Insufficient Number of Controls for Low SARS-CoV-2 Seroprevalence: Are the Positive Rates Statistically Different between Pre-pandemic and Post-pandemic Samples?

Tomoko Fujitani Department of Health Environmental Sciences Kyoto University Graduate School of Medicine Kyoto, Japan E-mail: kharada-hes@umin.ac.jp.

Search for other papers by Tomoko Fujitani in
Current site
Google Scholar
PubMed
Close
and
Kouji H. Harada Department of Health Environmental Sciences Kyoto University Graduate School of Medicine Kyoto, Japan E-mail: kharada-hes@umin.ac.jp.

Search for other papers by Kouji H. Harada in
Current site
Google Scholar
PubMed
Close

Dear Sir,

We read the article by Nguyen et al.1 in The American Journal of Tropical Medicine and Hygiene with great interest. The authors surveyed the seroprevalence of neutralizing antibodies against SARS-CoV-2 in Vietnam in 2020 and considered the positives in plaque reduction neutralization tests (PRNT) as SARS-CoV-2 infection. SARS-CoV-2 neutralizing antibodies were identified in two blood donors in samples collected in 2020 (N = 885; 0.23%; 95% confidence interval: 0.06–0.82).

We have comments on this finding. The PRNT is considered specific unless there is a cross-reactivity from neutralizing antibodies to other coronaviruses. Antibodies to seasonal common cold coronaviruses (CCC; 229E, NL63, HKU1, or OC43) might cross-react with SARS-CoV-2. A study reported that two of 40 CCC convalescent sera had inconclusive results in a SARS-CoV-2 micro-focus reduction neutralization test.2 Another study showed SARS-CoV-2 PRNT titers of 1:20 and 1:10 for OC43 and 229E convalescent sera, respectively.3

The authors conducted the PRNT for 46 pre-pandemic stored sera and found no positive result. The false-positive rate was 0%, but the 95% confidence interval was 0 to 7.7%. As already mentioned, PRNT for SARS-CoV-2 could show cross-reactivity to anti-CCC antibodies, and therefore, the false-positive rate should be determined accurately. In this case, the number of positive results should be statistically different between pre-pandemic (2017) and post-pandemic (2020) samples. To verify this point, we analyzed the rates by Fisher’s exact test (Table 1), which showed no significant difference in SARS-CoV-2 positivity between the two sample sets (P = 0.90). The number of controls is apparently too small to provide adequate power to evaluate the difference. In our previous study, 400 pre-pandemic samples were assayed by lateral flow assay and ELISA and showed 1.5% and 1.8% SARS-CoV-2 positives, respectively.4

Table 1

The number of positive and negative plaque reduction neutralization tests in blood donors (2017 and 2020)

2017 2020
PRNT positive 0 2
PRNT negative 46 883

PRNT = plaque reduction neutralization tests.

P = 0.90 by Fisher’s exact test.

We think that the results in the paper by Nguyen et al. should be interpreted with caution. In particular, it should be noted that the seroprevalence in a low-prevalence situation of COVID-19 would be biased by the specificity of the test.

REFERENCES

  • 1.

    Nguyen HHH et al., 2022. Seroprevalence of SARS-CoV-2 neutralizing antibodies among blood donors in Ho Chi Minh City, Vietnam, August–November 2020. Am J Trop Med Hyg 106: 891895.

    • Search Google Scholar
    • Export Citation
  • 2.

    Dhochak N , Agrawal T , Shaman H , Khan NA , Kumar P , Kabra SK , Medigeshi GR , Lodha R , 2022. Humoral cross-reactivity towards SARS-CoV-2 in young children with acute respiratory infection with low-pathogenicity coronaviruses. J Clin Virol Plus 2: 100061.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Kohmer N , Westhaus S , Rühl C , Ciesek S , Rabenau HF , 2020. Brief clinical evaluation of six high-throughput SARS-CoV-2 IgG antibody assays. J Clin Virol 129: 104480.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Lyu Z , Harada Sassa M , Fujitani T , Harada KH , 2020. Serological tests for SARS-CoV-2 coronavirus by commercially available point-of-care and laboratory diagnostics in pre-COVID-19 samples in Japan. Diseases 8: 36.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 1.

    Nguyen HHH et al., 2022. Seroprevalence of SARS-CoV-2 neutralizing antibodies among blood donors in Ho Chi Minh City, Vietnam, August–November 2020. Am J Trop Med Hyg 106: 891895.

    • Search Google Scholar
    • Export Citation
  • 2.

    Dhochak N , Agrawal T , Shaman H , Khan NA , Kumar P , Kabra SK , Medigeshi GR , Lodha R , 2022. Humoral cross-reactivity towards SARS-CoV-2 in young children with acute respiratory infection with low-pathogenicity coronaviruses. J Clin Virol Plus 2: 100061.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Kohmer N , Westhaus S , Rühl C , Ciesek S , Rabenau HF , 2020. Brief clinical evaluation of six high-throughput SARS-CoV-2 IgG antibody assays. J Clin Virol 129: 104480.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Lyu Z , Harada Sassa M , Fujitani T , Harada KH , 2020. Serological tests for SARS-CoV-2 coronavirus by commercially available point-of-care and laboratory diagnostics in pre-COVID-19 samples in Japan. Diseases 8: 36.

    • Crossref
    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 8670 8633 18
PDF Downloads 218 211 11
 
Membership Banner
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save