Design: This systematic review was conducted to address the following question, “Is there a vertical transmission and antibody responses against SARS-CoV-2 in infants born to mothers with COVID-19?”. A systematic review protocol was developed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines19 and registered in the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/prospero/: PROSPERO database registration number: CRD42020185362)
Search strategy: Articles were retrieved using online search engines and library sources, including PubMed/MEDLINE and Google Scholar. Additionally, websites of key healthcare organizations such as WHO and centre for disease prevention and control (CDC) were also searched. Similarly, a grey literature search was done with the help of Google. Data from December 1, 2019 to May 18, 2020 conducted in human beings, and published in English language were included. The strategy was developed for PubMed/MEDLINE (Additional file 1) using keywords and MeSH (MEDLINE) then adapted to other databases. To be as inclusive as possible, the search strategy included the terms covering the concept of immunity and infection among infants born to mothers with COVID-19. Keywords such as vertical transmission, antibody, immunoglobulin, pregnant mother, pregnancy, child, infant, new-born, SARS-CoV-2 and COVID-19 were used.
Eligibility criteria and study selection: To exclude irrelevant studies, two reviewers (GMB and BJN) independently screened the titles and abstracts, and a full-text articles were assessed for further consideration for inclusion. Disagreements on study eligibility were resolved by consensus, and/or a third reviewer was consulted if necessary. If the information on eligibility was unavailable and/ or unclear, study authors were contacted to clarify. The selected studies were included based on laboratory-confirmed COVID-19 infection using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) or dual fluorescence PCR and immunoassay such as enzyme linked immunosorbent assay (ELISA) and flow cytometry for antibodies detection, patient pregnant on admission, infant’s COVID-19 status soon after birth and infection control and prevention (IPC) measures during and after delivery, i.e., mother wore N-95 during delivery, personnel protective equipment wore by health care workers, infants immediately separated with her mother to a negative pressure room and infants did not breastfeed before samples were taken. This review included, letter to the editor, correspondence, editorial, research article (case report, case series, cross-sectional, clinical trial, cohort, case control study) etc., however, articles that reported on the secondary data such as review were excluded.
Data management: All article citations retrieved from database searches were exported into EndNote software version X7 (Thomson Reuters, 2015) where duplicates were identified and removed. Identified publication(s) were analyzed using criteria based on vertical transmission and/ or IgG/ IgM against SARS-CoV-2 and maximum correspondence with inclusion criteria (Fig. 1).
Data extraction and quality assessment: The reviewers independently extracted the variables of interest from the selected studies using data extraction. Data extraction form was developed in Excel spreadsheet 2010 (Microsoft Corporation, Redmond, WA), pre-tested on 3 eligible articles and adjusted accordingly (Table 1). The primary endpoints were birth outcomes, such as COVID-19 infection, IgM and IgG against SARS-CoV-2. PRISMA-P guideline19 recommends a quality assessment of the included literature, but given the time from the first report of COVID-19 (December 31, 2019), most of the extracted studies were case reports with a very small number of participants (mostly one participant) per study. In this case, authors decided not to perform the risk assessment as described elsewhere20, heterogeneity and meta-analysis
Summary measures and synthesis of results: A summary estimate of proportions for COVID-19 virus positive and IgG/IgM against SARS-CoV-2 among infants born to mothers with COVID-19 were determined using Open Meta Analyst software21.The statistical measures included along with 95% confidence interval (95%CI) for continuous variables. The narrative was written by the lead reviewer (GMB) and then checked independently by two reviewers (BJN and DLM). The variables that were missing from included articles were recorded as not reported. No statistical test was applied in handling missing data. However, available information was used in recalculating some variables using the Open Meta Analyst calculator.