Between Issues

Concerns with Perioperative Testing for the COVID-19 Virus

July 30, 2020

Rahul Chaturvedi, BS; Ramana Naidu, MD; Samir Sheth, MD; Krishnan Chakravarthy, MD, PhD

The authors of The ASA and APSF Joint Statement on Perioperative Testing for the COVID-19 Virus press release recommend that patients should be screened by PCR testing, and if negative, the OR staff can perform surgery with the use of droplet precautions. However given that the false negative rates for PCR testing can exceed 30%, this could lead to an unacceptable number of COVID-19 positive patients entering surgery centers weekly. Performing two PCR tests or a serology test followed by PCR can significantly reduce false negative rates and improve safety among patients and healthcare staff.

COVID-19 Test

Disclaimer: We aim to present letters from our readership that may generate further discussion on managing patients with COVID-19. Given the novelty of COVID-19, best-available clinical evidence is limited and supported from anecdotal reports from China, South Korea, Italy and other sites, and from studies of previous epidemics like SARS and MERS. The opinions expressed are those of the authors and not the APSF. These materials are presented for informational and educational purposes only and do not establish a standard of care or constitute medical or legal advice. The APSF does not support or endorse any specific idea, product, equipment, or trademarked technique. We strongly promote consistency with your governing bodies and organizations such as the CDC, WHO, ASA, AANA, and AAAA. Readers are reminded to consult with their institutions and medical/legal advisors regarding any of the views and opinions expressed by the authors.

Editor’s Note: Please note that the following link from the APSF website provides examples of preoperative testing pathways from institutions around the country at

Dear Editor,

We read with enthusiasm the timely press release: The ASA and APSF Joint Statement on Perioperative Testing for the COVID-19 Virus.1 The authors recommend that patients should be screened by PCR testing, and if negative, the operating room (OR) staff can perform surgery with the use of droplet precautions.1 Moreover, when claiming that the current sensitivity of polymerase chain reaction (PCR) testing ranges between 70-90%, the authors cite a recent study conducted in Wuhan, China, which has several issues to note.2 First, the researchers collected samples through various modalities (eg, bronchoalveolar lavage, nasal swabs, feces, etc), but most United States testing centers are solely using nasal or oropharyngeal swabs. Second, as described in the FDA’s Guidance for Industry and FDA Staff document, to calculate true sensitivity values, a reference-standard must be established.3 With the COVID-19 crisis being an ongoing pandemic, most of the new tests have only been authorized under emergency use authorization, which indicates that only “positive percent agreement” can be accurately reported. Therefore, true false negative rates could exceed well beyond 30%.

One study from Wuhan, China showed that 11% of sputum, 27% of nasal, and 40% of throat samples were deemed falsely negative by RT-PCR testing during the first week of illness.4,5 In a preprint systemic review of five alternate studies, the false negative rate for RT-PCR testing of respiratory swabs ranged anywhere from 2-29%.6 At this point, any false negative rates published by manufacturers is an estimate, as there is no accepted reference-standard for companies to compare their products to; as mentioned above, under the Emergency Use Authorization (EUA) act, the FDA has allowed companies to provide data comparing their product’s agreement with only a previously authorized RT-PCR test, making it even more difficult to assess sensitivity and specificity data.5 Given the lack of knowledge surrounding the true sensitivity data, we propose an alternate, albeit similar, protocol to restart elective procedures in specific locales. In addition to symptomatic screening prior to the day of surgery, we advise a second PCR test to reduce false negative rates.7 Additionally, we believe that testing should not only be used for incoming patients, but also for OR staff on a daily basis prior to the start of the workday if resources permit.8 This two-step testing approach will not only decrease false negative rates, but also can help to establish more accurate sensitivity data for the newly emerging testing kits. For instance, even if two separate PCR tests each with individual false negative rates of 30% are given sequentially to a patient, that already reduces the false negative rate to around 9%.7

The authors also note that antibody testing currently has no role in perioperative screening due to the timing of antibody production and possible cross-reactivity with other coronaviruses. In addition to the reasons mentioned by the authors above,1 the presence of IgG immunoglobulins does not necessarily signify immunity, as COVID-19 has been known to develop “escape mutants,” or alterations in the epitope of the S protein that lead to host antibody formation.9 Additionally, previous studies have shown that immunoglobulins themselves are not sufficient to confer immunity, and that CD4+ T-cells and memory CD8+ T-cells are vital, which cannot be accurately detected from serology testing.10 Nevertheless, there is a potential case for serology testing if used in conjunction with PCR testing. One possible testing protocol could include PCR testing followed by serology testing. This may allow us to catch the false negatives that initially resulted from specimen collection error during PCR testing, as serology testing does not require an adequate sample of viral particles deep in the nasopharynx.11 In a recent study, while the presence of antibodies was found in <40% of patients within 1 week of illness onset, the seroconversion rate was nearly 100% by 15 days from illness onset.12 Additionally, the use of combining RNA and antibody testing significantly improved the sensitivity of COVID-19 detection rates, even within the first week of illness onset.5, 12 Additionally, presence of IgM in the serum does not require an adequate viral sample from nasal or oropharyngeal swab collection. As the authors mentioned, there are some patients who have a false positive result due to cross-reactivity from alternative coronaviruses.13 However, a few patients being turned away temporarily due to false positive results may be warranted to prevent allowing a large number of false negative patients into our surgical centers on a weekly basis, as some universities have reported positive results in <1% of asymptomatic individuals.14,15

Lastly, widespread testing of healthcare staff during the COVID-19 pandemic is also another consideration to potentially reduce transmission of this virus. However, it may be difficult in locations where the number of cases surpasses health care system capacity. In general, open communication about the number of testing kits, incoming supply chain, case counts and trends must be considered prior to utilizing testing kits for healthcare staff on a routine basis. However, routine testing of healthcare staff may decrease transmission rates up to 25-33%, and may be worth the financial cost and resources during the COVID-19 pandemic.8

During this pandemic, the most important factor to consider when resuming elective procedures is the safety of both patients and healthcare staff. Until a proper reference-standard is established and more data is gathered, the results of PCR testing must be analyzed with caution. Performing a two-step approach for patients, with two PCR tests, or one PCR and one antibody test, can reduce false negative rates and prevent further spread of SARS-CoV-2 among patients and healthcare staff. Testing patients should take precedence over healthcare staff, but if resources permit, testing healthcare staff, as mentioned above, also may decrease transmission rates.


Rahul Chaturvedi, BS
Division of Pain Medicine, Department of Anesthesiology, University of California San Diego, 9400 Campus Point Dr, La Jolla, CA 92037

Ramana Naidu, MD
California Orthopedics & Spine, Larkspur, CA

Samir Sheth, MD
Sutter Roseville Pain Management, 151 North Sunrise Avenue, Suite 611, Roseville, CA 95661

Krishnan Chakravarthy, MD, PhD
Division of Pain Medicine, Department of Anesthesiology, University of California San Diego, 9400 Campus Point Dr, La Jolla, CA 92037
VA San Diego Health Care, 3350 La Jolla Village Dr, San Diego, CA 92161

Conflicts of Interest:

Dr. Naidu is a consultant for Abbott, Avanos, Boston Scientific, Nalu, Omnia Medical, SonoSite and SPR Therapeutics. He has stock options in Bicycle Health, CereVu, DoctorPlan, ExerAI, and KarunaLabs.

Dr. Chakravarthy is a consultant for Abbott, Medtronic, Medincell, Bioness, Saluda Medical, and SPR Therapeutics. He has stock options in Nalu Medical, Oska Wellness, and Higgs Boson Health. He is the founder of Douleur Therapeutics and Newrom Biomedical.

Dr. Sheth and Mr. Chaturvedi have no conflicts of interest.


  1. The ASA and APSF Joint Statement on Perioperative Testing for the COVID-19 Virus. American Society of Anesthesiologists Webpage. Published 2020.
  2. Wang W, Xu Y, Gao R, et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA – J Am Med Assoc. 2020;323:1843-1844. doi:10.1001/jama.2020.3786
  3. Meier K. Guidance for industry and FDA staff: statistical guidance on reporting results from studies evaluating diagnostic tests. Cent Devices Radiol Heal. 2007:1-39.
  4. Yang Y, Yang M, Shen C, et al. Evaluating the accuracy of different respiratory specimens in the laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections. medRxiv. 2020. doi:10.1101/2020.02.11.20021493
  5. Woloshin S, Patel N, Kesselheim AS. False Negative Tests for SARS-CoV-2 Infection — Challenges and Implications. N Engl J Med. 2020. doi:10.1056/nejmp2015897
  6. Arevalo-Rodriguez I,Buitrago-Garcia D, Simancas-Racines D, et al. False-negative results of initial RT-PCR assays for COVID-19: a systematic review. April 21, 2020 ( opens in new tab). preprint.
  7. Ramdas K, Darzi A, Jain S. ‘Test, re-test, re-test’: using inaccurate tests to greatly increase the accuracy of COVID-19 testing. Nat Med. 2020;26:810-811. doi:10.1038/s41591-020-0891-7
  8. Nicholas C Grassly, Marga Pons-Salort, Edward PK Parker, Peter J White, Kylie Ainslie, Marc Baguelin, Sangeeta Bhatia, Samir Bhatt, Isobel Blake, Adhiratha Boonyasiri, Olivia Boyd, Nick Brazeau, Lorenzo Cattarino, Giovanni Charles, Constanze Ciavarella, L NF. Report 16: Role of Testing in COIVD-19 Control.; 2020.
  9. Sui J, Li W, Roberts A, et al. Evaluation of Human Monoclonal Antibody 80R for Immunoprophylaxis of Severe Acute Respiratory Syndrome by an Animal Study, Epitope Mapping, and Analysis of Spike Variants. J Virol. 2005;79(10):5900-5906. doi:10.1128/jvi.79.10.5900-5906.2005
  10. Channappanavar R, Fett C, Zhao J, Meyerholz DK, Perlman S. Virus-Specific Memory CD8 T Cells Provide Substantial Protection from Lethal Severe Acute Respiratory Syndrome Coronavirus Infection. J Virol. 2014;88:11034-11044. doi:10.1128/jvi.01505-14
  11. Prinzi A. False Negatives and Reinfections: the Challenges of SARS-CoV-2 RT-PCR Testing. American Society for Microbiology. Published 2020. Accessed July 22, 2020.
  12. Zhao J, Yuan Q, Wang H, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis. 2020. doi:10.1093/cid/ciaa344
  13. Long QX, Liu BZ, Deng HJ, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. 2020;26:845-848. doi:10.1038/s41591-020-0897-1
  14. Morris M, Pierce A, Carlisle B, Vining B, Dobyns J. Pre-operative COVID-19 testing and decolonization. Am J Surg. May 2020. doi:10.1016/j.amjsurg.2020.05.027
  15. COVID-19: Updated pre-operative testing for COVID for surgical patients. UCSF Department of Orthopedics. Published 2020. Accessed July 27, 2020.