- Monique Anderssoninfection consultant1,
- Nikola Lowe, Professor of Epidemiology and Public Health and Director of Research2
- Neil FrenchHead of the Department of Clinical Infectious Microbiology and Immunology, Department of Infectious Diseases and Global Health, and Honorary Consultant for Infectious Diseases3
- Trisha GreenhalgProfessor of Medical Sciences in Primary Care4,
- Katie Jeffreyinfection consultantfive,
- Andrew Brent, consultant for infections and medicinefive,
- Jonathan BallProfessor of Molecular Virology and Director of the Center for Global Viral Research6
- Allison Pollockprofessor of public health7,
- David mccoyprofessor of global public health8,
- Miren Iturriz-Gomaradirectornine,
- Ian Buchanexecutive deanten,
- Helen Salisbury, Honorary Senior Clinical Lecturer4,
- Dinan Pillay, about vice provost (international)professor of virologyeleven,
- Will Irving, professor and honorary consultant in virology12
- 1Department of Microbiology Hospital John Radcliffe, Oxford OX3 9DU, UK
2Institute for Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland
3University of Liverpool and Royal Liverpool and Broadgreen University Trust Hospital, Liverpool, UK
4Department of Primary Care Sciences, Nuffield, Oxford University, Oxford, UK
fiveOxford University Hospital NHS Foundation Trust, Oxford, UK
6University of Nottingham, Nottingham, UK
7Faculty of Health Sciences, University of Newcastle, Newcastle, UK
8Queen Mary University of London, London, UK
nineNIHR Division of Gastrointestinal Infections Health, University of Liverpool, Liverpool, UK
tenInstitute for Public Health, University of Liverpool, Liverpool, UK
elevenUniversity College London, London, UK
12University of Nottingham and University Hospital of Nottingham NHS Trust, Nottingham, UK
We write to express concern about aspects of the organization of testing for antibodies to SARS-CoV-2 in England. On May 25, 2020, NHS England and NHS Improvement contacted the NHS Trust and Pathology Network to propose antibody testing in the short term and increase productivity to up to a thousand samples per day.12
We have three problems about the request. Firstly, there are no specific clinical indications for the test on an individual basis. Secondly, the effectiveness of these analyzes has not yet been evaluated according to the standard that is usually required for a new test. And thirdly, resource implications are not considered.
We support the rapid provision of diagnostic tests for individual and public health and recognize the need for delivery at a pace. However, it is important that quality systems that have evolved over the years and are the basis for providing the right result of the right test to the right person at the right time, are not dispensed with.
No clinical indication
In normal clinical practice, antibody testing performs several tasks. In acute disease, the response of IgM antibodies can be used to diagnose an infectious cause. The presence of IgG antibodies may be evidence of a previous infection or vaccination and likely immunity to a future infection by the same agent for some viruses, such as measles or hepatitis A. For other viruses (including hepatitis C virus, influenza virus, respiratory syncytial virus) IgG antibodies they do not guarantee immunity, but because they indicate a previous exposure (infection), population testing can provide useful information about the previous spread of the infection.
Sweep tests for antibodies to SARS-CoV-2 detect antibodies of the IgG class or “total” and do not correspond to these first two indications. These are not diagnostic tests for which genome detection tests are used. And since the test was made available to all patients who would like to conduct the test, and not according to specific clinical indications, neither a positive nor a negative result can change the clinical management, and a positive result does not indicate immunity.
The concept of “immune passports”, which allows health workers or others to work, has not been established. Those with a positive antibody test should continue to consider themselves at risk and adhere to an infection control policy designed to prevent nosocomial transmission and risk of infection. Therefore, it is currently not useful for health organizations or others to know about the status of employees.
For tests for antibodies to SARS-CoV-2, a reference standard was not defined. Access to “truly positive” and “truly negative” samples is difficult even in large training hospitals. It will be difficult for laboratories across the country to achieve the required standard test within a few days, not least because different platforms from manufacturers such as Abbott, Roche, Siemens, Ortho and Diasorin will be used for this test. There is currently no open data to compare the performance of these platforms. England’s public health has published the audit data, but concerns remain about the breadth of the audit. Elderly people, black people and ethnic minorities, as well as people with weakened immune systems are most at risk of dying from this infection. There are currently no data showing the effectiveness of the tests in these groups. The right way to get reliable data about test results is with well-planned prospective clinical trials. The analysis is carried out at an unprecedented pace and scale without an adequate assessment, which could jeopardize public confidence in pathology services in the future.
NHS England requires the result to be available within 24 hours. Given that routine testing of patients is not clinically urgent and does not meet the obvious needs of public health, this push to introduce an unidentified test for uncertain benefits risks the inefficient use of limited resources. Its implementation also entails additional costs for emergency care for patients and limited laboratory resources and time.
NHS England and NHS Improvement state that patient consent must be documented in patient notes. Patient consent must always be obtained, but the need for explicitly documented consent is thus not consistent with routine antibody testing for other acute viral infections and reflects the uncertain usefulness and effectiveness of the test. General practitioners are expected to provide phlebotomy services and advise patients. Given the uncertainty surrounding this test, counseling before the test and discussing the results are likely to be difficult and time-consuming.
Monitoring the Covid 19 epidemic is important. The only current rationale for large-scale IgG SARS-CoV-2 IgG testing is for research purposes, including public health surveillance to inform epidemiology. This should be done through carefully designed studies with clear objectives, sample frames, inclusion criteria and consent procedures. Without this structure, it will be difficult to interpret the results of a special examination of patients, and their applicability will be uncertain.
Royal College of Pathologists has developed seven testing principles. 3 Based on them and on sound principles for testing healthy asymptomatic people 4, we would like to see a carefully designed and clearly formulated serological testing strategy with clear scientific or clinical goals (or both) as part of a single strategy for responding to Covid-19 coordinated between NHS England and NHS Improvement, Public Health England and the Emergency Scientific Advisory Group.
Competing interests: IB: AstraZeneca Principal Scientific Advisor through the University of Liverpool. WI: Payments for speakers and consultants from Roche, Janssen Cilag, Gilead Sciences and Novartis; educational grants from Boehringer Ingelheim, Merck Sharp and Dohme and Gilead Sciences; and research grant support from GlaxoSmithKline, Pfizer, Gilead Sciences, Janssen Silag, Abbvie and Bristol-Myers Squibb. All other authors: no one announced.