The rapid onset and growth of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occupied the attention of medical and public health researchers to an unprecedented extent.
The protean manifestations of the disease, and its fairly unpredictable progression to severe and critical disease, has rendered reliable and consistent diagnostic criteria difficult to apply. A new study by researchers from Emory and Yale Universities in the USA discusses a design for quickly launching serological surveys to assess the prevalence of this infection in a given population.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
The research team has released their findings on the preprint medRxiv* server.
Challenges in clinical research during a pandemic
The absence of diagnostic algorithms has made SARS-CoV-2 tracking difficult in the USA. At the same time, some groups, especially elderly and frail people, are known to be at higher risk of adverse outcomes following SARS-CoV-2 infection. The exact impact of these risk factors, and the mechanisms by which they operate, are alike unknown.
The need to observe social distancing, avoid infection, maintain personal protection despite the shortage of personal protective equipment (PPE), and the changing guidelines for more rapid regulatory review, have added to the challenges associated with rigorous research.
The various hindrances addressed include the shortage of testing kits and reagents, poor test sensitivity, and the entry of many substandard commercial kits into the market by virtue of the US Food and Drug Administration’s older COVID-19 Emergency Use Authorization procedure.
Especially with lateral flow testing, the sensitivity may be only about 65%. Poor access to testing in the early part of the pandemic, with inequities in testing within minority ethnic or racial groups, further aggravated the poor outcomes in these communities.
Thus, those with suspected and confirmed COVID-19 are mingled in the same group, making the validity of studies based on such definitions suspect. To overcome such issues, the researchers carried out a cross-sectional serological survey, on a cohort of 369 people from Georgia.
The current preprint is aimed at demonstrating how a well-thought-out design for prospective serological surveys can promote successful implementation even while the pandemic is still active.
Study design
The study cohort was rapidly gathered from asymptomatic individuals in the community, between April and May 2020, before the peak of the COVID-19 pandemic in Georgia. The survey was conducted in two phases.
The first included ~300 healthy middle-aged and older adults in the community, 57% of which being female. The mean age of the subjects was 43 years. Over 90% were non-Latino/Hispanic, and 77% were white. Over 90% had four or more years of a college education. About 60% were healthcare workers (HCWs).
About half had been exposed to COVID-19, and roughly the same proportion had a history of one or more symptoms related to this condition. The most common symptom were cough, stuffiness of the nose, and myalgia, in 60% to 75% of the participants.
The second was carried out on 70 first responders at the DeKalb County Fire and Rescue team. These included firefighters, emergency medical technicians [EMTs], and police officers. While 84% were male, the vast majority were non-Latino/Hispanic, and about 70% were white. Here again, 64% were HCWs.
Over half reported exposure to, and less than 30% reported symptoms of, COVID-19. Interestingly, all symptomatic participants reported anosmia, pneumonia, and dizziness, followed by cough and nasal stuffiness in 75% and 70%, respectively.
The prerequisites
The design of the study required attention to several key areas. For instance, the researchers found that they had to fulfill several criteria for a suitable outpatient space where the subjects could be tested. These included having cleaning services and being equipped with adequate HVAC, being away from areas on other floors that may be in use, distant from any COVID-19 testing center in use, and approved by the relevant authorities.
Another challenge is the need for strong partnerships between the researchers and the community, which in this case led to a doubling of the participants in the first phase of the study, and made phase two possible.
Thirdly, logistical challenges must be anticipated and overcome, and extra care must be taken to ensure the modified protocols are adhered to by all researchers. For the specific challenge of sample collection and biobanking the samples, while a pandemic is going on, they recommend bundling all the paperwork for each participant for the time of use, and pre-labeling sample collection tubes.
Finally, feasibility must be addressed. Since a prospective observational study is cheaper and less complex than a randomized, double-blinded placebo-controlled clinical trial, it may be a better choice during such a situation as a pandemic. The data it yields is often adequate to supplement that gained from retrospective studies and epidemiological studies.
What are the implications?
The process of conducting the current study was often “more fragmented and reactive” than would have been the case before the COVID-19 pandemic began. However, with careful attention to the details, the researchers managed to complete a cross-sectional serological survey within the required ethical and regulatory framework.
They also achieved a somewhat modified community framework for the survey, while holding scientific rigor firmly in the study design and implementation. The requirements for this type of successful research during such times include unified teamwork, involving both scientific and logistical tasks. Less tangible needs include encouragement and ideas to overcome tangles and hurdles while the study is being planned and executed.
The current study was planned to be repeated towards October/November of 2020. This was in order to explore the presence of persistent antibody responses in those already tested seropositive in this cohort, as well as the change from early to late antibody responses. Finally, this follow-up study could help detect new serological responses in previously seronegative individuals in the same cohort.
Lessons here could help others launch similar rapid prospective studies, while others – including dedication and collaboration of co-investigators who brought willingness and skillsets to the frontline – do not have easy prescriptions.”
However, with the right spirit and support, a prospective study can be designed with safe sample collection and biobanking, to provide scientifically valuable data during a pandemic.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
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