Free access
Clinical Guidelines
25 January 2022

What Is the Antibody Response and Role in Conferring Natural Immunity After SARS-CoV-2 Infection? Rapid, Living Practice Points From the American College of Physicians (Version 2)FREE

Publication: Annals of Internal Medicine
Volume 175, Number 4

Abstract

Description:

The Scientific Medical Policy Committee (SMPC) of the American College of Physicians (ACP) developed these living, rapid practice points to summarize the current best available evidence on the antibody response to SARS-CoV-2 infection and protection against reinfection with SARS-CoV-2. This is version 2 of the ACP practice points, which serves to update version 1, published on 16 March 2021. These practice points do not evaluate vaccine-acquired immunity or cellular immunity.

Methods:

The SMPC developed this version of the living, rapid practice points based on an updated living, rapid, systematic review conducted by the Portland VA Research Foundation and funded by the Agency for Healthcare Research and Quality.

Practice Point 1:

Do not use SARS-CoV-2 antibody tests for the diagnosis of SARS-CoV-2 infection.

Practice Point 2:

Do not use SARS-CoV-2 antibody tests to predict the degree or duration of natural immunity conferred by antibodies against reinfection, including natural immunity against different variants.

Retirement From Living Status:

Although natural immunity remains a topic of scientific interest, this topic is being retired from living status given the availability of effective vaccines for SARS-CoV-2 and widespread recommendations for and prevalence of their use. Currently, vaccination is the best clinical recommendation for preventing infection, reinfection, and serious illness from SARS-CoV-2 and its variants.
The Scientific Medical Policy Committee (SMPC) of the American College of Physicians (ACP) has been maintaining these living, rapid practice points to summarize the current best available evidence on the antibody response to SARS-CoV-2 infection and protection against reinfection with SARS-CoV-2 (Table 1). This is version 2 of the ACP practice points, which serves to update version 1, published on 16 March 2021 (3, 4). It is based on a focused update of a living, rapid, systematic review conducted by the Portland VA Research Foundation and funded by the Agency for Healthcare Research and Quality (5, 6). The SMPC developed these practice points according to ACP's practice points development process, details of which can be found in ACP's methods paper (7).
Table 1. Practice Points
The intended audience for these practice points includes clinicians, patients, the public, and public health officials. The population includes adults who have been previously infected with SARS-CoV-2.
This version was approved by the ACP Executive Committee of the Board of Regents on behalf of the Board of Regents on 9 August 2021 and was submitted to Annals of Internal Medicine on 6 August 2021.
Although vaccine-acquired immunity and cellular immunity are important areas of research, this article does not evaluate them.

Key Questions Addressed in the Living and Rapid Systematic Review

Key Question 1 (not updated): What are the prevalence, level, and duration of detectable anti–SARS-CoV-2 antibodies among patients infected with or recovered from reverse transcriptase polymerase chain reaction (RT-PCR)–diagnosed SARS-CoV-2 infection?
Key Question 1a (not updated): Do the levels and durability of detectable antibodies vary by patient characteristics (for example, age, sex, race/ethnicity, and comorbidities), COVID-19 severity (severity of the initial infection), presence of symptoms, time from symptom onset, or the characteristics of the immunoassay (sensitivity, specificity)?
Key Question 2 (updated): What is the risk for reinfection with SARS-CoV-2 among adults with prior SARS-CoV-2 infection?
Key Question 2a (updated): Does the risk for reinfection vary by patient characteristics (for example, age, sex, race/ethnicity, and comorbidities), severity of the initial infection, initial antibody levels, or SARS-CoV-2 variants?
Key Question 2b (updated): Is there a threshold level of detectable anti–SARS-CoV-2 antibodies necessary to confer natural immunity, and if so, does this threshold vary by patient characteristics (for example, age, sex, race/ethnicity, and comorbidities)?
Key Question 3 (updated): What is the duration of protection against reinfection among adults with prior SARS-CoV-2 infection?
Key Question 3a (updated): Does the duration of protection vary by patient characteristics (for example, age, sex, race/ethnicity, and comorbidities), severity of initial infection, initial antibody levels, SARS-CoV-2 variants, or case identification method (for example, surveillance, symptomatic testing only)?
Key Question 4 (not updated): What are the unintended consequences of antibody testing after SARS-CoV-2 infection?

Key Questions: Rationale for a Focused Update to the Living and Rapid Systematic Review

Updates to key questions in the living, rapid, systematic review are prioritized on the basis of identification of new evidence from literature surveillance that will likely substantially modify the conclusions or the certainty of evidence. Based on literature surveillance, the Portland VA Research Foundation and the SMPC determined that there was a signal to perform a focused update of key questions 2, 2a, 2b, 3, and 3a (large population-based studies that included uninfected comparison groups were published) and that the evidence for key questions 1, 1a, and 4 had not matured enough to evaluate the long-term persistence of antibodies, which would substantially modify the conclusions or certainty of evidence in the previous version. Consistent with methods for living systematic reviews and our living, rapid practice points (7), the inclusion criteria were modified to include large longitudinal studies with control groups to evaluate the risk for reinfection, and key questions were modified for clarity (Appendix Table).
Appendix Table. Key Questions Version History

Overview of New Evidence

The evidence update (5, 6) identified 18 new studies (8–25) informing key questions 2, 2a, and 3, for which there were previously no studies that met the inclusion criteria in version 1 (3). These studies were initiated before the emergence of the Delta and Omicron variants and before the U.S. Food and Drug Administration's emergency use authorization of vaccines late in 2020 (5, 6). The new studies compared the risk for symptomatic reinfection (as a primary outcome) among adults with a recent SARS-CoV-2 infection with the risk for infection among adults without a recent infection, with “recent” defined as within 7 months of initial SARS-CoV-2 infection. These studies were designed to evaluate risk for symptomatic reinfection, with risk for asymptomatic reinfection as a secondary outcome. The new studies showed that patients with a recent SARS-CoV-2 infection have a substantially reduced risk for symptomatic reinfection (88% in the general population and 87% in health care workers) compared with those without a recent infection (key question 2) over follow-up of 4 to 13 months. There is also protection for asymptomatic reinfections, but the evidence is unclear about whether the degree of protection for asymptomatic reinfections is as high as it is for symptomatic reinfections. No evidence was identified on threshold levels of antibodies needed to confer protection from reinfection or the contribution of the antibody response to this protection (key question 2b). The systematic review update did not identify evidence from included studies on whether risk for reinfection varied by patient comorbidities (including immunosuppression) or by viral variants other than the Alpha variant (including the Delta and Omicron variants) (key question 2a), or whether the variation in the duration of protection varies by patient or clinical characteristics (key question 3a).

Updated Practice Points and Rationales (Version 2)

Evidence continues to emerge about the antibody response to SARS-CoV-2 infection and protection against future reinfection. The following practice points are based on the current best available evidence. The Figure, Table 2, and the accompanying systematic review (5, 6) summarize changes in the findings. Table 3 presents clinical considerations, and Table 4 identifies evidence gaps.
Figure. Evidence description.
The evidence search and assessment were conducted by the Portland VA Research Foundation (3, 5, 6). The evidence search was updated through 22 September 2021. PCR = polymerase chain reaction.
* Observational studies include studies estimating seroprevalence among a given population that includes a small subpopulation known to have SARS-CoV-2 infection; cross-sectional or cohort studies characterizing the antibody response among adults with SARS-CoV-2 infection; and large, population-based observational (cohort, case–control) studies comparing risk for reinfection in adults with and without recent SARS-CoV-2 infection (3,5,6). Immunoassay validation studies include those validating the diagnostic performance of 1 or more immunoassays (3).
Table 2. Evidence Summary
Table 3. Clinical Considerations
Table 4. Evidence Gaps
We have retired Practice Point 2 from version 1, which stated, “Antibody tests can be useful for the purpose of estimating community prevalence of SARS-CoV-2 infection.” The relevance of this statement is now limited given the increase in vaccinations in the United States and because antibody tests cannot differentiate antibodies that develop due to past SARS-CoV-2 infection from those that develop due to vaccination.
Practice Point 1: Do not use SARS-CoV-2 antibody tests for the diagnosis of SARS-CoV-2 infection.
Reaffirmed Rationale
Studies included in the version 1 systematic review evaluated the prevalence, levels, and duration of different types of antibodies after symptom onset or confirmation of SARS-CoV-2 infection with a positive RT-PCR result (3). These studies showed that most patients develop detectable antibodies after SARS-CoV-2 infection; however, the timing of when different antibodies peak and how long they remain detectable may vary (low to moderate certainty). Furthermore, the antibody response may vary by age, sex, race/ethnicity, and the severity of the initial infection (low certainty), and the evidence is very uncertain (insufficient) as to whether the response varies by comorbidities or type of immunoassay. In addition, the diagnostic test characteristics (for example, sensitivity, specificity, and accuracy) vary substantially across the antibody tests used in the included studies (3–6), contributing to differing risks for false-negative and false-positive results (94, 95). For these reasons, based on the studies included in version 1, antibody tests should not be used for the diagnosis of SARS-CoV-2 infection.
Practice Point 2: Do not use SARS-CoV-2 antibody tests to predict the degree or duration of natural immunity conferred by antibodies against reinfection, including natural immunity against different variants.
Updated Rationale
Because measuring antibodies is an approach for evaluating the immune response, questions arise about the role of antibody testing in assessing natural immunity and protection from reinfection after SARS-CoV-2 infection. Although new evidence (18 new studies) has emerged addressing the risk for reinfection among adults with recent SARS-CoV-2 infection, several important evidence gaps remain in the new body of evidence that limit the clinical role of antibody testing (Table 4).
Low- to moderate-certainty evidence showed that patients with asymptomatic and symptomatic initial infections develop detectable antibodies (3), and high-certainty evidence from new studies showed that recent initial SARS-CoV-2 infection reduced the risk for symptomatic reinfection by 84% to 90% in adults over follow-up ranging from 4 to 13 months. This degree of protection may be similar across age groups (low certainty), with the Alpha variant (low certainty), in persons in the general population and health care workers, and does not vary according to sex (high certainty). However, these studies do not establish that antibodies are primarily responsible for the observed natural immunity because none of the new studies examined the relationship between antibody levels and degree of natural immunity, including threshold levels of detectable SARS-CoV-2 antibodies necessary to confer natural immunity. Furthermore, the included studies were conducted before the Delta and Omicron variants became the dominant circulating strains. However, the systematic review identified 3 studies that were not yet fully reported (96) or were longitudinal uncontrolled studies (97, 98) and thus did not meet the inclusion criteria; these studies suggest that recent SARS-CoV-2 infection reduced risk for reinfection in adults after the Delta variant became the dominant strain.
It is important to note that none of the new included studies reported on the variation in risk for reinfection in patients who are immunocompromised or have other comorbidities, and evidence is very uncertain (insufficient) about other factors that may modify risk for reinfection, including initial antibody levels and race/ethnicity. Evidence is also conflicting about risk for reinfection in patients who had an asymptomatic initial infection (5, 6); studies show that risk for reinfection may be higher for patients who had a mild or asymptomatic initial infection compared with those who had a symptomatic initial infection (low certainty). Although evidence suggests a high degree of protection (>80%) against symptomatic SARS-CoV-2 reinfection in the short term (high certainty for up to 7 months and low certainty for 7 to 10 months), the duration of protection beyond 10 months is very uncertain (insufficient), and follow-up in the included studies is constrained by time elapsed since the beginning of the pandemic. Finally, none of the included studies reported on how the duration of protection might vary by such factors as variant strains, initial antibody levels, and patient characteristics.
Despite evidence that patients develop detectable antibodies (3) and have reduced risk for reinfection after initial SARS-CoV-2 infection, knowledge about the direct association of the antibody response and the degree of natural immunity to SARS-CoV-2 is still limited. In light of these evidence gaps, and considering previously reported insufficient (very uncertain) evidence (3) about the unintended consequences of antibody testing, we advise against antibody testing to evaluate for natural immunity. Patients with current or previous SARS-CoV-2 infection should continue to follow recommended infection prevention and control procedures to slow and reduce transmission of the virus (92, 93, 99).

Retirement From Living Status

The SMPC is retiring the ACP living, rapid practice points on the antibody response to SARS-CoV-2 infection and protection against reinfection with SARS-CoV-2 from living status (7), given the widespread availability and use of effective vaccines against SARS-CoV-2 infection in the United States. Vaccination is currently the best clinical recommendation for prevention of SARS-CoV-2 infection and reinfection, including from currently circulating viral variants (1, 2).

References

1.
Advisory Committee on Immunization Practices. COVID-19 ACIP Vaccine Recommendations. Accessed at www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/covid-19.html on 1 December 2021.
2.
World Health Organization. COVID-19 advice for the public: Getting vaccinated. Accessed at www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-vaccines/advice on 1 December 2021.
3.
Arkhipova-Jenkins I, Helfand M, Armstrong C, et al. Antibody response after SARS-CoV-2 infection and implications for immunity: a rapid living review. Ann Intern Med. 2021;174:811-21. [PMID: 33721517] doi: 10.7326/M20-7547
4.
Qaseem A, Yost J, Etxeandia-Ikobaltzeta I, et al; Scientific Medical Policy Committee of the American College of Physicians. What is the antibody response and role in conferring natural immunity after SARS-CoV-2 infection? Rapid, living practice points from the American College of Physicians (version 1). Ann Intern Med. 2021;174:828-35. [PMID: 33721518] doi: 10.7326/M20-7569
5.
Helfand M, Fiordalisi C, Wiedrick J, et al. Risk of reinfection after SARS-CoV-2. Living rapid review for ACP practice points on the role of the antibody response in conferring immunity following SARS-CoV-2 infection. Ann Intern Med. 2022;175:547-55.   doi: 10.7326/M21-4245
6.
Helfand M, Fiordalisi C, Wiedrick J, et al. Risk of Reinfection From SARS-CoV-2 – An Update of an Antibody Response Following SARS-CoV-2 Infection and Implications for Immunity: A Living Rapid Review. (Prepared by the Scientific Resource Center under contract no. 290-2017-0003.) AHRQ publication no. 21-EHC034. Agency for Healthcare Research and Quality; January 2022. Posted final reports are located on the Effective Health Care Program search page. doi: 10.23970/AHRQEPCCOVIDIMMUNITY2
7.
Qaseem A, Yost J, Forciea MA, et al; Scientific Medical Policy Committee of the American College of Physicians. The development of living, rapid practice points: summary of methods from the Scientific Medical Policy Committee of the American College of Physicians. Ann Intern Med. 2021;174:1126-32. [PMID: 34029483] doi: 10.7326/M20-7641
8.
Abo-Leyah H, Gallant S, Cassidy D, et al. The protective effect of SARS-CoV-2 antibodies in Scottish healthcare workers. ERJ Open Res. 2021;7. [PMID: 34104643] doi: 10.1183/23120541.00080-2021
9.
Abu-Raddad LJ, Chemaitelly H, Coyle P, et al. SARS-CoV-2 antibody-positivity protects against reinfection for at least seven months with 95% efficacy. EClinicalMedicine. 2021;35:100861. [PMID: 33937733] doi: 10.1016/j.eclinm.2021.100861
10.
Finch E, Lowe R, Fischinger S, et al. SARS-CoV-2 infection and reinfection in a seroepidemiological workplace cohort in the United States. medRxiv. Preprint posted online 6 May 2021. doi: 10.1101/2021.05.04.21256609
11.
Gallais F, Gantner P, Bruel T, et al. Anti-SARS-CoV-2 antibodies persist for up to 13 months and reduce risk of reinfection. medRxiv. Preprint posted online 17 May 2021. doi: 10.1101/2021.05.07.21256823
12.
Goldberg Y, Mandel M, Woodbridge Y, et al. Protection of previous SARS-CoV-2 infection is similar to that of BNT162b2 vaccine protection: a three-month nationwide experience from Israel. medRxiv. Preprint posted online 24 April 2021. doi: 10.1101/2021.04.20.21255670
13.
Hall VJ, Foulkes S, Charlett A, et al; SIREN Study Group. SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN). Lancet. 2021;397:1459-69. [PMID: 33844963] doi: 10.1016/S0140-6736(21)00675-9
14.
Hanrath AT, Payne BAI, Duncan CJA. Prior SARS-CoV-2 infection is associated with protection against symptomatic reinfection [Letter]. J Infect. 2021;82:e29-e30. [PMID: 33373652] doi: 10.1016/j.jinf.2020.12.023
15.
Hansen CH, Michlmayr D, Gubbels SM, et al. Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study. Lancet. 2021;397:1204-12. [PMID: 33743221] doi: 10.1016/S0140-6736(21)00575-4
16.
Harvey RA, Rassen JA, Kabelac CA, et al. Association of SARS-CoV-2 seropositive antibody test with risk of future infection. JAMA Intern Med. 2021;181:672-9. [PMID: 33625463] doi: 10.1001/jamainternmed.2021.0366
17.
Jeffery-Smith A, Iyanger N, Williams SV, et al. Antibodies to SARS-CoV-2 protect against re-infection during outbreaks in care homes, September and October 2020. Euro Surveill. 2021;26. [PMID: 33541486] doi: 10.2807/1560-7917.ES.2021.26.5.2100092
18.
Krutikov M, Palmer T, Tut G, et al. Incidence of SARS-CoV-2 infection according to baseline antibody status in staff and residents of 100 long term care facilities (VIVALDI study). medRxiv. Preprint posted online 10 March 2021. doi: 10.1101/2021.03.08.21253110
19.
Leidi A, Koegler F, Dumont R, et al; SEROCoV-POP study group. Risk of reinfection after seroconversion to SARS-CoV-2: a population-based propensity-score matched cohort study. Clin Infect Dis. 2021. [PMID: 34043763] doi: 10.1093/cid/ciab495
20.
Lumley SF, O’Donnell D, Stoesser NE, et al; Oxford University Hospitals Staff Testing Group. Antibody status and incidence of SARS-CoV-2 infection in health care workers. N Engl J Med. 2021;384:533-40. [PMID: 33369366] doi: 10.1056/NEJMoa2034545
21.
Manica M, Pancheri S, Poletti P, et al. The risk of symptomatic reinfection during the second COVID-19 wave in individuals previously exposed to SARS-CoV-2. medRxiv. Preprint posted online 20 April 2021. doi: 10.1101/2021.04.14.21255502
22.
Pilz S, Chakeri A, Ioannidis JP, et al. SARS-CoV-2 re-infection risk in Austria. Eur J Clin Invest. 2021;51:e13520. [PMID: 33583018] doi: 10.1111/eci.13520
23.
Rennert L, McMahan C. Risk of SARS-CoV-2 reinfection in a university student population. Clin Infect Dis. 2021. [PMID: 33993225] doi: 10.1093/cid/ciab454
24.
Sheehan MM, Reddy AJ, Rothberg MB. Reinfection rates among patients who previously tested positive for coronavirus disease 2019: a retrospective cohort study. Clin Infect Dis. 2021;73:1882-6. [PMID: 33718968] doi: 10.1093/cid/ciab234
25.
Vitale J, Mumoli N, Clerici P, et al. Assessment of SARS-CoV-2 reinfection 1 year after primary infection in a population in Lombardy, Italy [Letter]. JAMA Intern Med. 2021;181:1407-8. [PMID: 34048531] doi: 10.1001/jamainternmed.2021.2959
26.
Andrey DO, Cohen P, Meyer B, et al. Head-to-head accuracy comparison of three commercial COVID-19 IgM/IgG serology rapid tests. J Clin Med. 2020;9. [PMID: 32722191] doi: 10.3390/jcm9082369
27.
Andrey DO, Cohen P, Meyer B, et al; Geneva Centre for Emerging Viral Diseases. Diagnostic accuracy of Augurix COVID-19 IgG serology rapid test. Eur J Clin Invest. 2020;50:e13357. [PMID: 32691863] doi: 10.1111/eci.13357
28.
Bao Y, Ling Y, Chen YY, et al. Dynamic anti-spike protein antibody profiles in COVID-19 patients. Int J Infect Dis. 2021;103:540-8. [PMID: 33310028] doi: 10.1016/j.ijid.2020.12.014
29.
Blain H, Rolland Y, Tuaillon E, et al. Efficacy of a test-retest strategy in residents and health care personnel of a nursing home facing a COVID-19 outbreak. J Am Med Dir Assoc. 2020;21:933-6. [PMID: 32674822] doi: 10.1016/j.jamda.2020.06.013
30.
Bruni M, Cecatiello V, Diaz-Basabe A, et al. Persistence of anti-SARS-CoV-2 antibodies in non-hospitalized COVID-19 convalescent health care workers. J Clin Med. 2020;9. [PMID: 33019628] doi: 10.3390/jcm9103188
31.
Chen Y, Ke Y, Liu X, et al. Clinical features and antibody response of patients from a COVID-19 treatment hospital in Wuhan, China. J Med Virol. 2021;93:2782-9. [PMID: 33085103] doi: 10.1002/jmv.26617
32.
Chen Y, Zuiani A, Fischinger S, et al. Quick COVID-19 healers sustain anti-SARS-CoV-2 antibody production. Cell. 2020;183:1496-1507.e16. [PMID: 33171099] doi: 10.1016/j.cell.2020.10.051
33.
Chirathaworn C, Sripramote M, Chalongviriyalert P, et al. SARS-CoV-2 RNA shedding in recovered COVID-19 cases and the presence of antibodies against SARS-CoV-2 in recovered COVID-19 cases and close contacts, Thailand, April–June 2020. PLoS One. 2020;15:e0236905. [PMID: 33119712] doi: 10.1371/journal.pone.0236905
34.
Choe JY, Kim JW, Kwon HH, et al. Diagnostic performance of immunochromatography assay for rapid detection of IgM and IgG in coronavirus disease 2019. J Med Virol. 2020;92:2567-72. [PMID: 32458479] doi: 10.1002/jmv.26060
35.
Crawford KHD, Dingens AS, Eguia R, et al. Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection. J Infect Dis. 2021;223:197-205. [PMID: 33535236] doi: 10.1093/infdis/jiaa618
36.
Dave M, Poswal L, Bedi V, et al. Study of antibody-based rapid card test in COVID-19 patients admitted in a tertiary care COVID hospital in Southern Rajasthan. Journal, Indian Academy of Clinical Medicine. 2020;21:7-11.
37.
de la Iglesia J, Fernández-Villa T, Fegeneda-Grandes JM, et al. Concordance between two rapid diagnostic tests for the detection of antibodies against SARS-CoV-2. Semergen. 2020;46 Suppl 1:21-25. [PMID: 32675000] doi: 10.1016/j.semerg.2020.06.009
38.
Dellière S, Salmona M, Minier M, et al; Saint-Louis CORE (COvid REsearch) group. Evaluation of the COVID-19 IgG/IgM rapid test from Orient Gene Biotech. J Clin Microbiol. 2020;58. [PMID: 32518071] doi: 10.1128/JCM.01233-20
39.
Fafi-Kremer S, Bruel T, Madec Y, et al. Serologic responses to SARS-CoV-2 infection among hospital staff with mild disease in eastern France. EBioMedicine. 2020;59:102915. [PMID: 32747185] doi: 10.1016/j.ebiom.2020.102915
40.
Flannery DD, Gouma S, Dhudasia MB, et al. SARS-CoV-2 seroprevalence among parturient women in Philadelphia. Sci Immunol. 2020;5. [PMID: 32727884] doi: 10.1126/sciimmunol.abd5709
41.
Gudbjartsson DF, Norddahl GL, Melsted P, et al. Humoral immune response to SARS-CoV-2 in Iceland. N Engl J Med. 2020;383:1724-34. [PMID: 32871063] doi: 10.1056/NEJMoa2026116
42.
Hou H, Wang T, Zhang B, et al. Detection of IgM and IgG antibodies in patients with coronavirus disease 2019. Clin Transl Immunology. 2020;9:e01136. [PMID: 32382418] doi: 10.1002/cti2.1136
43.
Huang M, Lu QB, Zhao H, et al. Temporal antibody responses to SARS-CoV-2 in patients of coronavirus disease 2019 [Letter]. Cell Discov. 2020;6:64. [PMID: 32983570] doi: 10.1038/s41421-020-00209-2
44.
Imai K, Tabata S, Ikeda M, et al. Clinical evaluation of an immunochromatographic IgM/IgG antibody assay and chest computed tomography for the diagnosis of COVID-19. J Clin Virol. 2020;128:104393. [PMID: 32387968] doi: 10.1016/j.jcv.2020.104393
45.
Infantino M, Grossi V, Lari B, et al. Diagnostic accuracy of an automated chemiluminescent immunoassay for anti-SARS-CoV-2 IgM and IgG antibodies: an Italian experience. J Med Virol. 2020;92:1671-5. [PMID: 32330291] doi: 10.1002/jmv.25932
46.
Isho B, Abe KT, Zuo M, et al. Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients. Sci Immunol. 2020;5. [PMID: 33033173] doi: 10.1126/sciimmunol.abe5511
47.
Iversen K, Bundgaard H, Hasselbalch RB, et al. Risk of COVID-19 in health-care workers in Denmark: an observational cohort study. Lancet Infect Dis. 2020;20:1401-8. [PMID: 32758438] doi: 10.1016/S1473-3099(20)30589-2
48.
Iyer AS, Jones FK, Nodoushani A, et al. Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients. Sci Immunol. 2020;5. [PMID: 33033172] doi: 10.1126/sciimmunol.abe0367
49.
Jääskeläinen AJ, Kekäläinen E, Kallio-Kokko H, et al. Evaluation of commercial and automated SARS-CoV-2 IgG and IgA ELISAs using coronavirus disease (COVID-19) patient samples. Euro Surveill. 2020;25. [PMID: 32400364] doi: 10.2807/1560-7917.ES.2020.25.18.2000603
50.
Ko JH, Joo EJ, Park SJ, et al. Neutralizing antibody production in asymptomatic and mild COVID-19 patients, in comparison with pneumonic COVID-19 patients. J Clin Med. 2020;9. [PMID: 32708872] doi: 10.3390/jcm9072268
51.
Koblischke M, Traugott MT, Medits I, et al. Dynamics of CD4 T cell and antibody responses in COVID-19 patients with different disease severity. Front Med (Lausanne). 2020;7:592629. [PMID: 33262993] doi: 10.3389/fmed.2020.592629
52.
Kwon JS, Kim JY, Kim MC, et al. Factors of severity in patients with COVID-19: cytokine/chemokine concentrations, viral load, and antibody responses. Am J Trop Med Hyg. 2020;103:2412-8. [PMID: 33124544] doi: 10.4269/ajtmh.20-1110
53.
Li K, Huang B, Wu M, et al. Dynamic changes in anti-SARS-CoV-2 antibodies during SARS-CoV-2 infection and recovery from COVID-19. Nat Commun. 2020;11:6044. [PMID: 33247152] doi: 10.1038/s41467-020-19943-y
54.
Liu J, Guo J, Xu Q, et al. Detection of IgG antibody during the follow-up in patients with COVID-19 infection [Letter]. Crit Care. 2020;24:448. [PMID: 32690058] doi: 10.1186/s13054-020-03138-4
55.
Liu J, Lian R, Zhang G, et al. Changes in serum virus-specific IgM/IgG antibody in asymptomatic and discharged patients with reoccurring positive COVID-19 nucleic acid test (RPNAT). Ann Med. 2021;53:34-42. [PMID: 32808808] doi: 10.1080/07853890.2020.1811887
56.
Liu L, Liu W, Zheng Y, et al. A preliminary study on serological assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 238 admitted hospital patients. Microbes Infect. 2020;22:206-11. [PMID: 32425648] doi: 10.1016/j.micinf.2020.05.008
57.
Liu R, Liu X, Yuan L, et al. Analysis of adjunctive serological detection to nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis. Int Immunopharmacol. 2020;86:106746. [PMID: 32619956] doi: 10.1016/j.intimp.2020.106746
58.
Liu X, Wang J, Xu X, et al. Patterns of IgG and IgM antibody response in COVID-19 patients [Letter]. Emerg Microbes Infect. 2020;9:1269-74. [PMID: 32515684] doi: 10.1080/22221751.2020.1773324
59.
Lynch KL, Whitman JD, Lacanienta NP, et al. Magnitude and kinetics of anti-severe acute respiratory syndrome coronavirus 2 antibody responses and their relationship to disease severity. Clin Infect Dis. 2021;72:301-8. [PMID: 33501951] doi: 10.1093/cid/ciaa979
60.
Pancrazzi A, Magliocca P, Lorubbio M, et al. Comparison of serologic and molecular SARS-CoV 2 results in a large cohort in Southern Tuscany demonstrates a role for serologic testing to increase diagnostic sensitivity. Clin Biochem. 2020;84:87-92. [PMID: 32702365] doi: 10.1016/j.clinbiochem.2020.07.002
61.
Payne DC, Smith-Jeffcoat SE, Nowak G, et al; CDC COVID-19 Surge Laboratory Group. SARS-CoV-2 infections and serologic responses from a sample of U.S. Navy service members—USS Theodore Roosevelt, April 2020. MMWR Morb Mortal Wkly Rep. 2020;69:714-21. [PMID: 32525850] doi: 10.15585/mmwr.mm6923e4
62.
Petersen LR, Sami S, Vuong N, et al. Lack of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large cohort of previously infected persons. Clin Infect Dis. 2021;73:e3066-e3073. [PMID: 33147319] doi: 10.1093/cid/ciaa1685
63.
Qu J, Wu C, Li X, et al. Profile of immunoglobulin G and IgM antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020;71:2255-8. [PMID: 32337590] doi: 10.1093/cid/ciaa489
64.
Robbins T, Kyrou I, Laird S, et al. Healthcare staff perceptions and misconceptions regarding antibody testing in the United Kingdom: implications for the next steps for antibody screening. J Hosp Infect. 2021;111:102-6. [PMID: 33309938] doi: 10.1016/j.jhin.2020.11.019
65.
Schaffner A, Risch L, Weber M, et al. Sustained SARS-CoV-2 nucleocapsid antibody levels in nonsevere COVID-19: a population-based study [Letter]. Clin Chem Lab Med. 2020;59:e49-e51. [PMID: 33554502] doi: 10.1515/cclm-2020-1347
66.
Seow J, Graham C, Merrick B, et al. Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans. Nat Microbiol. 2020;5:1598-607. [PMID: 33106674] doi: 10.1038/s41564-020-00813-8
67.
Shang Y, Liu T, Li J, et al. Factors affecting antibody response to SARS-CoV-2 in patients with severe COVID-19 [Letter]. J Med Virol. 2021;93:612-4. [PMID: 33289107] doi: 10.1002/jmv.26379
68.
Shen B, Zheng Y, Zhang X, et al. Clinical evaluation of a rapid colloidal gold immunochromatography assay for SARS-Cov-2 IgM/IgG. Am J Transl Res. 2020;12:1348-54. [PMID: 32355546]
69.
Shu H, Wang S, Ruan S, et al. Dynamic changes of antibodies to SARS-CoV-2 in COVID-19 patients at early stage of outbreak. Virol Sin. 2020;35:744-51. [PMID: 32720214] doi: 10.1007/s12250-020-00268-5
70.
Staines HM, Kirwan DE, Clark DJ, et al. IgG seroconversion and pathophysiology in severe acute respiratory syndrome coronavirus 2 infection. Emerg Infect Dis. 2021;27. [PMID: 33256890] doi: 10.3201/eid2701.203074
71.
Stock da Cunha T, Gomá-Garcés E, Avello A, et al. The spectrum of clinical and serological features of COVID-19 in urban hemodialysis patients. J Clin Med. 2020;9. [PMID: 32708750] doi: 10.3390/jcm9072264
72.
Sun B, Feng Y, Mo X, et al. Kinetics of SARS-CoV-2 specific IgM and IgG responses in COVID-19 patients. Emerg Microbes Infect. 2020;9:940-8. [PMID: 32357808] doi: 10.1080/22221751.2020.1762515
73.
Suthar MS, Zimmerman MG, Kauffman RC, et al. Rapid generation of neutralizing antibody responses in COVID-19 patients. Cell Rep Med. 2020;1:100040. [PMID: 32835303] doi: 10.1016/j.xcrm.2020.100040
74.
Takahashi T, Wong P, Ellingson MK, et al; Yale IMPACT research team. Sex differences in immune responses to SARS-CoV-2 that underlie disease outcomes. med. Rxiv. 2020. [PMID: 32577695] doi: 10.1101/2020.06.06.20123414
75.
Terpos E, Politou M, Sergentanis TN, et al. Anti-SARS-CoV-2 antibody responses in convalescent plasma donors are increased in hospitalized patients; subanalyses of a phase 2 clinical study. Microorganisms. 2020;8. [PMID: 33260775] doi: 10.3390/microorganisms8121885
76.
Theel ES, Harring J, Hilgart H, et al. Performance characteristics of four high-throughput immunoassays for detection of IgG antibodies against SARS-CoV-2. J Clin Microbiol. 2020;58. [PMID: 32513859] doi: 10.1128/JCM.01243-20
77.
Traugott M, Aberle SW, Aberle JH, et al. Performance of severe acute respiratory syndrome coronavirus 2 antibody assays in different stages of infection: comparison of commercial enzyme-linked immunosorbent assays and rapid tests. J Infect Dis. 2020;222:362-6. [PMID: 32473021] doi: 10.1093/infdis/jiaa305
78.
Van Elslande J, Decru B, Jonckheere S, et al. Antibody response against SARS-CoV-2 spike protein and nucleoprotein evaluated by four automated immunoassays and three ELISAs. Clin Microbiol Infect. 2020;26:1557.e1-1557.e7. [PMID: 32745595] doi: 10.1016/j.cmi.2020.07.038
79.
Wang B, Van Oekelen O, Mouhieddine TH, et al. A tertiary center experience of multiple myeloma patients with COVID-19: lessons learned and the path forward. medRxiv. Preprint posted online 29 June 2020. doi: 10.1101/2020.06.04.20122846
80.
Wang K, Long QX, Deng HJ, et al. Longitudinal dynamics of the neutralizing antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Clin Infect Dis. 2021;73:e531-e539. [PMID: 32745196] doi: 10.1093/cid/ciaa1143
81.
Wang P. Combination of serological total antibody and RT-PCR test for detection of SARS-COV-2 infections. J Virol Methods. 2020;283:113919. [PMID: 32554043] doi: 10.1016/j.jviromet.2020.113919
82.
Wendel S, Kutner JM, Fontao-Wendel R, et al. Screening for SARS-CoV-2 antibodies in convalescent plasma (CCP) in Brazil: results from a voluntary convalescent donor program. Transfusion. 2020;60:296A.
83.
Wolff F, Dahma H, Duterme C, et al. Monitoring antibody response following SARS-CoV-2 infection: diagnostic efficiency of 4 automated immunoassays. Diagn Microbiol Infect Dis. 2020;98:115140. [PMID: 32829098] doi: 10.1016/j.diagmicrobio.2020.115140
84.
Xiang F, Wang X, He X, et al. Antibody detection and dynamic characteristics in patients with coronavirus disease 2019. Clin Infect Dis. 2020;71:1930-4. [PMID: 32306047] doi: 10.1093/cid/ciaa461
85.
Xie L, Wu Q, Lin Q, et al. Dysfunction of adaptive immunity is related to severity of COVID-19: a retrospective study. Ther Adv Respir Dis. 2020;14:1753466620942129. [PMID: 32684101] doi: 10.1177/1753466620942129
86.
Xu X, Sun J, Nie S, et al. Seroprevalence of immunoglobulin M and G antibodies against SARS-CoV-2 in China. Nat Med. 2020;26:1193-5. [PMID: 32504052] doi: 10.1038/s41591-020-0949-6
87.
Young BE, Ong SWX, Ng LFP, et al; Singapore 2019 Novel Coronavirus Outbreak Research Team. Viral dynamics and immune correlates of coronavirus disease 2019 (COVID-19) severity. Clin Infect Dis. 2021;73:e2932-e2942. [PMID: 32856707] doi: 10.1093/cid/ciaa1280
88.
Zhang B, Zhou X, Zhu C, et al. Immune phenotyping based on the neutrophil-to-lymphocyte ratio and IgG level predicts disease severity and outcome for patients with COVID-19. Front Mol Biosci. 2020;7:157. [PMID: 32719810] doi: 10.3389/fmolb.2020.00157
89.
Zhao G, Su Y, Sun X, et al. A comparative study of the laboratory features of COVID-19 and other viral pneumonias in the recovery stage. J Clin Lab Anal. 2020;34:e23483. [PMID: 32696465] doi: 10.1002/jcla.23483
90.
Zhao J, Yuan Q, Wang H, et al. Antibody responses to SARS-CoV-2 in patients with novel coronavirus disease 2019. Clin Infect Dis. 2020;71:2027-34. [PMID: 32221519] doi: 10.1093/cid/ciaa344
91.
Zheng Y, Yan M, Wang L, et al. Analysis of the application value of serum antibody detection for staging of COVID-19 infection. J Med Virol. 2021;93:899-906. [PMID: 32779744] doi: 10.1002/jmv.26330
92.
World Health Organization. Advice on the use of masks in the context of COVID-19: interim guidance, 5 June 2020. Accessed at https://apps.who.int/iris/handle/10665/332293 on 1 December 2021.
93.
Centers for Disease Control and Prevention. Interim Public Health Recommendations for Fully Vaccinated People. Accessed at www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated-guidance.html on 1 December 2021.
94.
Centers for Disease Control and Prevention. Using Antibody Tests for COVID-19. Accessed at www.cdc.gov/coronavirus/2019-ncov/lab/resources/antibody-tests.html on 1 December 2021.
95.
Watson J, Richter A, Deeks J. Testing for SARS-CoV-2 antibodies. BMJ. 2020;370:m3325. [PMID: 32900692] doi: 10.1136/bmj.m3325
96.
Gazit S, Shlezinger R, Perez G, et al. Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections. medRxiv. Preprint posted online 25 August 2021. doi: 10.1101/2021.08.24.21262415
97.
Cavanaugh AM, Spicer KB, Thoroughman D, et al. Reduced risk of reinfection with SARS-CoV-2 after COVID-19 vaccination—Kentucky, May–June 2021. MMWR Morb Mortal Wkly Rep. 2021;70:1081-3. [PMID: 34383732] doi: 10.15585/mmwr.mm7032e1
98.
Hagan LM, McCormick DW, Lee C, et al. Outbreak of SARS-CoV-2 B.1.617.2 (Delta) variant infections among incarcerated persons in a federal prison—Texas, July–August 2021. MMWR Morb Mortal Wkly Rep. 2021;70:1349-54. [PMID: 34555009] doi: 10.15585/mmwr.mm7038e3
99.
Centers for Disease Control and Prevention. How to Protect Yourself & Others. Accessed at www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html on 1 December 2021.

Comments

0 Comments
Sign In to Submit A Comment
Jeffrey Fessel MD21 April 2022
SARS-CoV-2 may cause reduced numbers of oligodendrocytes, leading to cognitive dysfunction or dementia.

The article by Qaseem et al (Annals, April 2022) regarding the antibody response to SARS-CoV-2 infection, describes its diagnostic value and protection against severity of clinical response or against future infection. Omitted by the article is that antibodies provoked by the infection may cause organ damage. Brain damage is not common because brain’s expression of the ACE2 receptor is ~120-fold less than by the small intestine and ~20-fold less than by the kidneys (1). Nevertheless, besides by infection, the brain may be damaged by antibodies that are provoked by SARS-CoV-2, because several of those antibodies affect surface markers of oligodendrocytes or their precursor cells (OPC). If that happens, it could cause apoptosis and reduce the numbers of myelinating oligodendrocytes, producing an adverse effect on neural tracts.

Affected surface markers (contact the author for references) with antibodies include PGDF, Olig2, MOG, CXCR1, and CXCR3. Antibodies are not the only cause of reduced oligodendrocyte numbers, because the ACE2 receptor is expressed by OPCs, permitting their infection by SARS-CoV-2.

That reduction may have important clinical manifestations because abnormalities of myelination involving neural tracts cause microcircuit and brain network dysfunction that affects cognition, as explained by Mattson in an extensive review (2). From 110 healthcare facilities, Qureshi et al identified 10,403 adult patients with new onset pneumonia due to SARS-CoV-2 infection, and matched them for age, gender, and race/ethnicity with 10,403 contemporary, control pneumonia patients without SARS-CoV-2 infection. For patients over age 70, new dementia incidence was 6.4% in those with pneumonia due to SARS-CoV-2 versus 5.0% in the control group (p = .04) (3). In another report that also compared SARS-CoV-2 infected patients with an uninfected control group, concentration or memory issues occurred in 4.1% versus 0.2% (P < 0.0005); those symptoms lasted ≥28 days in 13.3%, ≥8 weeks in 4.5% and ≥12 weeks in 2.3% (4). Past morbidity is important: among 44,779 persons, 18.1% of those with a prior history of a psychiatric diagnosis experienced a new episode during 14 to 90 days after an acute SARS-CoV-2 infection, and 5.8% had a new one among those with no previous psychiatric history; 1.6% of persons over age 65, suffered a first diagnosis of dementia during those 14 to 90 days versus 0.66% in controls (p = .0044) (5).

In brief, besides the antibodies directed against the virus itself, the antibodies provoked by SARS-CoV-2 infection may be disastrous by causing a major neurocognitive disorder in some patients.

REFERENCES

  1. Hikmet F, Méar L, Edvinsson Å, Micke P, Uhlén M, Lindskog C. The protein expression profile of ACE2 in human tissues. Molecular systems biology. 2020;16(7):e9610.
  2. Kapogiannis D, Mattson MP. Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's disease. The Lancet Neurology. 2011;10(2):187-98.
  3. Qureshi AI, Baskett WI, Huang W, Naqvi SH, Shyu C-R. New-Onset Dementia Among Survivors of Pneumonia Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection. Open Forum Infectious Diseases, 2022. Oxford University Press US: ofac115.
  4. Sudre CH, Murray B, Varsavsky T, Graham MS, Penfold RS, Bowyer RC, et al. Attributes and predictors of long COVID. Nature medicine. 2021;27(4):626-31.
  5. Taquet M, Luciano S, Geddes JR, Harrison PJ. Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA. The Lancet Psychiatry. 2021;8(2):130-40.

 

Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 175Number 4April 2022
Pages: 556 - 565

History

Published online: 25 January 2022
Published in issue: April 2022

Keywords

Authors

Affiliations

Amir Qaseem, MD, PhD, MHA https://orcid.org/0000-0001-6866-7985
American College of Physicians, Philadelphia, Pennsylvania (A.Q., I.E.)
American College of Physicians, Philadelphia, and Villanova University, Villanova, Pennsylvania (J.Y.)
Itziar Etxeandia-Ikobaltzeta, PharmD, PhD https://orcid.org/0000-0001-6606-649X
American College of Physicians, Philadelphia, Pennsylvania (A.Q., I.E.)
Penn Medicine, Philadelphia, Pennsylvania (M.A.F.)
George M. Abraham, MD, MPH https://orcid.org/0000-0003-4296-8362
University of Massachusetts Medical School/Saint Vincent Hospital, Worcester, Massachusetts (G.M.A.)
Penn Medicine Radnor, Radnor, Pennsylvania (M.C.M.)
Adam J. Obley, MD
Portland Veterans Affairs Medical Center and Oregon Health & Science University, Portland, Oregon (A.J.O., L.L.H.).
Linda L. Humphrey, MD, MPH
Portland Veterans Affairs Medical Center and Oregon Health & Science University, Portland, Oregon (A.J.O., L.L.H.).
Scientific Medical Policy Committee of the American College of Physicians
Note: The practice points are meant to guide care based on the best available evidence and may not apply to all patients or individual clinical situations. They should not be used as a replacement for a clinician's judgment. Any reference to a product or process contained in a practice point is not intended as an endorsement of any specific commercial product. All practice points are considered automatically withdrawn or invalid 5 years after publication or once an update has been issued.
Financial Support: Financial support for the development of the practice points comes exclusively from the ACP operating budget.
Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M21-3272. All financial and intellectual disclosures of interest were declared, and potential conflicts were discussed and managed. Dr. Jokela participated in discussion of the practice points but was recused from authorship and voting due to a moderate-level conflict of interest (authored recent relevant publications). Dr. Marcucci participated in the discussion of the practice points but was recused from authorship and voting due to a moderate-level conflict of interest (author of relevant systematic review). A record of disclosures of interest and management of conflicts is kept for each SMPC meeting and conference call and can be viewed at www.acponline.org/about-acp/who-we-are/leadership/boards-committees-councils/scientific-medical-policy-committee/disclosure-of-interests-and-conflict-of-interest-management-summary-for-scientific-medical-policy.
Corresponding Author: Amir Qaseem, MD, PhD, MHA, American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106; e-mail, [email protected].
Author Contributions: Conception and design: M.A. Forciea, A.J. Obley, A. Qaseem, J. Yost.
Analysis and interpretation of the data: E.A. Akl, A. Dunn, I. Etxeandia-Ikobaltzeta, M.A. Forciea, L.L. Humphrey, D.L. Kansagara, M.C. Miller, A.J. Obley, A. Qaseem, M.P. Tschanz, J. Yost.
Drafting of the article: G.M. Abraham, I. Etxeandia-Ikobaltzeta, M.A. Forciea, A.J. Obley, A. Qaseem, J. Yost.
Critical revision for important intellectual content: G.M. Abraham, E.A. Akl, R. Andrews, A. Dunn, I. Etxeandia-Ikobaltzeta, M.A. Forciea, R. Haeme, L.L. Humphrey, D.L. Kansagara, M.C. Miller, A.J. Obley, A. Qaseem, M.P. Tschanz, J. Yost.
Final approval of the article: G.M. Abraham, E.A. Akl, R. Andrews, A. Dunn, I. Etxeandia-Ikobaltzeta, M.A. Forciea, R. Haeme, L.L. Humphrey, D.L. Kansagara, M.C. Miller, A.J. Obley, A. Qaseem, M.P. Tschanz, J. Yost.
Statistical expertise: A. Qaseem, J. Yost.
Administrative, technical, or logistic support: I. Etxeandia-Ikobaltzeta, A. Qaseem, J. Yost.
Collection and assembly of data: A.J. Obley, J. Yost.
This article was published at Annals.org on 25 January 2022.
* This paper, written by Amir Qaseem, MD, PhD, MHA; Jennifer Yost, RN, PhD; Itziar Etxeandia-Ikobaltzeta, PharmD, PhD; Mary Ann Forciea, MD; George M. Abraham, MD, MPH; Matthew C. Miller, MD; Adam J. Obley, MD; and Linda L. Humphrey, MD, MPH, was developed for the Scientific Medical Policy Committee of the American College of Physicians. Individuals who served on the Scientific Medical Policy Committee from initiation of the project until its approval were Linda L. Humphrey, MD, MPH† (Chair); Adam J. Obley, MD† (Vice Chair); Robert M. Centor, MD‡ (Immediate Past Vice Chair); Elie A. Akl, MD, MPH, PhD†; Rebecca Andrews, MS, MD†; Thomas A. Bledsoe, MD‡; Andrew Dunn, MD, MPH†; Mary Ann Forciea, MD†; Ray Haeme†§; Janet A. Jokela, MD, MPH‡; Devan L. Kansagara, MD, MCR†; Maura Marcucci, MD, MSc‡; Matthew C. Miller, MD†; and CDR Mark P. Tschanz, DO†. Kate Carroll, MPH, and Shannon Merillat, MPH, MLIS, were nonauthor contributors from ACP staff. Approved by the ACP Executive Committee of the Board of Regents on behalf of the Board of Regents on 9 August 2021.
† Author.
‡ Nonauthor contributor.
§ Nonphysician public representative.
Update Alerts: The literature update end date is 22 September 2021. No further updates for this topic are planned at this time.

Metrics & Citations

Metrics

Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. For an editable text file, please select Medlars format which will download as a .txt file. Simply select your manager software from the list below and click Download.

For more information or tips please see 'Downloading to a citation manager' in the Help menu.

Format





Download article citation data for:
Amir Qaseem, Jennifer Yost, Itziar Etxeandia-Ikobaltzeta, et al; Scientific Medical Policy Committee of the American College of Physicians . What Is the Antibody Response and Role in Conferring Natural Immunity After SARS-CoV-2 Infection? Rapid, Living Practice Points From the American College of Physicians (Version 2). Ann Intern Med.2022;175:556-565. [Epub 25 January 2022]. doi:10.7326/M21-3272

View More

Get Access

Login Options:
Purchase

You will be redirected to acponline.org to sign-in to Annals to complete your purchase.

Access to EPUBs and PDFs for FREE Annals content requires users to be registered and logged in. A subscription is not required. You can create a free account below or from the following link. You will be redirected to acponline.org to create an account that will provide access to Annals. If you are accessing the Free Annals content via your institution's access, registration is not required.

Create your Free Account

You will be redirected to acponline.org to create an account that will provide access to Annals.

View options

PDF/ePub

View PDF/ePub

Media

Figures

Other

Tables

Share

Share

Copy the content Link

Share on social media