Evaluation of Real-life Use of Point-of-care Rapid Antigen Testing for SARS-CoV-2 in Schools (EPOCRATES): a cohort study.

BACKGROUND: SARS-CoV-2 transmission has an impact on education. In this study, we assessed the performance of rapid antigen detection tests (RADTs) versus polymerase chain reaction (PCR) for the diagnosis of SARS-CoV-2 infection in school settings, and RADT use for monitoring exposed contacts. METHODS: In this real-world, prospective observational cohort study, high-school students and staff were recruited from 2 high schools in Montréal, Canada, and followed from Jan. 25 to June 10, 2021. Twenty-five percent of asymptomatic participants were tested weekly by RADT (nasal) and PCR (gargle). Class contacts of cases were tested. Symptomatic participants were tested by RADT (nasal) and PCR (nasal and gargle). The number of cases and outbreaks were compared with those of other high schools in the same area. RESULTS: Overall, 2099 students and 286 school staff members consented to participate. The overall specificity of RADTs varied from 99.8% to 100%, with a lower sensitivity, varying from 28.6% in asymptomatic to 83.3% in symptomatic participants. Secondary cases were identified in 10 of 35 classes. Returning students to school after a 7-day quarantine, with a negative PCR result on days 6-7 after exposure, did not lead to subsequent outbreaks. Of cases for whom the source was known, 37 of 51 (72.5%) were secondary to household transmission, 13 (25.5%) to intraschool transmission, and 1 to community contacts between students in the same school. INTERPRETATION: Rapid antigen detection tests did not perform well compared with PCR in asymptomatic individuals. Reinforcing policies for symptom screening when entering schools and testing symptomatic individuals with RADTs on the spot may avoid subsequent substantial exposures in class. Preprint: medRxiv - doi.org/10.1101/2021.10.13.21264960.

From common colds to COVID-19: potential neurological consequences of a coronavirus infection / Des rhumes à la Covid-19 : conséquences neurologiques potentielles d'une infection par les coronavirus

For a large proportion of mankind, the word coronavirus only became a reality in the year 2020, as it was the cause of one of the worst pandemics of the last two centuries. Nevertheless, well before this ominous moment, human coronaviruses (HCoV) were well characterized respiratory pathogens since the 1960s. The most recent discovery of SARS-CoV and MERS-CoV showed that coronaviruses have a pandemic potential with important consequences. With the COVID-19 pandemic caused by SARS-CoV-2, this potential is now certain. Moreover, accumulating evidence support an association between coronaviruses and extra-respiratory pathologies, in particular of the central and peripheral nervous system. Linked or not with a neuro-invasive and neurotropic potential, it is now clear that coronaviruses can be associated with the development of neurological disorders.

Pour une grande partie de l'humanité, le terme coronavirus n'est devenu réalité qu'au début de l'année 2020, associé à une des plus importantes pandémies des deux derniers siècles. Pourtant, bien avant ce moment fatidique, les coronavirus humains (HCoV) étaient bien caractérisés en tant que pathogènes respiratoires depuis la fin des années 1960. Depuis le début du XXIe siècle, deux autres coronavirus pouvant infecter l'humain (SARS-CoV et MERS-CoV), ont montré que ces virus avaient un potentiel pandémique pouvant entraîner des conséquences importantes. Avec la survenue de la pandémie de Covid-19 créée par le SARS-CoV-2, ce potentiel ne fait aujourd'hui plus aucun doute. De plus, un nombre grandissant d'études supporte l'idée d'une association entre les coronavirus et diverses pathologies extra-respiratoires, en particulier au niveau des systèmes nerveux central et périphérique. Liés ou non à un véritable potentiel neuro-invasif et neurotrope, il apparaît maintenant de façon claire que les coronavirus peuvent être associés au développement de divers désordres neurologiques.

Natural spring water gargle samples as an alternative to nasopharyngeal swabs for SARS-CoV-2 detection using a laboratory-developed test.

The objective of this study was to validate the use of spring water gargle (SWG) as an alternative to oral and nasopharyngeal swab (ONPS) for SARS-CoV-2 detection with a laboratory-developed test. Healthcare workers and adults from the general population, presenting to one of two COVID-19 screening clinics in Montréal and Québec City, were prospectively recruited to provide a gargle sample in addition to the standard ONPS. The paired specimens were analyzed using thermal lysis followed by a laboratory-developed nucleic acid amplification test (LD-NAAT) to detect SARS-CoV-2, and comparative performance analysis was performed. An individual was considered infected if a positive result was obtained on either sample. A total of 1297 adult participants were recruited. Invalid results (n = 18) were excluded from the analysis. SARS-CoV-2 was detected in 144/1279 (11.3%) participants: 126 from both samples, 15 only from ONPS, and 3 only from SWG. Overall, the sensitivity was 97.9% (95% CI: 93.7-99.3) for ONPS and 89.6% (95% CI: 83.4-93.6; p = 0.005) for SWG. The mean ONPS cycle threshold (Ct ) value was significantly lower for the concordant paired samples as compared to discordant ones (22.9 vs. 32.1; p < 0.001). In conclusion, using an LD-NAAT with thermal lysis, SWG is a less sensitive sampling method than the ONPS. However, the higher acceptability of SWG might enable a higher rate of detection from a population-based perspective. Nonetheless, in patients with a high clinical suspicion of COVID-19, a repeated analysis with ONPS should be considered. The sensitivity of SWG using NAAT preceded by chemical extraction should be evaluated.

Natural spring water gargle and direct RT-PCR for the diagnosis of COVID-19 (COVID-SPRING study).

BACKGROUND: Nasopharyngeal swab has long been considered the specimen of choice for the diagnosis of respiratory viral infections, including SARS-CoV-2 infection, but it suffers from several drawbacks: its discomfort limits screening acceptability, and it is vulnerable to shortages in both specialized materials and trained healthcare workers in the context of a pandemic. METHODS: We prospectively compared natural spring water gargle to combined oro-nasopharyngeal swab (ONPS) for the diagnosis of coronavirus disease 2019 (COVID-19) in paired clinical specimens (1005 ONPS and 1005 gargles) collected from 987 unique early symptomatic as well as asymptomatic individuals from the community. RESULTS: Using a direct RT-PCR method with the Allplex™ 2019-nCoV Assay (Seegene), the clinical sensitivity of the gargle was 95.3% (95% confidence interval [CI], 90.2 - 98.3%), similar to the sensitivity of the ONPS (93.8%; 95% CI, 88.2 - 97.3%), despite significantly lower viral RNA concentration in gargles, as reflected by higher cycle threshold values. No single specimen type detected all COVID-19 cases. SARS-CoV-2 RNA was stable in gargles at room temperature for at least 7 days. CONCLUSION: The simplicity of this sampling method coupled with the accessibility of spring water are clear advantages in a pandemic situation where testing frequency, turnaround time and shortage of consumables and trained staff are critical elements.

Uncertainty around the Long-Term Implications of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 231 million people globally, with more than 4.7 million deaths recorded by the World Health Organization as of 26 September 2021. In response to the pandemic, some countries (New Zealand, Vietnam, Taiwan, South Korea and others) have pursued suppression strategies, so-called Zero COVID policies, to drive and maintain infection rates as close to zero as possible and respond aggressively to new cases. In comparison, European countries and North America have adopted mitigation strategies (of varying intensity and effectiveness) that aim primarily to prevent health systems from being overwhelmed. With recent advances in our understanding of SARS-CoV-2 and its biology, and the increasing recognition there is more to COVID-19 beyond the acute infection, we offer a perspective on some of the long-term risks of mutational escape, viral persistence, reinfection, immune dysregulation and neurological and multi-system complications (Long COVID).

Potential differences in cleavage of the S protein and type-1 interferon together control human coronavirus infection, propagation, and neuropathology within the central nervous system.

Human coronaviruses (HCoV) are respiratory pathogens which have been known since the 1960's. In December 2019, a new betacoronavirus, SARS-CoV-2, was reported and is responsible for one of the biggest pandemics of the last two centuries. Similar to the HCoV-OC43 strain, available evidence suggests SARS-CoV-2 neuroinvasion associated with potential neurological disorders. Coronavirus infection of the central nervous system (CNS) is largely controlled by a viral factor, the spike glycoprotein (S) and a host factor, innate immunity. However, the interaction between these two factors remains elusive. Proteolytic cleavage of the S protein can occur at the interface between receptor binding (S1) and fusion (S2) domains (S1/S2), as well as in a position adjacent to a fusion peptide within S2 (S2'). Herein, using HCoV-OC43 as a surrogate for SARS-CoV-2, we report that both S protein sites are involved in neurovirulence and are required for optimal CNS infection. Whereas efficient cleavage at S1/S2 is associated with decreased virulence, the potentially cleavable putative S2' site is essential for efficient viral infection. Furthermore, type 1 interferon (IFN 1)-related innate immunity also plays an important role in the control of viral spread towards the spinal cord, by preventing infection of ependymal cells. Our results underline the link between the differential S cleavage and IFN 1 in the prevention of viral spread, to control the severity of infection and pathology in both immunocompetent and immunodeficient mice. Taken together, these results point towards two potential therapeutic anti-viral targets: cleavage of the S protein in conjunction with efficient IFN 1-related innate immunity to prevent or at least reduce neuroinvasion, neural spread, and potential associated neurovirulence of human coronaviruses.ImportanceHuman coronaviruses (HCoV) are recognized respiratory pathogens. The emergence of the novel pathogenic member of this family in December 2019 (SARS-CoV-2, which causes COVID-19) poses a global health emergency. As with other coronaviruses reported previously, invasion of the human central nervous system (CNS), associated with diverse neurological disorders, was suggested for SARS-CoV-2. Herein, using the related HCoV-OC43 strain, we show that the viral spike protein constitutes a major neurovirulence factor and that type 1 interferon (IFN 1), in conjunction with cleavage of S protein by host proteases, represent important host factors that participate in the control of CNS infection.To our knowledge, this is the first demonstration of a direct link between cleavage of the S protein, innate immunity and neurovirulence. Understanding mechanisms of viral infection and spread in neuronal cells is essential to better design therapeutic strategies, and to prevent infection by human coronaviruses such as SARS-CoV-2 in human CNS especially in the vulnerable populations such as the elderly and immune-compromised individuals.

Cross-Sectional Evaluation of Humoral Responses against SARS-CoV-2 Spike.

SARS-CoV-2 is responsible for the coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The Spike glycoproteins of SARS-CoV-2 mediate viral entry and are the main targets for neutralizing antibodies. Understanding the antibody response directed against SARS-CoV-2 is crucial for the development of vaccine, therapeutic, and public health interventions. Here, we perform a cross-sectional study on 106 SARS-CoV-2-infected individuals to evaluate humoral responses against SARS-CoV-2 Spike. Most infected individuals elicit anti-Spike antibodies within 2 weeks of the onset of symptoms. The levels of receptor binding domain (RBD)-specific immunoglobulin G (IgG) persist over time, and the levels of anti-RBD IgM decrease after symptom resolution. Although most individuals develop neutralizing antibodies within 2 weeks of infection, the level of neutralizing activity is significantly decreased over time. Our results highlight the importance of studying the persistence of neutralizing activity upon natural SARS-CoV-2 infection.

Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System?

Respiratory viruses infect the human upper respiratory tract, mostly causing mild diseases. However, in vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, causing a more severe disease (e.g., pneumonia). Respiratory viruses can also exacerbate asthma and lead to various types of respiratory distress syndromes. Furthermore, as they can adapt fast and cross the species barrier, some of these pathogens, like influenza A and SARS-CoV, have occasionally caused epidemics or pandemics, and were associated with more serious clinical diseases and even mortality. For a few decades now, data reported in the scientific literature has also demonstrated that several respiratory viruses have neuroinvasive capacities, since they can spread from the respiratory tract to the central nervous system (CNS). Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Like other well-recognized neuroinvasive human viruses, respiratory viruses may damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuro-immunopathology) and/or viral replication, which directly causes damage to CNS cells (virus-induced neuropathology). The etiological agent of several neurological disorders remains unidentified. Opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of these disorders whose etiology remains poorly understood. Herein, we present a global portrait of some of the most prevalent or emerging human respiratory viruses that have been associated with possible pathogenic processes in CNS infection, with a special emphasis on human coronaviruses.