COVID-19 Publications

29

Mar, 2021

COVID-19 vaccine response in pregnant and lactating women: a cohort study

 

Authors: Kathryn J. Gray, MD PhD, Evan A. Bordt, PhD, Caroline Atyeo, BS, Elizabeth Deriso, PhD, Babatunde Akinwunmi, MD MPH MMSc, Nicola Young, BA, Aranxta Medina Baez, BS, Lydia L. Shook, MD, Dana Cvrk, CNM, Kaitlyn James, PhD, MPH, Rose De Guzman, PhD, Sara Brigida, BA, Khady Diouf, MD, Ilona Goldfarb, MD MPH, Lisa M. Bebell, MD, Lael M. Yonker, MD, Alessio Fasano, MD, S. Alireza Rabi, MD, Michal A. Elovitz, MD, Galit Alter, PhD, Andrea G. Edlow, MD, MSc

Published in: American journal of obstetrics and gynecology

 

Abstract

Background: Pregnant and lactating women were excluded from initial COVID-19 vaccine trials; thus, data to guide vaccine decision-making are lacking.

Objectives: To evaluate the immunogenicity and reactogenicity of COVID-19 mRNA vaccination in pregnant and lactating women compared to: (1) non-pregnant controls and (2) natural COVID-19 infection in pregnancy.

Study Design: 131 reproductive-age vaccine recipients (84 pregnant, 31 lactating, and 16 non-pregnant) were enrolled in a prospective cohort study at two academic medical centers. Titers of SARS-CoV-2 Spike and RBD IgG, IgA and IgM were quantified in participant sera (N=131) and breastmilk (N=31) at baseline, second vaccine dose, 2-6 weeks post second vaccine, and at delivery by Luminex. Umbilical cord sera (N=10) titers were assessed at delivery. Titers were compared to those of pregnant women 4-12 weeks from natural infection (N=37) by ELISA. A pseudovirus neutralization assay was used to quantify neutralizing antibody titers for the subset of women who delivered during the study period. Post-vaccination symptoms were assessed via questionnaire. Kruskal-Wallis tests and a mixed effects model, with correction for multiple comparisons, were used to assess differences between groups.

Results: Vaccine-induced antibody titers were equivalent in pregnant and lactating compared to non-pregnant women (median [IQR] 5.59 [4.68-5.89] pregnant, 5.74 [5.06-6.22] lactating, 5.62 [4.77-5.98] non-pregnant, p = 0.24). All titers were significantly higher than those induced by SARS-CoV-2 infection during pregnancy (p < 0.0001). Vaccine-generated antibodies were present in all umbilical cord blood and breastmilk samples. Neutralizing antibody titers were lower in umbilical cord compared to maternal sera, although this finding did not achieve statistical significance (median [IQR] 104.7 [61.2-188.2] maternal sera, 52.3 [11.7-69.6] cord sera, p=0.05). The second vaccine dose (boost dose) increased SARS-CoV-2-specific IgG, but not IgA, in maternal blood and breastmilk. No differences were noted in reactogenicity across the groups.

Conclusions: COVID-19 mRNA vaccines generated robust humoral immunity in pregnant and lactating women, with immunogenicity and reactogenicity similar to that observed in non-pregnant women. Vaccine-induced immune responses were significantly greater than the response to natural infection. Immune transfer to neonates occurred via placenta and breastmilk.

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24

Mar, 2021

SARS-CoV-2 infection and transmission in primary schools in England in June–December, 2020 (sKIDs): an active, prospective surveillance study

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Authors: Shamez N Ladhani, Frances Baawuah, Joanne Beckmann, Ifeanichukwu O Okike, Shazaad Ahmad, Joanna Garstang, Andrew J Brent, Bernadette Brent, Jemma Walker, Nick Andrews, Georgina Ireland, Felicity Aiano, Zahin Amin-Chowdhury, Louise Letley, Jessica Flood, Samuel E I Jones, Ray Borrow, Ezra Linley, Maria Zambon, John Poh, Vanessa Saliba, Gayatri Amirthalingam, Jamie Lopez Bernal, Kevin E Brown, Mary E Ramsay

Published in: The Lancet

 

Summary Background: Little is known about the risk of SARS-CoV-2 infection and transmission in educational settings. Public Health England initiated a study, COVID-19 Surveillance in School KIDs (sKIDs), in primary schools when they partially reopened from June 1, 2020, after the first national lockdown in England to estimate the incidence of symptomatic and asymptomatic SARS-CoV-2 infection, seroprevalence, and seroconversion in staff and students.

Methods: sKIDs, an active, prospective, surveillance study, included two groups: the weekly swabbing group and the blood sampling group. The swabbing group underwent weekly nasal swabs for at least 4 weeks after partial school reopening during the summer half-term (June to mid-July, 2020). The blood sampling group additionally underwent blood sampling for serum SARS-CoV-2 antibodies to measure previous infection at the beginning (June 1–19, 2020) and end (July 3–23, 2020) of the summer half-term, and, after full reopening in September, 2020, and at the end of the autumn term (Nov 23–Dec 18, 2020). We tested for predictors of SARS-CoV-2 antibody positivity using logistic regression. We calculated antibody seroconversion rates for participants who were seronegative in the first round and were tested in at least two rounds.

Findings: During the summer half-term, 11 966 participants (6727 students, 4628 staff, and 611 with unknown staff or student status) in 131 schools had 40 501 swabs taken. Weekly SARS-CoV-2 infection rates were 4·1 (one of 24463; 95% CI 0·1–21·8) per 100000 students and 12·5 (two of 16 038; 1·5–45·0) per 100000 staff. At recruitment, in 45 schools, 91 (11·2%; 95% CI 7·9–15·1) of 816 students and 209 (15·1%; 11·9–18·9) of 1381 staff members were positive for SARS-CoV-2 antibodies, similar to local community seroprevalence. Seropositivity was not associated with school attendance during lockdown (p=0·13 for students and p=0·20 for staff) or staff contact with students (p=0·37). At the end of the summer half-term, 603 (73·9%) of 816 students and 1015 (73·5%) of 1381 staff members were still participating in the surveillance, and five (four students, one staff member) seroconverted. By December, 2020, 55 (5·1%; 95% CI 3·8–6·5) of 1085 participants who were seronegative at recruitment (in June, 2020) had seroconverted, including 19 (5·6%; 3·4–8·6) of 340 students and 36 (4·8%; 3·4–6·6) of 745 staff members (p=0·60).

Interpretation: In England, SARS-CoV-2 infection rates were low in primary schools following their partial and full reopening in June and September, 2020.

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24

Mar, 2021

Testing for SARS-CoV-2 infection: a key strategy to keeping schools and universities open

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Authors: Archana Koirala, Nicholas Wood, Kristine Macartney

Published in: The Lancet

 

Introduction: Education has been profoundly affected by the COVID-19 pandemic. Lack of access to education has exacerbated the divide between rich and poor and left vulnerable children exposed to domestic violence and hunger. The best way of keeping educational institutions open for in-person learning is to control transmission of SARS-CoV-2 in the wider community1 and to ensure rapid identification of infected staff and students to support timely and tailored public health responses. A comprehensive testing strategy is a core tenet in control, especially as a majority (40–60%) of children and young people have asymptomatic COVID-19,2 and individuals who are pre-symptomatic also present a transmission risk. Mitigation measures such as physical distancing, use of masks, and ensuring adequate ventilation within classrooms are also key, especially when community based transmission exists.

SARS-CoV-2 infection can be diagnosed by two methods: direct testing for the viral RNA with highly sensitive SARS-CoV-2 RT-PCR tests or viral antigen detection tests, which identify active (or resolving) infection on a nasal, oropharyngeal, or salivary sample and allow early case identification to contain outbreaks. Testing for antibodies against the virus diagnose previous or recent infection (with onset of 10 or more days previously). The delayed nature of virus-specific antibody testing precludes it as tool for rapid outbreak suppression; rather, its predominant public health utility is to understand infection and transmission rates and patterns in a community or clusters.

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22

Mar, 2021

Increased incidence of precocious and accelerated puberty in females during and after the Italian lockdown for the coronavirus 2019 (COVID-19) pandemic

 

Authors: Stefano Stagi, Salvatore De Masi, Erica Bencini, Stefania Losi, Silvia Paci, Maria Parpagnoli, Franco Ricci, Daniele Ciofi and Chiara Azzari

Published in: Italian Journal of Pediatrics

 

Abstract

Background: The timing of puberty in girls is occurring at an increasingly early age. While a positive family history is recognised as a predisposing factor for early or precocious puberty, the role of environmental factors is not fully understood.

Aims of the study: To make a retrospective evaluation of the incidence of newly diagnosed central precocious puberty (CPP) and the rate of pubertal progression in previously diagnosed patients during and after the Italian lockdown for COVID-19, comparing data with corresponding data from the previous 5 years. To determine whether body mass index (BMI) and the use of electronic devices increased during lockdown in these patients.

Patients and methods: The study included 49 females with CPP. We divided the patients into two groups: group 1, patients presenting a newly diagnosed CPP and group 2, patients with previously diagnosed slow progression CPP whose pubertal progression accelerated during or after lockdown. We collected auxological, clinical, endocrinological and radiological data which were compared with data from two corresponding control groups (patients followed by our Unit, March to July 2015–2019). Patients’ families completed a questionnaire to assess differences in the use of electronic devices before and during lockdown.

Results: Thirty-seven patients presented newly diagnosed CPP (group 1) and 12, with previously diagnosed but untreated slow progression CPP presented an acceleration in the rate of pubertal progression (group 2). The number of new CPP diagnoses was significantly higher than the mean for the same period of the previous 5 years (p < 0.0005). There were no significant differences between patients in group 1 and control group 1 regarding time between appearance of B2 and CPP diagnosis, although group 1 patients had a significantly earlier chronological age at B2, a more advanced Tanner stage at diagnosis (p < 0.005), higher basal LH and E2 levels, higher LH peak after LHRH test (p < 0.05) and increased uterine length (p < 0.005) and ovarian volume (p < 0.0005). The number of patients with previously diagnosed CPP whose pubertal development accelerated was also statistically higher compared to controls (p < 0.0005). In this group, patients’ basal LH (p < 0.05) and E2 levels (p < 0.0005) became more markedly elevated as did the LH peak after LHRH test (p < 0.05). These patients also showed a significantly accelerated progression rate as measured by the Tanner scale (p < 0.0005), uterine length (p < 0.005), and ovarian volume (p < 0.0005). In both group 1 and group 2, BMI increased significantly (p < 0.05) and patients’ families reported an increased use of electronic devices (p < 0.0005).

Conclusion: Our data show an increased incidence of newly diagnosed CPP and a faster rate of pubertal progression in patients with a previous diagnosis, during and after lockdown compared to previous years. We hypothesize that triggering environmental factors, such as the BMI and the use of electronic devices, were enhanced during lockdown, stressing their possible role in triggering/influencing puberty and its progression. However, more studies are needed to determine which factors were involved and how they interacted.

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22

Mar, 2021

COVID-19 Infections among Students and Staff in New York City Public Schools

 

Authors: Jay K. Varma, MD, Jeff Thamkittikasem, MPA, Katherine Whittemore, MPH, Mariana Alexander, MSc, Daniel H. Stephens, MD, Kayla Arslanian, JD, Jackie Bray, MPH, Theodore G. Long, MD

Published in: American Academy of Pediatrics

 

Abstract:

Background: The 2019 novel coronavirus disease (COVID-19) pandemic led many jurisdictions to close in- person school instruction.

Methods: We collected data about COVID-19 cases associated with New York City public schools from polymerase chain reaction (PCR) testing performed in each school on a sample of asymptomatic students and staff and from routine reporting . We compared prevalence from testing done in schools to community prevalence estimates from statistical models. We compared cumulative incidence for school-associated cases to all cases reported to the city. School-based contacts were monitored to estimate the secondary attack rate and possible direction of transmission.

Results: To assess prevalence, we analyzed data from 234,132 persons tested for SARS-CoV-2 infection in 1,594 New York City public schools during October 9–December 18, 2020; 986 (0.4%) tested positive. COVID-19 prevalence in schools was similar to or less than estimates of prevalence in the community for all weeks. To assess cumulative incidence, we analyzed data for 2,231 COVID-19 cases that occurred in students and staff compared with the 86,576 persons in New York City diagnosed during the same period; the overall incidence was lower for persons in public schools compared with the general community. Of 36,423 school-based close contacts, 191 (0.5%) subsequently tested positive for COVID-19; the likely index case was an adult for 78.0% of secondary cases.

Conclusions: We found that in-person learning in New York City public schools was not associated with increased prevalence or incidence overall of COVID-19 infection compared with the general community.

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22

Mar, 2021

Behavioural and Emotional Changes during COVID-19 Lockdown in an Italian Paediatric Population with Neurologic and Psychiatric Disorders

 

Authors: Eugenia Conti, Giuseppina Sgandurra, Giacomo De Nicola Tommaso Biagioni, Silvia Boldrini, Eleonora Bonaventura, Bianca Buchignani, Stefania Della Vecchia, Francesca Falcone, Caterina Fedi et al.

Published in: MDPI

Abstract: On 11 March 2020, a national lockdown was imposed by the Italian government to contain the spread of COVID19 disease. This is an observational longitudinal study conducted at Fondazione Stella Maris (FSM), Italy to investigate lockdown-related emotional and behavioural changes in paediatric neuropsychiatric population. Families having children (1.5–18 years) with neuropsychiatric disorders referred to FSM have been contacted and proposed to fulfil two online questionnaires (General questionnaire and Child Behaviour Check List (CBCL)) to (i) compare (paired two-sample t-tests) the CBCL scores during lockdown with previous ones, and (ii) investigate the influence (multiple linear regression models) of variables such as age, diagnosis grouping (neurological, neurodevelopmental, emotional, and behavioural disorders) and financial hardship. One hundred and forty-one parents fulfilled the questionnaires. Anxiety and somatic problems increased in 1.5–5 years subpopulation, while obsessive-compulsive, post-traumatic and thought problems increased in 6–18 years subpopulation. In the regression models, younger age in the 1.5–5 years subpopulation resulted as “protective” while financial hardship experienced by families during lockdown was related to psychiatric symptoms increasing in the 6–18 years subpopulation. Some considerations, based on first clinical impressions, are provided in text together with comments in relation to previous and emerging literature on the topic.

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19

Mar, 2021

Vaccinating Children against Covid-19 — The Lessons of Measles

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Authors: Perri Klass, M.D. and Adam J. Ratner, M.D., M.P.H.

Published in: The New England Journal of Medicine

 

Introduction: Imagine a highly contagious virus circulating in the community. Many infected children have fever and some general misery but recover without incident. Rarely, devastating complications occur, leading to hospitalization, severe illness, and occasional deaths. Susceptible adults fare worse, with higher rates of poor outcomes. Would you want your child vaccinated against this disease?

You guessed we were talking about measles, right?

As the first SARS-CoV-2 vaccines are rolled out to the highest-risk groups, the current stage of the Covid-19 pandemic is pregnant with possibility. Even as cases multiply and new restrictions loom, we gaze longingly toward the next few months, hoping vaccines will deliver us. Vaccination could liberate us to return to school or work, celebrate holidays, eat in restaurants, travel, run marathons, and [fill in your own deprivations]. Early announcements of vaccine efficacy send stocks soaring, and suddenly everyone knows about phase 3 trials and cold-chain logistics. We look to vaccines to give us back our world.

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19

Mar, 2021

Characteristics of SARS-CoV-2 patients dying in Italy Report based on available data on March 1st, 2021

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Authors: Luigi Palmieri, Elvira Agazio, Xanthi Andrianou, Pierfrancesco Barbariol, Antonino Bella, Eva Benelli, Luigi Bertinato, Matilde Bocci, Stefano Boros, Giovanni Calcagnini, Marco Canevelli, Federica Censi, Alessandra Ciervo, Elisa Colaizzo, Martina Del Manso, Corrado Di Benedetto, Chiara Donfrancesco, Massimo Fabiani, et al.

Published in: Epicentro

 

Sample: The present report describes the characteristics of 96,149 SARS-CoV-2 patients dying in Italy*, as reported by the Integrated Covid-19 Surveillance System coordinated by the National Institute of Health-ISS. Geographic distribution across the 19 regions and 2 autonomous provinces of Trento and Bozen is presented in Table 1. Absolute number and percentage of deaths are reported according to the 3 phases that characterized the pandemic from the beginning in 2020 to the 1st of March 2021: the first wave (March-May 2020), the low incidence phase (June-September 2020), and the second wave (October 2020 – March 2021), the latter is still ongoing. The surveillance data on deaths are constantly updated and consolidated and both activities require time to be carried out. Each Region has its own organization for updating data and related execution times. Therefore, when reading the data by Region, it is necessary to take into account that the timing of notification, control, verification and updating of data varies from Region to Region and from period to period; this may involve variations (increasing and/or decreasing) and differences both with the data already published in the previous reports, and with the data published by the Civil Protection. It should also be considered that the regional differences in the percentage of deaths reported in the table should not be interpreted in terms of risk. In fact, case fatality depends on the number of infections occurring in each region over a period of time compatible with the possible observation of the fatal event. In this regard, it should also be taken into account that the difference between the number of infections and the notified cases may vary regionally and over time as a function of different test access strategies adopted during the epidemic, thus distorting the comparison of regional case fatality.

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19

Mar, 2021

Virological and immunological features of SARS COV 2 infected children who who developed neutralizing antibodies

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Authors: Nicola Cotugno, Alessandra Ruggiero, Francesco Bonfante, Paolo Rossi, Anita De Rossi, Paolo Palma et al.

Published in: Cell Reports

 

Summary: As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS- CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies.

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23

Feb, 2021

What does 95% COVID-19 vaccine efficacy really mean?

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Author: Piero Olliaro

Published in: The Lancet

Introduction: It is imperative to dispel any ambiguity about how vaccine efficacy shown in trials translates into protecting individuals and populations. The mRNA-based Pfizer1,2 and Moderna3 vaccines were shown to have 94–95% efficacy in preventing symptomatic COVID-19, calculated as 100 × (1 minus the attack rate with vaccine divided by the attack rate with placebo). It means that in a population such as the one enrolled in the trials, with a cumulated COVID-19 attack rate over a period of 3 months of about 1% without a vaccine, we would expect roughly 0·05% of vaccinated people would get diseased. It does not mean that 95% of people are protected from disease with the vaccine—a general misconception of vaccine protection also found in a Lancet Infectious Diseases Editorial.

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