-delta infections (Ct value of 16.5 versus 19), but also generates greater transmission between HCW as compared to B.1.1.7 or B.1.617.1 (p=0.02). In vitro, the Delta variant shows 8 fold approximately reduced sensitivity to vaccine-elicited antibodies compared to wild type Wuhan-1 bearing D614G. Serum neutralising titres against the SARS-CoV-2 Delta variant were significantly lower in participants vaccinated with ChadOx-1 as compared to BNT162b2 (GMT 3372 versus 654, p<0001). These combined epidemiological and in vitro data indicate that the dominance of the Delta variant in India has been most likely driven by a combination of evasion of neutralising antibodies in previously infected individuals and increased virus infectivity. Whilst severe disease in fully vaccinated HCW was rare, breakthrough transmission clusters in hospitals associated with the Delta variant are concerning and indicate that infection control measures need continue in the post-vaccination era.
, Shay Fleishon, Efrat Bucris, Dana Bar-Ilan, Michal Linial, Itay Bar-Or, Victoria Indenbaum, Merav Weil, Israel National Consortium for SARS-CoV-2 sequencing, Ella Mendelson, et al.
Published: 28 March 2021
Abstract:
Routine detection, surveillance and reporting of SARS-CoV-2 novel variants is important, as these threaten to hinder vaccination efforts. Herein we report a local novel strain that includes a non-synonymous mutation in the spike (S) protein - P681H and additional synonymous mutations. The P681H Israeli strain has not been associated with higher infection rates and was neutralized by sera from vaccinated individuals in comparable levels to the B.1.1.7 strain and a non-P681H strain from Israel.
, , David Roca Pascual, María Slöcker Barrio, Juan Carlos De Carlos Vicente, Amaya Bustinza Arriortua, , Maite Cuervas-Mons Tejedor, Pedro Pablo Oyágüez Ugidos, Iolanda Jordan, et al.
Published: 22 June 2020
Intensive Care Medicine, Volume 46, pp 1774-1776; https://doi.org/10.1007/s00134-020-06146-8

, Emilie Jolly, Tiffany Pascreau, Marianne Asso-Bonnet, Laurence Mazaux, Marc Vasse, on behalf of the SARS-CoV-2 Foch Hospital study group
Published: 25 May 2020
Infectious Diseases, Volume 52, pp 583-584; https://doi.org/10.1080/23744235.2020.1769178

Oscar F. Chacón-Camacho, Rocío Arce-González,
Boletín Médico del Hospital Infantil de México, Volume 77, pp 252-261; https://doi.org/10.24875/bmhim.20000191

Abstract:
Since the emergence of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China at the end of 2019, when its characteristics were practically unknown, one aspect was evident: its high contagion rate. This high infection rate resulted in the spread of the virus in China, Europe, and, eventually, the rest of the world, including Mexico. At present, around 9 million people are infected, and around 470,000 have died worldwide. In this context, the need to generate protective immunity, and especially the generation of a vaccine that can protect the world population against infection in the shortest possible time, is a challenge that is being addressed in different countries using different strategies in multiple clinical trials. This opinion article will present the evidence of the induction of immune response in some of the viruses of the coronavirus family before COVID-19, such as SARS-CoV and MERS-CoV (Middle East respiratory syndrome coronavirus). The information collected about the induction of an immune response by SARS-CoV-2 will be presented, as well as a description of the vaccine candidates reported to date in the various ongoing clinical trials. Finally, an opinion based on the evidence presented will be issued on the potential success of developing vaccine prototypes.
, , , , , EMEA-MESuRS working group on the nosocomial modelling of SARS-CoV-2
Published: 29 September 2021
Abstract:
Covid-19 poses significant risk of nosocomial transmission, and preventing this requires good estimates of the basic reproduction number R0 in hospitals and care facilities, but these are currently lacking. Such estimates are challenging due to small population sizes in these facilities and inconsistent testing practices. We estimate the patient-to-patient R0 and daily transmission rate of SARS-CoV-2 using data from a closely monitored hospital outbreak in Paris 2020 during the first wave. We use a realistic epidemic model which accounts for progressive stages of infection, stochastic effects and a large proportion of asymptomatic infections. Innovatively, we explicitly include changes in testing capacity over time, as well as the evolving sensitivity of PCR testing at different stages of infection. We conduct rigorous statistical inference using iterative particle filtering to fit the model to the observed patient data and validate this methodology using simulation. We provide estimates for R0 across the entire hospital (2.6) and in individual wards (from 3 to 15), possibly reflecting heterogeneity in contact patterns or control measures. An obligatory mask-wearing policy introduced during the outbreak is likely to have changed the R0, and we estimate values before (8.7) and after (1.3) its introduction, corresponding to a policy efficacy of 85%.
, Eko W. Putro, Asep M. Ridwanuloh, Satrio H.B. Wibowo, Hariyatun Hariyatun, Gita Syahputra, Gilang Akbariani, Ahmad R. Utomo, Mohammad Ilyas, , et al.
Published: 7 July 2021
Abstract:
A year after the World Health Organisation (WHO) declared COVID-19 as a pandemic, much has been learned regarding SARS-CoV-2 epidemiology, vaccine production, and disease treatment. Whole-genome sequencing (WGS) has played a significant role in contributing to our understanding of the epidemiology and biology of this virus. In this paper, we investigate the use of SARS-CoV-2 WGS in Southeast and East Asia and the impact of technological development, access to resources, and demography of individual countries on its uptake. Using Oxford Nanopore Technology (ONT), Nottingham-Indonesia Collaboration for Clinical Research and Training (NICCRAT) initiative has facilitated collaboration between the University of Nottingham and a team in Research Centre for Biotechnology, Indonesian Institute of Sciences (Lembaga Ilmu Pengetahuan Indonesia/LIPI) to carry out a small number of SARS-CoV-2 WGS in Indonesia. The ONT offers sequencing advantages that fit within the Indonesian context. Analyses of SARS-CoV-2 genomes deposited on GISAID from Southeast and East Asian countries reveal the importance of collecting clinical and demographic metadata and the importance of open access and data sharing. Lineage and phylogenetic analyses per 1 June 2021 found that: 1) B.1.466.2 variants were the most predominant in Indonesia, with mutations in the spike protein including D614G at 100%, N439K at 99.1%, and P681R at 69.7% frequency, 2) The variants of concern (VoCs) B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta) were first detected in Indonesia in January 2021, 3) B.1.470 was first detected in Indonesia and spread to the neighbouring regions, and 4) The highest rate of virus transmissions between Indonesia and the rest of the world appears to be through interactions with Singapore and Japan, two neighbouring countries with a high degree of access and travels to and from Indonesia.
, , , , Maria Luisa Gomez-Calvo, Olga Fedorova, Mallery I. Breban, , Huiping Dong, Melissa Linehan, et al.
Journal of Experimental Medicine, Volume 219; https://doi.org/10.1084/jem.20211818

Abstract:
As SARS-CoV-2 continues to cause morbidity and mortality around the world, there is an urgent need for the development of effective medical countermeasures. Here, we assessed the antiviral capacity of a minimal RIG-I agonist, stem-loop RNA 14 (SLR14), in viral control, disease prevention, post-infection therapy, and cross-variant protection in mouse models of SARS-CoV-2 infection. A single dose of SLR14 prevented viral infection in the lower respiratory tract and development of severe disease in a type I interferon (IFN-I)–dependent manner. SLR14 demonstrated remarkable prophylactic protective capacity against lethal SARS-CoV-2 infection and retained considerable efficacy as a therapeutic agent. In immunodeficient mice carrying chronic SARS-CoV-2 infection, SLR14 elicited near-sterilizing innate immunity in the absence of the adaptive immune system. In the context of infection with variants of concern (VOCs), SLR14 conferred broad protection against emerging VOCs. These findings demonstrate the therapeutic potential of SLR14 as a host-directed, broad-spectrum antiviral for early post-exposure treatment and treatment of chronically infected immunosuppressed patients.
, , , , , , , , , Israel National Consortium for SARS-CoV-2 Sequencing, et al.
Published: 23 August 2021
by MDPI
Abstract:
Emerging SARS-CoV-2 variants may threaten global vaccination efforts and the awaited reduction in outbreak burden. In this study, we report a novel variant carrying the L452R mutation that emerged from a local B.1.362 lineage, B.1.362+L452R. The L452R mutation is associated with the Delta and Epsilon variants and was shown to cause increased infection and reduction in neutralization in pseudoviruses. Indeed, the B.1.362+L452R variant demonstrated a X4-fold reduction in neutralization capacity of sera from BNT162b2-vaccinated individuals compared to a wild-type strain. The variant infected 270 individuals in Israel between December 2020 and March 2021, until diminishing due to the gain in dominance of the Alpha variant in February 2021. This study demonstrates an independent, local emergence of a variant carrying a critical mutation, L452R, which may have the potential of becoming a variant of concern and emphasizes the importance of routine surveillance and detection of novel variants among efforts undertaken to prevent further disease spread.
Md Antonio Sanna, Antonio Foresi, Matteo Siciliano, Roberto Torchio, Antonio Sanna, Antonino Attinà, Elvia Giovanna Battaglia, Salvatore Bellofiore, Elisabetta Bertocco, Serafina Bevilacqua, et al.
Journal of Clinical Sleep Medicine, Volume 17, pp 2337-2338; https://doi.org/10.5664/jcsm.9572

, , , Andrew H. Doudna Cate, Lea B. Witkowsky, , Ariana Hirsh, Kerrie Barry, Jennifer R. Hamilton, , et al.
Published: 25 January 2021
Abstract:
Summary Regular surveillance testing of asymptomatic individuals for SARS-CoV-2 has played a vital role in SARS-CoV-2 outbreak prevention on college and university campuses. Here we describe the voluntary saliva testing program instituted at the University of California, Berkeley during an early period of the SARS-CoV-2 pandemic in 2020. The program was administered as a research study ahead of clinical implementation, enabling us to launch surveillance testing while continuing to optimize the assay. Results of both the testing protocol itself and the study participants’ experience show how the program succeeded in providing routine, robust testing capable of contributing to outbreak prevention within a campus community and offer strategies for encouraging participation and a sense of civic responsibility.
Grupo de trabajo Grupo de trabajo para la elaboración de criterios para la gestión de personas especialmente vulnerables y trabajadores/as especialmente sensibles frente al SARS-CoV-2 en las empresas de Cataluña.GTPSVTESSARS-CoV-2
Published: 15 April 2020
, David R. Peaper, Brendan J. Kelly, , Andrew Marques, Hriju Adhikari, Zheng Jin Tu, Rebecca Marrero Rolon, Lars F. Westblade, Daniel A. Green, et al.
Published: 28 April 2022
Abstract:
Mutations in the viral genome of SARS-CoV-2 can impact the performance of molecular diagnostic assays. In some cases, such as S gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here we describe partial ORF1ab gene target failure (pOGTF) on the cobas® SARS-CoV-2 assays, defined by a ≥2 thermocycles delay in detection of the ORF1ab gene compared to the E gene. We demonstrate that pOGTF is 97% sensitive and 99% specific for SARS-CoV-2 lineage BA.2.12.1, an emerging variant in the United States with spike L452Q and S704L mutations that may impact transmission, infectivity, and/or immune evasion. Increasing rates of pOGTF closely mirrored rates of BA.2.12.1 sequences uploaded to public databases, and, importantly increasing local rates of pOGTF also mirrored increasing overall test positivity. Use of pOGTF as a proxy for BA.2.12.1 provides faster tracking of the variant than whole-genome sequencing and can benefit laboratories without sequencing capabilities.
Mario A. Peña-Hernández, Jon Klein, Amyn A. Malik, Andreas Coppi, , Chantal B. F. Vogels, , David R. Peaper, Marie-Louise Landry, Craig Wilen, et al.
Published: 4 January 2022
Abstract:
The frequency of SARS-CoV-2 breakthrough infections in fully vaccinated individuals increased with the emergence of the Delta variant, particularly with longer time from vaccine completion. However, whether breakthrough infections lead to onward transmission remains unclear. Here, we conducted a study involving 125 patients comprised of 72 vaccinated and 53 unvaccinated individuals, to assess the levels of infectious virus in vaccinated and unvaccinated individuals. Quantitative plaque assays showed no significant differences in the titers of virus between these cohorts. However, the proportion of nasopharyngeal samples with culturable virus was lower in the vaccinated patients relative to unvaccinated patients (21% vs. 40%). Finally, time-to-event analysis with Kaplan-Myer curves revealed that protection from culturable infectious virus waned significantly starting at 5 months after completing a 2-dose regimen of mRNA vaccines. These results have important implications in timing of booster dose to prevent onward transmission from breakthrough cases.
Yongliang Zhao, Wenjia Ni, Simeng Liang, Lianghui Dong, Min Xiang, Zeng Cai, Danping Niu, Qiuhan Zhang, Dehe Wang, Yucheng Zheng, et al.
Published: 23 December 2021
Abstract:
SARS-CoV-2 continued to spread globally along with different variants. Here, we systemically analyzed viral infectivity and immune-resistance of SARS-CoV-2 variants to explore the underlying rationale of viral mutagenesis. We found that the Beta variant harbors both high infectivity and strong immune resistance, while the Delta variant is the most infectious with only a mild immune-escape ability. Remarkably, the Omicron variant is even more immune-resistant than the Beta variant, but its infectivity increases only in Vero E6 cells implying a probable preference for the endocytic pathway. A comprehensive analysis revealed that SARS-CoV-2 spike protein evolved into distinct evolutionary paths of either high infectivity plus low immune resistance or low infectivity plus high immune resistance, resulting in a narrow spectrum of the current single-strain vaccine. In light of these findings and the phylogenetic analysis of 2674 SARS-CoV-2 S-protein sequences, we generated a consensus antigen (S6) taking the most frequent mutations as a pan-vaccine against heterogeneous variants. As compared to the ancestry SWT vaccine with significantly declined neutralizations to emerging variants, the S6 vaccine elicits broadly neutralizing antibodies and full protections to a wide range of variants. Our work highlights the importance and feasibility of a universal vaccine strategy to fight against antigen drift of SARS-CoV-2.
, Chantal B. F. Vogels, Inci Yildirim, Jessica E. Rothman, Peiwen Lu, Valter Monteiro, Jeff R. Gelhausen, Melissa Campbell, , Alexandra Tabachikova, et al.
Published: 18 July 2021
Abstract:
The emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination1–6. We analysed the development of anti-SARS-CoV-2 antibody and T cell responses in previously infected (recovered) or uninfected (naive) individuals that received mRNA vaccines to SARS-CoV-2. While previously infected individuals sustained higher antibody titers than uninfected individuals post-vaccination, the latter reached comparable levels of neutralization responses to the ancestral strain than previously infected individuals 7 days after the second vaccine dose. T cell activation markers measured upon spike or nucleocapsid peptide in vitro stimulation showed a progressive increase after vaccination in the time-points analysed. Comprehensive analysis of plasma neutralization using 16 authentic isolates of distinct locally circulating SARS-CoV-2 variants revealed a range of reduction in the neutralization capacity associated with specific mutations in the spike gene: lineages with E484K and N501Y/T (e.g., B.1.351 and P.1) had the greatest reduction, followed by lineages with L452R (e.g., B.1.617.2) or with E484K (without N501Y/T). While both groups retained neutralization capacity against all variants, plasma from previously infected vaccinated individuals displayed overall better neutralization capacity when compared to plasma from uninfected individuals that also received two vaccine doses, pointing to vaccine boosters as a relevant future strategy to alleviate the impact of emerging variants on antibody neutralizing activity.
Sabrina Jungnick, Bernhard Hobmaier, Lena Mautner, Mona Hoyos, Maren Haase, Armin Baiker, Heidi Lahne, Ute Eberle, Clara Wimmer, Sabrina Hepner, et al.
Abstract:
SARS-CoV-2 variants of concern (VOC) should not escape molecular surveillance. We investigated if SARS-CoV-2 rapid antigen tests (RATs) could detect B.1.1.7 and B.1.351 VOCs in certain laboratory conditions. Infectious cell culture supernatants containing B.1.1.7, B.1.351 or non-VOC SARS-CoV-2 were respectively diluted both in DMEM and saliva. Dilutions were analysed with Roche, Siemens, Abbott, nal von minden and RapiGEN RATs. While further studies with appropriate real-life clinical samples are warranted, all RATs detected B.1.1.7 and B.1.351, generally comparable to non-VOC strain.
, Connor A. Tsuchida, Jennifer R. Hamilton, Enrique Lin-Shiao, Shana L. McDevitt, Erica A. Moehle, Lea B. Witkowsky, C. Kimberly Tsui, Kathleen Pestal, Holly K. Gildea, et al.
Published: 11 December 2020
Abstract:
Commonly used RT-qPCR-based SARS-CoV-2 diagnostics require 2-3 separate reactions or rely on detection of a single viral target, adding time and cost or risk of false-negative results. Currently, no test combines detection of widely used SARS-CoV-2 E- and N-gene targets and a sample control in a single, multiplexed reaction. We developed the IGI-LuNER RT-qPCR assay using the Luna Probe Universal One-Step RT-qPCR master mix with publicly available primers and probes to detect SARS-CoV-2 N gene, E gene, and human RNase P (NER). This combined, cost-effective test can be performed in 384-well plates with detection sensitivity suitable for clinical reporting, and will aid in future sample pooling efforts, thus improving throughput of SARS-CoV-2 detection.Graphical Abstract
Wiep van der Toorn, Djin-Ye Oh, , Daniel Bourquain, Janine Michel, Eva Krause, Andreas Nitsche, on behalf of the working group on SARS-CoV-2 Diagnostics at RKI
Published: 18 November 2020
Abstract:
Summary While large-scale vaccination campaigns against SARS-CoV-2 are rolled out at the time of writing, non-pharmaceutical interventions (NPIs), including the isolation of infected individuals, and quarantine of exposed individuals remain central measures to contain the spread of SARS-CoV-2. Strategies that combine NPIs with innovative SARS-CoV-2 testing strategies may increase containment efficacy and help to shorten quarantine durations. We developed a user-friendly software-tool that implements a recently published stochastic within-host viral dynamics model that captures temporal attributes of the viral infection, such as test sensitivity, infectiousness and the occurrence of symptoms. Based on this model, the software allows to evaluate the efficacy of user-defined, arbitrary NPI and testing strategies in reducing the transmission potential in different contexts. The software thus enables decision makers to explore NPI strategies and perform hypothesis testing, e.g. with regards to the utilization of novel diagnostics or with regards to containing novel virus variants.
Committee on Data Needs to Monitor Evolution of SARS-CoV-2, Board on Health Sciences Policy, Health and Medicine Division, Board on Life Sciences, Division on Earth and Life Studies
Genomic Epidemiology Data Infrastructure Needs for SARS-CoV-2; https://doi.org/10.17226/25879

Abstract:
Download a PDF of "Genomic Epidemiology Data Infrastructure Needs for SARS-CoV-2" by the National Academies of Sciences, Engineering, and Medicine for free.
Vignesh Chidambaram, Nyan Lynn Tun, Waqas Z Haque, Marie Gilbert Majella, Ranjith Kumar Sivakumar, Amudha Kumar, Angela Ting-Wei Hsu, Izza A Ishak, Aqsha A Nur, Samuel K Ayeh, et al.
Published: 1 January 2020
SSRN Electronic Journal; https://doi.org/10.2139/ssrn.3633158

Abstract:
Background: The COVID-19 pandemic has overwhelmed the global health systems, and it is imperative to understand how to effectively triage patients. Deeper understanding of predictors of disease severity and mortality is pivotal to effectively triage patients with COVID-19 to maximize the benefit of scarce intensive care unit resources, while minimizing the potential harm of outpatient management of ill patients. Methods: We performed a systematic review and meta-analysis of observational studies, assessing factors associated with severity and mortality among laboratory confirmed COVID-19 patients. We searched PubMed, Embase and WHO database for articles up to May 8, 2020. Randomized trials were excluded. Odds ratios (with 95% CI) and risk ratios (with 95% CI) were used to determine the association between the various demographic, clinical, laboratory and radiological factors and the development of severe disease or mortality. We performed meta-regression to determine the percentage change in the occurrence of the outcomes. Heterogeneity across studies were assessed using I2 and Tau2 statistics. Findings: Among 15680 articles obtained from the literature search, 109 articles were included in the analysis. Increasing age and male gender were associated with higher mortality rates and severe disease. The risk of mortality was higher in patients presenting with dyspnea (RR 2·55, 95% CI 1·88–2·46) and hemoptysis (RR 1·62, 95%CI 1·25–2·11). Co-morbidities such as diabetes (RR 1·59, 95%CI 1·41–1·78), hypertension (RR 1·90, 95%CI 1·69–2·15), cardiovascular diseases (RR 2·27, 95% CI 1·88–2·79) and chronic obstructive pulmonary disease (RR 2·29, 95% CI 1·90–2·75) were associated with a higher risk of death. In-hospital complications such as acute respiratory distress syndrome (ARDS), sepsis, shock and acute cardiac injury had adverse outcomes, with ARDS having the highest risk ratio (RR 20·19, 95% CI 10·87–37·52). Lung consolidation on computed tomography (CT) had significant association with death (RR 2·07, 95% CI 1·35–3·16). Congestive heart failure (OR 4·76, 95% CI 1·34–16·97) had greater odds of developing severe disease. Among the radiological features, hilar lymphadenopathy (OR 8·34, 95%CI 2·57–27·08), bilateral lung involvement (OR 4·86, 95%CI 3·19–7·39) and reticular pattern (OR 5·54, 95%CI 1·24–24·67) were more frequently seen in patients with severe disease. Patients with leukocytosis, lymphopenia, elevated C-reactive protein and D-dimer levels had higher odds of severe disease and greater risk of mortality. Interpretation: Our study identified several important predictors of disease severity and mortality among patients with COVID-19. Knowledge of these predictors might help in the prioritization and management of these patients. Funding: None Declaration of Interests: The authors declare no competing interests.
Ashish Kumar, Anil Arora, Praveen Sharma, Shrihari Anil Anikhindi, Naresh Bansal, Vikas Singla, Shivam Khare, Abhishyant Srivastava
Published: 1 January 2020
SSRN Electronic Journal; https://doi.org/10.2139/ssrn.3566166

Abstract:
Background: COVID-19 is a new disease which has become a global pandemic, and is caused by a novel coronavirus, SARS-CoV-2. The disease is still not very well characterized, and factors associated with severe clinical course are not well known. Methods: The main objectives were to determine the demographic, clinical and laboratory manifestations of COVID-19 and to identify the factors associated with severe clinical course. We searched the PubMed for studies published between Jan 1, 2020 and Mar 17, 2020, and included them if they were in English language, published in full, were retrospective or prospective observational or case control study with data on clinical, laboratory and imaging features of adult patients with COVID-19 disease from single or multiple centers. Studies that included exclusively pediatric patients were excluded. The demographic, clinical and laboratory data was displayed as n (%) or mean (SD). The meta-analysis on factors associated with severe clinical course was performed using the random effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated as the effect sizes. Findings: We included 58 studies (6892 patients) for the systematic review on clinical manifestations and 21 studies (3496 patients) for meta-analysis on factors associated with severe clinical course. The mean age of patients with COVID-19 is 49.7±16.3 years with a male to female ratio of 1.2:1. Common symptoms and their frequency are: fever (83.4%), cough (60.5%), fatigue (33.8%), sputum (28.9%), dyspnea (22.1%), myalgia (20.6%), chest tightness / pain (16.3%), sore throat (13.5%), headache (11.2%), diarhhea (7.5%), nasal congestion / rhinorrhea (6.7%), nausea / vomiting (5.6%), pain abdomen (4.6%), and hemoptysis (1.7%). The comorbidities associated with COVID-19 are: hypertension (18.4%), diabetes mellitus (9.8%), cardiovascular diseases (8.8%), endocrine diseases (5.8%), gastrointestinal diseases (5%), CLD (3%), and COPD (2.8%). Among the laboratory parameters WBC was low in 27%, high in 9%, platelets were low in 22.9%, creatinine was high in 6.5%, AST was high in 25.3%, ALT was high in 22.7%, bilirubin was high in 8.8%, albumin was low 60.1%, CT chest was abnormal in 89%, CRP was high in 67.5%, LDH was high in 52%, D-dimer was high in 34.8%, CK was high in 14.4%, and procalcitonin was high in 15.4%. Factors significantly associated severe clinical course (with their ORs) are as follows: High CRP (5.78), high procalcitonin (5.45), age >60 (4.82), dyspnea (4.66), high LDH (4.59), COPD (4.37), low albumin (4.34), high D-dimer (4.03), cardiac disease (3.88), low lymphocyte count (3.22), any associated comorbidity (3.16), diabetes mellitus (3.11), high WBC count (2.67), high bilirubin level (2.55), high creatinine (2.34), high AST (2.31), hypertension (2.30), low platelets (1.78), High ALT (1.69), high CK (1.66), fever spikes ≥39°C (1.59), diarrhea (1.55), male gender (1.47), and sputum (1.35). Interpretation: Identification of these factors associated with severe COVID-19 will help the physicians working at all levels of healthcare (primary, secondary, tertiary and ICU) in determining which patients need home care, hospital care, HDU care, and ICU admission; and thus, prioritize the scarce healthcare resource use more judiciously. Many of these identified factors can also help the public at large in the current COVID-19 epidemic setting, to judge when they should seek immediate medical care.Funding Statement: None.Declaration of Interests: The authors declare no competing interests.
Paediatrics and International Child Health, Volume 41, pp 36-55; https://doi.org/10.1080/20469047.2020.1781356

Abstract:
Coronaviruses, seven of which are known to infect humans, can cause a spectrum of clinical presentations ranging from asymptomatic infection to severe illness and death. Four human coronaviruses (hCoVs)—229E, HKU1, NL63 and OC43—circulate globally, commonly infect children and typically cause mild upper respiratory tract infections. Three novel coronaviruses of zoonotic origin have emerged during the past two decades: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV) and the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. These novel coronaviruses are known to cause severe illness and death predominantly in older adults and those with underlying comorbidities. Consistent with what has been observed during the outbreaks of SARS and MERS, children with COVID-19 are more likely to be asymptomatic or to have mild-to-moderate illness, with few deaths reported in children globally thus far. Clinical symptoms and laboratory and radiological abnormalities in children have been similar to those reported in adults but are generally less severe. A rare multisystem inflammatory syndrome in children (MIS-C) which has resulted in critical illness and some deaths has recently been described. Clinical trials for therapeutics and vaccine development should include paediatric considerations. Children may play an important role in the transmission of infection and outbreak dynamics and could be a key target population for effective measures to control outbreaks. The unintended consequences of the unprecedented scale and duration of pandemic control measures for children and families around the world should be carefully examined. 2019-nCoV, 2019 novel coronavirus; ADEM, acute demyelinating encephalomyelitis; AAP, American Academy of Pediatrics; ACE-2, angiotensin-converting enzyme 2; ARDS, acute respiratory distress syndrome; BCG, bacillus Calmette–Guérin; BNP, brain natriuretic peptide; CDC, Centers for Disease Control and Prevention; CRP, C-reactive protein; CSF, cerebrospinal fluid; COVID-19, coronavirus disease 2019; CT, computed tomography; CXR, chest X-ray; DOL, day of life; hCoV, human coronavirus; ICU, intensive care unit; IL, interleukin; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; LDH, lactate dehydrogenase; MERS, Middle East respiratory syndrome; MERS-CoV, Middle East respiratory syndrome coronavirus; MEURI, monitored emergency use of unregistered and experimental interventions; MIS-C, multi-system inflammatory syndrome in children; PCR, polymerase chain reaction; PICU, paediatric intensive care unit; RNA, ribonucleic acid; RCT, randomised-controlled trial; RSV, respiratory syncytial virus; SARS, severe acute respiratory syndrome; SARS-CoV-1, severe acute respiratory syndrome coronavirus 1; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF-alpha, tumour necrosis factor alpha; UK United Kingdom; UNICEF, United Nations Children’s Fund; USA, United States of America; WHO, World Health Organization
Justin Coyle, Efehi Igbinomwanhia, , Sorin Danciu, Chae Chu, Nishit Shah
Published: 3 May 2020
JACC: Case Reports, Volume 2, pp 1331-1336; https://doi.org/10.1016/j.jaccas.2020.04.025

The publisher has not yet granted permission to display this abstract.
, Rebecca Rockett, , Hossinur Rahman, , James Hadfield, Matthew Storey, Xiaoyun Ren, Rachel Tulloch, , et al.
Published: 1 January 2020
Virus Evolution, Volume 6; https://doi.org/10.1093/ve/veaa027

Abstract:
The SARS-CoV-2 epidemic has rapidly spread outside China with major outbreaks occurring in Italy, South Korea, and Iran. Phylogenetic analyses of whole-genome sequencing data identified a distinct SARS-CoV-2 clade linked to travellers returning from Iran to Australia and New Zealand. This study highlights potential viral diversity driving the epidemic in Iran, and underscores the power of rapid genome sequencing and public data sharing to improve the detection and management of emerging infectious diseases.
Published: 25 February 2020
by MDPI
Viruses, Volume 12; https://doi.org/10.3390/v12030254

Abstract:
The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the 120 available SARS-CoV-2 sequences (as of 21 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.
Published: 10 February 2020
by MDPI
Viruses, Volume 12; https://doi.org/10.3390/v12020194

Abstract:
In early December 2019 a cluster of cases of pneumonia of unknown cause was identified in Wuhan, a city of 11 million persons in the People’s Republic of China. Further investigation revealed these cases to result from infection with a newly identified coronavirus, initially termed 2019-nCoV and subsequently SARS-CoV-2. The infection moved rapidly through China, spread to Thailand and Japan, extended into adjacent countries through infected persons travelling by air, eventually reaching multiple countries and continents. Similar to such other coronaviruses as those causing the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), the new coronavirus was reported to spread via natural aerosols from human-to-human. In the early stages of this epidemic the case fatality rate is estimated to be approximately 2%, with the majority of deaths occurring in special populations. Unfortunately, there is limited experience with coronavirus infections during pregnancy, and it now appears certain that pregnant women have become infected during the present 2019-nCoV epidemic. In order to assess the potential of the Wuhan 2019-nCoV to cause maternal, fetal and neonatal morbidity and other poor obstetrical outcomes, this communication reviews the published data addressing the epidemiological and clinical effects of SARS, MERS, and other coronavirus infections on pregnant women and their infants. Recommendations are also made for the consideration of pregnant women in the design, clinical trials, and implementation of future 2019-nCoV vaccines.
, Anil Arora, Praveen Sharma, Shrihari Anil Anikhindi, Naresh Bansal, Vikas Singla, Shivam Khare, Abhishyant Srivastava
Indian Journal of Gastroenterology, Volume 39, pp 268-284; https://doi.org/10.1007/s12664-020-01058-3

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Update
Kumari G. Lokugamage, , Maren de Vries, Ana M. Valero-Jimenez, Craig Schindewolf, , Ricardo Rajsbaum,
Journal of Virology, Volume 94; https://doi.org/10.1128/jvi.01410-20

Abstract:
With the ongoing outbreak of COVID-19, differences between SARS-CoV-2 and the original SARS-CoV could be leveraged to inform disease progression and eventual treatment options. In addition, these findings could have key implications for animal model development as well as further research into how SARS-CoV-2 modulates the type I IFN response early during infection.
, Monique Coetzee, Gustav Schellack, Michelle Gijzelaar, Zeenat Hassim, Marnus Milne, , , Nirasha Singh, Sonya Kolman, et al.
Southern African Journal of Infectious Diseases, Volume 35; https://doi.org/10.4102/sajid.v35i1.206

Abstract:
Since the outbreak of COVID-19, and its declaration as a pandemic by the World Health Organization (WHO), the reliance on pharmacists as one of the first points of contact within the healthcare system has been highlighted. This evidence-based review is aimed at providing guidance for pharmacists in community, hospital and other settings in South Africa, on the management of patients with suspected or confirmed coronavirus disease 2019, or COVID-19. The situation is rapidly evolving, and new evidence continues to emerge on a daily basis. This guidance document takes into account and includes newly available evidence and recommendations, particularly around the following aspects relating to COVID-19:EpidemiologyThe virus, its modes of transmission and incubation periodSymptom identification, including the differentiation between influenza, allergic rhinitis, sinusitis and COVID-19Social media myths and misinformationTreatment guidelines and medicines that may need to be kept in stockTreatment and prevention options, including an update on vaccine developmentThe case for and against the use of NSAIDs, ACE-inhibitors and angiotensin receptor blockers (ARBs) in patients with COVID-19Interventions and patient counselling by the pharmacist.It is critical, though, that pharmacists access the most recent and authoritative information to guide their practice. Key websites that can be relied upon are:World Health Organization (WHO): https://www.who.int/emergencies/diseases/novel-coronavirus-2019National Institute for Communicable Diseases (NICD): https://www.nicd.ac.za/diseases-a-z-index/covid-19/National Department of Health (NDoH): http://www.health.gov.za/index.php/outbreaks/145-corona-virus-outbreak/465-corona-virus-outbreak; https://sacoronavirus.co.za/
Manasi P Jogalekar, Anurag Veerabathini,
Experimental Biology and Medicine, Volume 245, pp 964-969; https://doi.org/10.1177/1535370220920540

Abstract:
Novel 2019 coronavirus has created havoc across the globe since its emergence in December 2019 in Wuhan, China, and fast spreading potential. While we were able to identify the causative agent within a few days of the disease outbreak, several questions still remain unanswered. In this review, we discuss the extent of virus spread, current statistics, SARS-CoV-2 genome organization, comparison between the novel coronavirus and causative agents involved in previous outbreaks, ongoing clinical trials and myths associated with the virus. Lastly, we provide insights into the future perspectives which could prove useful for the scientific community as they work on finding the cure against the disease. Impact statement Early availability of the sequence, the genetic material of SARS-CoV-2 (the virus that causes COVID-19), has prompted efforts towards identifying a safe and effective vaccine in the current public health emergency. To that end, understanding the pathophysiology of disease is crucial for scientists around the world. Since conventional vaccine development and manufacturing may take several years, it is important to think about alternative strategies that we could use to mitigate imminent catastrophe. We hope that this article will open up new avenues and provide insights that could potentially save hundreds of lives affected by COVID-19.
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