[Pneumococcal conjugate vaccines in pediatrics, its impact on Public Health]. / Vacunas conjugadas contra neumococo en pediatría, su impacto en la Salud Pública.

Streptococcus pneumoniae (also known as pneumococcus) is part of the natural bacterial flora of the nasal and pharyngeal mucosa, colonizes mainly the nasopharynx, and causes this carriage to precede pneumococcal disease, thus becoming the main source of propagation among people, especially in children. Since 1983, when the first 23-component anti-pneumococcal vaccine was authorized, different conjugated vaccines have been developed according to the circulating serotypes that cause invasive pneumococcal diseases (IPD), reducing the incidence and mortality of these diseases considerably. In November 2021, a group of experts held a virtual meeting to update and analyze the impact that pneumococcal vaccines have generated on the countries' public health, especially during the COVID-19 pandemic. The recommendations that emerged included the need to look for alternatives in serotype-independent vaccines after the introduction of pneumococcal conjugate vaccines (PCV) in the national immunization schedules, as well as to strengthen the surveillance of serotypes, focusing on those not included in the current vaccines. The objective of this report is to communicate the conclusions of the group of experts that in November 2021 analyzed the impact of pneumococcal vaccines on public health in the countries, in order to generate recommendations applicable in Latin America.

Pneumococcal carriage among high-risk adults in a country with nonmandatory pneumococcal vaccination during the coronavirus disease 2019 pandemic.

BACKGROUND: Streptococcus pneumoniae carriage is a prerequisite for clinical infections and is used to make public health decisions on vaccine licensure. Pneumococcal carriage data among high-risk Thai adults are needed before national vaccine program introduction. The association between coronavirus disease 2019 (COVID-19) and pneumococcal carriage were also investigated. METHODS: During the COVID-19 pandemic, a multi-center cross-sectional study was conducted among high-risk Thai adults from September 2021 to November 2022. Pneumococcal carriage and serotypes were investigated using both conventional and molecular methods. Demographics and co-morbidities were determined for carriage while accounting for case clustering from various study sites. RESULTS: A total of 370 individuals were enrolled. The prevalence of pneumococcal carriage, as determined by the molecular method, was 30.8 % (95 % confidence interval (CI): 26.1-35.8), while after excluding non-typeable pneumococci from the oropharyngeal sample, the carriage prevalence was 20.8 % (95 % CI: 16.79-25.31). The serotype coverage rates by pneumococcal vaccine were 12.3 %, 13.1 %, and 16.4 % for PCV13, PCV15 or PCV20, and PPSV23, respectively, while the non-vaccine type was the majority (45.1 %). The most common serotype was 19B/C (35.5 %), followed by 6 A/B/C/D (10.7 %). The age group under 65 years was associated with a higher pneumococcal carriage rate than the age group 85 and older (odds ratio (OR): 5.01, 95 % CI: 1.75-14.36). There was no significant difference between SARS-CoV-2 and carriage status. CONCLUSIONS: The prevalence of pneumococcal carriage in Thais was high. The majority of serotypes were not covered by the vaccine. Further studies on the link between carriage serotypes and disease are required. The magnitude and serotype distribution of carriage were comparable in the SARS-CoV-2 positive and negative groups.

Persistence of Pneumococcal Carriage among Older Adults in the Community despite COVID-19 Mitigation Measures.

Reported rates of invasive pneumococcal disease were markedly lower than normal during the 2020/2021 winter in the Northern Hemisphere, the first year after the start of the COVID-19 pandemic. However, little is known about rates of carriage of pneumococcus among adults during this period. Between October 2020-August 2021, couples in the Greater New Haven Area, USA, were enrolled if both individuals were aged 60 years and above and did not have any individuals under the age of 60 years living in the household. Saliva samples and questionnaires regarding social activities and contacts and medical history were obtained every 2 weeks for a period of 10 weeks. Following culture-enrichment, extracted DNA was tested using qPCR for pneumococcus-specific sequences piaB and lytA. Individuals were considered positive for pneumococcal carriage when Ct values for piaB were ≤40. Results. We collected 567 saliva samples from 95 individuals (47 household pairs and 1 singleton). Of those, 7.1% of samples tested positive for pneumococcus, representing 22/95 (23.2%) individuals and 16/48 (33.3%) households. Study participants attended few social events during this period. However, many participants continued to have regular contact with children. Individuals who had regular contact with preschool and school-aged children (i.e., 2 to 9 year olds) had a higher prevalence of carriage (15.9% versus 5.4%). Despite COVID-19-related disruptions, a large proportion of older adults continued to carry pneumococcus. Prevalence was particularly high among those who had contact with school-aged children, but carriage was not limited to this group. IMPORTANCE Carriage of Streptococcus pneumoniae (pneumococcus) in the upper respiratory tract is considered a prerequisite to invasive pneumococcal disease. During the first year of the COVID-19 pandemic, markedly lower rates of invasive pneumococcal disease were reported worldwide. Despite this, by testing saliva samples with PCR, we found that older adults continued to carry pneumococcus at pre-pandemic levels. Importantly, this study was conducted during a period when transmission mitigation measures related to the COVID-19 pandemic were in place. However, our observations are in line with reports from Israel and Belgium where carriage was also found to persist in children. In line with this, we observed that carriage prevalence was particularly high among the older adults in our study who maintained contact with school-aged children.

The challenge of asymptomatic carriers of COVID-19: A rapid review of literature.

OBJECTIVES: To describe the epidemiological and sociodemographic characteristics of asymptomatic carriers reported in the literature, and to review the strategies used for diagnosis and control. METHODS: Systematic literature review approach. As inclusion criteria, all studies published between January 1 and June 26, 2020, conducted in humans, that reported people who remained asymptomatic of COVID-19. Descriptors were adapted to the interfaces of eight bibliographic databases were configured: PubMed, Ovid, SciELO, Ebsco, Scopus, LILACS, Epistemonikos and Embase. RESULTS: About 45% of the articles reported adult population, thirteen reported mixed population (adult and pediatric). 3 525 asymptomatic people were reported, with an average of 37,1 years [0.5-82 years]. Although the effectiveness of the control and prevention measures was not reported, the identification, isolation and follow-up of contacts stands out as a potential effective mechanism to prevent the transmission. CONCLUSIONS: The use of this information could be relevant to guide evidence-based public health policies and the protection of populations and the improvement of health care that contributes to stopping this pandemic.

Impact of COVID-19 Nonpharmaceutical Interventions on Pneumococcal Carriage Prevalence and Density in Vietnam.

Nonpharmaceutical interventions (NPIs) implemented to contain SARS-CoV-2 have decreased invasive pneumococcal disease. Previous studies have proposed the decline is due to reduced pneumococcal transmission or suppression of respiratory viruses, but the mechanism remains unclear. We undertook a secondary analysis of data collected from a clinical trial to evaluate the impact of NPIs on pneumococcal carriage and density, drivers of transmission and disease, during the COVID-19 pandemic in Ho Chi Minh City, Vietnam. Nasopharyngeal samples from children aged 24 months were assessed in three periods - one pre-COVID-19 period (n = 1,537) and two periods where NPIs were implemented with increasing stringency (NPI period 1 [NPI-1, n = 307], and NPI period 2 [NPI-2, n = 262]). Pneumococci were quantified using lytA quantitative PCR and serotyped by DNA microarray. Overall, capsular, and nonencapsulated pneumococcal carriage and density were assessed in each NPI period compared with the pre-COVID-19 period using unadjusted log-binomial and linear regression. Pneumococcal carriage was generally stable after the implementation of NPIs. In contrast, overall pneumococcal carriage density decreased by 0.44 log10 genome equivalents/mL (95% confidence interval [CI]: 0.19 to 0.69) in NPI-1 and by 0.84 log10 genome equivalents/mL (95% CI: 0.55 to 1.13) in NPI-2 compared with the pre-COVID-19 period. Reductions in overall pneumococcal density were driven by reductions in capsular pneumococci, with no corresponding reduction in nonencapsulated density. As higher pneumococcal density is a risk factor for disease, the decline in density provides a plausible explanation for the reductions in invasive pneumococcal disease that have been observed in many countries in the absence of a substantive reduction in pneumococcal carriage. IMPORTANCE The pneumococcus is a major cause of mortality globally. Implementation of NPIs during the COVID-19 pandemic led to reductions in invasive pneumococcal disease in many countries. However, no studies have conducted a fully quantitative assessment on the impact of NPIs on pneumococcal carriage density, which could explain this reduction. We evaluated the impact of COVID-19 NPIs on pneumococcal carriage prevalence and density in 2,106 children aged 24 months in Vietnam and found pneumococcal carriage density decreased up to 91.5% after NPI introduction compared with the pre-COVID-19 period, which was mainly attributed to capsular pneumococci. Only a minor effect on carriage prevalence was observed. As respiratory viruses are known to increase pneumococcal carriage density, transmission, and disease, this work suggests that interventions targeting respiratory viruses may have the added benefit of reducing invasive pneumococcal disease and explain the reductions observed following NPI implementation.

Impact of COVID-19 Containment Strategies and Meningococcal Conjugate ACWY Vaccination on Meningococcal Carriage in Adolescents.

OBJECTIVES: To examine if COVID-19 containment strategies were associated with reduced pharyngeal carriage of meningococci in adolescents. Also, to observe if carriage prevalence of meningococcal A, C, W and Y differed in meningococcal conjugate ACWY vaccinated and unvaccinated adolescents. DESIGN: Repeat cross-sectional study of pharyngeal carriage. SETTING: In 2020, recruitment commenced from February to March (pre-COVID-19) and recommenced from August to September (during COVID-19 measures) in South Australia. PARTICIPANTS: Eligible participants were between 17 and 25 years of age and completed secondary school in South Australia in 2019. RESULTS: A total of 1338 school leavers were enrolled in 2020, with a mean age of 18.6 years (standard deviation 0.6). Pharyngeal carriage of disease-associated meningococci was higher during the COVID-19 period compared with the pre-COVID-19 period (41/600 [6.83%] vs. 27/738 [3.66%]; adjusted odds ratio [aOR], 2.03; 95% CI: 1.22-3.39; P = 0.01). Nongroupable carriage decreased during COVID period (1.67% vs. 3.79%; aOR, 0.45; 95% CI: 0.22-0.95). Pharyngeal carriage of groups A, C, W and Y was similar among school leavers vaccinated with meningococcal conjugate ACWY (7/257 [2.72%]) compared with those unvaccinated (29/1081 [2.68%]; aOR, 0.86; 95% CI: 0.37-2.02; P = 0.73). Clonal complex 41/44 predominated in both periods. CONCLUSIONS: Meningococcal carriage prevalence was not impacted by public health strategies to reduce severe acute respiratory syndrome coronavirus 2 transmission and is unlikely to be the mechanism for lower meningococcal disease incidence. As international travel resumes and influenza recirculates, clinicians must remain vigilant for signs and symptoms of meningococcal disease. Vaccinating people at the highest risk of invasive meningococcal disease remains crucial despite containment strategies.

Pneumococcal carriage in adults aged 50 years and older in outpatient health care facility during pandemic COVID-19 in Novi Sad, Serbia.

BACKGROUND: Data related to carriage of Streptococcus pneumoniae (Spn) and antimicrobial resistance patterns in middle-aged and older adults are limited. We assessed the carriage of Spn, and its antibiotic resistance patterns, among participants ≥50 years of age living in the city of Novi Sad during the second year of COVID-19 pandemic. METHODS: Analysis of prospectively collected data among participants with or without symptoms of upper respiratory tract infection who visited their elected physicians in the Primary Health Care Centre of Novi Sad (outpatient facility) was conducted from May 18, 2021 to December 7, 2021. Both nasopharyngeal (NP) and oropharyngeal (OP) samples from each participant were collected. RESULTS: A total of 1042 samples from 521 study subjects (1 NP and 1 OP sample from each person) were collected. Sixteen samples from the same number of persons (3.1%, 95% confidence interval: 1.76%-4.94%) were culture positive for the presence of Spn. Overall, the median age of study participants was 71 years (range, 50-93 years; 90th percentile, 77 years), and most (197/521, 37.8%) of them were 70-79 years of age. A majority of the study subjects were: females (324/521; 62.2%), sampled during May and June 2021 (376/521, 72.2%), those who did not have contact with children aged 0-10 years in the family (403/521; 77.4%), without smokers in the household (443/521; 85.0%), and those who did not receive vaccine against Spn (519/521; 99.6%). Out of 16 Spn positive samples, for six participants, Spn carriage serotypes were obtained and there were four vaccine (6A, 11A, 15B, and 18C) serotypes, and two (6C and 35F) non-vaccine serotypes. Remaining 10 (62.50%) samples were non-typeable isolates of pneumococci. Among four vaccine serotypes, two (6A and 18C) were represented in PCV13, and 18C along with the other two (11A and 15B) in PPSV23 vaccine. The highest level of resistance of Spn isolates was observed for erythromycin, (10 or 62.50%), and tetracycline, (7 or 43.75%), one isolate showed resistance to penicillin, ampicillin, and amoxicillin/amoxicillin-clavulanic acid, while none of them were resistant to ceftriaxone, trimethoprim/sulfamethoxazole and levofloxacin. There were three multi-drug resistant isolates; one was identified as 6C (non-vaccine serotype), and two other were non-typeable isolates of Spn. CONCLUSIONS: In this first study conducted in Serbia on Spn carriage in adults ≥50 years of age, we found low prevalence of Spn carriage and identified 6 serotypes of Spn, four of which were represented in vaccines. These results may support future Spn colonization studies among middle-aged and older adults.

Effect of the of 10-valent pneumococcal conjugate vaccine in Nepal 4 years after introduction: an observational cohort study.

BACKGROUND: In Nepal, Streptococcus pneumoniae (pneumococcus) is a common cause of bacterial pneumonia in children, and is a major health concern. There are few data on the effect of vaccination on the disease or colonisation with pneumococci in the nasopharynx of children in this setting. The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the routine infant immunisation schedule in Nepal in 2015. We aimed to investigate the effect of the introduction of PCV10 on pneumococcal carriage and disease in children in Nepal. METHODS: We did an observational cohort study in children in Nepal. The hospital surveillance study took place in Patan Hospital, Kathmandu, and community studies in healthy children took place in Kathmandu and Okhaldhunga district. For the surveillance study, all children admitted to Patan Hospital between March 20, 2014, and Dec 31, 2019, aged between 2 months and 14 years with clinician-suspected pneumonia, were eligible for enrolment. For the community study, healthy children aged 0-8 weeks, 6-23 months, and 24-59 months were recruited from Kathmandu, and healthy children aged 6-23 months were recruited from Okhaldhunga. We assessed the programmatic effect of PCV10 introduction using surveillance for nasopharyngeal colonisation, pneumonia, and invasive bacterial disease from 1·5 years before vaccine introduction and 4·5 years after vaccine introduction. For the surveillance study, nasopharyngeal swabs, blood cultures, and chest radiographs were obtained from children admitted to Patan Hospital with suspected pneumonia or invasive bacterial disease. For the community study, nasopharyngeal swabs were obtained from healthy children in the urban and rural settings. Pneumonia outcomes were analysed using log-binomial models and adjusted prevalence ratios (aPR) comparing each calendar year after the introduction of the vaccine into the national programme with the pre-vaccine period (2014-15), adjusted for calendar month, age, and sex. FINDINGS: Between March 20, 2014, and Dec 31, 2019, we enrolled 2051 children with suspected pneumonia, and 11 354 healthy children (8483 children aged 6-23 months, 761 aged 24-59 months, and 2110 aged 0-8 weeks) to assess nasopharyngeal colonisation. Among clinical pneumonia cases younger than 2 years, vaccine serotype carriage declined 82% (aPR 0·18 [95% CI 0·07-0·50]) by 2019. There was no decrease in vaccine serotype carriage in cases among older unvaccinated age groups. Carriage of the additional serotypes in PCV13 was 2·2 times higher by 2019 (aPR 2·17 [95% CI 1·16-4·05]), due to increases in serotypes 19A and 3. Vaccine serotype carriage in healthy children declined by 75% in those aged 6-23 months (aPR 0·25 [95% CI 0·19-0·33]) but not in those aged 24-59 months (aPR 0·59 [0·29-1·19]). A decrease in overall vaccine serotype carriage of 61% by 2019 (aPR 0·39 [95% CI 0·18-0·85]) was also observed in children younger than 8 weeks who were not yet immunised. Carriage of the additional PCV13 serotypes in children aged 6-23 months increased after PCV10 introduction for serotype 3 and 19A, but not for serotype 6A. The proportion of clinical pneumonia cases with endpoint consolidation on chest radiographs declined from 41% in the pre-vaccine period to 25% by 2018, but rose again in 2019 to 36%. INTERPRETATION: The introduction of the PCV10 vaccine into the routine immunisation programme in Nepal has reduced vaccine serotype carriage in both healthy children and children younger than 2 years with pneumonia. Increases in serotypes 19A and 3 highlight the importance of continued surveillance to monitor the effect of vaccine programmes. This analysis demonstrates a robust approach to assessing vaccine effect in situations in which pneumococcal disease endpoint effectiveness studies are not possible. FUNDING: Gavi, the Vaccine Alliance and the World Health Organization.

Association of pneumococcal carriage in infants with the risk of carriage among their contacts in Nha Trang, Vietnam: A nested cross-sectional survey.

BACKGROUND: Infants are at highest risk of pneumococcal disease. Their added protection through herd effects is a key part in the considerations on optimal pneumococcal vaccination strategies. Yet, little is currently known about the main transmission pathways to this vulnerable age group. Hence, this study investigates pneumococcal transmission routes to infants in the coastal city of Nha Trang, Vietnam. METHODS AND FINDINGS: In October 2018, we conducted a nested cross-sectional contact and pneumococcal carriage survey in randomly selected 4- to 11-month-old infants across all 27 communes of Nha Trang. Bayesian logistic regression models were used to estimate age specific carriage prevalence in the population, a proxy for the probability that a contact of a given age could lead to pneumococcal exposure for the infant. We used another Bayesian logistic regression model to estimate the correlation between infant carriage and the probability that at least one of their reported contacts carried pneumococci, controlling for age and locality. In total, 1,583 infants between 4 and 13 months old participated, with 7,428 contacts reported. Few infants (5%, or 86 infants) attended day care, and carriage prevalence was 22% (353 infants). Most infants (61%, or 966 infants) had less than a 25% probability to have had close contact with a pneumococcal carrier on the surveyed day. Pneumococcal infection risk and contact behaviour were highly correlated: If adjusted for age and locality, the odds of an infant's carriage increased by 22% (95% confidence interval (CI): 15 to 29) per 10 percentage points increase in the probability to have had close contact with at least 1 pneumococcal carrier. Moreover, 2- to 6-year-old children contributed 51% (95% CI: 39 to 63) to the total direct pneumococcal exposure risks to infants in this setting. The main limitation of this study is that exposure risk was assessed indirectly by the age-dependent propensity for carriage of a contact and not by assessing carriage of such contacts directly. CONCLUSIONS: In this study, we observed that cross-sectional contact and infection studies could help identify pneumococcal transmission routes and that preschool-age children may be the largest reservoir for pneumococcal transmission to infants in Nha Trang, Vietnam.

Risk Factors Associated With COVID-19 Transmission Among US Air Force Trainees in a Congregant Setting.

Importance: Owing to concerns of coronavirus disease 2019 (COVID-19) outbreaks, many congregant settings are forced to close when cases are detected because there are few data on the risk of different markers of transmission within groups. Objective: To determine whether symptoms and laboratory results on the first day of COVID-19 diagnosis are associated with development of a case cluster in a congregant setting. Design, Setting, and Participants: This cohort study of trainees with COVID-19 from May 11 through August 24, 2020, was conducted at Joint Base San Antonio-Lackland, the primary site of entry for enlistment in the US Air Force. Symptoms and duration, known contacts, and cycle threshold for trainees diagnosed by reverse transcription-polymerase chain reaction were collected. A cycle threshold value represents the number of nucleic acid amplification cycles that occur before a specimen containing the target material generates a signal greater than the predetermined threshold that defines positivity. Cohorts with 5 or more individuals with COVID-19 infection were defined as clusters. Participants included 10 613 trainees divided into 263 parallel cohorts of 30 to 50 people arriving weekly for 7 weeks of training. Exposures: All trainees were quarantined for 14 days on arrival. Testing was performed on arrival, on day 14, and anytime during training when indicated. Protective measures included universal masking, physical distancing, and rapid isolation of trainees with COVID-19. Main Outcomes and Measures: Association between days of symptoms, specific symptoms, number of symptoms, or cycle threshold values of individuals diagnosed with COVID-19 via reverse transcription-polymerase chain reaction and subsequent transmission within cohorts. Results: In this cohort study of 10 613 US Air Force basic trainees in 263 cohorts, 403 trainees (3%) received a diagnosis of COVID-19 in 129 cohorts (49%). Among trainees with COVID-19 infection, 318 (79%) were men, and the median (interquartile range [IQR]) age was 20 (19-23) years; 204 (51%) were symptomatic, and 199 (49%) were asymptomatic. Median (IQR) cycle threshold values were lower in symptomatic trainees compared with asymptomatic trainees (21.2 [18.4-27.60] vs 34.8 [29.3-37.4]; P < .001). Cohorts with clusters of individuals with COVID-19 infection were predominantly men (204 cohorts [89%] vs 114 cohorts [64%]; P < .001), had more symptomatic trainees (146 cohorts [64%] vs 53 cohorts [30%]; P < .001), and had more median (IQR) symptoms per patient (3 [2-5] vs 1 [1-2]; P < .001) compared with cohorts without clusters. Within cohorts, subsequent development of clusters of 5 or more individuals with COVID-19 infection compared with those that did not develop clusters was associated with cohorts that had more symptomatic trainees (31 of 58 trainees [53%] vs 43 of 151 trainees [28%]; P = .001) and lower median (IQR) cycle threshold values (22.3 [18.4-27.3] vs 35.3 [26.5-37.8]; P < .001). Conclusions and Relevance: In this cohort study of US Air Force trainees living in a congregant setting during the COVID-19 pandemic, higher numbers of symptoms and lower cycle threshold values were associated with subsequent development of clusters of individuals with COVID-19 infection. These values may be useful if validated in future studies.

Estimating the Proportion of Asymptomatic COVID-19 Cases in an Italian Region with Intermediate Incidence during the First Pandemic Wave: An Observational Retrospective Study.

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.

Asymptomatic carriage and transmission of SARS-CoV-2: What do we know?

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.

Air dispersal of meticillin-resistant Staphylococcus aureus in residential care homes for the elderly: implications for transmission during the COVID-19 pandemic.

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.

Infant Pneumococcal Carriage in Belgium Not Affected by COVID-19 Containment Measures.

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.

Clinical characteristics and COVID-19 outcomes in a regional cohort of pediatric patients with rheumatic diseases.

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.

Efficient and targeted COVID-19 border testing via reinforcement learning.

Throughout the coronavirus disease 2019 (COVID-19) pandemic, countries have relied on a variety of ad hoc border control protocols to allow for non-essential travel while safeguarding public health, from quarantining all travellers to restricting entry from select nations on the basis of population-level epidemiological metrics such as cases, deaths or testing positivity rates1,2. Here we report the design and performance of a reinforcement learning system, nicknamed Eva. In the summer of 2020, Eva was deployed across all Greek borders to limit the influx of asymptomatic travellers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and to inform border policies through real-time estimates of COVID-19 prevalence. In contrast to country-wide protocols, Eva allocated Greece's limited testing resources on the basis of incoming travellers' demographic information and testing results from previous travellers. By comparing Eva's performance against modelled counterfactual scenarios, we show that Eva identified 1.85 times as many asymptomatic, infected travellers as random surveillance testing, with up to 2-4 times as many during peak travel, and 1.25-1.45 times as many asymptomatic, infected travellers as testing policies that utilize only epidemiological metrics. We demonstrate that this latter benefit arises, at least partially, because population-level epidemiological metrics had limited predictive value for the actual prevalence of SARS-CoV-2 among asymptomatic travellers and exhibited strong country-specific idiosyncrasies in the summer of 2020. Our results raise serious concerns on the effectiveness of country-agnostic internationally proposed border control policies3 that are based on population-level epidemiological metrics. Instead, our work represents a successful example of the potential of reinforcement learning and real-time data for safeguarding public health.

Seroprevalence of IgM and IgG Antibodies against SARS-CoV-2 in Asymptomatic People in Wuhan: Data from a General Hospital Near South China Seafood Wholesale Market during March to April in 2020.

The aim of this study was to estimate the seroprevalence of immunoglobulin M (IgM) and G (IgG) antibodies against SARS-CoV-2 in asymptomatic people in Wuhan. This was a cross-sectional study, which enrolled 18,712 asymptomatic participants from 154 work units in Wuhan. Pearson Chi-square test, t-test, and Mann-Whitney test were used to compare the standardized seroprevalence of IgG and IgM for age and gender between different groups. The results indicated the standardized seroprevalence of IgG and IgM showed a downward trend and was significantly higher among females than males. Besides, different geographic areas and workplaces had different seroprevalence of IgG among asymptomatic people, and the number of abnormalities in CT imaging were higher in IgG antibody-positive cases than IgG-negative cases. We hope these findings can provide references for herd immunity investigation and provide basis for vaccine development.

The incidence, characteristics and outcomes of pregnant women hospitalized with symptomatic and asymptomatic SARS-CoV-2 infection in the UK from March to September 2020: A national cohort study using the UK Obstetric Surveillance System (UKOSS).

BACKGROUND: There is a lack of population level data on risk factors, incidence and impact of SARS-CoV-2 infection in pregnant women and their babies. The primary aim of this study was to describe the incidence, characteristics and outcomes of hospitalized pregnant women with symptomatic and asymptomatic SARS-CoV-2 in the UK compared to pregnant women without SARS-CoV-2. METHODS AND FINDINGS: We conducted a national, prospective cohort study of all hospitalized pregnant women with confirmed SARS-CoV-2 from 01/03/2020 to 31/08/2020 using the UK Obstetric Surveillance System. Incidence rates were estimated using national maternity data. Overall, 1148 hospitalized women had confirmed SARS-CoV-2 in pregnancy, 63% of which were symptomatic. The estimated incidence of hospitalization with symptomatic SARS-CoV-2 was 2.0 per 1000 maternities (95% CI 1.9-2.2) and for asymptomatic SARS-CoV-2 was 1.2 per 1000 maternities (95% CI 1.1-1.4). Compared to pregnant women without SARS-CoV-2, women hospitalized with symptomatic SARS-CoV-2 were more likely to be overweight or obese (adjusted OR 1.86, (95% CI 1.39-2.48) and aOR 2.07 (1.53-2.29)), to be of Black, Asian or Other minority ethnic group (aOR 6.24, (3.93-9.90), aOR 4.36, (3.19-5.95) and aOR 12.95, (4.93-34.01)), and to have a relevant medical comorbidity (aOR 1.83 (1.32-2.54)). Hospitalized pregnant women with symptomatic SARS-CoV-2 were more likely to be admitted to intensive care (aOR 57.67, (7.80-426.70)) but the absolute risk of poor outcomes was low. Cesarean births and neonatal unit admission were increased regardless of symptom status (symptomatic aOR 2.60, (1.97-3.42) and aOR 3.08, (1.99-4.77); asymptomatic aOR 2.02, (1.52-2.70) and aOR 1.84, (1.12-3.03)). The risks of stillbirth or neonatal death were not significantly increased, regardless of symptom status. CONCLUSIONS: We have identified factors that increase the risk of symptomatic and asymptomatic SARS-CoV-2 in pregnancy. Clinicians can be reassured that the majority of women do not experience severe complications of SARS-CoV-2 in pregnancy.

[Transmission of SARS-CoV-2 through contact with a SARS-CoV-2-infected individual in the presymptomatic or asymptomatic state in Japan: A case series].

Objectives　There is little evidence supporting the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from presymptomatic or asymptomatic SARS-CoV-2-infected individuals in Japan, where the incidence of SARS-CoV-2 infection is lower than that in other developed countries. This study aimed to determine whether SARS-CoV-2 transmission can occur from presymptomatic or asymptomatic SARS-CoV-2-infected individuals.Methods　We surveyed all directors of Japanese public health centers for index cases and secondary patients who possibly contracted SARS-CoV-2 infection from a presymptomatic or asymptomatic SARS-CoV-2-infected individual who came under their care before June 20, 2020. The professional staff at the centers routinely perform contact tracing of infected persons based on the guidelines of the Infection Control Act. Four authors independently reviewed reports of 9 index cases of SARS-CoV-2-infected individuals with 17 secondary patients from 8 prefectures and examined the cases to determine whether transmission from a SARS-CoV-2-infected individual in the presymptomatic or asymptomatic state occurred.Results　We reported 7 index cases with 13 secondary patients. 1) An elderly woman acquired SARS-CoV-2 infection from her sustained asymptomatic granddaughter at home, 2) 4 guests and 1 accompanying child waiting at a hair salon acquired infection from the presymptomatic female hair stylist, 3) 2 inpatients acquired infection from a presymptomatic nurse while providing nursing care in close contact, 4) an elderly couple acquired SARS-CoV-2 infection from their presymptomatic relative who was in the 50s during household care at their home, 5) a man acquired SARS-CoV-2 infection from a presymptomatic adult neighbor in an enclosed space with poor ventilation, 6) a presymptomatic man had transmitted infection to another man at a coffee shop while having a discussion on business, and 7) a man in his 50s acquired SARS-CoV-2 infection from a presymptomatic man during 50 minutes of close contact at their office and in a car. These secondary patients had no other likely routes of infection. The interval between the date of symptom onset in the presymptomatic index case and the secondary patient ranged from 2 to 6 days. The incidence rates at the time these infections occurred in the corresponding prefectures ranged from 0.00 to 6.56 cases/1 million person-days.Conclusion　We report the first case of SARS-CoV-2 transmission from a sustained asymptomatic index case in Japan. All secondary patients came into close contact with presymptomatic index cases in areas with poor ventilation.

Analysis of COVID-19 pandemics in Kazakhstan.

BACKGROUND: This study aimed to analyze the demographic and epidemiological features of identified COVID-19 cases in Kazakhstan. STUDY DESIGN: A cross-sectional study. METHODS: This cross-sectional study aimed to analyze COVID-19 cases (n=5116) collected from March 13 to June 6, 2020, in Kazakhstan. The data were obtained from a state official medical electronic database. The study investigated the geographic and demographic data of patients as well as the association of COVID-19 cases with gender and age. The prevalence of symptoms, the presence of comorbidities, complications, and COVID-19 mortality were determined for all patients. RESULTS: The mean±SD age of the patients in this study was 34.8±17.6 years, and the majority (55.7%) of COVID-19 cases were male and residents of cities (79.6%). In total, 80% of the cases had the asymptomatic/mild form of the disease. Cough (20.8 %) and sore throat (17.1%) were the most common symptoms among patients, and pneumonia was diagnosed in 1 out of 5 cases. Acute respiratory distress syndrome (ARDS) was recorded in 1.2% of the patients. The fatality rate was 1% in the study population and lethality was 2.6 times higher in males compared to females.  Each additional year in age increased the probability of COVID-19 infection by 1.06 times. The presence of cardiovascular, diabetes, respiratory, and kidney diseases affected the rate of mortality (P<0.05). CONCLUSION: The results demonstrated a high proportion (40%) of the asymptomatic type of coronavirus infection in the Kazakhstan population. The severity of COVID-19 symptoms and lethality were directly related to the age of patients and the presence of comorbidities.