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1.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.12.17.21267997

ABSTRACT

Introduction This study aims to characterize attitudes towards COVID-19 vaccination and to evaluate factors associated with vaccine uptake amongst pregnant individuals. Methods An anonymous survey was distributed to a convenience sample of pregnant individuals receiving prenatal care at two large urban academic hospitals in a single healthcare network in Massachusetts. Individual demographic variables were included in the survey along with questions assessing attitudes towards COVID-19 and vaccination in pregnancy. Results Of 477 respondents, 233 (49.3%) had received or were scheduled to receive a COVID-19 vaccine. Age, White race, non-Hispanic/LatinX ethnicity, working from home, and typical receipt of the influenza vaccine were associated with COVID-19 vaccination. 276 respondents (58.4%) reported that their provider recommended the COVID-19 vaccine in pregnancy; these participants were more likely to have received a vaccine (OR 5.82, 95% confidence interval [CI] 3.68-9.26). Vaccinated individuals were less likely to be worried about the effects of the vaccine on themselves (OR 0.18, 95% CI 0.12-0.27) or their developing babies (OR 0.17, 95% CI 0.11-0.26). Unvaccinated individuals were less likely to report that it is easy to schedule a COVID-19 vaccine (OR 0.56, 95% CI 0.34-0.93), to travel to receive a vaccine (OR 0.19, 95% CI 0.10-0.36), and to miss work to receive a vaccine (OR 0.30, 95% CI 0.18-0.48). Conclusions Strategies are needed to improve patient education regarding vaccine side effects and safety in pregnancy and to change policy to make it feasible for pregnant patients to schedule and miss work without loss of pay to get vaccinated. Key Points There were racial and ethnic disparities in COVID-19 vaccination. Unvaccinated respondents were more likely to be concerned about vaccine effects for themselves or their growing babies. Unvaccinated respondents cited work and scheduling-related barriers to vaccination, indicating areas for advocacy


Subject(s)
COVID-19
2.
ssrn; 2021.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3845685

ABSTRACT

Antibody transfer via breastmilk represents an evolutionary strategy to boost immunity in early life. Although SARS-CoV-2-specific antibodies have been observed in the breastmilk of mothers with COVID-19, the functional quality of these antibodies remains unclear. Here, we applied systems serology to characterize SARS-CoV-2-specific antibodies in maternal serum and breastmilk to define the mechanism of antibody transfer into breastmilk. Distinct SARS-CoV-2-specific antibody responses were observed in the serum and breastmilk of lactating individuals previously infected with SARS-CoV-2, with a dominant transfer of both IgA and IgM into breastmilk. A spike-specific functional IgG were present in breastmilk, breastmilk IgGs were functionally attenuated. Breastmilk antibodies were less inflammatory than maternal serum antibodies, pointing to a sieve offunctional antibodies to breastmilk. These data highlight the preferential breastmilk transfer of SARS-CoV-2-specific IgA and IgM to neonates, accompanied by selected subpopulations of IgG, positioned to create a non-pathologic, but highly protective barrier against COVID-19 disease.Funding Statement: This work was supported by by NHLBI (grants K08HL1469630-02 and K08HL146963-02S1, to KJG), the National Science Foundation Graduate Research Fellowship under Grant No. (#1745302, to KMP), the NIH (U19 AI142790, U19 AI135995, R37AI080289), the Massachusetts Consortium on Pathogen Readiness (MassCPR). Declaration of Interests: G.A. is the founder of Seromyx. K.J.G. has consulted for BillionToOne, Illumina, and Aetion. INCOMPLETE Ethics Approval Statement: This study was approved by the MGH-BWH Institutional Review Board and the BIDMC Institutional Review Board.


Subject(s)
COVID-19
3.
medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.10.10.20207449

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in the clinical syndrome COVID-19 is associated with an exaggerated immune response and monocyte infiltrates in the lungs and other peripheral tissues. It is now increasingly recognised that chronic morbidity persists in some patients. We recently demonstrated profound alterations of monocytes in hospitalised COVID-19 patients. It is currently unclear whether these abnormalities resolve or progress following patient discharge. We show here that blood monocytes in convalescent patients at their 12 week follow up, have a greater propensity to produce pro-inflammatory cytokines TNF and IL-6, which was consistently higher in patients with resolution of lung injury as indicated by a normal chest X-ray and no shortness of breath (a key symptom of lung injury). Furthermore, monocytes from convalescent patients also displayed enhanced levels of molecules involved in leucocyte migration, including chemokine receptor CXCR6, adhesion molecule CD31/PECAM and integrins VLA-4 and LFA-1. Expression of migration molecules on monocytes was also consistently higher in convalescent patients with a normal chest X-ray. These data suggest persistent changes in innate immune function following recovery from COVID-19 and indicate that immune modulating therapies targeting monocytes and leucocyte migration may be useful in recovering COVID-19 patients with persistent symptoms.


Subject(s)
Coronavirus Infections , Lung Diseases , Dyspnea , COVID-19
4.
biorxiv; 2020.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2020.10.13.337212

ABSTRACT

The Spike (S) protein is the main handle for SARS-CoV-2 to enter host cells through surface ACE2 receptors. How ACE2 binding activates proteolysis of S protein is unknown. Here, we have mapped the S:ACE2 interface and uncovered long-range allosteric propagation of ACE2 binding to sites critical for viral host entry. Unexpectedly, ACE2 binding enhances dynamics at a distal S1/S2 cleavage site and flanking protease docking site ~27 [A] away while dampening dynamics of the stalk hinge (central helix and heptad repeat) regions ~ 130 [A] away. This highlights that the stalk and proteolysis sites of the S protein are dynamic hotspots in the pre-fusion state. Our findings provide a mechanistic basis for S:ACE2 complex formation, critical for proteolytic processing and viral-host membrane fusion and highlight protease docking sites flanking the S1/S2 cleavage site, fusion peptide and heptad repeat 1 (HR1) as allosterically exposed cryptic hotspots for potential therapeutic development.

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