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1.
Biomed Res Int ; 2022: 3401566, 2022.
Article in English | MEDLINE | ID: covidwho-1794376

ABSTRACT

Early in the COVID-19 pandemic, asymptomatic transmission represented an important challenge for controlling the spread of SARS-CoV-2 through the traditional public health strategies. Further understanding of the contribution of asymptomatic infections to SARS-CoV-2 transmission has been of crucial importance for pandemic control. We conducted a retrospective epidemiological study to characterize asymptomatic COVID-19 cases occurred in the Apulia region, Italy, during the first epidemic wave of COVID-19 outbreak (February 29-July 7, 2020). We analyzed data collected in a regional platform developed to manage surveillance activities, namely, investigation and follow-up of cases and contacts, contact tracing, and laboratory and clinical data collection. We included all asymptomatic cases that were laboratory-confirmed during the appropriate follow-up, defined as persons infected with SARS-CoV-2 who did not develop symptoms/clinical signs of the disease. Between February 29 and July 7, 2020, a total of 4,536 cases were diagnosed with COVID-19 among 193,757 tests performed. The group of persons with asymptomatic SARS-CoV-2 infection consisted of 903 cases; the asymptomatic proportion was 19.9% (95% CI: 18.8-21.1%); this decreased with increasing age (OR: 0.89, 95% CI: 0.83-0.96; p = 0.001), in individuals with underlying comorbidities (OR: 0.55, 95% CI: 0.41-0.73; p < 0.001), and in males (OR: 0.69, 95% CI: 0.54-0.87; p = 0.002). The median asymptomatic SARS-CoV-2 RNA positive period was 19 days (IQR: 14-31) and the cumulative proportion of persons with resolution of infection 14 days after the first positive PCR test was 74%. As the public health community is debating the question of whether asymptomatic and late spreaders could sustain virus transmission in the communities, such cases present unique opportunities to gain insight into SARS-CoV-2 adaptation to human host. This has important implications for future COVID-19 surveillance and prevention.


Subject(s)
Asymptomatic Infections/epidemiology , COVID-19/epidemiology , Carrier State/epidemiology , Adaptation, Physiological , Adult , Aged , COVID-19/transmission , Contact Tracing , Disease Outbreaks , Female , Humans , Incidence , Italy/epidemiology , Male , Middle Aged , Pandemics , RNA, Viral , Retrospective Studies , Risk Factors , SARS-CoV-2/pathogenicity
2.
Can J Anaesth ; 67(10): 1424-1430, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1777852

ABSTRACT

PURPOSE: Risk to healthcare workers treating asymptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the operating room depends on multiple factors. This review examines the evidence for asymptomatic or pre-symptomatic carriage of SARS-CoV-2, the risk of transmission from asymptomatic patients, and the specific risks associated with aerosol-generating procedures. Protective measures, such as minimization of aerosols and use of personal protective equipment in the setting of treating asymptomatic patients, are also reviewed. SOURCE: We examined the published literature as well as Societal guidelines. PRINCIPAL FINDINGS: There is evidence that a proportion of those infected with SARS-CoV-2 have detectable viral loads prior to exhibiting symptoms, or without ever developing symptoms. The degree of risk of transmission from asymptomatic patients to healthcare providers will depend on the prevalence of disease in the population, which is difficult to assess without widespread population screening. Aerosol-generating procedures increase the odds of viral transmission from infected symptomatic patients to healthcare providers, but transmission from asymptomatic patients has not been reported. Techniques to minimize aerosolization and appropriate personal protective equipment may help reduce the risk to healthcare workers in the operating room. Some societal guidelines recommend the use of airborne precautions during aerosol-generating procedures on asymptomatic patients during the coronavirus disease pandemic, although evidence supporting this practice is limited. CONCLUSION: Viral transmission from patients exhibiting no symptoms in the operating room is plausible and efforts to reduce risk to healthcare providers include reducing aerosolization and wearing appropriate personal protective equipment, the feasibility of which will vary based on geographic risk and equipment availability.


RéSUMé: OBJECTIF: Le risque encouru par les travailleurs de la santé traitant des patients asymptomatiques infectés par le syndrome respiratoire aigu sévère du coronavirus 2 (SARS-CoV-2) en salle d'opération dépend de plusieurs facteurs. Ce compte rendu examine les données probantes concernant la présence asymptomatique ou pré-symptomatique du SARS-CoV-2, le risque de transmission des patients asymptomatiques, et les risques spécifiques associés aux interventions générant des aérosols. Nous passons également en revue différentes mesures de protection, telles que la minimisation des aérosols et l'utilisation d'équipements de protection individuelle, dans un contexte de traitement de patients asymptomatiques. SOURCE: Nous avons examiné la littérature publiée ainsi que les directives sociétales. CONSTATATIONS PRINCIPALES: Selon certaines données probantes, une proportion des personnes infectées par le SARS-CoV-2 possèdent des charges virales détectables avant la présence de symptômes, voire même sans manifestation de symptômes. Le degré de risque de transmission des patients asymptomatiques aux travailleurs de la santé dépendra de la prévalence de la maladie dans la population, une donnée difficile à évaluer sans dépistage généralisé. Les interventions générant des aérosols augmentent le risque de transmission virale des patients symptomatiques infectés aux travailleurs de la santé, mais la transmission de patients asymptomatiques n'a pas été rapportée. Les techniques visant à minimiser l'aérosolisation et les équipements de protection individuelle adaptés pourraient être utiles pour réduire le risque des travailleurs de la santé en salle d'opération. Certaines directives régionales et nationales recommandent le recours à des précautions contre la transmission par voie aérienne durant les interventions générant des aérosols pratiquées sur des patients asymptomatiques pendant la pandémie de coronavirus, bien que les données probantes appuyant cette pratique soient limitées. CONCLUSION: La transmission virale des patients asymptomatiques en salle d'opération est plausible et les efforts visant à réduire le risque pour les travailleurs de la santé comprennent la réduction de l'aérosolisation et le port d'équipements de protection individuelle adaptés, deux mesures dont la faisabilité variera en fonction du risque géographique et de la disponibilité des équipements.


Subject(s)
Asymptomatic Infections/epidemiology , Coronavirus Infections/transmission , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Pneumonia, Viral/transmission , Aerosols , Betacoronavirus/isolation & purification , COVID-19 , Carrier State/epidemiology , Carrier State/virology , Coronavirus Infections/epidemiology , Health Personnel , Humans , Pandemics , Personal Protective Equipment , Pneumonia, Viral/epidemiology , SARS-CoV-2
3.
PLoS Negl Trop Dis ; 14(2): e0008065, 2020 02.
Article in English | MEDLINE | ID: covidwho-1765523

ABSTRACT

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe acute respiratory illness with a case fatality rate (CFR) of 35,5%. The highest number of MERS-CoV cases are from Saudi-Arabia, the major worldwide hotspot for this disease. In the absence of neither effective treatment nor a ready-to-use vaccine and with yet an incomplete understanding of its epidemiological cycle, prevention and containment measures can be derived from mathematical models of disease epidemiology. We constructed 2-strain models to predict past outbreaks in the interval 2012-2016 and derive key epidemiological information for Macca, Madina and Riyadh. We approached variability in infection through three different disease incidence functions capturing social behavior in response to an epidemic (e.g. Bilinear, BL; Non-monotone, NM; and Saturated, SAT models). The best model combination successfully anticipated the total number of MERS-CoV clinical cases for the 2015-2016 season and accurately predicted both the number of cases at the peak of seasonal incidence and the overall shape of the epidemic cycle. The evolution in the basic reproduction number (R0) warns that MERS-CoV may easily take an epidemic form. The best model correctly captures this feature, indicating a high epidemic risk (1≤R0≤2,5) in Riyadh and Macca and confirming the alleged co-circulation of more than one strain. Accurate predictions of the future MERS-CoV peak week, as well as the number of cases at the peak are now possible. These results indicate public health agencies should be aware that measures for strict containment are urgently needed before new epidemics take off in the region.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Epidemics , Middle East Respiratory Syndrome Coronavirus , Models, Biological , Carrier State , Computer Simulation , Humans , Risk Factors
4.
J Hosp Infect ; 123: 52-60, 2022 May.
Article in English | MEDLINE | ID: covidwho-1757533

ABSTRACT

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) infections are rampant in hospitals and residential care homes for the elderly (RCHEs). AIM: To analyse the prevalence of MRSA colonization among residents and staff, and degree of environmental contamination and air dispersal of MRSA in RCHEs. METHODS: Epidemiological and genetic analysis by whole-genome sequencing (WGS) in 12 RCHEs in Hong Kong. FINDINGS: During the COVID-19 pandemic (from September to October 2021), 48.7% (380/781) of RCHE residents were found to harbour MRSA at any body site, and 8.5% (8/213) of staff were nasal MRSA carriers. Among 239 environmental samples, MRSA was found in 39.0% (16/41) of randomly selected resident rooms and 31.3% (62/198) of common areas. The common areas accessible by residents had significantly higher MRSA contamination rates than those that were not accessible by residents (37.2%, 46/121 vs. 22.1%, 17/177, P=0.028). Of 124 air samples, nine (7.3%) were MRSA-positive from four RCHEs. Air dispersal of MRSA was significantly associated with operating indoor fans in RCHEs (100%, 4/4 vs. 0%, 0/8, P=0.002). WGS of MRSA isolates collected from residents, staff and environmental and air samples showed that ST 1047 (CC1) lineage 1 constituted 43.1% (66/153) of all MRSA isolates. A distinctive predominant genetic lineage of MRSA in each RCHE was observed, suggestive of intra-RCHE transmission rather than clonal acquisition from the catchment hospital. CONCLUSION: MRSA control in RCHEs is no less important than in hospitals. Air dispersal of MRSA may be an important mechanism of dissemination in RCHEs with operating indoor fans.


Subject(s)
COVID-19 , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Aged , COVID-19/epidemiology , Carrier State/epidemiology , Humans , Methicillin , Methicillin-Resistant Staphylococcus aureus/genetics , Pandemics , Staphylococcal Infections/epidemiology
7.
Microbiol Spectr ; 10(1): e0245521, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1691400

ABSTRACT

Containment measures employed during the COVID-19 pandemic included prompt recognition of cases, isolation, and contact tracing. Bilateral nasal (NA) swabs applied to a commercial antigen-based rapid diagnostic test (Ag-RDT) offer a simpler and more comfortable alternative to nasopharyngeal (NP) collection; however, little is known about the sensitivity of this method in an asymptomatic population. Participants in community-based asymptomatic testing sites were screened for SARS-CoV-2 using an Ag-RDT with NP sampling. Positive individuals returned for confirmatory molecular testing and consented to repeating the Ag-RDT using a bilateral NA swab for comparison. Residual test buffer (RTB) from Ag-RDTs was subjected to real-time reverse transcription-PCR (RT-PCR). Of 123,617 asymptomatic individuals, 197 NP Ag-RDT-positive participants were included, with 175 confirmed positive by RT-PCR. Of these cases, 154 were identified from the NA swab collection with Ag-RDT, with a sensitivity of 88.0% compared to the NP swab collection. Stratifying results by RT-PCR cycle threshold demonstrated that sensitivity of the nasal collection method varied based on the cycle threshold (CT) value of the paired RT-PCR sample. RT-PCR testing on the RTB from the Ag-RDT using NP and NA swab collections resulted in 100.0% and 98.7% sensitivity, respectively. NA swabs provide an adequate alternative to NP swab collection for use with Ag-RDT, with the recognition that the test is most sensitive in specimens with high viral loads. With the high sensitivity of RT-PCR testing on RTB from Ag-RDT, a more streamlined approach to confirmatory testing is possible without recollection or use of paired collections strategies. IMPORTANCE Nasal swabbing for SARS-CoV-2 (COVID-19) comes with many benefits but is slightly less sensitive than traditional nasopharyngeal swabbing; however, confirmatory lab-based testing could be performed directly from the residual buffer from either sample type.


Subject(s)
Antigens, Viral/analysis , COVID-19/virology , Carrier State/virology , Nasopharynx/virology , Nose/virology , SARS-CoV-2/isolation & purification , Specimen Handling/methods , Antigens, Viral/genetics , Antigens, Viral/immunology , Asymptomatic Diseases , COVID-19/diagnosis , COVID-19 Serological Testing , Humans , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Sensitivity and Specificity
8.
Front Cell Infect Microbiol ; 11: 825427, 2021.
Article in English | MEDLINE | ID: covidwho-1690458

ABSTRACT

Streptococcus pneumoniae is an important and frequently carried respiratory pathogen that has the potential to cause serious invasive diseases, such as pneumonia, meningitis, and sepsis. Young children and older adults are among the most vulnerable to developing serious disease. With the arrival of the COVID-19 pandemic and the concomitant restrictive measures, invasive disease cases caused by respiratory bacterial species, including pneumococci, decreased substantially. Notably, the stringency of the containment measures as well as the visible reduction in the movement of people appeared to coincide with the drop in invasive disease cases. One could argue that wearing protective masks and adhering to social distancing guidelines to halt the spread of the SARS-CoV-2 virus, also led to a reduction in the person-to-person transmission of respiratory bacterial species. Although plausible, this conjecture is challenged by novel data obtained from our nasopharyngeal carriage study which is performed yearly in healthy daycare center attending children. A sustained and high pneumococcal carriage rate was observed amid periods of stringent restrictive measures. This finding prompts us to revisit the connection between nasopharyngeal colonization and invasion and invites us to look closer at the nasopharyngeal microbiome as a whole.


Subject(s)
COVID-19 , Pneumococcal Infections , Aged , Belgium , Carrier State/epidemiology , Child , Child, Preschool , Humans , Infant , Nasopharynx , Pandemics , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines , SARS-CoV-2 , Streptococcus pneumoniae
9.
PLoS One ; 16(12): e0260894, 2021.
Article in English | MEDLINE | ID: covidwho-1623649

ABSTRACT

BACKGROUND: Performance of the SD Biosensor saliva antigen rapid test was evaluated at a large designated testing site in non-hospitalized patients, with or without symptoms. METHOD: All eligible people over 18 years of age presenting for a booked appointment at the designated SARS-CoV-2 testing site were approached for inclusion and enrolled following verbal informed consent. One nasopharyngeal swab was taken to carry out the default antigen rapid test from which the results were reported back to the patient and one saliva sample was self-taken according to verbal instruction on site. This was used for the saliva antigen rapid test, the RT-PCR and for virus culture. Sensitivity of the saliva antigen rapid test was analyzed in two ways: i, compared to saliva RT-PCR; and ii, compared to virus culture of the saliva samples. Study participants were also asked to fill in a short questionnaire stating age, sex, date of symptom onset. Recommended time of ≥30mins since last meal, drink or cigarette if applicable was also recorded. The study was carried out in February-March 2021 for 4 weeks. RESULTS: We could include 789 people with complete records and results. Compared to saliva RT-PCR, overall sensitivity and specificity of the saliva antigen rapid test was 66.1% and 99.6% which increased to 88.6% with Ct ≤30 cutoff. Analysis by days post onset did not result in higher sensitivities because the large majority of people were in the very early phase of disease ie <3 days post onset. When breaking down the data for symptomatic and asymptomatic individuals, sensitivity ranged from 69.2% to 50% respectively, however the total number of RT-PCR positive asymptomatic participants was very low (n = 5). Importantly, almost all culture positive samples were detected by the rapid test. CONCLUSION: Overall, the potential benefits of saliva antigen rapid test, could outweigh the lower sensitivity compared to nasopharyngeal antigen rapid test in a comprehensive testing strategy, especially for home/self-testing and in vulnerable populations like elderly, disabled or children where in intrusive testing is either not possible or causes unnecessary stress.


Subject(s)
Biosensing Techniques/methods , COVID-19 Serological Testing/methods , Saliva/virology , Adolescent , Adult , Aged , COVID-19/diagnosis , COVID-19/etiology , Carrier State/virology , Female , Hospitalization , Humans , Male , Middle Aged , Nasopharynx/virology , Sensitivity and Specificity , Young Adult
10.
Sci Rep ; 12(1): 212, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1621266

ABSTRACT

In response to the COVID19 pandemic, many countries have implemented lockdowns in multiple phases to ensure social distancing and quarantining of the infected subjects. Subsequent unlocks to reopen the economies started next waves of infection and imposed an extra burden on quarantine to keep the reproduction number ([Formula: see text]) < 1. However, most countries could not effectively contain the infection spread, suggesting identification of the potential sources weakening the effect of lockdowns could help design better informed lockdown-unlock cycles in the future. Here, through building quantitative epidemic models and analyzing the metadata of 50 countries from across the continents we first found that the estimated value of [Formula: see text], adjusted w.r.t the distribution of medical facilities and virus clades correlates strongly with the testing rates in a country. Since the testing capacity of a country is limited by its medical resources, we investigated if a cost-benefit trade-off can be designed connecting testing rate and extent of unlocking. We present a strategy to optimize this trade-off in a country specific manner by providing a quantitative estimate of testing and quarantine rates required to allow different extents of unlocks while aiming to maintain [Formula: see text]. We further show that a small fraction of superspreaders can dramatically increase the number of infected individuals even during strict lockdowns by strengthening the positive feedback loop driving infection spread. Harnessing the benefit of optimized country-specific testing rates would critically require minimizing the movement of these superspreaders via strict social distancing norms, such that the positive feedback driven switch-like exponential spread phase of infection can be avoided/delayed.


Subject(s)
COVID-19/prevention & control , Contact Tracing , Disease Transmission, Infectious/prevention & control , Physical Distancing , Quarantine , SARS-CoV-2/growth & development , Virus Replication , COVID-19/epidemiology , COVID-19/transmission , COVID-19/virology , COVID-19 Testing , Carrier State , Humans , Metadata , SARS-CoV-2/pathogenicity , Time Factors
11.
JCI Insight ; 6(24)2021 12 22.
Article in English | MEDLINE | ID: covidwho-1598468

ABSTRACT

mRNA vaccines for SARS-CoV-2 have shown exceptional clinical efficacy, providing robust protection against severe disease. However, our understanding of transcriptional and repertoire changes following full vaccination remains incomplete. We used scRNA-Seq and functional assays to compare humoral and cellular responses to 2 doses of mRNA vaccine with responses observed in convalescent individuals with asymptomatic disease. Our analyses revealed enrichment of spike-specific B cells, activated CD4+ T cells, and robust antigen-specific polyfunctional CD4+ T cell responses following vaccination. On the other hand, although clonally expanded CD8+ T cells were observed following both vaccination and natural infection, CD8+ T cell responses were relatively weak and variable. In addition, TCR gene usage was variable, reflecting the diversity of repertoires and MHC polymorphism in the human population. Natural infection induced expansion of CD8+ T cell clones that occupy distinct clusters compared to those induced by vaccination and likely recognize a broader set of viral antigens of viral epitopes presented by the virus not seen in the mRNA vaccine. Our study highlights a coordinated adaptive immune response in which early CD4+ T cell responses facilitate the development of the B cell response and substantial expansion of effector CD8+ T cells, together capable of contributing to future recall responses.


Subject(s)
/immunology , COVID-19/immunology , Immunity, Cellular/immunology , Immunity, Humoral/immunology , /therapeutic use , Adaptive Immunity/genetics , Adaptive Immunity/immunology , Adult , Aged , Antigens, Viral , B-Lymphocytes , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , COVID-19/prevention & control , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Carrier State , Convalescence , Epitopes , Female , Humans , Immunity, Cellular/genetics , Immunity, Humoral/genetics , Immunogenicity, Vaccine , Immunologic Memory , Male , Middle Aged , RNA-Seq , SARS-CoV-2 , Single-Cell Analysis , Spike Glycoprotein, Coronavirus/immunology , Th1 Cells , Th17 Cells , Vaccines, Synthetic/immunology , Vaccines, Synthetic/therapeutic use , Young Adult , /therapeutic use
12.
PLoS One ; 16(12): e0261956, 2021.
Article in English | MEDLINE | ID: covidwho-1597233

ABSTRACT

A direct, real-time reverse transcriptase PCR test on pooled saliva was validated in 2,786 participants against oropharyngeal swabs. Among asymptomatic/pre-symptomatic participants, the test was found to be in 99.21% agreement and 45% more sensitive than contemporaneous oropharyngeal swabs. The test was then used for surveillance testing on 44,242 saliva samples from asymptomatic participants. Those whose saliva showed evidence of SARS-CoV-2 within 50 cycles of amplification were referred for confirmatory testing, with 87% of those tested by nasal swab within 72 hours receiving a positive diagnostic result on Abbott ID NOW or real-time PCR platforms. Median Ct values on the saliva PCR for those with a positive and negative confirmatory tests was 30.67 and 35.92 respectively, however, binary logistic regression analysis of the saliva Ct values indicates that Ct thresholds as high as 47 may be useful in a surveillance setting. Overall, data indicate that direct RT-PCR testing of pooled saliva samples is an effective method of SARS-CoV-2 surveillance.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , Carrier State/diagnosis , Diagnostic Tests, Routine/methods , Real-Time Polymerase Chain Reaction/methods , Saliva/virology , Humans , Sensitivity and Specificity
13.
J Clin Lab Anal ; 36(1): e24080, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1574871

ABSTRACT

BACKGROUND: COVID-19 has become a global pandemic, and close contacts and asymptomatic patients are worthy of attention. METHODS: A total of 1844 people in close contacts with 76 COVID-19 patients were investigated, and nasopharyngeal swabs and venous blood were collected for centralized medical quarantine observation. Real-time fluorescence was used to detect SARS-CoV-2 nucleic acid in nasopharyngeal swabs of all close contacts, and the colloidal gold method was used to detect serum-specific antibodies. Levels of IgM- and IgG-specific antibodies were detected quantitatively through chemiluminescence from the first nucleic acid turned negative date (0 week) and on weekly intervals of ≤1 week, 1-2 weeks, 2-3 weeks, 3-4 weeks, 4-5 weeks, 5-6 weeks, and 6-7 weeks. RESULTS: The total positive rate of the colloidal gold method (88.5%, 23/26) was significantly higher (χ2  = 59.182, p < 0.001) than that of the healthy control group (2.0%, 1/50). There was significant difference in IgG concentration at different time points (0-7 weeks) after negative nucleic acid conversion (χ2  = 14.034, p = 0.029). Serum IgG levels were significantly higher at weekly time points of 4-5 weeks (Z = -2.399, p = 0.016), 5-6 weeks (Z = -2.049, p = 0.040), and 6-7 weeks (Z = -2.197, p = 0.028) compared with 1-2 weeks after negative nucleic acid conversion. However, there was no significant difference (χ2  = 4.936, p = 0.552) in IgM concentration between time points tested (0-7 weeks) after negative nucleic acid conversion. The positive rates of IgM and IgG in asymptomatic patients (χ2  = 84.660, p < 0.001) were significantly higher than those in the healthy control group (χ2  = 9.201, p = 0.002) within 7 weeks of negative nucleic acid conversion. CONCLUSIONS: The IgG concentration in asymptomatic cases remained at a high level after nucleic acid turned negative. Nucleic acid detection combined with IgM and IgG antibody detection is an effective way to screen asymptomatic infections.


Subject(s)
COVID-19 Serological Testing/methods , Immunoglobulin G/blood , Immunoglobulin M/blood , Adult , Aged , COVID-19/epidemiology , Carrier State/blood , China/epidemiology , Female , Gold Colloid , Humans , Male , Middle Aged
14.
Microb Genom ; 7(11)2021 11.
Article in English | MEDLINE | ID: covidwho-1541625

ABSTRACT

Understanding the evolution of the SARS-CoV-2 virus in various regions of the world during the Covid-19 pandemic is essential to help mitigate the effects of this devastating disease. We describe the phylogenomic and population genetic patterns of the virus in Mexico during the pre-vaccination stage, including asymptomatic carriers. A real-time quantitative PCR screening and phylogenomic reconstructions directed at sequence/structure analysis of the spike glycoprotein revealed mutation of concern E484K in genomes from central Mexico, in addition to the nationwide prevalence of the imported variant 20C/S:452R (B.1.427/9). Overall, the detected variants in Mexico show spike protein mutations in the N-terminal domain (i.e. R190M), in the receptor-binding motif (i.e. T478K, E484K), within the S1-S2 subdomains (i.e. P681R/H, T732A), and at the basis of the protein, V1176F, raising concerns about the lack of phenotypic and clinical data available for the variants of interest we postulate: 20B/478K.V1 (B.1.1.222 or B.1.1.519) and 20B/P.4 (B.1.1.28.4). Moreover, the population patterns of single nucleotide variants from symptomatic and asymptomatic carriers obtained with a self-sampling scheme confirmed the presence of several fixed variants, and differences in allelic frequencies among localities. We identified the mutation N:S194L of the nucleocapsid protein associated with symptomatic patients. Phylogenetically, this mutation is frequent in Mexican sub-clades. Our results highlight the dual and complementary role of spike and nucleocapsid proteins in adaptive evolution of SARS-CoV-2 to their hosts and provide a baseline for specific follow-up of mutations of concern during the vaccination stage.


Subject(s)
COVID-19/virology , Coronavirus Nucleocapsid Proteins/genetics , Phylogeny , SARS-CoV-2/genetics , COVID-19/epidemiology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Carrier State/prevention & control , Carrier State/virology , Genome, Viral , Humans , Mexico , Mutation , Phosphoproteins/genetics , SARS-CoV-2/classification , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Vaccination
15.
Nat Med ; 28(1): 175-184, 2022 01.
Article in English | MEDLINE | ID: covidwho-1541244

ABSTRACT

Early detection of infectious diseases is crucial for reducing transmission and facilitating early intervention. In this study, we built a real-time smartwatch-based alerting system that detects aberrant physiological and activity signals (heart rates and steps) associated with the onset of early infection and implemented this system in a prospective study. In a cohort of 3,318 participants, of whom 84 were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), this system generated alerts for pre-symptomatic and asymptomatic SARS-CoV-2 infection in 67 (80%) of the infected individuals. Pre-symptomatic signals were observed at a median of 3 days before symptom onset. Examination of detailed survey responses provided by the participants revealed that other respiratory infections as well as events not associated with infection, such as stress, alcohol consumption and travel, could also trigger alerts, albeit at a much lower mean frequency (1.15 alert days per person compared to 3.42 alert days per person for coronavirus disease 2019 cases). Thus, analysis of smartwatch signals by an online detection algorithm provides advance warning of SARS-CoV-2 infection in a high percentage of cases. This study shows that a real-time alerting system can be used for early detection of infection and other stressors and employed on an open-source platform that is scalable to millions of users.


Subject(s)
COVID-19/diagnosis , Carrier State/diagnosis , Exercise , Heart Rate/physiology , Wearable Electronic Devices , Accelerometry , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/physiopathology , Carrier State/physiopathology , Early Diagnosis , Female , Fitness Trackers , Humans , Male , Middle Aged , SARS-CoV-2 , Sleep , Young Adult
16.
Pediatr Rheumatol Online J ; 19(1): 162, 2021 Nov 27.
Article in English | MEDLINE | ID: covidwho-1538079

ABSTRACT

BACKGROUND: This study aimed to assess the baseline characteristics and clinical outcomes of coronavirus disease 2019 (COVID-19) in pediatric patients with rheumatic and musculoskeletal diseases (RMD) and identify the risk factors associated with symptomatic or severe disease defined as hospital admission, intensive care admission or death. METHODS: An observational longitudinal study was conducted during the first year of the SARS-CoV-2 pandemic (March 2020-March 2021). All pediatric patients attended at the rheumatology outpatient clinics of six tertiary referral hospitals in Madrid, Spain, with a diagnosis of RMD and COVID-19 were included. Main outcomes were symptomatic disease and hospital admission. The covariates were sociodemographic and clinical characteristics and treatment regimens. We ran a multivariable logistic regression model to assess associated factors for outcomes. RESULTS: The study population included 77 pediatric patients. Mean age was 11.88 (4.04) years Of these, 30 patients (38.96%) were asymptomatic, 41 (53.25%) had a mild-moderate COVID-19 and 6 patients (7.79%) required hospital admission. The median length of hospital admission was 5 (2-20) days, one patient required intensive care and there were no deaths. Previous comorbidities increased the risk for symptomatic disease and hospital admission. Compared with outpatients, the factor independently associated with hospital admission was previous use of glucocorticoids (OR 3.51; p = 0.00). No statistically significant risk factors for symptomatic COVID-19 were found in the final model. CONCLUSION: No differences in COVID-19 outcomes according to childhood-onset rheumatic disease types were found. Results suggest that associated comorbidities and treatment with glucocorticoids increase the risk of hospital admission.


Subject(s)
Antirheumatic Agents/therapeutic use , COVID-19/physiopathology , Glucocorticoids/therapeutic use , Hospitalization/statistics & numerical data , Rheumatic Diseases/drug therapy , Adolescent , Arthritis, Juvenile/drug therapy , Arthritis, Juvenile/epidemiology , Asthma/epidemiology , COVID-19/epidemiology , Carrier State/epidemiology , Child , Cohort Studies , Comorbidity , Female , Heart Diseases/epidemiology , Hereditary Autoinflammatory Diseases/drug therapy , Hereditary Autoinflammatory Diseases/epidemiology , Humans , Intensive Care Units, Pediatric , Length of Stay , Logistic Models , Longitudinal Studies , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/epidemiology , Male , Multivariate Analysis , Obesity/epidemiology , Renal Insufficiency, Chronic/epidemiology , Rheumatic Diseases/epidemiology , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Spain/epidemiology
17.
Sci Rep ; 11(1): 22958, 2021 11 25.
Article in English | MEDLINE | ID: covidwho-1537338

ABSTRACT

Understanding key host protective mechanisms against SARS-CoV-2 infection can help improve treatment modalities for COVID-19. We used a blood transcriptome approach to study biomarkers associated with differing severity of COVID-19, comparing severe and mild Symptomatic disease with Asymptomatic COVID-19 and uninfected Controls. There was suppression of antigen presentation but upregulation of inflammatory and viral mRNA translation associated pathways in Symptomatic as compared with Asymptomatic cases. In severe COVID-19, CD177 a neutrophil marker, was upregulated while interferon stimulated genes (ISGs) were downregulated. Asymptomatic COVID-19 cases displayed upregulation of ISGs and humoral response genes with downregulation of ICAM3 and TLR8. Compared across the COVID-19 disease spectrum, we found type I interferon (IFN) responses to be significantly upregulated (IFNAR2, IRF2BP1, IRF4, MAVS, SAMHD1, TRIM1), or downregulated (SOCS3, IRF2BP2, IRF2BPL) in Asymptomatic as compared with mild and severe COVID-19, with the dysregulation of an increasing number of ISGs associated with progressive disease. These data suggest that initial early responses against SARS-CoV-2 may be effectively controlled by ISGs. Therefore, we hypothesize that treatment with type I interferons in the early stage of COVID-19 may limit disease progression by limiting SARS-CoV-2 in the host.


Subject(s)
COVID-19/immunology , Carrier State/immunology , Interferon Type I/immunology , Adult , Aged , Antiviral Agents , COVID-19/genetics , Computational Biology/methods , Female , Gene Expression/genetics , Gene Expression Regulation/genetics , Humans , Interferon Type I/genetics , Interferon Type I/metabolism , Male , Middle Aged , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Severity of Illness Index , Up-Regulation
18.
Immunology ; 165(2): 250-259, 2022 02.
Article in English | MEDLINE | ID: covidwho-1511322

ABSTRACT

Accurate assessment of SARS-CoV-2 immunity is critical in evaluating vaccine efficacy and devising public health policies. Whilst the exact nature of effective immunity remains incompletely defined, SARS-CoV-2-specific T-cell responses are a critical feature that will likely form a key correlate of protection against COVID-19. Here, we developed and optimized a high-throughput whole blood-based assay to determine the T-cell response associated with prior SARS-CoV-2 infection and/or vaccination amongst 231 healthy donors and 68 cancer patients. Following overnight in vitro stimulation with SARS-CoV-2-specific peptides, blood plasma samples were analysed for TH 1-type cytokines. Highly significant differential IFN-γ+ /IL-2+ SARS-CoV-2-specific T-cell responses were seen amongst previously infected COVID-19-positive healthy donors in comparison with unknown / naïve individuals (p < 0·0001). IFN-γ production was more effective at identifying asymptomatic donors, demonstrating higher sensitivity (96·0% vs. 83·3%) but lower specificity (84·4% vs. 92·5%) than measurement of IL-2. A single COVID-19 vaccine dose induced IFN-γ and/or IL-2 SARS-CoV-2-specific T-cell responses in 116 of 128 (90·6%) healthy donors, reducing significantly to 27 of 56 (48·2%) when measured in cancer patients (p < 0·0001). A second dose was sufficient to boost T-cell responses in the majority (90·6%) of cancer patients, albeit IFN-γ+ responses were still significantly lower overall than those induced in healthy donors (p = 0·034). Three-month post-vaccination T-cell responses also declined at a faster rate in cancer patients. Overall, this cost-effective standardizable test ensures accurate and comparable assessments of SARS-CoV-2-specific T-cell responses amenable to widespread population immunity testing, and identifies individuals at greater need of booster vaccinations.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , Carrier State/immunology , Immunity, Cellular , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Th1 Cells/immunology , Vaccination , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/prevention & control , Female , Humans , Interferon-gamma/immunology , Male , Middle Aged
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