Decreasing Incidence of the Multisystem Inflammatory Syndrome in Children Over 3 Pandemic Waves.

In this nationwide retrospective study, a substantial decline in the incidence of multisystem inflammatory syndrome in children over 3 successive pandemic waves characterized by different severe acute respiratory syndrome coronavirus 2 variants was documented-from 3.4 of 1000 to 1.1 of 1000 and finally to 0.25 of 1000 confirmed severe acute respiratory syndrome coronavirus 2 positive cases (P < 0.0001), respectively, whereas clinical findings and severity did not significantly vary.

Clinical outcome in newborns of perinatally COVID-19 infected women.

OBJECTIVE: Maternal COVID-19 infection during pregnancy has been associated with adverse neonatal outcomes, such as prematurity and neonatal morbidity. Those adverse events are mainly attributed to maternal factors, rather than to the neonatal infection itself. Our aim is to add our experience and present the neonatal outcome of neonates born to mothers with perinatal SARS-CoV-2 infection. METHODS: This is a prospective case-control study with data from two Academic Tertiary Referral Hospitals in Greece. Electronic records of all births from SARS-CoV-2 positive mothers between March 2020 and April 2021 were analyzed. Demographic data, the severity of maternal COVID-19 disease, gestational age (GA), mode of delivery, birth weight (BW), need for resuscitation and/or supplemental oxygen and duration of hospitalization were recorded. A comparison with 2:1 matched neonates according to sex, GA, and BW born to SARS-CoV-2 negative mothers during the same period was performed. Chi-square and Mann-Whitney U test were used for categorical and non-categorical variables respectively. RESULTS: A total of eighty-one neonates were born to SARS-CoV-2 positive mothers during this period. Forty-three percent of pregnant mothers were asymptomatic. Median GA and median BW were 38 weeks (Interquantile range (IQR): 36-39 weeks) and 2940 gr (IQR: 2560-3340 gr) respectively. Prematurity was observed in 24.7% of the cases. Only 2 (2.4%) neonates were PCR positive after delivery. SARS-CoV-2 positive women were more likely to undergo Cesarean section. APGAR score at 5 min and the need for resuscitation did not differ between the two groups. In comparison with the control group, neonates born to SARS-CoV-2 positive mothers presented with gastrointestinal symptoms (53.6% vs 5.1%, p-value= <.001) and hospitalization was longer, mostly due to maternal factors. CONCLUSION: In our study neonatal positivity was limited and no vertical transmission was noted. Neonatal outcomes were comparable to the control group. However, the presence of gastrointestinal symptoms in neonates born to PCR-positive women compared to controls needs further investigation.

Early human milk lactoferrin during SARS-CoV-2 infection.

BACKGROUND/AIM: Early human milk provides protection against viral infections due to its high nutritional value, abundance of maternal antibodies and the specific role of lactoferrin (Lf). Lf blocks the early interaction between SARS-CoV-2 and host cells by binding to specific cell receptors and has been proposed as a preventative and adjunct treatment for COVID-19. This preliminary report aimed to investigate concentrations of Lf in early milk of SARS-CoV-2 positive mothers versus non-infected controls. MATERIAL AND METHODS: In a cohort of 13 SARS-CoV-2 positive mothers and 15 controls, breast milk concentrations of Lf were determined by ELISA on day 3 postpartum. Additionally, colostrum samples of infected mothers were analyzed for SARS-CoV-2 RNA detection and anti-SARS-CoV-2 IgA and IgG determination using RT-qPCR and ELISA, respectively. RESULTS: No differences were found in breast milk Lf concentrations between SARS-CoV-2 positive mothers and controls. In a subgroup analysis, however, symptomatic mothers (n = 7) presented with lower breast milk Lf concentrations, as compared to asymptomatic mothers (p = .041) and healthy controls (p = .029). All milk samples tested negative for SARS-CoV-2 RNA. Early human milk of infected mothers displayed IgA and IgG SARS-CoV-2 specific reactivity. CONCLUSIONS: Our data showed a different early breast milk Lf "profile" between COVID-19 symptomatic and asymptomatic mothers with the latter being at non-COVID levels (control group). SARS-CoV-2 RNA was not detected in any breast milk sample. Early human milk Lf levels are potentially influenced by the severity of maternal COVID-19 infection during pregnancy.

Seroprevalence of anti-SARS-CoV-2 antibodies among children and their parents in Greece.

School closures were enforced as measures to restrain the COVID-19 pandemic, based on the assumption that young children may play a key role in SARS-CoV-2 spread. This study aims to determine the prevalence of SARS-CoV-2 IgG antibodies in children and corresponding parents, in order to improve surveillance and estimate the prevalence of asymptomatic or subclinical COVID-19 cases. A prospective multicenter study was conducted between March and June 2021 in Greece. Children admitted to the hospital or examined in outpatient clinics for reasons other than COVID-19 and their parents were tested for anti-Spike SARS-CoV-2 IgG in serum. A questionnaire about clinical and demographic data was completed. The study included 823 participants: 427 children and 396 corresponding parents. The overall seroprevalence was 16.4% in parents and 13.8% in children. Among families with ≥ 1 seropositive child or parent, the combination of a seropositive parent and a corresponding seronegative child was 29.6%, a seronegative parent and a corresponding seropositive child was 24.7%, and a seropositive child with a corresponding seropositive parent was 45.7%. Age, level of education, and school or work attendance were not significantly associated with increased seropositivity. On the contrary, ethnic minority of Roma, close contact with known COVID-19 case, previous symptoms consistent with COVID-19, and mass gatherings were risk factors for seropositivity. CONCLUSION: The spread of SARS-CoV-2 during a period of lockdown in Greece was low in children and comparable to adults most likely due to intrafamilial transmission. Accordingly, it is unlikely that children have boosted virus transmission. WHAT IS KNOWN: • In the earliest months of the pandemic, it was demonstrated that children had significantly lower seroprevalence rates than the older age groups, due to the fact that children had decreased exposure to the virus, because of early public health interventions, such as school and day care closure. • Later, further studies reported that children have similar incidence rate of SARS-CoV-2 infection compared to adults in households and community settings. WHAT IS NEW: • In this seroprevalence study, the spread of SARS-CoV-2 infection during a period of lockdown in Greece with the predominance of the Alpha-variant was particularly low in children and comparable to adults, most likely due to intrafamilial transmission. • These study findings will be useful for decisions regarding non-pharmaceutical interventions during the pandemic, and especially, to guide in designing and implementing appropriate containment measures for schools and social gatherings.

COVID-19 in patients with pulmonary alveolar proteinosis: a European multicentre study.

Adult PAP patients experience similar #COVID19 rates to the general population, and high rates of hospitalisation and deaths, underscoring their vulnerability and the need for measures to prevent infection. The impact of iGM-CSF must be considered. https://bit.ly/3M0wKnZ.

The Psychological Impact of COVID-19 Admission on Families: Results from a Nationwide Sample in Greece.

The aim of the present study was to assess the psychological impact of hospitalization during the COVID-19 pandemic on parents and their offspring. We performed a nationwide cross-sectional study in Greece based on an Internet questionnaire survey. A convenience sample of parents whose offspring had been hospitalized due to COVID-19 (including multisystem inflammatory syndrome in children, MIS-C), diagnosed with COVID-19 but not hospitalized, and hospitalized for another reason during the pandemic were enrolled. Parental stress was assessed using the Perceived Stress Scale (PSS) and the Revised Impact of Event Scale (IES-R) tools, and childhood mental wellbeing with the Children's Revised Impact of Event 13 (CRIES-13) scale. Out of 214 received responses, stress levels were significantly higher in parents whose children had been admitted for COVID-19 or MIS-C versus those not admitted or admitted for other reasons (p < 0.001, for PSS/IES-R). Parental and childhood stress levels were correlated. In the multivariable linear regression analysis, children's hospitalization because of COVID-19 or MIS-C, younger parental age, the existence of comorbidities, and another family member's hospitalization because of COVID-19 were independent factors for higher stress. In light of the above, stricter hospital admission criteria for COVID-19 could be implemented, and psychological support for eventually admitted families may be beneficial.

Time Lag between COVID-19 Diagnosis and Symptoms Onset for Different Population Groups: Evidence That Self-Testing in Schools Was Associated with Timely Diagnosis among Children.

Early identification of COVID-19 cases has been vital for reducing transmission and enabling treatment. In Greece, in autumn 2021 when Delta was the predominant circulating variant, unvaccinated citizens had to be tested before attending activities, and self-testing was required twice a week for students (5-17 years). Here, we describe the time of diagnosis by age group and possible exposure to assess testing strategies (September to November 2021). Information on the presence of symptoms at the time of diagnosis was available for 69,298 cases; 24,855 (36%) were asymptomatic or tested the same day as onset (early diagnosis), 21,310 (31%) reported testing one day after, and 23,133 (33%) did so two or more days after the onset of symptoms. The median lag was 2 days (1-14). Early diagnosis significantly differed among age groups (p-value < 0.001) and was higher among children. For every one-year increase of age, the odds of an early diagnosis were reduced by 1%. Cases exposed during training activities or in settings such as accommodation centers and hospitals were more frequently diagnosed early. The percentage of persons having a positive self-test before a rapid test/PCR diagnosis ranged from 7% in the age group of 60 years and above to 86% in the age group of 5-17 years. The provision of self-tests in schools and increased testing in closed settings led to an earlier diagnosis and probably to a decreased transmission of the virus in the period during which Delta was the predominant variant in Greece. However, more effort is needed for early diagnosis of adults in the community, especially after the onset of symptoms.

Action is needed to tackle the clinical, psychological and socioeconomic impact of perinatal COVID-19.

The COVID-19 pandemic has turned perinatal healthcare into a worldwide public health challenge. Although initial data did not demonstrate pregnancy as a more susceptible period to adverse outcomes of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, an increasing number of reports now certify maternal illness as a high-risk condition for the development of maternal-fetal complications. Despite the rarity of SARS-CoV-2 vertical transmission, severe maternal illness might induce adverse perinatal and neonatal outcomes. Additionally, perinatal COVID-19 data may raise concerns about long-term harmful consequences to the offspring in the framework of non-communicable diseases. The World Health Organisation, as well as scientific literature, consider the protection of the maternal-fetal dyad against COVID-19 as a critical issue and, therefore, strongly promote and encourage the vaccination of pregnant and lactating women. Furthermore, the pandemic has triggered an unprecedented recession, leading to historic levels of unemployment and deprivation, while health, societal, economic and gender inequities particularly affecting low-income and middle-income countries, have increased. This mini-review provides an updated brief report on historical, clinical, psychological and socioeconomic aspects of the COVID-19 pandemic based on 10 lectures presented at the 9th Maria-Delivoria-Papadopoulos Perinatal Symposium, held virtually on 19 March 2022.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection Versus Vaccination in Pregnancy: Implications for Maternal and Infant Immunity.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with adverse maternal and neonatal outcomes, yet uptake of SARS-CoV-2 vaccines during pregnancy and lactation has been slow. As a result, millions of pregnant and lactating women and their infants remain susceptible to the virus. METHODS: We measured spike-specific immunoglobulin G (anti-S IgG) and immunoglobulin A (anti-S IgA) in serum and breastmilk (BM) samples from 3 prospective mother-infant cohorts recruited in 2 academic medical centers. The primary aim was to determine the impact of maternal SARS-CoV-2 immunization vs infection and their timing on systemic and mucosal immunity. RESULTS: The study included 28 mothers infected with SARS-CoV-2 in late pregnancy (INF), 11 uninfected mothers who received 2 doses of the BNT162b2 vaccine in the latter half of pregnancy (VAX-P), and 12 uninfected mothers who received 2 doses of BNT162b2 during lactation. VAX dyads had significantly higher serum anti-S IgG compared to INF dyads (P < .0001), whereas INF mothers had higher BM:serum anti-S IgA ratios compared to VAX mothers (P = .0001). Median IgG placental transfer ratios were significantly higher in VAX-P compared to INF mothers (P < .0001). There was a significant positive correlation between maternal and neonatal serum anti-S IgG after vaccination (r = 0.68, P = .013), but not infection. CONCLUSIONS: BNT161b2 vaccination in late pregnancy or lactation enhances systemic immunity through serum anti-S immunoglobulin, while SARS-CoV-2 infection induces mucosal over systemic immunity more efficiently through BM immunoglobulin production. Next-generation vaccines boosting mucosal immunity could provide additional protection to the mother-infant dyad. Future studies should focus on identifying the optimal timing of primary and/or booster maternal vaccination for maximal benefit.

Transmission of Infections during Cardiopulmonary Resuscitation.

Cardiopulmonary resuscitation (CPR) is an emergency lifesaving endeavor, performed in either the hospital or outpatient settings, that significantly improves outcomes and survival rates when performed in a timely fashion. As with any other medical procedure, CPR can bear potential risks not only for the patient but also for the rescuer. Among those risks, transmission of an infectious agent has been one of the most compelling triggers of reluctance to perform CPR among providers. The concern for transmission of an infection from the resuscitated subject may impede prompt initiation and implementation of CPR, compromising survival rates and neurological outcomes of the patients. Infections during CPR can be potentially acquired through airborne, droplet, contact, or hematogenous transmission. However, only a few cases of infection transmission have been actually reported globally. In this review, we present the available epidemiological findings on transmission of different pathogens during CPR and data on reluctance of health care workers to perform CPR. We also outline the levels of personal protective equipment and other protective measures according to potential infectious hazards that providers are potentially exposed to during CPR and summarize current guidelines on protection of CPR providers from international societies and stakeholders.

COVID-19 in patients with Pulmonary Alveolar Proteinosis A European multicenter study

Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) signaling is essential in both alveolar macrophages (AMs) differentiation and activation of lung immune cells [1]. Differentiated AMs are crucial in both the elimination of alveolar microbes and surfactant clearance. The disruption of the GM-CSF axis in alveolar macrophages leads to the development of pulmonary alveolar proteinosis (PAP) [1]. In the majority of patients this relates to the presence of autoantibodies against GM-CSF autoimmune (a)PAP but there are multiple other causes [1, 2, 3]. GM-CSF deficient animals may have impaired lung inflammatory response to commensal microbes and humans with PAP may occasionally develop opportunistic lung infections [4]. The mainstay of pharmacological treatment in aPAP is inhaled GM-CSF which is off-label but increasingly used worldwide [5, 6, 7, 8, 9].

Autoimmune pulmonary alveolar proteinosis in children.

In childhood, a multitude of causes lead to pulmonary alveolar proteinosis (PAP), an excessive surfactant accumulation in the alveolar space, limiting gas exchange. Autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) causing autoimmune PAP, the principal aetiology in adults, are rare. In this first case series on autoimmune PAP, we detail the presentation and management issues of four children. Whereas three children presented insidiously with progressive dyspnoea, one was acutely sick with suspected pneumonia. During management, one patient was hospitalised with coronavirus disease 2019, noninvasively ventilated, and recovered. All treatment modalities known from adults including whole-lung lavage, augmentation of GM-CSF by inhaled GM-CSF, removal of neutralising antibody by plasmapheresis and interruption of antibody production using rituximab were considered; however, not all options were available at all sites. Inhaled GM-CSF appeared to be a noninvasive and comfortable therapeutic approach. The management with best benefit-to-harm ratio in autoimmune PAP is unknown and specialised physicians must select the least invasive and most effective treatment. To collect this cohort in a rare condition became feasible as patients were submitted to an appropriate registry. To accelerate the authorisation of novel treatments for autoimmune PAP, competent authorities should grant an inclusion of adolescents into trials in adults.

Population-based study of influenza and invasive meningococcal disease among Greek children during the COVID-19 pandemic.

BACKGROUND: Aiming to the containment of the coronavirus disease 2019 (COVID-19) pandemic, governments worldwide have implemented a series of non-pharmaceutical interventions. Many of them and especially school closures have impacted the circulation of multiple airborne pathogens among children and adolescents. This study investigates the incidence of influenza and invasive meningococcal disease among children aged 0-14 years in Greece during the COVID-19 pandemic. METHODS: Data regarding the number of influenza-like illness cases, influenza-related paediatric intensive care unit (PICU) admissions and invasive meningococcal disease cases among children 0-14 years old were obtained from the National Public Health Organization. The incidence of the two diseases during the COVID-19 pandemic period (2020/2021) was compared with that of the six preceding seasons (2014-2019). RESULTS: A notable decrease was observed in both influenza and invasive meningococcal disease cases during the period 2020/2021 compared with the years 2014-2019. The mean annual rate of influenza-like illness cases and influenza-related PICU admissions in children 0-14 years old has reduced by 66.9% and 100%, respectively, while the mean annual invasive meningococcal disease rate has declined by 70%. Both weekly influenza-like illness and monthly invasive meningococcal disease rates were significantly decreased. CONCLUSIONS: The activity of influenza and invasive meningococcal disease in the children and adolescents of Greece has decreased during the COVID-19 pandemic period. Reduced transmission is likely related to the public health measures that were implemented to control the pandemic. The value of these measures may have relevance to the future management of influenza or invasive meningococcal disease epidemics.

Global Perspectives on Immunization Against SARS-CoV-2 During Pregnancy and Priorities for Future Research: An International Consensus Paper From the World Association of Infectious Diseases and Immunological Disorders.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with a higher risk for severe morbidity and mortality when compared with infection in non-pregnant women of childbearing age. An increasing number of countries recommend immunization against SARS-CoV-2 in pregnant women. Recent studies provide preliminary and supportive evidence on safety, immunogenicity and effectiveness of coronavirus disease 2019 (COVID-19) vaccines in pregnant women; however, important knowledge gaps remain which warrant further studies. This collaborative consensus paper provides a review of the current literature on COVID-19 vaccines in pregnant women, identifies knowledge gaps and outlines priorities for future research to optimize protection against SARS-CoV-2 in the pregnant women and their infants.

Clinical symptoms associated with laboratory findings and placental histopathology in full-term, non-infected neonates born to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive mothers.

This study comprehensively examines clinical symptoms, laboratory findings, and placental pathology in 40 cases of singleton full-term SARS-CoV-2 negative neonates. Their mothers, previously healthy, with uncomplicated pregnancies, were infected peripartum and presented COVID-19 symptoms of various severity. Neonates had predominately diarrhea, the yet unreported absent sucking reflex, elevated COVID-19 inflammatory and ischemia/asphyxia markers as serum ferritin, interleukin-6 and cardiac troponin-T, while placentas demonstrated mild vascular and/or inflammatory lesions. We hypothesize that the above placental lesions may be associated with transient perinatal hypoxia resulting in absent sucking reflex, as well as with inflammatory cytokines transfer causing diarrhea.

Factors Associated with Healthcare Workers' (HCWs) Acceptance of COVID-19 Vaccinations and Indications of a Role Model towards Population Vaccinations from a Cross-Sectional Survey in Greece, May 2021.

A Knowledge, Attitudes and Practices (KAP) study was conducted at the end of May 2021 engaging 1456 healthcare workers (HCWs) from 20 hospitals throughout Greece. Acceptance of vaccination against coronavirus disease 2019 (COVID-19) was estimated at 77.7%, with lower vaccine acceptance identified in nurses compared to physicians. Fears related to vaccine safety, lack of information and general knowledge about vaccinations, influenza vaccine acceptance, education level and years of practice were among the factors independently associated with vaccine acceptance. A strong association was identified between vaccination of HCWs in each health region and the population coverage, indicating that HCWs may be role models for the general population. Information campaigns should continue despite decisions taken regarding mandatory vaccinations.

Repeated Leftover Serosurvey of SARS-CoV-2 IgG Antibodies in Greece, May to August 2020.

A serosurvey of IgG antibodies against SARS-CoV-2 was conducted in Greece between May and August 2020. It was designed as a cross-sectional survey and was repeated at monthly intervals. The leftover sampling methodology was used and a geographically stratified sampling plan was applied. Of 20,110 serum samples collected, 89 (0.44%) were found to be positive for anti-SARS-CoV-2 antibodies, with higher seroprevalence (0.35%) observed in May 2020. The highest seroprevalence was primarily observed in the "30-49" year age group. Females presented higher seroprevalence compared to males in May 2020 (females: 0.58% VS males: 0.10%). This difference reversed during the study period and males presented a higher proportion in August 2020 (females: 0.12% VS males: 0.58%). Differences in the rate of seropositivity between urban areas and the rest of the country were also observed during the study period. The four-month infection fatality rate (IFR) was estimated to be 0.47%, while the respective case fatality rate (CFR) was at 1.89%. Our findings confirm low seroprevalence of COVID-19 in Greece during the study period. The young adults are presented as the most affected age group. The loss of the cumulative effect of seropositivity in a proportion of previous SARS-CoV-2 infections was indicated.