Understanding COVID-19 Infection in Pregnant Women and Their Babies
Conditions: Corona Virus Infection, Pregnancy Related, Neonatal Infection, Breastfeeding
Sponsor: St George's, University of London

 
IRAS 287478 periCOVID UK 
Protocol V1.0 dated 17Nov2020 
Page 1 of 24 
 
 
 
FULL/LONG TITLE OF THE STUDY 
 
Understanding COVID-19 infection in 
pregnant women and their babies 
SHORT STUDY TITLE / ACRONYM 
periCOVID 
PROTOCOL VERSION NUMBER AND DATE 
V1.0 dated 17Nov2020 
IRAS Number: 
287478 
JRES Reference Number 
2020.0276 
This protocol has regard for the HRA guidance and order of content 
 
 

 
IRAS 287478 periCOVID UK 
Protocol V1.0 dated 17Nov2020 
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SIGNATURE PAGE 
The undersigned confirm that the following protocol has been agreed and accepted and that the Chief 
Investigator agrees to conduct the study in compliance with the approved protocol and will adhere to 
the principles outlined in the Declaration of Helsinki, the Sponsor’s SOPs, and other regulatory 
requirement. 
I agree to ensure that the confidential information contained in this document will not be used for any 
other purpose other than the evaluation or conduct of the investigation without the prior written consent 
of the Sponsor. 
I also confirm that I will make the findings of the study publicly available through publication or other 
dissemination tools without any unnecessary delay and that an honest accurate and transparent 
account of the study will be given; and that any discrepancies from the study as planned in this protocol 
will be explained. 
 
For and on behalf of the Study Sponsor: 
Signature: 
 
 
 
Date: 
17/11/2020 
Name (please print): Joe Montebello 
 
 
Position: Senior Clinical Research Facilitator 
 
 
 
Chief Investigator: 
Signature: 
...................................................................................................... 
 
Date: 17/11/20. 
Name: (please print): Professor Kirsty Le Doare 
...................................................................................................... 
 
 
 
 
 
 

 
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LIST of CONTENTS 
Page No. 
PROTOCOL COMPLIANCE DECLARATION  
2 
TITLE PAGE  
1 
SIGNATURE PAGE 
2 
LIST OF CONTENTS  
3 
KEY STUDY CONTACTS 
4 
STUDY SUMMARY 
5 
FUNDING 
 
5 
ROLE OF SPONSOR AND FUNDER 
5 
ROLES & RESPONSIBILITIES OF STUDY STEERING GROUPS AND INDIVIDUALS   
5 
STUDY FLOW CHART 
 
6 
ABBREVIATIONS 
7 
1. BACKGROUND 
 
8 
2. RATIONALE 
 
8 
3. THEORETICAL FRAMEWORK 
9 
4. RESEARCH QUESTION/AIM(S)  
9 
5. STUDY DESIGN/METHODS 
10 
6. STUDY SETTING 
13 
7. SAMPLE AND RECRUITMENT 
13 
8. ETHICAL AND REGULATORY COMPLIANCE 
16 
9. DISSEMINATION  POLICY 
19 
10. REFERENCES 
20 
11. APPENDICES 
22 
 
 

 
IRAS 287478 periCOVID UK 
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KEY STUDY CONTACTS 
Chief Investigator 
Dr Kirsty Le Doare 
Paediatric Infectious Diseases Research Group 
Institute of Infection of Immunity 
St Georges University of London 
Crammer Terrace 
Tooting  
London 
SW17 0RE 
 
Co-investigators 
Professor Paul Heath 
Study Co-ordinator 
Dr Sarah Sturrock 
Institute of Infection of Immunity 
St Georges University of London 
Crammer Terrace 
Tooting  
London 
SW17 0RE 
 
Sponsor 
St Georges University of London 
Crammer Terrace 
Tooting  
London 
SW17 0RE 
 
Name: Joe Montebello 
Position: Senior Clinical Research Facilitator 
Email:   researchgovernance@sgul.ac.uk 
St Georges Joint Research & Enterprise Service (JRES), 
Cranmer Terrace SW17 ORE 
Funder(s) 
Action Medical Research for Children (Decision Pending) 
Key Protocol Contributors 
Dr Melanie Etti (metti@sgul.ac.uk) 
 
 
 
 

 
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STUDY SUMMARY 
Study Title 
Understanding COVID-19 infection in pregnant women and 
their babies 
Internal ref. no. (or short title) 
periCOVID 
Study Design 
Observational cohort 
Study Participants 
Pregnant women in England, any gestation ≥24 weeks 
Planned Size of Sample (if applicable) 1200 
Follow up duration (if applicable) 
1 month 
Planned Study Period 
12 months 
Research Question/Aim(s) 
 
To determine the seroepidemiology of SARS-CoV-2 in 
pregnant women in England 
 
FUNDING AND SUPPORT  
FUNDER(S) 
 
FINANCIAL AND NON FINANCIALSUPPORT 
GIVEN 
Funding application made to Action Medical 
Research 
Decision expected end November 2020 
 
 

 
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PROTOCOL CONTRIBUTORS 
Dr Kirsty Le Doare, Dr Paul Heath, Dr Melanie Etti, and Dr Sarah Sturrock all contributed to the design 
of this protocol.  
 
STUDY Schematic 
 
 
 
Guthrie card 

 
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ABBREVIATIONS 
AE  
Adverse Event  
AR  
Adverse Reaction  
CI  
Chief Investigator  
CRF  
Case Report Form  
GCP  
Good Clinical Practice  
GP  
General Practitioner  
HRA 
Health Research Authority  
ICF  
Informed Consent Form  
ISF  
Investigator Site File  
NHS  
National Health Service  
NIHR  
National Institute for Health Research  
PI  
Principal Investigator  
REC 
Research Ethics Committee 
SAE 
Serious Adverse Event 
SGUL 
St Georges, University of London 
SGHFT 
St Georges, University Hospitals NHS 
Foundation Trust 
JRES 
(St Georges) Joint Research and 
Enterprise Services 

 
 
 
   
 
 
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STUDY PROTOCOL 
Understanding COVID-19 infection in pregnant women and their babies (periCOVID) 
 
1 
BACKGROUND 
This protocol is intended to follow on from the existing PHE periCOVID national surveillance 
programme, to provide further clarity on the seroepidemiology of the disease in pregnant women, and 
the risk of vertical transmission between mothers and their infants. 
Since the first report (December 2019) of the novel coronavirus disease 2019 (COVID-19) 
caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the number of cases, 
mortality and morbidity have increased rapidly[1]. Pregnant women are a high risk group because of 
the possible effect of COVID-19 during and after pregnancy, and on their infants[2]. Early reviews of 
COVID-19 in pregnancy mostly included case reports and series that were often inappropriately meta-
analysed. Subsequent reviews differed little from each other, many with duplicate data[3]. Moreover, 
sampling frames in primary studies have varied from universal SARS-CoV-2 testing for all hospitalised 
pregnant women to symptom-based testing. Testing strategies have differed widely, with diagnosis in 
many studies based on epidemiological risk assessment and clinical features without confirmed 
infection[4]. Limitations in the external and internal validity of studies make it challenging to provide 
recommendations regarding SARS-COV-2 in pregnancy and for infants of women who may be 
affected[4]. 
Coronaviruses have caused two previous significant outbreaks: MERS and SARS. In both, 
pregnancy complications were more common in infected women[5][6]. In 2009, pregnant women 
accounted for 1% of patients infected with influenza A subtype H1N1 virus but 5% of all H1N1-related 
deaths[7][8].  A systematic review of published reports on Coronaviruses (COVID-19, SARS and 
MERS) found preterm birth <37 weeks to be the most common adverse pregnancy outcome (14/32 
pregnancies; 41%)[6]. A retrospective multicentre cohort study of 388 pregnant women testing positive 
for SARS-COV-2 supported this finding, with preterm birth implicated in 23% with a 4.1% rate of 
perinatal death[9]. Our systematic review and meta-analysis, including 2567 pregnant women who 
tested positive for SARS-COV-2 by rT-PCR, has also indicated that preterm birth is common (21.8%) 
[10]. Another review found an increased risk of admission to the neonatal unit (odds ratio 3.13, 95% 
confidence interval 2.05 to 4.78; 1 study, 1121 neonates) in infants born to mothers testing positive for 
SARS-COV-2[2]. In a living systematic review that includes 2557 neonates born to women testing 
positive for SARS-COV-2, 25% were admitted to the neonatal intensive care unit (including because of 
COVID-19 policy), fetal distress was observed in 8% and 4% of neonates were diagnosed with 
neonatal sepsis[11]. 
Vertical transmission has been documented in several small case studies, but without 
standardised definitions and sampling methods. In an unreviewed systematic review of case reports / 
series, the vertical transmission rate was estimated to be 11% [12]. However, other studies do not 
substantiate this finding and it remains unclear whether this transmission occurred at or soon after 
birth. A case series  tested amniotic fluid, cord blood, neonatal throat swabs and breastmilk samples 
from SARS-CoV-2 infected mothers and all samples tested negative[13]. In other studies, by the same 
group, three placentas of infected mothers tested negative for the virus, and none of three infants born 
to symptomatic mothers had positive tests for COVID-19. The most comprehensive review to date of 
31 pregnancies complicated by SARS-COV-2 did not find evidence of vertical transmission. However, 
whilst these data are reassuring, other studies have found SARS-CoV-2 in the placentas of mothers 
with COVID-19[14][15]. 
 

 
 
 
   
 
 
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2 
RATIONALE  
We at SGUL propose a rapid national study which aligns closely with the WHO MNCAH generic 
protocol, to inform public health policy within a 12 month timeframe by collecting samples from 
pregnant women during pregnancy and at delivery and from their infants to assess exposure and 
immunity to SARS-CoV-2. We are already linked with existing UK surveillance studies (UKOSS, PAN 
COVID, BPSU) to ensure a joined up approach to data collection. Our study also leverages an existing 
framework, iGBS3, set up to understand the seroepidemiology of Group B Streptococcal disease in 
320,000 pregnant women in the UK. Knowledge of protective immunity will also be of critical value in 
considering the role for COVID-19 vaccines in pregnant women.     
 
3 
THEORETICAL FRAMEWORK 
Approximately 650,000 women deliver annually in the UK[16], and approximately 7% of 
pregnant women have been exposed to SARS-COV-2[17]. These data represent women with severe 
disease requiring hospitalisation, so may not represent the full impact of SARS-CoV-2 on pregnancy 
and infant outcomes, as many may be asymptomatic(16,17,18). Studying women for SARS-CoV-2 
antibodies and viral DNA regardless of symptomatology is required to estimate the true burden among 
mothers and babies and to determine the extent of mother-to-child transmission.  
Placental transfer of IgG during pregnancy provides passive immunity that is critical in 
protecting newborns against infections[20]. Maternal immunization can boost protective IgG, reducing 
neonatal morbidity, as seen with tetanus [21] and influenza [22,23].  A number of COVID-19 vaccines 
are now in clinical development[24], which may be suitable for pregnant women. We must now gather 
data on natural immunity to SARS-CoV-2 in pregnant women, including seroprevalence, placental 
transfer and the duration of antibody persistence in infants to understand the role for maternal 
vaccination, ensure equitable inclusion of pregnant women into trials of candidate vaccines and, 
ultimately, to provide effective and safe COVID-19 vaccines [25]. 
 
Many maternity units are now routinely swabbing pregnant women, presenting a unique 
opportunity to understand the seroepidemiology of  SARS-CoV-2 in pregnancy and the peripartum and 
to prospectively monitor vertical transmission. By collecting samples from a large cohort of pregnant 
women, and from the newborns of women who had COVID-19 infection during pregnancy (irrespective 
of symptoms), we hope to understand the seroepidemiology of SARS-COV-2 and the risk and mode of 
perinatal transmission of the novel coronavirus.  This study will provide a robust evidence base to 
inform guidance and policy decisions for the clinical and public health management of pregnant 
women, their infants and the staff that care for them. 
 
4 
RESEARCH QUESTION/AIM(S) 
 
4.1 
Objectives 
 
Primary objectives 
• 
Determine the seroepidemiology of SARS-CoV-2 in pregnant women in England 
Secondary objectives 
• 
Determine the placental transfer ratio of antibodies specific to SARS-CoV-2 

 
 
 
   
 
 
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• 
Determine the concentration of SARS-CoV-2 antibodies in breastmilk of mothers who have tested 
rtPCR positive at any point during pregnancy 
• 
Determine the rate of mother to child transmission of SARS-CoV-2 in women who have tested 
rtPCR positive at any point during pregnancy 
• 
Determine the quantity (of both DNA and live virus) of SARS-COV-2 in maternal bodily fluids, 
including breastmilk, and in the placenta, in women who have tested positive for SARS-COV-2 by 
rtPCR at any point during pregnancy 
 
4.2 
Outcomes 
1. Antibody concentrations in maternal and cord blood in pregnant women in England and in infant 
blood if mothers are rtPCR positive for SARS-COV-2 
2. Number (%) of mother who have antibodies specific to SARS-CoV-2 in breastmilk 
3. Number (%) of mother-infant pairs who are both rtPCR positive in blood or secretions at birth and 
at six weeks and number (%) in whom the virus can be grown in vitro 
4. Number (%) of breastmilk samples that are rtPCR positive and number (%) in whom the virus can 
be grown in vitro. 
5. Number (%) of placental samples that are rtPCR positive and number (%) in whom the virus can 
be grown in vitro. 
 
5 
STUDY DESIGN and METHODS of DATA COLLECTION AND DATA ANALYIS 
 
An online CRF will be designed to capture the following information from all enrolled women:  
• 
Maternal characteristics (age, ethnicity, significant past medical history) 
• 
Pregnancy information (gestational age at diagnosis, number of foetuses, pregnancy related 
complications, radiology findings, laboratory findings, ventilation support, ICU admission, 
estimated foetal weight, foetal abnormalities).  Delivery information (Gestational age at delivery, 
delivery method, intrapartum complications, postpartum complications, placental pathology) 
• 
Neonatal outcomes (evidence of COVID-19, NICU admission, respiratory morbidity, duration and 
type of ventilation support, infectious morbidity, neurological morbidity, weight at day 5 postpartum 
check) 
• 
Onset and duration of symptoms of COVID-19 (if present) 
• 
Breastfeeding outcomes 
 

 
 
 
   
 
 
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All women will enter the study either having had a positive throat or nasopharyngeal aspirate (NPA) 
swab for SARS-CoV-2 RNA (as part of routine screening or due to symptom development), or having 
been recruited at one of our partner sites.  Therefore, women will effectively be screened for COVID-
19 by throat or nasopharyngeal aspirate (NPA) swab for SARS-CoV-2 RNA prior to enrolment into the 
study.  
If the rTPCR result for the throat/NPA swab is positive for SARS-CoV-2 RNA, the woman will be 
invited to enrol into the exposed group within the study. 
If the rTPCR result for the throat/NPA swab is negative for SARS-CoV-2 RNA, the woman will have a 
blood sample taken for SARS-CoV-2 IgM/IgG at the time of delivery. 
 
If the SARS-CoV-2 IgM/IgG result is positive, the woman should be placed into the seropositive 
group within the study.  
If the SARS-CoV-2 IgM/IgG result is negative, the woman should be placed into the unexposed 
group within the study.  
 
Participants in the exposed group will have the following samples taken at delivery: 
• 
Placental tissue (swab or biopsy) – for rtPCR for SARS-CoV-2 and viral culture 
• 
Cord blood (5mls) or neonatal blood sample (2mls)–serology (SARS-CoV-2 IgM/IgG) 
• 
Breast milk sample – for rtPCR for SARS-CoV-2, viral culture and SARS-COV-2 IgA/G/M 
• 
Neonatal nasal/throat swab – for rtPCR for SARS-CoV-2 and viral culture 
• 
Neonatal stool sample  – for rtPCR for SARS-CoV-2 and viral culture 
 
Participants in the exposed group will have the following samples taken at 6 weeks postpartum: 
• 
Maternal blood sample (5ml) – serology (SARS-CoV-2 IgM/IgG) 
• 
Breast milk sample – SARS-CoV-2 IgM/IgG 
• 
Neonatal blood sample (2ml)/dried blood spot – serology (SARS-CoV-2 IgM/IgG) 
• 
Neonatal nasal/throat swab – for rtPCR for SARS-CoV-2 and viral culture 
• 
Neonatal stool sample  – for rtPCR for SARS-CoV-2 and viral culture 
• 
Dried blood spots – for SARS-COV-2 IgA/G/M 
 
 
Participants in the seropositive group will have the following samples taken at delivery: 
• 
Maternal blood sample (SARS-CoV-2 IgM/IgG) 

 
 
 
   
 
 
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• 
Cord blood (SARS-CoV-2 IgM/IgG) 
 
Participants in the unexposed group will have the following samples taken at delivery: 
• 
Maternal blood sample (SARS-CoV-2 IgM/IgG) 
• 
Cord blood (SARS-CoV-2 IgM/IgG) 
 
Crossover between the study groups will be permitted; women may move from the unexposed group 
to the exposed group if a repeat throat/NPA swab performed after enrolment is positive for SARS-
CoV-2 RNA.  
 
 
 

 
 
 
   
 
 
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The flow chart below describes the sequence of events for all women who are screened and enrolled 
into the study: 
 
Laboratory tests 
All samples will be sent to St. George’s, University of London using appropriate pre-addressed 
packaging supplied on sites joining the study.  Samples will be processed at the PHE laboratory at St 
George’s. Secretions, placental tissue and breastmilk samples will be analysed by rT-PCR and if 
positive for viral culture using standard NHS methods[26]. Serum and dried blood spots will be frozen 
at -70C and will be analysed by validated assays at National Institute for Health Protection laboratories 
using previously published methods[17,27]: 
 
Swab, breastmilk, urine faeces testing 
Briefly, RNA will be extracted using commercial kits and run in the rTPCR published in February 2020 
by the CDC “CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel”.  
 
Serum testing 
Serum samples will be tested in a commercial ELISA (EDITM) that uses an immunocomplex of the 
novel CoVID19 recombinant antigen-human anti-CoVID19 IgG/IgM HRP-labelled anti-human IgG/IgM 
tracer antibody, already in use at PHE Porton. 
 
Sequencing 

 
 
 
   
 
 
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Extracted viral genomic material will be sent to the COVID-19 genetics consortium UK based at the 
Sanger Centre for sequencing. 
 
 
Data Analysis  
We will perform descriptive analyses of the characteristics of our cohort of mother and infant pairs. 
This will take place at St George’s University, London.  Pseudonymised test results will be transferred 
from the PHE laboratory and inputted to REDCap to facilitate this.  Maternal factors will include age, 
maternal comorbidities, parity, and antenatal history and COVID-19 symptoms. Infant factors will 
include gestational age, birth weight, condition at birth, breastfeeding status, weight at 6 weeks, 
symptoms and admission to the special care baby unit.   
We will estimate seroprevalence of COVID-19 in women/infants as the proportion with a positive 
antibody test. The proportion of women PCR positive during pregnancy will be estimated with 95% CI. 
The proportion of infants PCR positive at day 0 based on the various tissue samples tested will be 
calculated with 95% CI overall and within the subset of infected or PCR positive. Antibody transfer 
ratios (with 95% CI) for mother-baby pairs where the mother or baby is antibody positive at birth will be 
calculated with analysis of logged antibody concentrations. Antibody kinetics will be assessed in 
mothers who are antibody positive prior to birth and their infants by assessing geometric mean fold 
changes between diagnosis, birth and six weeks post-delivery and by fitting decline curves with a 
mixed model. Multivariable logistic regression will assess risk factors associated with the outcomes. 
 
 
 
 
6 
STUDY SETTING 
 
This is a multisite study which will be open to and recruiting participants from all maternity units 
(obstetric unit or alongside maternity unit) in England. 
 
7 
SAMPLE AND RECRUITMENT 
7.1  
Eligibility Criteria 
All pregnant women ≥ 24 weeks gestation in England. 
 
7.1.1 Inclusion criteria  
• 
Signed informed consent form 
• 
Any woman pregnant in selected hospitals in England who has no signs or symptoms 
of COVID-19 disease during pregnancy and is rtPCR negative at delivery   
• 
Any woman pregnant in any hospital in England who tests positive by rtPCR at any 
point during pregnancy, regardless of signs and symptoms 

 
 
 
   
 
 
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7.1.2 Exclusion criteria  
• 
If the pregnant woman is under 18 years in prison or unable to make an informed 
consent for other reasons (e.g. learning difficulties, language barriers) 
 
7.2  
Sampling 
 
7.2.1  Size of sample 
We aim to recruit 1200 pregnant women over a period of 12 months. 
Seroepidemiology: around 1000 women will allow good precision for estimation of an overall 
seroprevalence in the pregnant woman population. 
The precision (95% CI width) 
Observed % with antibodies                       95% CI (N=1000)             95%CI (N=2000) 
5%                                                                     3.7%-6.5%                     4.1%-6.0% 
10%                                                                   8.2%12.0%                   8.7%11.3%      
15%                                                                   12.8%-17.4%                   13.5%16.6% 
                                                          
Vertical transmission: around 200 rT-PCR positive women will allow good precision for estimation of 
the infant also being rT-PCR positive: 
Observed % with PCR detected in baby   95% CI (N=100)                95% CI (N=200) 
5%                                                                     1.6%-11.2%                   2.4%-9.0% 
10%                                                                   4.9%-17.6%                   6.2%-15.0% 
15%                                                                   8.6%-23.5%                   10.4%-20.7% 
 
7.2.2  Sampling technique 
All eligible women should be sensitised to the study by staff at the maternity units. Allocation to each of 
the study groups will be dependent on the outcome of their screening samples. 
 
7.3 
 Recruitment 
We anticipate that many (or all) hospitals in England will begin to screen all pregnant women for 
SARS-CoV-2 and have identified ten hospitals (in London, Birmingham, Manchester, Leeds, Bristol, 
Cambridge, Newcastle, Maidstone, Liverpool) who are screening pregnant women antenatally and at 
delivery and will be part of the periCOVID study. There will be two possible entry points to the study. 
Women will either enter the study after testing positive for SARS-CoV-2 (by rtPCR) during their 
antenatal care at any hospital in England and will then be referred to the study team at St George’s 
University of London or will be recruited from one of the participating NHS sites.  
 

 
 
 
   
 
 
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7.3.1 Participant identification  
Participants who fulfil the eligibility criteria will be identified by the direct care team who are involved in 
their care. The responsibility of sensitisation and recruitment of participants will be delegated to 
research staff based at the NHS maternity units where these women are receiving their care.  
Eligible participants should be sensitised to the study by their direct care team. Women should be 
sensitised and recruited during their routine appointments where possible to minimise the number of 
additional visits required for the study. Participants will also be able to self-refer to the study via the 
study website.  
 
7.3.2 Consent 
Eligible women should be sensitised to the study through the provision of a participant information 
leaflet and informed consent form (ICF) which will be made available to hospital-based recruiting 
clinicians and will also be available to download from the periCOVID website 
(http://www.pericovid.com).  
The woman should be given sufficient time by the clinician to consider the information provided and 
ask any questions. If she agrees to take part, then she will be asked to complete and sign the ICF. 
The woman should then be provided with a copy of the ICF for her records and the original document 
stored locally.  
Women who cannot provide informed consent (e.g. due to learning difficulties) are not eligible for the 
study. Women will be asked to give consent for collection of samples from their infant. 
 
Consent provisions for collection and use of participant data and biological specimens  
Data and biological specimens will be acquired locally, and transferred and stored as detailed above. 
Data collection will be coordinated between the PHE laboratory at St Geroge’s and SGUL, where all the 
data will be held and all data analysis performed.  A secure electronic database using REDCap will be 
developed for this purpose and sites will be asked to complete questionnaires directly online. 
 
 Pseudonymised demographic and clinical data may also be obtained from our collaborative partners 
working within the UKOSS and PANCOVID studies via REDCap, a secure web-browser based 
application designed to capture data for clinical research. Each participant will be allocated a study 
number, and demographic and clinical data relating to each participant will be recorded into REDCap 
under their study number.  This relates only to participants who are co-enrolled in these studies and 
who provide consent to their data being shared.  
Anonymised data collected during this study will be reported monthly to the WHO so that important 
results can be widely disseminated in real time. Anonymised data and/or samples may also be 
transferred to our other collaborators for use in research that is being conducted at their site(s). 
Participants will also be asked to provide consent for this in the informed consent form.  

 
 
 
   
 
 
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If a participant loses the capacity to consent during the study, they will be withdrawn from the study.  
Identifiable data or tissue already collected with consent would be retained and used in the study.  No 
further data or tissue would be collected or any other research procedures carried out on or in relation 
to the participant.  Participants will also be able to withdraw their consent at any time, and hence 
withdraw from the study.  If participants withdraw consent, we will retain samples and data already 
collected, with their consent. 
 
7.3.3 Data collection tool  
Case Report Forms will be designed by the CI and uploaded to REDCap to facilitate data collection. 
The CI or delegated individual on behalf of the Sponsor will provide logins to relevant and 
trained site level members of the research team.  
It is the Investigator’s responsibility to ensure the accuracy of all data entered and recorded in the 
CRFs. The Staff Delegation of Responsibilities Log should identify all trial personnel responsible for 
data collection, entry, handling and managing the database. 
 
7.3.4 Biological Sample Handling 
 
All samples will be stored at -70C until analysis.  Samples will be sent to St George’s, and then 
analysed in the PHE laboratory at St George’s.  Pending ethical approval, samples will be held in long-
term storage in the Institute of Infection and Immunity Research Tissue Bank for as yet unidentified, 
future research projects. 
 
5.4.3.1. Throat/NPA swab, breastmilk, cord blood, amniotic fluid, placental and stool swab testing 
Briefly, RNA will be extracted using commercial kits and run in the rTPCR published in February 2020 
by the CDC “CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel”.  
 
5.4.3.2. Serum and cord blood testing 
Serum and cord blood samples will be tested in a commercial ELISA (EDITM) that uses an 
immunocomplex of the novel CoVID19 recombinant antigen-human anti-CoVID19 IgG/IgM HRP-
labelled anti-human IgG/IgM tracer antibody, already in use at PHE Porton. 
 
8 
ETHICAL AND REGULATORY CONSIDERATIONS 
 
 
8.1 
Assessment and management of risk 
Where possible, we will ask site level study staff to collect samples at the same time that routine 
samples are being collected and will work with the obstetric and neonatal teams to ensure that 
samples are collected by experienced members of staff to minimise the risk of harm and discomfort to 
participants. Participants may have the burden of extra visits for sample collection and follow-up if self-

 
 
 
   
 
 
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isolating. There is the risk of causing worry to participants who are asymptomatic but are antibody 
positive on testing.  There is the risk of exposing study staff to SARS-CoV-2, but standard infection 
control practices from participating trusts will be followed to minimise this risk. 
 
8.2  
 Research Ethics Committee (REC) and other Regulatory review & reports 
Before the start of the study, a favourable opinion will be sought from an appropriate REC for the 
study protocol, informed consent forms and other relevant documents e.g. advertisements.  
For HRA- NHS REC reviewed research 
• 
Substantial amendments that require review by NHS REC will not be implemented until 
that review is in place and other mechanisms are in place to implement at site.   
• 
It is the Chief Investigator’s responsibility to produce the annual reports and submit the 
REC within 30 days of the anniversary date on which the favourable opinion was given, 
and annually until the study is declared ended. 
• 
The Chief Investigator will notify the REC of the end of the study within one year after 
the end of the study. 
• 
If the study is ended prematurely, the Chief Investigator will notify the REC, including 
the reasons for the premature termination. 
 
Regulatory Review & Compliance  
Before any site can enrol patients into the study, the Chief Investigator/Principal Investigator or 
designee will ensure that appropriate approvals from participating organisations are in place. Specific 
arrangements on how to gain approval from participating organisations are in place and comply with 
the relevant guidance. 
Amendments  
For any amendment to the study, the Chief Investigator or designee, in agreement with the sponsor 
will submit information to the appropriate body in order for them to issue approval for the amendment. 
The Chief Investigator or designee will work with sites (R&D departments at NHS sites as well as the 
study delivery team) so they can put the necessary arrangements in place to implement the 
amendment to confirm their support for the study as amended. 
8.3  
Peer review 
The protocol has been reviewed and amended in collaboration with members of the Infection and 
Immunity Research Institute at St George's University. The statistics have been reviewed by Public 
Health England and the London School of Hygiene and Tropical Medicine.  
 
8.4  
Patient & Public Involvement 
As part of our study, periCOVID is committed to ensuring that our research into SARS-CoV-2 in 
pregnant women and their babies is participant friendly and ethically sound by fostering patient and 
public involvement in order to help us; 

 
 
 
   
 
 
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• 
Define the most relevant research question to ask within the study; 
• 
Identify the outcomes of importance to be measured within; 
• 
Develop the study protocol appropriate to the needs and lifestyles of the patient community it 
serves; 
• 
Identify appropriate and ethically acceptable research tools and methods; 
• 
Develop study participant materials, including but not limited to the patient information sheet and 
consent form, patient diaries and questionnaires; 
• 
Conduct the study in a participant friendly and ethically acceptable way; 
• 
Provide a public perspective on the interpretation of trial findings; 
 
We have set up an online periCOVID patient and public group using social media that members of the 
public can access to learn about the most recent research into SARS-CoV-2 in pregnancy. We have 
used this platform to generate and disseminate online surveys and questionnaires in order to ascertain 
what research questions the public would like answered, the results of which have been instrumental 
to the design of our study.  
 
8.5 
Protocol compliance  
All protocol deviations will be adequately documented on the relevant forms and reported to the Chief 
Investigator and Sponsor immediately.  
 
8.6 
Data protection and patient confidentiality  
All data should be handled in accordance with the Data Protection Act 2018 (UK implementation of the 
EU General Data Protection Regulation (GDPR)).  
Any Case Report Forms (CRFs), including the electronic study database, will not bear the participant’s 
name or other directly identifiable data. The participant’s trial Identification Number (ID) only, will be 
used for identification. The Subject ID log can be used to cross reference participant’s identifiable 
information. 
Once written informed consent has been obtained for study participation, the patient will be allocated a 
unique study identifier (consisting of a site number and sequential participant number), which will be 
utilised to code all depersonalised data. The patient’s unique study number (ID) only, will be used for 
identification. 
The Subject ID log can be used to cross reference participant’s identifiable information, which will be a 
minimum of 2 patient identifiers (such as name and date of birth) in order to avoid errors in the 
allocation of a unique subject ID. The subject ID log will be stored on Trust computers at each 
participating site and will only be accessible to the researchers via unique username and password. 
Only delegated members of the research team, who form part of the direct clinical care team will have 
access to patient identifiable data. 

 
 
 
   
 
 
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The informed consent forms will contain patient identifiable data (name), but these will be stored in a 
locked filing cabinet, in an office at each participating site which will only be accessible to the 
researchers. 
As no personal identifiable data is being collected, there will be no personal identifiable data included in 
the results. 
Data collected will comprise the de-identified clinical information from the clinical care team, and the 
results of analyses conducted on the study samples. They will be stored on a secure local computer 
(with appropriate back-up) that can only be accessed by the CI/PI and delegated members of the 
research team for patients recruited at their sites.  
Data collection will be co-ordinated between the PHE laboratory and SGUL.  Samples will be received 
at St George’s and processed in the PHE laboratory at St George’s.  Results will be communicated via 
secure channels to St George’s, where all the data will be held and all data analysis performed. A 
secure electronic database will be developed for this purpose and sites will be asked to complete 
questionnaires directly online. Anonymised demographic and clinical data may also be obtained from 
our collaborative partners working within the UKOSS and PANCOVID studies via our secure REDCap 
database. This relates only to participants who are co-enrolled in these studies and who provide 
consent to their data being shared. 
All data collected during this study will be anonymised and reported monthly to the WHO so that 
important results can be widely disseminated in real time. Anonymised data and/or samples may also 
be transferred to our other collaborators for use in research that is being conducted at their site(s) (see 
Appendix 4 for details of collaborating study sites). Participants will also be asked to provide consent 
for this in the informed consent form. 
We will perform interim analysis weekly. We will produce an interim report for the PHE COVID 
response team. The final results will be reported to relevant authorities. A paper containing the overall 
results may be submitted for publication in a peer-reviewed journal. 
 
8.7 
Indemnity 
 
St George’s University of London sponsored research: 
St George’s University of London holds insurance to cover participants for injury caused by their 
participation in the clinical trial. Participants may be able to claim compensation if they can prove that St 
George’s has been negligent. This includes negligence in the writing of the protocol, or selection of trial 
resources.  
Where the Trial is conducted in a hospital, the hospital has a duty of care to participants. St George’s 
University of London will not accept liability for any breach in the hospital’s duty of care, or any negligence 
on the part of hospital employees.  . 
If a participant indicates that they wish to make a claim for compensation, this needs to be brought to the 
attention of St George’s University of London immediately.   
Failure to alert St George’s University of London without delay and to comply with requests for 
information by the sponsor or any designated Agents may lead to a lack of insurance cover for the 
incident.   

 
 
 
   
 
 
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8.8 
Access to the final study dataset 
The final study dataset will contain only de-identified patient data, and should be accessible only to the 
Chief Investigator and delegated members of the research team. 
 
9 
DISSEMINIATION POLICY 
9.1  
Dissemination policy 
Publication: “Any activity that discloses, outside of the circle of trial investigators, any final or interim data 
or results of the Trial, or any details of the Trial methodology that have not been made public by the 
Sponsor including, for example, presentations at symposia, national or regional professional meetings, 
publications in journals, theses or dissertations.” 
All scientific contributors to the Trial have a responsibility to ensure that results of scientific interest arising 
from Trial are appropriately published and disseminated. The Sponsor has a firm commitment to publish 
the results of the Trial in a transparent and unbiased manner without consideration for commercial 
objectives.  
To maximise the impact and scientific validity of the Trial, data shall be consolidated over the duration of 
the trial, reviewed internally among all investigators and not be submitted for publication prematurely. 
Lead in any publications arising from the Trial shall lie with the Sponsor in the first instance.  
Before the official completion of the Trial,  
All publications during this period are subject to permission by the Sponsor. If an investigator wishes to 
publish a sub-set of data without permission by the Sponsor during this period, the Steering 
Committee/the Funder shall have the final say.  
Exempt from this requirement are student theses that can be submitted for confidential evaluation but are 
subject to embargo for a period not shorter than the anticipated remaining duration of the trial.      
Up to 180 days after the official completion of the Trial  
During this period the Chief Investigator shall liaise with all investigators and strive to consolidate data 
and results and submit a manuscript for peer-review with a view to publication in a reputable academic 
journal or similar outlet as the Main Publication.  
• 
The Chief Investigator shall be senior and corresponding author of the Main Publication.  
• 
Insofar as compatible with the policies of the publication outlet and good academic practice, 
the other Investigators shall be listed in alphabetic order.  
• 
Providers of analytical or technical services shall be acknowledged, but will only be listed as 
co-authors if their services were provided in a non-routine manner as part of a scientific 
collaboration.  
• 
Members of the Steering Group shall only be acknowledged as co-authors if they contributed 
in other capacities as well.   
• 
If there are disagreements about the substance, content, style, conclusions, or author list of 
the Main Publication, the Chief Investigator shall ask the Steering Group to arbitrate.     
Beyond 180 days after the official completion of the Trial  

 
 
 
   
 
 
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After the Main Publication or after 180 days from Trial end date any Investigator or group of investigators 
may prepare further publications.  In order to ensure that the Sponsor will be able to make comments and 
suggestions where pertinent, material for public dissemination will be submitted to the Sponsor for review 
at least sixty (60) days prior to submission for publication, public dissemination, or review by a publication 
committee. Sponsor’s reasonable comments shall be reflected. All publications related to the Trial shall 
credit the Chief and Co-Investigators as co-authors where this would be in accordance with normal 
academic practice and shall acknowledge the Sponsor and the Funders.    
 
9.2          Archiving Arrangements  
Each site will be responsible for their onsite level study archiving. The trial essential TMF along with any 
central trial database will be archived in accordance with the sponsor SOP.  
 
10 
REFERENCES 
1  
Johns Hopkins University. COVID-19 Tracker map.  
2  
Allotey J, Stallings E, Bonet M, et al. Clinical manifestations, risk factors, and maternal and 
perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and 
meta-analysis. BMJ Published Online First: 2020. doi:10.1136/bmj.m3320 
3  
Ripe Tomato.  
4  
Dean A. Blumberg, Mark A. Underwood, Herman L. Hedriana SL. Vertical Transmission of 
SARS-CoV-2: What is the Optimal Definition? Am J Perinatol 2020;37:769–72. 
5  
Assiri A, Abedi GR, Al Masri M, et al. Middle East Respiratory Syndrome Coronavirus Infection 
during Pregnancy: A Report of 5 Cases from Saudi Arabia. Clin Infect Dis Published Online 
First: 2016. doi:10.1093/cid/ciw412 
6  
Di Mascio D, Khalil A, Saccone G, et al. Outcome of coronavirus spectrum infections (SARS, 
MERS, COVID-19) during pregnancy: a systematic review and meta-analysis. Am J Obstet 
Gynecol MFM Published Online First: 2020. doi:10.1016/j.ajogmf.2020.100107 
7  
Pierce M, Kurinczuk JJ, Spark P, et al. Perinatal outcomes after maternal 2009/H1N1 infection: 
National cohort study. BMJ Published Online First: 2011. doi:10.1136/bmj.d3214 
8  
Jamieson DJ, Honein MA, Rasmussen SA, et al. H1N1 2009 influenza virus infection during 
pregnancy in the USA. Lancet Published Online First: 2009. doi:10.1016/S0140-
6736(09)61304-0 
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COVID-19. DMDW (The WA of PM working group on. Maternal and Perinatal Outcomes of 
Pregnant Women with SARS-COV-2 infection. Ultrasound Obs Gynecol 2020. 
10  
Khalil A, Kalafat E, Benlioglu C, et al. SARS-CoV-2 infection in pregnancy: A systematic review 
and meta-analysis of clinical features and pregnancy outcomes. EClinicalMedicine Published 
Online First: 2020. doi:10.1016/j.eclinm.2020.100446 
11  
PREGCOV.  
12  
Gajbhiye R, Modi D, Mahale S. Pregnancy outcomes, Newborn complications and Maternal-
Fetal Transmission of SARS-CoV-2 in women with COVID-19: A systematic review. medRxiv 
Published Online First: 2020. doi:10.1101/2020.04.11.20062356 
13  
Chen H, Guo J, Wang C, et al. Clinical characteristics and intrauterine vertical transmission 
potential of COVID-19 infection in nine pregnant women: a retrospective review of medical 
records. Lancet Published Online First: 2020. doi:10.1016/S0140-6736(20)30360-3 
14  
Facchetti F, Bugatti M, Drera E, et al. SARS-CoV2 vertical transmission with adverse effects on 
the newborn revealed through integrated immunohistochemical, electron microscopy and 
molecular analyses of Placenta. EBioMedicine 2020;59:102951. 

 
 
 
   
 
 
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doi:10.1016/j.ebiom.2020.102951 
15  
Sisman J, Jaleel MA, Moreno W, et al. Intrauterine Transmission of SARS-CoV-2 infection in a 
pretern infant. Pediatr Infect Dis J 2020;Publish Ah. doi:10.1097/INF.0000000000002815 
16  
Overview of the UK population - Office for National Statistics.  
17  
Khalil A, Hill R, Ladhani S, et al. SARS-CoV-2 in pregnancy: symptomatic pregnant women are 
only the tip of the iceberg. Am J Obstet Gynecol Published Online First: 2020. 
doi:10.1016/j.ajog.2020.05.005 
18  
Sutton D, Fuchs K, D’Alton M, et al. Universal screening for SARS-CoV-2 in women admitted 
for delivery. N Engl J Med 2020;382:2163–4. doi:10.1056/NEJMc2009316 
19  
Knight M, Bunch K, Vousden N, et al. Characteristics and outcomes of pregnant women 
admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based 
cohort study. BMJ Published Online First: 2020. doi:10.1136/bmj.m2107 
20  
Marchant A, Sadarangani M, Garand M, et al. Maternal immunisation: collaborating with mother 
nature. Lancet Infect. Dis. 2017. doi:10.1016/S1473-3099(17)30229-3 
21  
Blencowe H, Lawn J, Vandelaer J, et al. Tetanus toxoid immunization to reduce mortality from 
neonatal tetanus. Int J Epidemiol Published Online First: 2010. doi:10.1093/ije/dyq027 
22  
Benowitz I, Esposito DB, Gracey KD, et al. Influenza vaccine given to pregnant women reduces 
hospitalization due to influenza in their infants. Clin Infect Dis Published Online First: 2010. 
doi:10.1086/657309 
23  
Nunes MC, Cutland CL, Jones S, et al. Duration of infant protection against influenza illness 
conferred by maternal immunization secondary analysis of a randomized clinical trial. JAMA 
Pediatr Published Online First: 2016. doi:10.1001/jamapediatrics.2016.0921 
24  
COVID-19 vaccine tracker.  
25  
Heath PT, Le Doare K, Khalil A. Inclusion of pregnant women in COVID-19 vaccine 
development. Lancet Infect. Dis. 2020. doi:10.1016/S1473-3099(20)30638-1 
26  
NHS England. Guidance and Standard Operating ProcedureCOVID-19 Virus Testing in NHS 
Laboratories. 2020.  
27  
Ladhani SN, Jeffery-Smith AJ, Patel M, et al. High prevalence of SARS-CoV-2 antibodies in 
care homes affected by COVID-19 a prospective cohort study in England. Medrxiv Published 
Online First: 2020. doi:10.1101/2020.08.10.20171413 
 
 

 
 
 
   
 
 
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11.  
APPENDICIES 
 
 
11.1  Appendix 1 – Amendment Log 
Amendment Log 
Amendment 
No. 
Protocol 
version no. 
Date issued 
Author(s) of 
changes 
Details of changes made