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, , , Gabriel W. Hassler, Chaney C. Kalinich, , , Houriiyah Tegally, , , et al.
Published: 16 November 2022
Nature Communications, Volume 13, pp 1-13; https://doi.org/10.1038/s41467-022-33713-y

Abstract:
Genomic sequencing is essential to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments, vaccines, and guide public health responses. To investigate the global SARS-CoV-2 genomic surveillance, we used sequences shared via GISAID to estimate the impact of sequencing intensity and turnaround times on variant detection in 189 countries. In the first two years of the pandemic, 78% of high-income countries sequenced >0.5% of their COVID-19 cases, while 42% of low- and middle-income countries reached that mark. Around 25% of the genomes from high income countries were submitted within 21 days, a pattern observed in 5% of the genomes from low- and middle-income countries. We found that sequencing around 0.5% of the cases, with a turnaround time <21 days, could provide a benchmark for SARS-CoV-2 genomic surveillance. Socioeconomic inequalities undermine the global pandemic preparedness, and efforts must be made to support low- and middle-income countries improve their local sequencing capacity.
New version
, Verity Hill, Oliver G. Pybus, Alexander Watts, , Kamran Khan, Jane P. Messina, Houriiyah Tegally, , Jennifer Giandhari, et al.
Published: 17 September 2021
Wellcome Open Research, Volume 6; https://doi.org/10.12688/wellcomeopenres.16661.2

Abstract:
Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.
Covid-19 Host Genetics Initiative, Gita A. Pathak, Juha Karjalainen, Christine Stevens, Benjamin M. Neale, Mark Daly, , Shea J. Andrews, Masahiro Kanai, Mattia Cordioli, et al.
Published: 3 August 2022
Journal: Nature
, David Ellinghaus, , Jon Lerga-Jaso, Mareike Wendorff, Douglas Maya-Miles, Florian Uellendahl-Werth, Hesham ElAbd, , Jatin Arora, et al.
Published: 23 July 2021
Abstract:
Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a highly pleiotropic ∼0.9-Mb inversion polymorphism and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.
Isabella Ferreira, Rawlings Datir, Guido Papa, Steven Kemp, Bo Meng, Partha Rakshit, Sujeet Singh, Rajesh Pandey, Kalaiarasan Ponnusamy, Venkatraman Srinivasan Radhakrishnan, et al.
Published: 9 May 2021
Abstract:
The SARS-CoV-2 B.1.617.2 (Delta) variant was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha). In vitro, B.1.617.2 is 6-fold less sensitive to serum neutralising antibodies from recovered individuals, and 8-fold less sensitive to vaccine-elicited antibodies as compared to wild type Wuhan-1 bearing D614G. Serum neutralising titres against B.1.617.2 were lower in ChAdOx-1 versus BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies against the receptor binding domain (RBD) and N-terminal domain (NTD), in particular to the clinically approved bamlavinimab and imdevimab monoclonal antibodies. B.1.617.2 demonstrated higher replication efficiency in both airway organoid and human airway epithelial systems as compared to B.1.1.7, associated with B.1.617.2 spike being in a predominantly cleaved state compared to B.1.1.7. Additionally we observed that B.1.617.2 had higher replication and spike mediated entry as compared to B.1.617.1, potentially explaining B.1.617.2 dominance. In an analysis of over 130 SARS-CoV-2 infected healthcare workers across three centres in India during a period of mixed lineage circulation, we observed substantially reduced ChAdOx-1 vaccine efficacy against B.1.617.2 relative to non-B.1.617.2. Compromised vaccine efficacy against the highly fit and immune evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.
, Philippe Lesprit, Benoit Visseaux, Tiffany Pascreau, Emilie Jolly, Nadira Houhou, Laurence Mazaux, Marianne Asso-Bonnet, Marc Vasse, Sars-Cov-2 Foch Hospital study group
Abstract:
Several commercial assays for SARS-CoV-2 RT-PCR are available but few of them were assessed. We evaluate the Allplex 2019-nCoV (Seegene) assay using 41 nasopharyngeal samples. The rates of agreement were 92.7% and 100% with the GeneFinder COVID-19 plus (Elitech) and the diagnosis of the infectious disease specialist respectively. Four samples display a Ct < 22.0 for the E and RdRp genes while the N gene was not detected, suggesting a variability of the viral sequence. There was no cross-reactivity with other respiratory viruses. The Allplex 2019-nCoV appears as a reliable method, but additional evaluations using more samples are needed. RT-PCR assays should probably include at least 2 viral targets.
, Mlcochova P, Kemp Sa, Dhar Ms, Papa G, Meng B, Ferreira Iatm, Datir R, Collier DA, Albecka A, et al.
Published: 1 December 2021
Abstract:
The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era. © 2021. The Author(s).
Petra Mlcochova, Steven A. Kemp, Mahesh Shanker Dhar, Guido Papa, Bo Meng, Isabella A. T. M. Ferreira, Rawlings Datir, Dami A. Collier, Anna Albecka, Sujeet Singh, et al.
Published: 6 September 2021
Journal: Nature
Nature, Volume 599, pp 114-119; https://doi.org/10.1038/s41586-021-03944-y

Abstract:
The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.
, Faustinos Tatenda Takawira, , Muchaneta Gudza-Mugabe, , Manes Munyanyi, , Andrew Tarupiwa, Hlanai Gumbo, Agnes Juru, et al.
Published: 6 January 2021
Abstract:
Zimbabwe reported its first case of SARS-Cov-2 infection in March 2020, and case numbers increased to more than 8,099 to 16th October 2020. An understanding of the SARS-Cov-2 outbreak in Zimbabwe will assist in the implementation of effective public health interventions to control transmission. Nasopharyngeal samples from 92,299 suspected and confirmed COVID-19 cases reported in Zimbabwe between 20 March and 16 October 2020 were obtained. Available demographic data associated with those cases identified as positive (8,099) were analysed to describe the national breakdown of positive cases over time in more detail (geographical location, sex, age and travel history). The whole genome sequence (WGS) of one hundred SARS-CoV-2-positive samples from the first 120 days of the epidemic in Zimbabwe was determined to identify their relationship to one another and WGS from global samples. Overall, a greater proportion of infections were in males (55.5%) than females (44.85%), although in older age groups more females were affected than males. Most COVID-19 cases (57 %) were in the 20-40 age group. Eight lineages, from at least 25 separate introductions into the region were found using comparative genomics. Of these, 95% had the D614G mutation on the spike protein which was associated with higher transmissibility than the ancestral strain. Early introductions and spread of SARS-CoV-2 were predominantly associated with genomes common in Europe and the United States of America (USA), and few common in Asia at this time. As the pandemic evolved, travel-associated cases from South Africa and other neighbouring countries were also recorded. Transmission within quarantine centres occurred when travelling nationals returning to Zimbabwe. International and regional migration followed by local transmission were identified as accounting for the development of the SARS-CoV-2 epidemic in Zimbabwe. Based on this, rapid implementation of public health interventions are critical to reduce local transmission of SARS-CoV-2. Impact of the predominant G614 strain on severity of symptoms in COVID-19 cases needs further investigation.
Paola Stefanelli, Filippo Trentini, Daniele Petrone, Alessia Mammone, Luigina Ambrosio, Mattia Manica, Giorgio Guzzetta, Valeria D'Andrea, Valentina Marziano, Agnese Zardini, et al.
Abstract:
Background: The SARS-CoV-2 variant of concern Omicron was first detected in Italy in November 2021. Aim: To comprehensively describe Omicron spread in Italy in the 2 subsequent months and its impact on the overall SARS-CoV-2 circulation at population level. Methods: We analyse data from four genomic surveys conducted across the country between December 2021 and January 2022. Combining genomic sequencing results with epidemiological records collated by the National Integrated Surveillance System, the Omicron reproductive number and exponential growth rate are estimated, as well as SARS-CoV-2 transmissibility. Results: Omicron became dominant in Italy less than 1 month after its first detection, representing on 3 January 76.9–80.2% of notified SARS-CoV-2 infections, with a doubling time of 2.7–3.3 days. As of 17 January 2022, Delta variant represented < 6% of cases. During the Omicron expansion in December 2021, the estimated mean net reproduction numbers respectively rose from 1.15 to a maximum of 1.83 for symptomatic cases and from 1.14 to 1.36 for hospitalised cases, while remaining relatively stable, between 0.93 and 1.21, for cases needing intensive care. Despite a reduction in relative proportion, Delta infections increased in absolute terms throughout December contributing to an increase in hospitalisations. A significant reproduction numbers’ decline was found after mid-January, with average estimates dropping below 1 between 10 and 16 January 2022. Conclusion: Estimates suggest a marked growth advantage of Omicron compared with Delta variant, but lower disease severity at population level possibly due to residual immunity against severe outcomes acquired from vaccination and prior infection.
, Peter Berlit, Hans-Christoph Diener, Christian Gerloff, Andreas Greinacher, , Gabor C. Petzold, Marco Piccininni Msc, , Rainer Röhrig, et al.
Published: 19 July 2021
by Wiley
Annals of Neurology, Volume 90, pp 627-639; https://doi.org/10.1002/ana.26172

Abstract:
Objective We aimed to estimate the incidence of cerebral sinus and venous thrombosis (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 0.55 (95% CI, 0.38-0.78) per 100,000 person-months (which corresponds to a risk of CVT within the first 31 days of 0.55 per 100,000 individuals) for all vaccines and 1.52 (1.00-2.21) 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. Interpretation Given an incidence of 0.02–0.15 per 100,000 person-months for CVT in the general population, these findings point towards a higher risk for CVT after ChAdOx1 vaccination, especially for women.
Covid-19 National Incident Room Surveillance Team
Published: 12 March 2021
Communicable Diseases Intelligence, Volume 45

Covid-19 National Incident Room Surveillance Team
Published: 29 June 2020
Communicable Diseases Intelligence, Volume 44

Abstract:
Notified cases of COVID-19 and associated deaths reported to the National Notifiable Diseases Surveillance System (NNDSS) to 21 June 2020. Confirmed cases in Australia notified up to 7 June 2020: notifications = 7,491; deaths = 102. The incidence of COVID-19 has markedly reduced since a peak in mid-March. A combination of early case identification, physical distancing, public health measures and a reduction in international travel have been effective in slowing the spread of disease in Australia. Of the 215 cases notified between 8 and 21 June, 75% (163 cases) were notified from Victoria. Most of these cases were acquired locally. In contrast, cases notified from other states (NSW, Qld and WA) over this period were mostly overseas-acquired. Of locally-acquired cases in Victoria in this period, 51% were associated with contacts of a confirmed case or in a known outbreak, while 49% were unable to be linked to another case or were under investigation at the time of reporting. There are several clusters across a range of settings, including extended families, hotel quarantine facilities and a retail store, with most cases limited in geographic spread to a number of Local Government Areas around Melbourne. In response, the Victorian Government has re-introduced restrictions for household and outdoor gatherings, has delayed plans to ease other restrictions and has implemented enhanced public health response activities, particularly with regard to testing and contact tracing. A small proportion of overall cases have experienced severe disease, requiring hospitalisation or intensive care, with some fatalities. The crude case fatality rate amongst Australian cases is 1.4%. People who are older and have one or more comorbidities are more likely to experience severe disease. The highest rate of COVID-19 continues to be among people aged 65-79 years. Three-quarters of all cases in this age group have been associated with overseas travel, including several outbreaks linked to cruise ships. The lowest rate of disease is in children under 18 years, a pattern reflected in international reports. Internationally, as of 21 June 2020, the largest numbers of both cases and deaths have been reported in the United States. Of the confirmed cases reported globally, the case fatality rate is approximately 5.3%. Other countries in the Americas region, such as Brazil and Chile, are seeing rapid growth in case numbers. Case numbers in Europe remain relatively steady, while there is significant growth in the South East Asia region, including in India and Bangladesh. Reported cases are increasing in Africa, although the numbers are much smaller. In the Pacific region there are few new cases reported daily.
Covid-19 National Incident Room Surveillance Team
Published: 4 March 2020
Communicable Diseases Intelligence, Volume 44

Abstract:
This is the fifth epidemiological report for coronavirus disease 2019 (COVID-19), reported in Australia as at 19:00 Australian Eastern Daylight Time [AEDT] 29 February 2020. It includes data on COVID-19 cases diagnosed in Australia, the international situation and a review of current evidence.
Covid-19 National Incident Room Surveillance Team
Published: 20 February 2020
Communicable Diseases Intelligence, Volume 44

Abstract:
This is the third epidemiological report for coronavirus disease 2019 (COVID-19), previously known as novel coronavirus (2019-nCoV), from the virus now known as SARS-CoV-2, reported in Australia as at 19:00 Australian Eastern Daylight Time [AEDT] 15 February 2020. It includes data on the COVID-19 Australian cases, the international situation and current information on the severity, transmission and spread.
Covid-19 National Incident Room Surveillance Team
Published: 9 April 2021
Communicable Diseases Intelligence, Volume 45

Covid-19 National Incident Room Surveillance Team
Published: 17 April 2020
Communicable Diseases Intelligence, Volume 44

Abstract:
Confirmed cases in Australia notified up to 12 April 2020: notifications = 6,394; deaths = 46. The reduction in international travel and domestic movement, social distancing measures and public health action have likely slowed the spread of the disease. Notifications in Australia remain predominantly among people with recent overseas travel, with some locally-acquired cases being detected. Most locally-acquired cases are able to be linked back to a confirmed case, with a small portion unable to be epidemiologically linked. The distribution of overseas-acquired cases to locally acquired cases varies by jurisdiction. Internationally, cases continue to increase. The rates of increase have started to slow in several regions, although it is too soon to tell whether this trend will be sustained. The epidemiology differs from country to country depending not only on the disease, but also on differences in case detection, testing and implemented public health measures.
, Mario Ruiz‐Bastián, Beatriz Díaz‐Pollán, Emilio Maseda, Julio García‐Rodríguez, SARS‐CoV‐2 Working Group
Published: 4 August 2020
by Wiley
Journal: Mycoses
Mycoses, Volume 63, pp 1144-1148; https://doi.org/10.1111/myc.13155

Abstract:
Background Invasive pulmonary aspergillosis (IPA) is a complication of respiratory bacterial and viral infections such as coronavirus disease 2019 (COVID‐19). Patients/Methods In University Hospital La Paz (Madrid, Spain), we reviewed the clinical and demographic characteristics of 10 patients with positive severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) PCR and Aspergillus spp. isolate in respiratory samples. We also recovered results of galactomannan tests in serum and/or bronchoalveolar lavage (BAL) samples. Results Eight male and two female from 51 to 76 years were recovered. They had reported risk factors to develop IPA (hematological malignancies, immunosuppression, diabetes, obesity, intensive care unit stay, among others). Azole susceptible Aspergillus fumigatus was isolated in nine patients and Aspergillus nidulans was isolated in one patient. Only one case was classified as probable aspergillosis, seven cases as putative aspergillosis, and two cases were not classifiable. Eight patients received antifungal treatment. Seven patients died (70%), two are still inpatient due to nosocomial infections and one was discharged referred to another institution. Conclusions This clinical entity has high mortality and therefore it should be performed surveillance with early galactomannan tests and cultures in respiratory samples in order to improve the outcome of the patients with this condition.
Michael Gottlieb, Ralph C Wang, Huihui Yu, Erica S Spatz, Juan Carlos C Montoy, Robert M Rodriguez, Anna Marie Chang, Joann G Elmore, Paavali A Hannikainen, Mandy Hill, et al.
Published: 27 January 2023
Clinical Infectious Diseases; https://doi.org/10.1093/cid/ciad045

Abstract:
Background: Most research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants focuses on initial symptomatology with limited longer-term data. We characterized prevalences of prolonged symptoms 3 months post–SARS-CoV-2 infection across 3 variant time-periods (pre-Delta, Delta, and Omicron). Methods: This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, organ system–based symptoms, and ≥3 symptoms across variants among participants with a positive (“COVID-positive”) or negative SARS-CoV-2 test (“COVID-negative”) at 3 months after SARS-CoV-2 testing. Variant periods were defined by dates with ≥50% dominant strain. We performed multivariable logistic regression modeling to estimate independent effects of variants adjusting for sociodemographics, baseline health, and vaccine status. Results: The study included 2402 COVID-positive and 821 COVID-negative participants. Among COVID-positives, 463 (19.3%) were pre-Delta, 1198 (49.9%) Delta, and 741 (30.8%) Omicron. The pre-Delta COVID-positive cohort exhibited more prolonged severe fatigue (16.7% vs 11.5% vs 12.3%; P = .017) and presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; P < .001) compared with the Delta and Omicron cohorts. No differences were seen in the COVID-negatives across time-periods. In multivariable models adjusted for vaccination, severe fatigue and odds of having ≥3 symptoms were no longer significant across variants. Conclusions: Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during pre-Delta than with Delta and Omicron; however, these differences were no longer significant after adjusting for vaccination status, suggesting a beneficial effect of vaccination on risk of long-term symptoms. Clinical Trials Registration. NCT04610515.
Published: 29 March 2022
by MDPI
Journal: Vaccines
Abstract:
Individuals with Down syndrome (DS) are among the groups with the highest risk for severe COVID-19. Better understanding of the efficacy and risks of COVID-19 vaccines for individuals with DS may help improve uptake of vaccination. The T21RS COVID-19 Initiative launched an international survey to obtain information on safety and efficacy of COVID-19 vaccines for individuals with DS. De-identified survey data collected between March and December 2021 were analyzed. Of 2172 individuals with DS, 1973 (91%) had received at least one vaccine dose (57% BNT162b2), 107 (5%) were unvaccinated by choice, and 92 (4%) were unvaccinated for other reasons. Most participants had either no side effects (54%) or mild ones such as pain at the injection site (29%), fatigue (12%), and fever (7%). Severe side effects occurred in <0.5% of participants. About 1% of the vaccinated individuals with DS contracted COVID-19 after vaccination, and all recovered. Individuals with DS who were unvaccinated by choice were more likely to be younger, previously recovered from COVID-19, and also unvaccinated against other recommended vaccines. COVID-19 vaccines have been shown to be safe for individuals with DS and effective in terms of resulting in minimal breakthrough infections and milder disease outcomes among fully vaccinated individuals with DS.
Andrea Pilotto, Stefano Masciocchi, Irene Volonghi, Massimo Crabbio, Eugenio Magni, Valeria De Giuli, Francesca Caprioli, Nicola Rifino, Maria Sessa, Michele Gennuso, et al.
Published: 28 September 2020
The Journal of Infectious Diseases, Volume 223, pp 28-37; https://doi.org/10.1093/infdis/jiaa609

Abstract:
Background: Several preclinical and clinical investigations have argued for nervous system involvement in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some sparse case reports have described various forms of encephalitis in coronavirus disease 2019 (COVID-19) disease, but very few data have focused on clinical presentations, clinical course, response to treatment, and outcomes. Methods: The SARS-CoV-2 related encephalopaties (ENCOVID) multicenter study included patients with encephalitis with full infectious screening, cerebrospinal fluid (CSF), electroencephalography (EEG), and magnetic resonance imaging (MRI) data and confirmed SARS-CoV-2 infection recruited from 13 centers in northern Italy. Clinical presentation and laboratory markers, severity of COVID-19 disease, response to treatment, and outcomes were recorded. Results: Twenty-five cases of encephalitis positive for SARS-CoV-2 infection were included. CSF showed hyperproteinorrachia and/or pleocytosis in 68% of cases whereas SARS-CoV-2 RNA by reverse-transcription polymerase chain reaction resulted negative. Based on MRI, cases were classified as acute demyelinating encephalomyelitis (ADEM; n = 3), limbic encephalitis (LE; n = 2), encephalitis with normal imaging (n = 13), and encephalitis with MRI alterations (n = 7). ADEM and LE cases showed a delayed onset compared to the other encephalitis cases (P = .001) and were associated with previous, more severe COVID-19 respiratory involvement. Patients with MRI alterations exhibited worse response to treatment and final outcomes compared to those with other encephalitis. Conclusions: SARS-CoV-2 infection is associated with a wide spectrum of encephalitis characterized by different clinical presentation, response to treatment, and outcomes.
, Ute Eberle, Durdica Marosevic, Bernhard Liebl, Nikolaus Ackermann, Katharina Katz, , Bavarian SARS-CoV-2-Group
Epidemiology and Infection, Volume 149, pp 1-16; https://doi.org/10.1017/s0950268821001345

Abstract:
We assessed severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) diagnostic sensitivity and cycle threshold (Ct) values relative to symptom onset in symptomatic coronavirus disease-2019 (COVID-19) patients from Bavaria, Germany, of whom a subset was repeatedly tested. Locally weighted scatterplot smoothing method was used to assess the relationship between symptom onset and Ct-values. Kaplan−Meier plots were used to visualise the empirical probability of detecting viral ribonucleic acid (RNA) over time and estimate the time until clearance of viral RNA among the repeatedly tested patients. Among 721 reported COVID-19 cases, the viral RNA was detected in specimens taken between three days before and up to 48 days after symptom onset. The mean Ct-value was 28.6 (95% confidence interval (CI) 28.2–29.0) with the lowest mean Ct-value (26.2) observed two days after symptom onset. Up to 7 days after symptom onset, the diagnostic sensitivity of the RT-PCR among repeatedly sampled patients (n = 208) remained above 90% and decreased to 50% at day 12 (95% CI 10.5–21.5). Our data provide valuable estimates to optimise the timing of sampling of individuals for SARS-CoV-2 detection. A considerable proportion of specimens sampled before symptom onset had Ct-values comparable with Ct-values after symptom onset, suggesting the probability of presymptomatic transmission.
, Ruth R Hagen, Jet Van Den Dijssel, Lisan H Kuijper, Christine Kreher, , Laura Yl Kummer, Maurice Steenhuis, Mariel Duurland, Rivka de Jongh, et al.
Published: 15 July 2022
Journal: Elife
Abstract:
Patients affected by different types of autoimmune diseases, including common conditions such as multiple sclerosis (MS) and rheumatoid arthritis (RA), are often treated with immunosuppressants to suppress disease activity. It is not fully understood how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific humoral and cellular immunity induced by infection and/or upon vaccination is affected by immunosuppressants.
Marissa K Hetrich, Jennifer Oliva, Kimberli Wanionek, Maria Deloria Knoll, Matthew Lamore, Ignacio Esteban, Vic Veguilla, Fatimah S Dawood, Ruth A Karron, Christine Council-DiBitetto, et al.
Published: 12 December 2022
Clinical Infectious Diseases; https://doi.org/10.1093/cid/ciac942

Abstract:
Background: During the coronavirus disease 2019 (COVID-19) pandemic, human parainfluenza type 3 (HPIV-3) and respiratory syncytial virus (RSV) circulation increased as nonpharmaceutical interventions were relaxed. Using data from 175 households (n = 690 members) followed between November 2020 and October 2021, we characterized HPIV-3 and RSV epidemiology in children aged 0–4 years and their households. Methods: Households with ≥1 child aged 0–4 years were enrolled; members collected weekly nasal swabs (NS) and additional NS with respiratory illnesses (RI). We tested NS from RI episodes in children aged 0–4 years for HPIV-3, RSV, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using reverse-transcriptase polymerase chain reaction (RT-PCR). Among children with HPIV-3 or RSV infection, we tested contemporaneous NS from household members. We compared incidence rates (IRs) of RI with each virus during epidemic periods and identified household primary cases (the earliest detected household infection), and associated community exposures. Results: 41 of 175 (23.4%) households had individuals with HPIV-3 (n = 45) or RSV (n = 46) infections. Among children aged 0–4 years, RI IRs /1000 person-weeks were 8.7 [6.0, 12.2] for HPIV-3, 7.6 [4.8, 11.4] for RSV, and 1.9 [1.0, 3.5] for SARS-CoV-2. Children aged 0-4 years accounted for 35 of 36 primary HPIV-3 or RSV cases. Children attending childcare or preschool had higher odds of primary infection (odds ratio, 10.81; 95% confidence interval, 3.14–37.23). Conclusions: Among children aged 0–4 years, RI IRs for HPIV-3 and RSV infection were 4-fold higher than for SARS-CoV-2 during epidemic periods. HPIV-3 and RSV were almost exclusively introduced into households by young children.
, Ioanna Magaziotou, Xanthi Dedoukou, Eirini Eleftheriou, Vasilios Raftopoulos, , Athanasia Lourida, Maria Panopoulou, Konstantinos Stamoulis, Vasiliki Papaevangelou, et al.
The Pediatric Infectious Disease Journal, Volume 39; https://doi.org/10.1097/inf.0000000000002899

Abstract:
Background: There is limited information on severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection in children. Methods: We retrieved data from the national database on SARS-CoV-2 infections. We studied in-family transmission. The level of viral load was categorized as high, moderate, or low based on the cycle threshold values. Results: We studied 203 SARS-CoV-2-infected children (median age: 11 years; range: 6 days to 18.4 years); 111 (54.7%) had an asymptomatic infection. Among the 92 children (45.3%) with coronavirus disease 2019 (COVID-19), 24 (26.1%) were hospitalized. Infants <1 year were more likely to develop COVID-19 (19.5% of all COVID-19 cases) (P-value = 0.001). There was no significant difference between viral load and age, sex, underlying condition, fever and hospitalization, as well as between type of SARS-CoV-2 infection and age, sex, underlying condition and viral load. Transmission from a household member accounted for 132 of 178 (74.2%) children for whom the source of infection was identified. An adult member with COVID-19 was the first case in 125 (66.8%) family clusters. Child-to-adult transmission was found in one occasion only. Conclusions: SARS-CoV-2 infection is mainly asymptomatic or mild during childhood. Adults appear to play a key role in spread of the virus in families. Most children have moderate or high viral loads regardless of age, symptoms or severity of infection. Further studies are needed to elucidate the role of children in the ongoing pandemic and particularly in light of schools reopening and the need to prioritize groups for vaccination, when COVID-19 vaccines will be available.
Published: 9 March 2021
JMIR Formative Research, Volume 5; https://doi.org/10.2196/27107

Abstract:
Background The COVID-19 pandemic has affected the response capacity of the health care workforce, and health care professionals have been experiencing acute stress reactions since the beginning of the pandemic. In Spain, the first wave was particularly severe among the population and health care professionals, many of whom were infected. These professionals required initial psychological supports that were gradual and in line with their conditions. Objective In the early days of the pandemic in Spain (March 2020), this study aimed to design and validate a scale to measure acute stress experienced by the health care workforce during the care of patients with COVID-19: the Self-applied Acute Stress Scale (EASE). Methods Item development, scale development, and scale evaluation were considered. Qualitative research was conducted to produce the initial pool of items, assure their legibility, and assess the validity of the content. Internal consistency was calculated using Cronbach α and McDonald ω. Confirmatory factor analysis and the Mann-Whitney-Wilcoxon test were used to assess construct validity. Linear regression was applied to assess criterion validity. Back-translation methodology was used to translate the scale into Portuguese and English. Results A total of 228 health professionals from the Spanish public health system responded to the 10 items of the EASE scale. Internal consistency was .87 (McDonald ω). Goodness-of-fit indices confirmed a two-factor structure, explaining 55% of the variance. As expected, the highest level of stress was found among professionals working in health services where a higher number of deaths from COVID-19 occurred (P<.05). Conclusions The EASE scale was shown to have adequate metric properties regarding consistency and construct validity. The EASE scale could be used to determine the levels of acute stress among the health care workforce in order to give them proportional support according to their needs during emergency conditions, such as the COVID-19 pandemic.
Enrico Bertino, Guido Eugenio Moro, Giuseppe De Renzi, Giuseppina Viberti, Rossana Cavallo, Alessandra Coscia, Carlotta Rubino, Paola Tonetto, Stefano Sottemano, Maria Francesca Campagnoli, et al.
Published: 27 October 2020
Frontiers in Pediatrics, Volume 8; https://doi.org/10.3389/fped.2020.597699

Abstract:
Background: In the current SARS-Coronavirus-2 (SARS-CoV-2) pandemic little is known about SARS-CoV-2 in human milk. It is important to discover if breast milk is a vehicle of infection. Objective: Our aim was to look for the presence of SARS-CoV-2 RNA in the milk of a group of SARS-CoV-2 positive mothers from North-West Italy. Methods: This is a prospective collaborative observational study where samples of human milk from 14 breastfeeding mothers positive for SARS-CoV-2 were collected. A search of viral RNA in breast milk samples was performed by RT-PCR (Real-Time reverse-transcriptase-Polymerase-Chain-Reaction) methodology tested for human milk. All the newborns underwent a clinical follow up during the first month of life or until the finding of two sequential negative swabs. Results: In 13 cases the search for SARS-CoV-2 RNA in milk samples resulted negative and in one case it was positive. Thirteen of the 14 newborns were exclusively breastfed and closely monitored in the first month of life. Clinical outcome was uneventful. Four newborns tested positive for SARS-CoV-2 and were all detected in the first 48 h of life, after the onset of maternal symptoms. Also the clinical course of these 4 infants, including the one who received mother's milk positive for SARS-CoV-2, was uneventful, and all of them became SARS-CoV-2 negative within 6 weeks of life. Conclusion: Our study supports the view that SARS-CoV-2 positive mothers do not expose their newborns to an additional risk of infection by breastfeeding.
Hernan P. Zamponi, Leonardo Juarez-Aguaysol, Gabriela Kukoc, Maria Eugenia Dominguez, Belén Pini, Eduardo G Padilla, Maria Calvó, Silvia Beatriz Molina-Rangeon, Gonzalo Guerrero, Mariana Figueredo-Aguiar, et al.
Published: 31 December 2021
by Wiley
Alzheimer's & Dementia, Volume 17; https://doi.org/10.1002/alz.057897

The publisher has not yet granted permission to display this abstract.
Vivian Pan, Megan Doerr, Christin Hoell, Lauren Ryan, Deanna J. Erwin, Gillian Hooker, Carrie Haverty, The National Society of Genetic Counselors GC SARS‐CoV‐2 Impact Survey Working Group
Published: 26 July 2021
by Wiley
Journal of Genetic Counseling, Volume 30, pp 989-998; https://doi.org/10.1002/jgc4.1484

Abstract:
The Genetic Counselor SARS-CoV-2 Impact Survey (GCSIS) describes the impact of the pandemic on genetic counselors and genetic counseling services. With this information, the National Society of Genetic Counselors (NSGC) can better: (1) support advocacy and access efforts for genetic counseling services at both federal- and state-level; (2) promote effective billing and reimbursement for genetic counseling services provided via telemedicine; and (3) make decisions about how to best support genetic counselors. The survey was hosted on a novel data collection and analysis platform from LunaDNA and was open to all genetic counselors (n = 5,531 based on professional society membership). Survey response rate was approximately 3.8% (n = 212/5,531), with a demographic distribution broadly representative of the North American genetic counseling field. Genetic counselors remained largely employed, providing genetic counseling services throughout the pandemic, although almost one in five respondents (17%, n = 35/211) reported experiencing some degree of pandemic-related financial hardship. Nearly all respondents (90%, n = 104/115) transitioned, at least in part, to remote work settings, with about half (47%. n = 88/189) reporting restrictions in the care they were able to provide. These shifts came at a cost: existing gaps in Medicare status for genetic counselors and attendant reimbursement concerns led to uncertainty about whether genetic counselors' work will be reimbursed. Outside of work, caregiving responsibilities increased for 34% (n = 74/212) of respondents. The results of the GCSIS amplify the importance of federal- and state-level advocacy efforts for genetic counselors and their employers. They also highlight the impact of broader cultural intransigence on our majority-female profession. During the pandemic, genetic counselors continued to provide care, but without consistent financial support or expectation of reimbursement. The ability to attract and retain talented professionals to the genetic counseling field will hinge on the success of continued advocacy efforts.
, Linda M. Niccolai, Hassan Sheikha, Lina Elmansy, Chaney C. Kalinich, Nathan D. Grubaugh, Eugene D. Shapiro, Kendall Billig, Mallery I. Breban, Anderson Brito, et al.
Published: 1 March 2022
Abstract:
Recent estimates from the American Academy of Pediatrics show that close to 6 million children younger than 18 years have been infected with SARS-CoV-2 in the United States alone, of whom 542 have died.1 The death toll of SARS-CoV-2 in children has surpassed that recorded from influenza during any season.2
Jennifer R. Hamilton, Elizabeth C. Stahl, Connor A. Tsuchida, Enrique Lin-Shiao, C. Kimberly Tsui, , , Lea B. Witkowsky, Erica A. Moehle, Shana L. McDevitt, et al.
Published: 5 August 2021
Journal: PLOS ONE
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 nasopharyngeal swab specimens and found saliva methods require further optimization to match this gold standard. 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.
, M Asso-Bonnet, M Vasse, SARS-CoV-2 Foch Hospital study group
Abstract:
The ID NOW COVID-19 assay is a promising tool for the rapid identification of COVID-19 patients. However, its performances were questioned. We evaluate the ID NOW COVID-19 in comparison to a reference RT-PCR using a collection of 48 fresh nasopharyngeal swabs sampled on universal transport media (UTM). Only 2 false negatives of the ID NOW COVID-19 were identified. They display PCR cycle threshold values of 37.5 and 39.2. The positive percent agreement and the negative percent agreement were 94.9% and 100%, respectively. The Kappa value was 0.88. The ID NOW COVID-19 combines high-speed and accurate processing. Using UTM, the ID NOW COVID-19 could be repeated in the case of invalid result. Further analyses, such as screening of genetic variants or genome sequencing, could also be performed with the same sample. As for all tests, the results should be interpreted according to clinical and epidemiological context.
, Ahmad Al Shafie, , , , the EMEA-MESuRS working group on nosocomial SARS-CoV-2 modelling
Published: 22 December 2020
Abstract:
In response to the COVID-19 epidemic, Egypt established a unique care model based on quarantine hospitals where only externally-referred confirmed COVID-19 patients were admitted, and healthcare workers resided continuously over 1- to 2-week working shifts. While the COVID-19 risk for HCWs has been widely reported in standard healthcare settings, it has not been evaluated yet in quarantine hospitals. Here, we relied on longitudinal data, including results of routine RT-PCR tests, collected within three quarantine hospitals located in Cairo and Fayoum, Egypt. Using a model-based approach that accounts for the time-since-exposure variation in false-negative rates of RT-PCR tests, we computed the incidence of SARS-CoV-2 infection among HCWs. Over a total follow-up of 6,064 person-days (PD), we estimated an incidence rate (per 100 PD) of 1.05 (95% CrI: 0.58-1.65) at Hospital 1, 1.92 (95% CrI: 0.93-3.28) at Hospital 2 and 7.62 (95% CrI: 3.47-13.70) at Hospital 3. The probability for an HCW to be infected at the end of a shift was 13.7% (95% CrI: 7.8%-20.8%) and 23.8% (95% CrI: 12.2%-37.3%) for a 2-week shift at Hospital 1 and Hospital 2, respectively, which lies within the range of risk levels previously documented in standard healthcare settings, whereas it was >3-fold higher for a 7-day shift at Hospital 2 (42.6%, 95%CrI: 21.9%-64.4%). Our model-based estimates unveil a proportion of undiagnosed infections among HCWs of 46.4% (95% CrI: 18.8%-66.7%), 45.0% (95% CrI: 5.6%-70.8%) and 59.2% (95% CrI: 34.8%-78.8%), for Hosp1 to 3, respectively. The large variation in SARS-CoV-2 incidence we document here suggests that HCWs from quarantine hospitals may face a high occupational risk of infection, but that, with sufficient anticipation and infection control measures, this risk can be brought down to levels similar to those observed in standard healthcare settings.
Olivier Vandenberg, Pascal Mertens, Nathalie De Vos, Delphine Martiny, Christian Jassoy, Ali Mirazimi, Lize Cuypers, Sigi Van Den Wijngaert, Vanessa Monteil, Pierrette Melin, et al.
Published: 29 April 2020
Abstract:
Introduction: COVID-19 Ag Respi-Strip, an immunochromatographic (ICT) assay for the rapid detection of SARS-CoV-2 antigen on nasopharyngeal specimen, has been developed to identify positive COVID-19 patients allowing prompt clinical and quarantine decisions. In this Original Research article, we describe the conception, the analytical and clinical performances as well as the risk management of implementing the COVID-19 Ag Respi-Strip in a diagnostic decision algorithm.Materials and Methods: Development of the COVID-19 Ag Respi-Strip resulted in a ready- to-use ICT assay based on a membrane technology with colloidal gold nanoparticles using monoclonal antibodies directed against the SARS-CoV and SARS-CoV-2 highly conserved nucleoprotein antigen. Four hundred observations were recorded for the analytical performance study and thirty tests were analysed for the cross-reactivity study. The clinical performance study was performed in a retrospective multi-centric evaluation on aliquots of 328 nasopharyngeal samples. COVID-19 Ag Respi-Strip results were compared with qRT-PCR as golden standard for COVID-19 diagnostics.Results: In the analytical performance study, the reproducibility showed a between-observer disagreement of 1.7%, a robustness of 98%, an overall satisfying user friendliness and no cross-reactivity with other virus-infected nasopharyngeal samples. In the clinical performance study performed in three different clinical laboratories we found an overall sensitivity and specificity of 57.6% and 99.5% respectively with an accuracy of 82.6%. The cut-off of the assay was found at Ct<22. User-friendliness analysis and risk management assessment through Ishikawa diagram demonstrate that COVID-19 Ag Respi-Strip may be implemented in clinical laboratories according to biosafety recommendations.Conclusion: The COVID-19 Ag Respi-Strip represents a promising rapid SARS-CoV-2 antigen assay for the first-line diagnosis of COVID-19 in 15 minutes. Its role in the proposed diagnostic algorithm is complementary to the currently-used molecular techniques.
Published: 14 October 2022
by MDPI
Journal: Viruses
Viruses, Volume 14; https://doi.org/10.3390/v14102256

Abstract:
Compared to adults, severe or fatal COVID-19 disease is much less common in children. However, a higher risk for progression has been reported in infants. Different pediatric COVID-19 severity scores are reported in the literature. Methods: Subjects under 90 days of age admitted to 35 Italian institutions for COVID-19 were included. The severity of COVID-19 was scored as mild/moderate or severe/critical following the classification reported in the literature by Venturini, Dong, Kanburoglu, and Gale. To assess the diagnostic accuracy of each classification system, we stratified all enrolled patients developing a posteriori severity score based on clinical presentation and outcomes and then compared all different scores analyzed. Results: We included 216 infants below 90 days of age. The most common symptom was fever, followed by coryza, poor feeding, cough, and gastrointestinal manifestations. According to Venturini, Dong, Kanburoglu, and Gale’s severity scores, 18%, 6%, 4.2%, and 29.6% of infants presented with severe/critical disease, respectively. A correlation analysis between these four scores and the a posteriori severity score assigned to all enrolled subjects was performed, and a crescent strength of correlation from Gale (R = 0.355, p < 0.001) to Venturini (R = 0.425, p < 0.001), Dong (R = 0.734, p < 0.001), and Kanburoglu (R = 0.859, p < 0.001) was observed. Conclusions: The percentage of infants with severe COVID-19 varies widely according to the score systems. A unique clinical score should be designed for neonates and infants with COVID-19.
, Mary Claire Worrell, Sara Malone, Patrick Dawson, Brett Maricque, Jessica L. Halpin, Sooji Lee, Stephanie A. Fritz, Sarah C. Tinker, Julie A. Neidich, et al.
Published: 9 February 2022
Public Health Reports, Volume 137, pp 557-563; https://doi.org/10.1177/00333549221074395

Abstract:
Objective: Saliva specimens collected in school populations may offer a more feasible, noninvasive alternative to nasal swabs for large-scale COVID-19 testing efforts in kindergarten through 12th grade (K-12) schools. We investigated acceptance of saliva-based COVID-19 testing among quarantined K-12 students and their parents, teachers, and staff members who recently experienced a SARS-CoV-2 exposure in school. Methods: We surveyed 719 participants, in person or by telephone, who agreed to or declined a free saliva-based COVID-19 reverse-transcription polymerase chain reaction test as part of a surveillance investigation about whether they would have consented to testing if offered a nasal swab instead. We conducted this investigation in 6 school districts in Greene County (n = 3) and St. Louis County (n = 3), Missouri, from January 25 through March 23, 2021. Results: More than one-third (160 of 446) of K-12 students (or their parents or guardians), teachers, and staff members who agreed to a saliva-based COVID-19 test indicated they would have declined testing if specimen collection were by nasal swab. When stratified by school level, 51% (67 of 132) of elementary school students or their parents or guardians would not have agreed to testing if a nasal swab was offered. Conclusions: Some students, especially those in elementary school, preferred saliva-based COVID-19 testing to nasal swab testing. Use of saliva-based testing might increase voluntary participation in screening efforts in K-12 schools to help prevent the spread of SARS-CoV-2.
, Erica A. Moehle, Cara E. Brook, Andrew H. Doudna Cate, Lea B. Witkowsky, Rohan Sachdeva, Ariana Hirsh, Kerrie Barry, Jennifer R. Hamilton, Enrique Lin-Shiao, et al.
Published: 26 May 2021
Journal: PLOS ONE
Abstract:
Regular surveillance testing of asymptomatic individuals for SARS-CoV-2 has been center to 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.
Andrea Lo Vecchio, Silvia Garazzino, Andrea Smarrazzo, Elisabetta Venturini, Marco Poeta, Paola Berlese, Marco Denina, Antonella Meini, Samantha Bosis, Luisa Galli, et al.
Published: 1 January 2021
Ssrn Electronic Journal; https://doi.org/10.2139/ssrn.3844828

Abstract:
Background: Severe gastrointestinal (GI) involvement has been occasionally reported in children with SARS-CoV-2 infection or among those with multisystem inflammatory syndrome (MIS-C). We aimed to investigate the clinical, radiological and histopathological GI characteristics in order to identify factors associated with severe outcome. Methods: In this multicenter retrospective nationwide cohort study, symptomatic children with laboratory confirmed SARS-CoV-2 infection or MIS-C were enrolled. Children who received a diagnosis of acute abdomen, appendicitis, intussusception, pancreatitis, diffuse adeno-mesenteritis or abdominal fluid collections requiring surgical consultation and temporally correlated with SARS-CoV-2 infection were classified as having a severe GI involvement. Logistic regression models were used to estimate odds ratios (OR [95% confidence intervals]) between potential explanatory factors and severe outcome. Findings: 685 children were enrolled between February 2020 and January 2021. The presence of GI symptoms was associated with a higher chance of hospital admission (OR 2·64 [1·89–3·69]) and of intensive care support (OR 3·90 [1·98–7·68]). Overall, 65 children (9.5%) showed a severe GI involvement featuring atypical presentations including disseminated adeno-mesenteritis (39·6%), appendicitis (33·5%), abdominal fluid collections (21·3%), pancreatitis (6·9%) or ileal intussusception (4·6%). Twenty-seven (42%) of these children underwent surgery, and remarkably only half of clinically suspected appendicitis were histologically confirmed. Children aged 5-10 years (OR 8·33 [2·62–26·5]) or > 10 years of age (OR 6·37 [2·12-19·1]) had a higher chance of severe outcome, compared to preschool-age children. Severe GI outcomes were more frequent in patients with abdominal pain (aOR 34·5 [10·1–118]), lymphopenia (aOR 8·93 [3·03-26·3]) or MIS-C (aOR 6·28 [1·92–20·5]). Diarrhea was associated with a higher chance of adeno-mesenteritis (aOR 3·13 [1·08–9·12]) and abdominal fluid collections (aOR 3·22 [1·03-10]). Interpretation: About 10% of symptomatic children with COVID-19 may have severe GI involvement, frequently associated with MIS-C. Early identification of at-risk patients can improve the management of serious complications.Funding Information: SARS-CoV-2, gastrointestinal tract, gut, COVID-19, children, MIS-CDeclaration of Interests: All authors declare no competing interests.Ethics Approval Statement: This study was undertaken in accordance with good clinical practice guidelines and the Declaration of Helsinki. Written informed consent was obtained from parents/caregivers, and the patient if appropriate. The study protocol was approved by the Ethical Committee of the coordinating center (protocol number 0031296) as well as by independent ethics committees and/or institutional review boards of any single enrolling center.
Andrea Lo Vecchio, Silvia Garazzino, Andrea Smarrazzo, Elisabetta Venturini, Marco Poeta, Paola Berlese, Marco Denina, Antonella Meini, Samantha Bosis, Luisa Galli, et al.
Published: 1 January 2021
Ssrn Electronic Journal; https://doi.org/10.2139/ssrn.3839459

Abstract:
Background: Severe gastrointestinal (GI) involvement has been occasionally reported in children with SARS-CoV-2 infection or among those with multisystem inflammatory syndrome (MIS-C). We aimed to investigate the clinical, radiological and histopathological GI characteristics in order to identify factors associated with severe outcome.Methods: In this multicenter retrospective nationwide cohort study, symptomatic children with laboratory confirmed SARS-CoV-2 infection or MIS-C were enrolled. Children who received a diagnosis of acute abdomen, appendicitis, intussusception, pancreatitis, diffuse adeno-mesenteritis or abdominal fluid collections requiring surgical consultation and temporally correlated with SARS-CoV-2 infection were classified as having a severe GI involvement. Logistic regression models were used to estimate odds ratios (OR [95% confidence intervals]) between potential explanatory factors and severe outcome.Findings: 685 children were enrolled between February 2020 and January 2021. The presence of GI symptoms was associated with a higher chance of hospital admission (OR 2·64 [1·89–3·69]) and of intensive care support (OR 3·90 [1·98–7·68]).Overall, 65 children (9.5%) showed a severe GI involvement featuring atypical presentations including disseminated adeno-mesenteritis (39·6%), appendicitis (33·5%), abdominal fluid collections (21·3%), pancreatitis (6·9%) or ileal intussusception (4·6%). Twenty-seven (42%) of these children underwent surgery, and remarkably only half of clinically suspected appendicitis were histologically confirmed. Children aged 5-10 years (OR 8·33 [2·62–26·5]) or > 10 years of age (OR 6·37 [2·12-19·1]) had a higher chance of severe outcome, compared to preschool-age children. Severe GI outcomes were more frequent in patients with abdominal pain (aOR 34·5 [10·1–118]), lymphopenia (aOR 8·93 [3·03-26·3]) or MIS-C (aOR 6·28 [1·92–20·5]). Diarrhea was associated with a higher chance of adeno-mesenteritis (aOR 3·13 [1·08–9·12]) and abdominal fluid collections (aOR 3·22 [1·03-10]).Interpretation: About 10% of symptomatic children with COVID-19 may have severe GI involvement, frequently associated with MIS-C. Early identification of at-risk patients can improve the management of serious complications.Funding Statement: None.Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: The study protocol was approved by the Ethical Committee of the coordinating center (protocol number 0031296) as well as by independent ethics committees and/or institutional review boards of any single enrolling center.
Fernando Lázaro-Perona, , , Almudena Gutiérrez-Arroyo, , Julio García-Rodriguez, on behalf of the SARS-CoV-2 Working Group
Published: 16 February 2021
Journal: PLOS ONE
Abstract:
Background: Two automatable in-house protocols for high-troughput RNA extraction from nasopharyngeal swabs for SARS-CoV-2 detection have been evaluated.Methods: One hundred forty one SARS-CoV-2 positive samples were collected during a period of 10-days. In-house protocols were based on extraction with magnetic beads and designed to be used with either the Opentrons OT-2 (OT-2in-house) liquid handling robot or the MagMAXTMExpress-96 system (MMin-house). Both protocols were tested in parallel with a commercial kit that uses the MagMAXTMsystem (MMkit). Nucleic acid extraction efficiencies were calculated from a SARS-CoV-2 DNA positive control.Results: No significant differences were found between both in-house protocols and the commercial kit in their performance to detect positive samples. The MMkitwas the most efficient although the MMin-housepresented, in average, lower Cts than the other two. In-house protocols allowed to save between 350€ and 400€ for every 96 extracted samples compared to the commercial kit.Conclusion: The protocols described harness the use of easily available reagents and an open-source liquid handling system and are suitable for SARS-CoV-2 detection in high throughput facilities.
, Heather Snyder, María Carrillo, Akram A. Hosseini, Traolach S. Brugha, Sudha Seshadri, the CNS SARS‐CoV‐2 Consortium
Published: 5 January 2021
by Wiley
Alzheimer's & Dementia, Volume 17, pp 1056-1065; https://doi.org/10.1002/alz.12255

Abstract:
Introduction The increasing evidence of SARS‐CoV‐2 impact on the central nervous system (CNS) raises key questions on its impact for risk of later life cognitive decline, Alzheimer's disease (AD), and other dementia. Methods The Alzheimer's Association and representatives from more than 30 countries—with technical guidance from the World Health Organization—have formed an international consortium to study the short‐and long‐term consequences of SARS‐CoV‐2 on the CNS—including the underlying biology that may contribute to AD and other dementias. This consortium will link teams from around the world covering more than 22 million COVID‐19 cases to enroll two groups of individuals including people with disease, to be evaluated for follow‐up evaluations at 6, 9, and 18 months, and people who are already enrolled in existing international research studies to add additional measures and markers of their underlying biology. Conclusions The increasing evidence and understanding of SARS‐CoV‐2's impact on the CNS raises key questions on the impact for risk of later life cognitive decline, AD, and other dementia. This program of studies aims to better understand the long‐term consequences that may impact the brain, cognition, and functioning—including the underlying biology that may contribute to AD and other dementias.
, , Helena Cortes-Martins, Sílvia Duarte, Luís Vieira, , , Constantino P. Caetano, Baltazar Nunes, Regina Sá, et al.
Published: 1 January 2020
Emerging Microbes & Infections, Volume 9, pp 2488-2496; https://doi.org/10.1080/22221751.2020.1844552

Abstract:
Genomic surveillance of SARS-CoV-2 was rapidly implemented in Portugal by the National Institute of Health in collaboration with a nationwide consortium of >50 hospitals/laboratories. Here, we track the geotemporal spread of a SARS-CoV-2 variant with a mutation (D839Y) in a potential host-interacting region involving the Spike fusion peptide, which is a target motif of anti-viral drugs that plays a key role in SARS-CoV-2 infectivity. The Spike Y839 variant was most likely imported from Italy in mid-late February and massively disseminated in Portugal during the early epidemic, becoming prevalent in the Northern and Central regions of Portugal where it represented 22% and 59% of the sampled genomes, respectively, by 30 April. Based on our high sequencing sampling during the early epidemics [15.5% (1275/8251) and 6.0% (1500/24987) of all confirmed cases until the end of March and April, respectively], we estimate that, between 14 March and 9 April (covering the epidemic exponential phase) the relative frequency of the Spike Y839 variant increased at a rate of 12.1% (6.1%–18.2%, CI 95%) every three days, being potentially associated with 24.8% (20.8–29.7%, CI 95%; 3177–4542 cases, CI 95%) of all COVID-19 cases in Portugal during this period. Our data supports population/epidemiological (founder) effects contributing to the Y839 variant superspread. The potential existence of selective advantage is also discussed, although experimental validation is required. Despite huge differences in genome sampling worldwide, SARS-CoV-2 Spike D839Y has been detected in 13 countries in four continents, supporting the need for close surveillance and functional assays of Spike variants.
Gladys Virginia Guedez-López, , Patricia González-Donapetry, Ivan Bloise, Carolina Tornero-Marin, Juan González-García, , Julio García-Rodríguez, María Dolores Montero-Vega, María Pilar Romero, et al.
European Journal of Clinical Microbiology & Infectious Diseases, Volume 39, pp 2289-2297; https://doi.org/10.1007/s10096-020-04010-7

The publisher has not yet granted permission to display this abstract.
, Ahmad Al Shafie, Essam Hassan, Laura Temime, Kévin Jean, Mohamed El-Kassas, EMAE-MESuRS working group on nosocomial SARS-CoV-2 modeling
Published: 11 August 2022
Abstract:
In response to the COVID-19 epidemic, Egypt established a unique care model based on quarantine hospitals where only externally-referred confirmed COVID-19 patients were admitted, and healthcare workers resided continuously over 1- to 2-week working shifts. While the COVID-19 risk for HCWs has been widely reported in standard healthcare settings, it has not been evaluated yet in quarantine hospitals. Here, we relied on longitudinal data, including results of routine RT-PCR tests, collected within three quarantine hospitals located in Cairo and Fayoum, Egypt. Using a mathematical model accounting for the time-since-exposure variation in false-negative rates of RT-PCR tests, we computed the incidence rate of SARS-CoV-2 infection among HCWs. Our results thus unveil the proportion of infections remaining undiagnosed despite routine testing. We estimated that the risk for an HCW to be infected during a working shift lied within the range of risk levels previously documented in standard healthcare settings for two quarantine hospitals, whereas it was > 3-fold higher for the third hospital. This large variation suggests that HCWs from quarantine hospitals may face a high occupational risk of infection, but that, with sufficient infection control measures, this risk can be brought down to levels similar to those observed in standard healthcare settings.
Charles M’Poca Charles, Nafissa Bique Osman, Domingos Arijama, Benjamim Matingane, Tomás Sitoé, Darlene Kenga, Cesaltina Lorenzoni, Elvira Luís, Rodolfo De Carvalho Pacagnella, Jahit Sacarlal, et al.
Reproductive Health, Volume 19, pp 1-11; https://doi.org/10.1186/s12978-022-01469-9

Abstract:
Background: Although there is a significant increase of evidence regarding the prevalence and impact of COVID-19 on maternal and perinatal outcomes, data on the effects of the pandemic on the obstetric population in sub-Saharan African countries are still scarce. Therefore, the study aims were to assess the prevalence and impact of COVID-19 on maternal and neonatal outcomes in the obstetric population at Central Hospital of Maputo (HCM), Mozambique. Methods: Prospective cohort study conducted at teaching and referral maternity, HCM, from 20 October 2020 to 22 July 2021. We collected maternal and perinatal outcomes up to 6 weeks postpartum of eligible women (pregnant and postpartum women—up to the 14th day postpartum) screened for COVID-19 (individual test for symptomatic participants and pool testing for asymptomatic). The primary outcome was maternal death, Severe Acute Respiratory Syndrome (SARS) and Intensive Care Unit (ICU) admission. We estimated the COVID-19 prevalence and the unadjusted RR (95% CI) for maternal and perinatal outcomes. We used the chi-square or Fisher's exact test to compare categorical variables (two-sided p-value < 0.05 for statistical significance). Results: We included 239 participants. The overall prevalence of COVID-19 was 9.2% (22/239) and in the symptomatic group was 32.4% (11/34). About 50% of the participants with COVID-19 were symptomatic. Moreover, the most frequent symptoms were dyspnoea (33.3%), cough (28.6%), anosmia (23.8%), and fever (19%). Not having a partner, being pregnant, and alcohol consumption were vulnerability factors for SARS-CoV-2 infection. The risk of adverse maternal and neonatal outcomes (abortion, foetal death, preterm birth, Apgar, and NICU admission) was not significantly increased with COVID-19. Moreover, we did not observe a significant difference in the primary outcomes (SARS, ICU admission and maternal death) between COVID-19 positive and COVID-19 negative groups. Conclusion: The prevalence of COVID-19 in the obstetric population is higher than in the general population, and fifty percent of pregnant and postpartum women with COVID-19 infection are asymptomatic. Not having a partner and alcohol consumption were factors of greatest vulnerability to SARS-COV-2 infection. Moreover, being pregnant versus postpartum was associated with increased vulnerability to COVID-19. Data suggest that pregnant women with COVID-19 may have a higher frequency of COVID-19 infection, reinforcing the need for universal testing, adequate follow-up for this population, and increasing COVID-19 therapy facilities in Mozambique. Moreover, provide counselling during Antenatal care for COVID-19 preventive measures. However, more prospective and robust studies are needed to assess these findings.
, , , Zaidat A. Musa, , Elsie Ilori, Natalia Blanco, Andrew Mitchell, , Mirna Moloney, et al.
Published: 17 June 2022
PLOS Global Public Health, Volume 2; https://doi.org/10.1371/journal.pgph.0000363

Abstract:
The observed epidemiology of SARS-CoV-2 in sub-Saharan Africa has varied greatly from that in Europe and the United States, with much lower reported incidence. Population-based studies are needed to estimate true cumulative incidence of SARS-CoV-2 to inform public health interventions. This study estimated SARS-CoV-2 seroprevalence in four selected states in Nigeria in October 2020. We implemented a two-stage cluster sample household survey in four Nigerian states (Enugu, Gombe, Lagos, and Nasarawa) to estimate age-stratified prevalence of SARS-CoV-2 antibodies. All individuals in sampled households were eligible for interview, blood draw, and nasal/oropharyngeal swab collection. We additionally tested participants for current/recent malaria infection. Seroprevalence estimates were calculated accounting for the complex survey design. Across all four states, 10,629 (96·5%) of 11,015 interviewed individuals provided blood samples. The seroprevalence of SARS-CoV-2 antibodies was 25·2% (95% CI 21·8–28·6) in Enugu State, 9·3% (95% CI 7·0–11·5) in Gombe State, 23·3% (95% CI 20·5–26·4) in Lagos State, and 18·0% (95% CI 14·4–21·6) in Nasarawa State. Prevalence of current/recent malaria infection ranged from 2·8% in Lagos to 45·8% in Gombe and was not significantly related to SARS-CoV-2 seroprevalence. The prevalence of active SARS-CoV-2 infection in the four states during the survey period was 0·2% (95% CI 0·1–0·4). Approximately eight months after the first reported COVID-19 case in Nigeria, seroprevalence indicated infection levels 194 times higher than the 24,198 officially reported COVID-19 cases across the four states; however, most of the population remained susceptible to COVID-19 in October 2020.
International Journal of Environmental Research and Public Health, Volume 19; https://doi.org/10.3390/ijerph19084637

Abstract:
Exposure to atmospheric particulate matter and nitrogen dioxide has been linked to SARS-CoV-2 infection and death. We hypothesized that long-term exposure to farming-related air pollutants might predispose to an increased risk of COVID-19-related death. To test this hypothesis, we performed an ecological study of five Italian Regions (Piedmont, Lombardy, Veneto, Emilia-Romagna and Sicily), linking all-cause mortality by province (administrative entities within regions) to data on atmospheric concentrations of particulate matter (PM2.5 and PM10) and ammonia (NH3), which are mainly produced by agricultural activities. The study outcome was change in all-cause mortality during March–April 2020 compared with March–April 2015–2019 (period). We estimated all-cause mortality rate ratios (MRRs) by multivariate negative binomial regression models adjusting for air temperature, humidity, international import-export, gross domestic product and population density. We documented a 6.9% excess in MRR (proxy for COVID-19 mortality) for each tonne/km2 increase in NH3 emissions, explained by the interaction of the period variable with NH3 exposure, considering all pollutants together. Despite the limitations of the ecological design of the study, following the precautionary principle, we recommend the implementation of public health measures to limit environmental NH3 exposure, particularly while the COVID-19 pandemic continues. Future studies are needed to investigate any causal link between COVID-19 and farming-related pollution.
Published: 8 June 2021
by MDPI
Journal: Vaccines
Abstract:
The routine detection, surveillance, and reporting of novel SARS-CoV-2 variants is crucial, as these threaten to hinder global vaccination efforts. Herein we report a novel local variant with a non-synonymous mutation in the spike (S) protein P681H. This local Israeli variant was not associated with a higher infection rate or higher prevalence. Furthermore, the local variant was successfully neutralized by sera from fully vaccinated individuals at a comparable level to the B.1.1.7 variant and an Israel wild-type strain. While it is not a variant of concern, routine monitoring by sequencing is still required.
, M. Asso-Bonnet, M. Vasse, Emilie Catherinot, Colas Tcherakian, Antoine Magnan, Simon Chauveau, Sylvie Colin de Verdière, Hélène Salvatore, Antoine Roux, et al.
European Journal of Clinical Microbiology & Infectious Diseases, Volume 40, pp 2041-2045; https://doi.org/10.1007/s10096-021-04243-0

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The SARS-CoV-2 variant with lineage B.1.351 clusters investigation team
Abstract:
Two cases of confirmed SARS-CoV-2 infection with the B.1.351 variant were reported in France in mid-January, 2020. These cases attended a gathering in Mozambique in mid-December 2020. Investigations led to the identification of five imported cases responsible for 14 transmission chains and a total 36 cases. Epidemiological characteristics seemed comparable to those described before the emergence of the South African variant B.1.351. The lack of tertiary transmission outside of the personal sphere suggests that distancing and barrier measures were effective.
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