Early epidemiological investigations: World Health Organization UNITY protocols provide a standardized and timely international investigation framework during the COVID‐19 pandemic

Background The declaration of Coronavirus disease 2019 (COVID‐19) as a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 required rapid implementation of early investigations to inform appropriate national and global public health actions. Methods The suite of existing pandemic preparedness generic epidemiological early investigation protocols was rapidly adapted for COVID‐19, branded the ‘UNITY studies’ and promoted globally for the implementation of standardized and quality studies. Ten protocols were developed investigating household (HH) transmission, the first few cases (FFX), population seroprevalence (SEROPREV), health facilities transmission (n = 2), vaccine effectiveness (n = 2), pregnancy outcomes and transmission, school transmission, and surface contamination. Implementation was supported by WHO and its partners globally, with emphasis to support building surveillance and research capacities in low‐ and middle‐income countries (LMIC). Results WHO generic protocols were rapidly developed and published on the WHO website, 5/10 protocols within the first 3 months of the response. As of 30 June 2021, 172 investigations were implemented by 97 countries, of which 62 (64%) were LMIC. The majority of countries implemented population seroprevalence (71 countries) and first few cases/household transmission (37 countries) studies. Conclusion The widespread adoption of UNITY protocols across all WHO regions indicates that they addressed subnational and national needs to support local public health decision‐making to prevent and control the pandemic.

Building on these global pandemic preparedness efforts, we describe the rapid adaptation and implementation of WHO early investigation protocols for COVID-19, branded the 'UNITY studies ', 9 to generate local data to better inform appropriate national and global public health actions and guidelines. The on-going and future value of such studies for pandemic preparedness and response is discussed.

| Generic protocol development
Ten generic protocols using eight study methodologies were developed (three adapted from available IPSS protocols). These investigate household (HH) transmission, the first few cases (FFX) and their contacts, population seroprevalence (SEROPREV), health facility transmission (two protocols), vaccine effectiveness (two protocols), pregnancy outcomes and transmission, school transmission, and surface contamination. More information on each protocol is described in Table 1.
Four protocols were designed from inception to be multi-country and multi-centre research studies with sharing of anonymised individual level data, a subsequent planned pooled analysis and related tools including joint data platforms (see Table 1). Remaining protocols were mostly considered to be enhanced surveillance protocols by implementing countries. T A B L E 1 UNITY protocols description by publication date on the World Health Organization (WHO)'s website and number of countries intending to or having implemented UNITY protocols 9 by investigation type, as of 30

| RESULTS
Five of the ten protocols were published on the WHO website within the first 3 months of response (before 1 April 2020). As of 30 June The most commonly implemented investigation was the SEROPREV investigation, which has been implemented by 71 countries (Table 1)

| DISCUSSION
The widespread adoption of UNITY protocols across all WHO regions indicates that they have addressed subnational and national needs to collect critical data to support local and regional public health decision-making to prevent and control the pandemic. The quarterly monitoring of the implementation of UNITY investigations as a performance indicator of the COVID-19 SPRP 10 further reinforces their significance and impact to also inform global normative work.
WHO rapidly adapted and established the suite of protocols as part of its pandemic preparedness and response planning, which were rapidly adopted by countries. FFX and HH investigations implementation was more relevant for country action early in the pandemic to robustly define key epidemiological and severity parameters of the infection. Nonetheless, the continued collection of such data can provide important insights into the transmission of variants viruses of interest or of concern. It is likely that SEROPREV investigations were of higher priority for countries for rapid policy decision making (and particularly in countries with low testing capacities or weak case-based reporting system) than for other less used protocols (e.g., school transmission and surface contamination). The assessment of uptake of the more recently developed pregnancy and Vaccine Effectiveness protocols will require more time.
F I G U R E 2 Countries that have started implementing at least one sero-epidemiological investigation aligned with WHO UNITY generic protocols, from Jan 2020 to 30 June 2021 The large number of LMIC, including those affected by armed conflict and political instability (HRP countries), that adopted a UNITY protocol is of note and indicates the value of having readily available, generic protocols that can be adapted for various settings. The number of adopted UNITY studies in this analysis is likely to be under-reported as institutions may have employed the publicly available protocols independent of WHO support or knowledge, particularly in HIC.
The first set of significant funding support arrived 4 months after the first protocols publication which hampered timely implementation in LMIC. Tight deadlines for fund expenditure from effective reception (ex: less than 3.5 months) was an issue for such activities.
The provision of technical, financial, and laboratory assay support by WHO and international partners and using existing surveillance were essential for the feasibility of such initiatives WHO is working with UNITY partners to summarise available study results and to conduct pooled analyses where relevant, by studying populations and at regional and global levels.
An after action review and evaluation of the UNITY initiatives and its protocols to assess their utility to countries in responding to this pandemic and whether they fulfilled key initial objectives started in September 2021 and will be valuable to inform future pandemic preparedness, readiness and response strategy to any respiratory pathogens.

ACKNOWLEDGEMENTS
The authors would like to thank people in all countries who are working in the global response effort to COVID-19, to thank all

PEER REVIEW
The peer review history for this article is available at https://publons. com/publon/10.1111/irv.12915.