Evaluation of Humoral Immunity Following COVID-19 in Pregnancy

NCT04568044 | Active Not Recruiting

• 1 other identifier: 20SM6089
• Study Type: observational
• Target: 128
• Locations: 1 country
• Sites: 2

Brief Summary

The proposed study is designed to investigate if and how pregnant women infected with Coronavirus Disease-19 (COVID-19) infection go on to develop long-term immunity. In December 2019, a group of people in Wuhan, China presented with symptoms of a pneumonia of an unknown cause that led to the discovery of a new coronavirus called COVID-19. COVID-19 has caused a global pandemic with 7,140,000 confirmed cases and 418,000 deaths as of 13th June 2020. In the United Kingdom (UK), there have been 294,000 cases and 41,662 deaths as of 13th June 2020. In humans, this infection primarily involves the upper part of the lungs, but it can also affect other organs. It causes mild symptoms in the majority of people affected but some people can have severe infections, with some even requiring critical care in hospital. During Severe acute respiratory syndrome (SARS), a previous coronavirus epidemic, pregnant women were disproportionately affected with severe illness. Understanding how the immune system responds long-term to this infection may hold the key to developing better vaccines and efficient treatment plans. Specialised immunity develops when individuals are infected by this and other viruses. The investigators of this study propose that, in pregnancy, this specialised immunity may not behave effectively. This may affect their ability to develop long lasting immunity and make them more vulnerable to re-infection. In this study, the investigators aim to recruit patients across 6 groups including COVID-19 newly infected pregnant women, and people with differing illness severity, mild to moderate, severe/critical, no infection (controls), as well as pregnant women with influenza and those receiving influenza vaccine. The study team will compare COVID-19 in pregnancy with non-pregnant infected and with influenza infected and vaccinated pregnant women. The study team will consent patients in all of these groups to provide a series of blood samples at different time points in a 12-month period.

Conditions

COVID-19; Pregnancy Related; Influenza, Human

Keywords

Pregnancy; COVID-19; Immunity; Influenza; Vaccination

Outcome Measures

Primary Outcomes (2)

• Phenotyping antibody secreting cells (ASCs) and memory B cells during COVID-19 infection, and post recovery.

  Devise a flow cytometry panel to phenotype B cells.

  Groups A, B, D: Between 4 months with a minimum of 2 time points (i.e. 8 and 12 months), and 12 months with a maximum 5 time points (i.e. 7-14 days, then 1, 4, 8, 12 months) post infection. Group C: 1 day. 1 time point.

• Quantification of SARS-CoV-2 specific IgG production by memory B cells to measure long-lasting immune protection against re-infection.

  B cell ELISpot assay and quantify Immunoglobulin A (IgA) and IgG using Enzyme-linked immunosorbent assay (ELISA) from plasma and/or serum from COVID-19 recovered individuals.

  Groups A, B, D: Between 4 months with a minimum of 2 time points (i.e. 8 and 12 months), and 12 months with a maximum 5 time points (i.e. 7-14 days, then 1, 4, 8, 12 months) post infection. Group C: 1 day. 1 time point.

Secondary Outcomes (4)

• Quantification of SARS-COV-2 viral load using PCR.

  Groups A, B, D: at 7-14 days and during recovery phase. Group C: 1 day. 1 time point.

• Immuno-phenotype circulatory T follicular helper cells (cTFH) cells post SARS-CoV-2 infection.

  Groups A, B, D: at 7-14 days post infection or vaccination. Group C: 1 day. 1 time point.

• Investigating T cell mediated immune function post COVID-19

  Groups A, B, D: Between 4 months with a minimum of 2 time points (i.e. 8 and 12 months), and 12 months with a maximum 5 time points (i.e. 7-14 days, then 1, 4, 8, 12 months) post infection/vaccination. Group C: 1 day. 1 time point.

• In pregnancy, comparing antibody production, and immune phenotype and function (as outlined above) between COVID-19 infection, and influenza infected or vaccinated.

  Groups A, B, D, E and F: Between 4 months with a minimum of 2 time points (i.e. 8 and 12 months), and 12 months with a maximum 5 time points (i.e. 7-14 days, then 1, 4, 8, 12 months) post infection/vaccination. Group C: 1 day. 1 time point.

Study Arms (8)

Group A: Mild to moderate COVID-19 (non-pregnant)

Current male or female COVID-19 infected (age 18-60 years old) with mild to moderate illness. Blood samples will be taken between 4 months with a minimum of 2 time points (i.e. 8 and 12 months), and 12 months with a maximum 5 time points (i.e. 7-14 days, then 1, 4, 8, 12 months).

Procedure: Blood sample

Group B: Severe to critical COVID-19 (non-pregnant)

Current male or female COVID-19 infected (age 18-60 years old) with severe to critical illness. Blood samples will be taken between 4 months with a minimum of 2 time points (i.e. 8 and 12 months), and 12 months with a maximum 5 time points (i.e. 7-14 days, then 1, 4, 8, 12 months).

Procedure: Blood sample

Group C: Controls (non-pregnant)

Male of female uninfected (age 18-60 years old) who have no history of COVID-19 symptoms or illness. A blood sample will be taken on 1 day and at 1 time point.

Procedure: Blood sample

Group D: Pregnant or postnatal with COVID-19

Current pregnant or postnatal COVID-19 infected (age 18-50 years old) Pregnant or postnatal who were diagnosed with COVID-19 less than 8 months previously (age 18-50 years old). Singleton pregnancies only. For most participants in this group, blood samples will be taken between 4 months with a minimum of 2 time points (i.e. 8 and 12 months), and 12 months with a maximum 5 time points (i.e. 7-14 days, then 1, 4, 8, 12 months). However, for pregnant women admitted to hospital with severe COVID-19, we will aim to collect earlier timepoints (day 1-3, day 5-7 and then day 7-14). Thereafter, we will follow the above mentioned the long-term schedule (i.e. 1, 4, 8, 12 months).

Procedure: Blood sample

Group E: Pregnant or postnatal with influenza

Current pregnant or postnatal influenza infected (age 18-50 years old). Singleton pregnancies only. Blood samples over 12 months and 5 time points (i.e. 7-14 days, then 1, 4, 8, 12 months).

Procedure: Blood sample

Group F: Pregnant and have received the influenza vaccine

Current pregnant and due to receive the influenza vaccine (age 18-50 years old). Singleton pregnancies only. Blood samples over 12 months and 6 time points (i.e. Before the vaccine, 7-14 days after the vaccine, then at 1, 4, 8, 12 months post vaccine).

Procedure: Blood sample

Group G: SARS-CoV-2 vaccinated pregnant/postnatal women

Current pregnant or postnatal (within 6 weeks of birth) and due to receive the SARS-CoV-2 vaccine (age 18-50 years old). Singleton pregnancies only. Blood samples over 12 months and 6 time points (i.e. Before the vaccine, 7-14 days after the vaccine, then at 1, 4, 8, 12 months post vaccine).

Group H: SARS-CoV-2 vaccinated non-pregnant women

Non-pregnant and due to receive the SARS-CoV-2 vaccine (age 18-50 years old). Blood samples over 12 months and 6 time points (i.e. Before the vaccine, 7-14 days after the vaccine, then at 1, 4, 8, 12 months post vaccine).

Interventions

Blood sample PROCEDURE

Peripheral blood sample will be obtained.

Group A: Mild to moderate COVID-19 (non-pregnant); Group B: Severe to critical COVID-19 (non-pregnant); Group C: Controls (non-pregnant); Group D: Pregnant or postnatal with COVID-19; Group E: Pregnant or postnatal with influenza; Group F: Pregnant and have received the influenza vaccine

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

16 patients per group will be required. In the COVID-19 infected, non-pregnant groups, the study team will be recruiting both male and female participants who would have been healthy prior to contracting SARS-CoV-2. Once all the samples have been collected, the investigators may stratify them based on gender, BMI, and ethnicity. Of note, in pregnant and postnatal women with COVID-19, the research team expect small numbers of recruits and currently the overall number of COVID-19 patients in London is on the decline. Therefore, the investigators will invite participants who were diagnosed up to the preceding 8 months to participate and have blood samples taken from the nearest time-point to the interval from their symptom onset and then continue with the sample collection schedule.

You may qualify if:

• Group A: Mild to moderate COVID-19 (non-pregnant)
• Current male or female COVID-19 infected (age 18-60 years old) with mild to moderate illness
• Group B: Severe to critical COVID-19 (non-pregnant)
• Current male or female COVID-19 infected (age 18-60 years old) with severe to critical illness
• Group C: Controls (non-pregnant)
• Male of female uninfected (age 18-60 years old) who have no history of COVID-19 symptoms or illness
• Group D: Pregnant or postnatal with COVID-19
• Current pregnant or postnatal COVID-19 infected (age 18-50 years old)
• Pregnant or postnatal (within 6 weeks since birth) who were diagnosed with COVID-19 less than 4 months previously (age 18-50 years old)
• Singleton pregnancy
• Group E: Pregnant or postnatal with influenza
• Current pregnant or postnatal influenza infected (age 18-50 years old)
• Pregnant or postnatal (within 6 weeks since birth) who were diagnosed with influenza less than 4 months previously (age 18-50 years old)
• Singleton pregnancy
• Group F: Pregnant and have received the influenza vaccine

You may not qualify if:

• Group A, Group B and Group C:
• Patients unable to understand verbal or written information in English, regarding the study. Lack of capacity to consent at the point of recruitment
• Pregnant
• Participants who have previously been part of any SARS-CoV-2 vaccine trial
• Evidence of HIV infection
• Participants on medication that may significantly affect their immune system such as chemotherapy drugs
• Vulnerable patients with known safe-guarding issues
• Pregnant with more than one baby
• Group D, E and F:
• Patients unable to understand verbal or written information in English, regarding the study.
• Lack of capacity to consent at the point of recruitment
• Participants who have previously been part of any SARS-CoV-2 vaccine trial
• Evidence of HIV infection
• Participants on medication that may significantly affect their immune system such as chemotherapy drugs other than steroids, which have been given for fetal lung maturity
• Vulnerable patients with known safe-guarding issues

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (2)

Chelsea and Westminster NHS Foundation Trust

London, SW10 9NH, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, W2 1NY, United Kingdom

Location

Related Publications (11)

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• Sahu KK, Mishra AK, Lal A. Coronavirus disease-2019: An update on third coronavirus outbreak of 21st century. QJM. 2020 May 1;113(5):384-386. doi: 10.1093/qjmed/hcaa081. No abstract available.

  PMID: 32125418 BACKGROUND

• Wong SF, Chow KM, Leung TN, Ng WF, Ng TK, Shek CC, Ng PC, Lam PW, Ho LC, To WW, Lai ST, Yan WW, Tan PY. Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome. Am J Obstet Gynecol. 2004 Jul;191(1):292-7. doi: 10.1016/j.ajog.2003.11.019.

  PMID: 15295381 BACKGROUND

• Bentebibel SE, Khurana S, Schmitt N, Kurup P, Mueller C, Obermoser G, Palucka AK, Albrecht RA, Garcia-Sastre A, Golding H, Ueno H. ICOS(+)PD-1(+)CXCR3(+) T follicular helper cells contribute to the generation of high-avidity antibodies following influenza vaccination. Sci Rep. 2016 May 27;6:26494. doi: 10.1038/srep26494.

  PMID: 27231124 BACKGROUND

• Matsui K, Adelsberger JW, Kemp TJ, Baseler MW, Ledgerwood JE, Pinto LA. Circulating CXCR5(+)CD4(+) T Follicular-Like Helper Cell and Memory B Cell Responses to Human Papillomavirus Vaccines. PLoS One. 2015 Sep 2;10(9):e0137195. doi: 10.1371/journal.pone.0137195. eCollection 2015.

  PMID: 26333070 BACKGROUND

• Brenna E, Davydov AN, Ladell K, McLaren JE, Bonaiuti P, Metsger M, Ramsden JD, Gilbert SC, Lambe T, Price DA, Campion SL, Chudakov DM, Borrow P, McMichael AJ. CD4+ T Follicular Helper Cells in Human Tonsils and Blood Are Clonally Convergent but Divergent from Non-Tfh CD4+ Cells. Cell Rep. 2020 Jan 7;30(1):137-152.e5. doi: 10.1016/j.celrep.2019.12.016.

  PMID: 31914381 BACKGROUND

• Victora GD, Nussenzweig MC. Germinal centers. Annu Rev Immunol. 2012;30:429-57. doi: 10.1146/annurev-immunol-020711-075032. Epub 2012 Jan 3.

  PMID: 22224772 BACKGROUND

• Herati RS, Reuter MA, Dolfi DV, Mansfield KD, Aung H, Badwan OZ, Kurupati RK, Kannan S, Ertl H, Schmader KE, Betts MR, Canaday DH, Wherry EJ. Circulating CXCR5+PD-1+ response predicts influenza vaccine antibody responses in young adults but not elderly adults. J Immunol. 2014 Oct 1;193(7):3528-37. doi: 10.4049/jimmunol.1302503. Epub 2014 Aug 29.

  PMID: 25172499 BACKGROUND

• Linterman MA. How T follicular helper cells and the germinal centre response change with age. Immunol Cell Biol. 2014 Jan;92(1):72-9. doi: 10.1038/icb.2013.77. Epub 2013 Nov 12.

  PMID: 24217812 BACKGROUND

• Zhou M, Zou R, Gan H, Liang Z, Li F, Lin T, Luo Y, Cai X, He F, Shen E. The effect of aging on the frequency, phenotype and cytokine production of human blood CD4 + CXCR5 + T follicular helper cells: comparison of aged and young subjects. Immun Ageing. 2014 Aug 23;11:12. doi: 10.1186/1742-4933-11-12. eCollection 2014.

  PMID: 25177353 BACKGROUND

• Tang F, Quan Y, Xin ZT, Wrammert J, Ma MJ, Lv H, Wang TB, Yang H, Richardus JH, Liu W, Cao WC. Lack of peripheral memory B cell responses in recovered patients with severe acute respiratory syndrome: a six-year follow-up study. J Immunol. 2011 Jun 15;186(12):7264-8. doi: 10.4049/jimmunol.0903490. Epub 2011 May 16.

  PMID: 21576510 BACKGROUND

Related Links

• Coronavirus disease (COVID-19) pandemic updates

Biospecimen

Retention: SAMPLES WITH DNA

Human blood components and/or immune cells will be stored for analysis as required during the study period. DNA/RNA analysis will be undertaken to complement our understanding of the assays of immune function used during laboratory experiments.

MeSH Terms

Conditions

COVID-19; Influenza, Human

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Orthomyxoviridae Infections

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Nishel M Shah, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2020
• First Posted: September 29, 2020
• Study Start: September 16, 2020
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: February 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)