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

Abstract

Background Since February 2020, Italian hospitals registered COVID-19 (COronaVIrus Disease 19) cases more often than the rest of the Europe. During this epidemic, health authorities requested swab tests, while seeking new patient paths. Methods A dual laboratory approach was evaluated, consisting of patient care reports for viral RNA detection on swabs and rapid serological tests in 516 patients (192 symptomatic or paucisymptomatic and 324 asymptomatic). Results We found the molecular positive fraction equal to 12% (23/192) among symptomatic/paucisymptomatic (S/P) and 15.4% (50/324) in asymptomatic (As) sets. Among subsets, we observed serologically positive results, corresponding to 35% (8/23) for S/P and 38% (19/50) for As. Among molecular negative cases, we detected specific Immunoglobulin G or M (Ig G or Ig M) positivity in the S/P cohort equal to 6.6% (11/167) and 6% (15/246) in As cases. For indeterminate molecular results, we found S/P serological positivity equal to 100% (1/1) and 54% (13/24) in As patients. We found higher (p < 0.05) seropositivity in older patients (n = 8) among symptomatic and positives for viral RNA (n.23). Conclusions It has been observed that a dual approach of serological and molecular tests detects a higher absolute number of disease cases in a pandemic context,which could improve monitoring and health surveillance efficacy. The age-related seropositivity frequency in this study, if confirmed, could enhance the validity of serological tests, especially in older patients.In these subjects, molecular positivity accompanied by serological positivity (distinct for M and G immunoglobulins) should help determine disease status and support decisions related to patient management.

Antibody Response After SARS-CoV-2 Infection and Implications for Immunity

“…Among cross-sectional and cohort studies with high risk of bias, the most serious methodological issues were unclear patient selection methods (that is, whether selection was random or consecutive) and lack of adjustment for confounding factors, like age, that could influence subgroup comparisons ( 16 , 18 , 24 , 40 , 42 , 45 , 51 , 54 , 57 , 66 , 68 , 74 , 76 , 77 , 79 ). In the immunoassay validation studies, inadequate reporting of patient selection methods and unclear or inconsistent criteria for interpreting immunoassay results meant that we could not rule out high risk of bias and limited the clinical applicability of results ( 14 , 15 , 22 , 25 , 26 , 32 , 33 , 37 , 43 , 44 , 48 , 56 , 64 , 65 , 69 , 71 , 72 ).…”

Performance of the FREND™ COVID-19 IgG/IgM Duo point-of-care test for SARS-CoV-2 antibody detection

“…Several indications for serological testing have been proposed such as providing epidemiological data and investigating seroconversion dynamics [ 8 ]. Although the diagnostic value of SARS-CoV-2 serological testing is still a matter of debate Pancrazzi et al demonstrated that combining RT-PCR with serology increases the diagnostic sensitivity [ 5 ]. Indeed, false negative RT-PCR tests are described due to inappropriate sampling, low viral loads or unsuitable transport conditions [ 9 , 10 ].…”

“…However, the sensitivity of molecular testing is highly influenced by sampling technique and differences in viral load in various parts of the respiratory tract [ 2 , 3 ]. Hence, serology testing might help in the identification of SARS-CoV-2-infected patients with negative RT-qPCR results, especially when clinical suspicion of COVID-19 infection is high [ 4 , 5 ]. In addition, the global nature of this epidemic is associated with logistic challenges for diagnostic laboratories, which may hamper the use of the recommended RT-qPCR, thus requiring alternative methods.…”

Antibody Response Following SARS-CoV-2 Infection and Implications for Immunity: A Rapid Living Review

“…18,20,41,43,47,52,55,58,67,69,77,78,80 In the immunoassay validation studies, inadequate reporting of patient selection methods and unclear or inconsistent criteria for interpreting immunoassay results meant we could not rule out high risk of bias and limited the clinical applicability of results. 16,17,24,27,28,33,34,38,45,46,49,57,65,66,70,72,73 Abbreviations: IgM/G/A = immunoglobulin M/G/A; Nab = neutralizing antibody; RT-PCR+ = reverse transcription polymerase chain reaction positive result; RT-PCR = reverse transcription polymerase chain reaction.…”