key: cord-0780194-48xjs2ow authors: Chen, Lin H; Freedman, David O; Visser, Leo G title: COVID-19 Immunity Passport to Ease Travel Restrictions? date: 2020-05-28 journal: J Travel Med DOI: 10.1093/jtm/taaa085 sha: e26d4853b049b5b080a07596625f21bb0c80a0d4 doc_id: 780194 cord_uid: 48xjs2ow nan As of May 2020, the SARS-CoV-2 Pandemic is ravaging the world. 1 Trade, travel, and most in-person interactions have come to a standstill. World Tourism Organization (WHO) data show that 100% of global destinations have restrictions on travel in place; 72% of countries have completely closed their borders to international tourism. 2 Re-start strategies for future months have raised the possibility of an "immunity certificate" (also called "immunity passport" or "immunity license") similar to the yellow fever vaccination certificate (International Certificate of Vaccination or Prophylaxis; ICVP issued by the WHO on the basis of the International Health Regulations). For example, if an air passenger could be documented as having recovered from SARS-Cov-2 infection or COVID-19 and is thus immune, they would be exempt from many airport, boarding gate, on-board processes, and port-of-entry procedures including many protective steps, such as face cover and quarantine/test on arrival. "Immunity certificate" would ideally require a global standard akin to the ICVP, and possibly require the corresponding documentation to be presented electronically. In the travel context the "immunity certificate" should serve to protect 1) the traveler; 2) his/her fellow travelers; and 3) residents at the destination as well as in-transit locales. In assessing evidence to support the concept and feasibility of the "immunity certificate", the following must be considered: 1) nearly all persons who have been infected will develop detectable antibodies; 2) antibodies detected are protective/neutralizing and preclude shedding of transmissible virus; 3) data establish the threshold of antibody titers necessary for protection; 4) data are available to assure that immunity is durable enough to invoke an expiry date for its validity; 5) acceptable antibody test(s) for certificate issuance comply with an international quality standard, is easily accessible and has high performance characteristics; and 6) documentation processes are highly resistant to fraud and includes a method to display exemption from certain requirements such as wearing face mask in public. An "immunity certificate" system unable to comply with all the above criteria is unlikely to be widely accepted. Accumulated evidence is encouraging but currently insufficient to address many of these considerations (Box). Extrapolating correlates of immunity and practical issues from other known virus to this unique pathogen is inadequate. The current state of knowledge on immunity and performance of available tests are summarized below. To date, studies confirm that most persons with clinically significant COVID-19 disease will develop antibodies; data is less available for asymptomatic or mild infection. Emerging data suggest that humans with detectable antibody to SARS-CoV-2 spike protein (SP) and nucleocapsid protein (NP) have neutralizing titers to live virus in tissue culture systems. 3, 4 Media reports and studies awaiting peer review for publication show <5% seropositivity in general population samples from over a dozen countries during or after peak pandemic activity, which speaks against widespread build-up of immunity. Only high-prevalence groups (e.g. New York City, HCWs, first responders, persons experiencing homelessness, and nursing home residents) reach >20% seropositivity. Thus, currently only a small minority of travelers may profit from such "immunity certificate". From the early epicenter of China, a rapid point-of-care lateral flow immunoassay for SARS-CoV-2 IgM and IgG derived an overall sensitivity of 88.66% and specificity of 90.63%. 5 Others evaluated IgA, IgM, and IgG by ELISA (n=208) and determined seropositivity rates of 85.4%, 92.7% and 77.9%, respectively. 6 The median time for IgM and IgA antibody detection was 5 days (IQR 3-6) while IgG was detected 14 days (IQR 10-18) after symptom onset. The variability in seroconversion rates were also evident in another study on confirmed COVID-19 patients (n=173), with rates of 93.1%, 82.7% and 64.7% for total antibodies, IgM and IgG, respectively. 7 Seroconversion occurred between days 11 and 14, and antibodies persisted up through 39 days after symptom onset. The presence of antibodies was <40% among patients within 1 week of illness onset, but rapidly increased to 100.0% (total Ig), 94.3% (IgM) and 79.8% (IgG) 15 days after symptom onset. 7 These studies demonstrated that higher antibody titers were associated with more severe disease, and also that the optimal timing for serologic testing depended on the specific test and ranged from 5 days to >3-4 weeks after symptom onset and >2 weeks after symptom resolution. 6, 7 Investigators that measured serum antibodies to NP and SP receptor binding domain (RBD) by enzyme immunoassay along with SARS-CoV-2 viral load found different seropositivity rates depending on antibody target. 8 Another assay on 40 confirmed SARS-CoV-2 serum samples for neutralizing, SP-specific, and NP-specific antibodies, detected seroconversion 2 weeks after illness onset. 4 The ELISA assays correlated with plaque reduction neutralization tests; IgA ELISA showed highest sensitivity; however, validation studies found that commercial S1 IgG or IgA ELISAs were of lower specificity, and sensitivity varied. 4 To date, the largest human study was conducted in New York City with 1343 participants whose median interval from symptom onset to serum antibody test was 24 days (range 3 -70), and median interval from symptom resolution to antibody test was 15 (4-77). 9 Antibody titers were higher with longer interval between symptom onset and testing and with longer symptom duration. IgG antibodies Emergency Committee regarding the outbreak of coronavirus disease (COVID-19) Report: Travel restrictions Virological assessment of hospitalized patients with COVID-2019 Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19) Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019 Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study Humoral immune response and prolonged PCR positivity in a cohort of 1343 SARS-CoV-2 patients in the New York City region Treatment of 5 critically ill patients with COVID-19 with convalescent plasma SARS-CoV-2 infection protects against rechallenge in rhesus macaques Conflict of interest: LC reports advisor fees from Shoreland Inc. and Data Safety Monitoring Board for Valneva Inc.; DF reports salaried compensation from Shoreland Travax for writing and editing an online clinical decision support tool and royalties from UpToDate, Inc.; LV reports no COI.