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On July 4, 2021, 3 confirmed coronavirus disease 2019 (COVID-19) patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.617.2 (Delta) variant were found through regular nucleic acid screening in Jiegao Community, Ruili City, Yunnan Province (1). During the epidemiological investigation conducted by local CDCs and the Yunnan Provincial CDC from July to September, 2021, many of the confirmed cases were found to have no clear history of contact to other cases, which made difficult the tracing of the source of cases and effective control of the recent outbreak. In a retrospective analysis of the epidemiological investigation and laboratory test data, we reported a phenomenon for the first time that the probable index case, who had a negative nucleic acid test but had a positive IgM test result and/or IgG test value of over 20 S/CO in antibodies testing, might have acted as a bridging case for SARS-CoV-2 transmission. Based on this finding, probable cases were considered as clues of case tracing in the following epidemiological investigation, and serological antibody monitoring was strengthened to include the probable cases. Our evidence indicated that strengthening the management of probable cases is essential to effectively control transmission, especially in border areas that may have increased contact with COVID-19 prevalent regions.
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The confirmed COVID-19 cases were diagnosed and classified according to severity (mild, moderate, severe, and critical) based on guidelines issued by the National Health Commission (2), which the local CDC confirmed. The biological samples of these cases were also sent to the China CDC for further virus genotyping. A detailed epidemiological investigation was conducted for these patients, including collecting their sociodemographic information, residential address, and history of travel, work, contacts, and activities. These patients were immediately transported to a designated quarantine site. Close contacts of these COVID-19 patients were found through epidemiological investigation and travel history big data and were quarantined for at least 14 days. Regular SARS-CoV-2 nucleic acid testing and antibody testing (IgM and IgG) was conducted on the COVID-19 patients and their close contacts. Their COVID-19 vaccination records were obtained from the vaccination database using ID numbers and names as unique identifiers. Compared with the confirmed COVID-19 cases, whose nucleic acid testing results were positive, we defined the probable cases as individuals who had negative results in nucleic acid testing but had positive IgM test results and/or IgG test values of over 20 S/CO in antibody testing. We set a value limit of 20 S/CO for the IgG test because the positive IgG value was common among people who have been vaccinated against COVID-19, and the value of 20 S/CO was a conservative limit that was about two times higher than the 98% quantile value (10.810 S/CO) of the 117 confirmed COVID-19 cases’ IgG test results in the one-month follow-up in Ruili City. Therefore, the probable cases had a high probability of infection but had not been detected by nucleic acid testing.
For laboratory testing, Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) targeting of ORF1ab and N genes was conducted on the viral RNA extracted from the nasopharyngeal swabs using the Novel Coronavirus 2019 Nucleic Acid Test Kit (manufactured by Bojie Medical Technology, Shanghai Municipality and Daan Gene Company, Guangzhou City, China). The detection limit of cycle threshold (Ct) of the above tests was 40, a Ct value of less than 40 was considered as a positive nucleic acid test result. The nucleic acid test reading positive or not was the key to distinguishing between the confirmed cases and the probable cases. Serum samples collected from confirmed COVID-19 patients and their close contacts were tested for antibodies IgM and IgG using Anti-SARS-CoV-2 Rapid Test Kit (manufactured by Antubio Diagnostics Company, Zhengzhou, China). A value of over 1 S/CO was considered a positive result for IgM and IgG tests.
Retrospective analysis was conducted based on the epidemiological investigation data from July to September 2021. Contact networks of confirmed COVID-19 patients and their close contacts were formed. The nodes in the contact networks represent the confirmed COVID-19 patients and their close contacts. Edges of the networks represent the contacts among these persons, including work and household contacts, environmental contacts, and so on. Statistical analysis was performed with IBM SPSS (version 21.0, IBM Corp., Armonk, NY, US). Network visualization was done with Cytoscape (version 3.5.1, NIH Biomedical Technology Research Center, Bethesda, MD, US).
In this study, we showed a representative example that 2 confirmed COVID-19 cases (C1 and C2) and their contact networks were linked by two probable cases (P1 and P2) that acted as bridges, which constituted a potential chain of Delta variant transmission (Figure 1). C1 was the first index case of the “July 4” COVID-19 outbreak in Ruili City, Yunnan Province and occurred in a 51-year-old Chinese man who lived in Jiegao Community. C2 occurred in a 25-year-old Chinese male diagnosed on August 2, 2021. The two confirmed cases were both infected with SARS-CoV-2 Delta variant, and the amino acid mutation sites in the S protein of the two patients’ viruses were the same, including T19R, G142D, R158G, L452R, T478K, D614G, P681R, D950N, E156del, and F157del. The two patients all declared that they had no contact with other COVID-19 patients or anyone with suspected symptoms before they were diagnosed (Table 1). A total of 238 close contacts were found through epidemiological investigation, of whom 85 were close contacts of C1, and 153 were close contacts of C2. The mean age of the contacts was 31.2±13.5 years, and most of them were aged 18–45 years (73.9%). C1 had more contacts with people in Myanmar than C2 (50.6% vs. 1.3%); 75.2% of the close contacts were vaccinated against COVID-19 (Table 2).
Figure 1.Contact network of two confirmed COVID-19 cases (C1 and C2) and two corresponding probable cases (P1 and P2) in Ruili City, Yunnan Province, China, July–September 2021.
Case* Sex Age (years) Community Nationality Date of symptom onset Date of positive nucleic acid test Severity Date of COVID-19 vaccination Antibody test results (S/CO) First time Last time First Dose Second Dose Date Results Date Results C1 Male 51 Jiegao China Jul 2, 2021 Jul 3, 2021 Moderate May 5, 2021† − Jul 5, 2021 IgM: 11.773(+);
IgG: 64.768(+)Aug 5, 2021 IgM: 7.684(+);
IgG: 7.154(+)C2 Male 25 Jiegao China Aug 2, 2021 Aug 2, 2021 Mild Mar 18, 2021 Apr 1, 2021 Aug 3, 2021 IgM: 0.032(−);
IgG: 0.343(−)Aug 23, 2021 IgM: 24.428(+);
IgG: 8.227(+)P1 Male 34 Jiegao Myanmar − − − Apr 25, 2021 May 26, 2021 Jul 5, 2021 IgM: 0.373(−);
IgG: 21.139(+)− − P2 Male 25 Jiegao China − − − May 6, 2021† − Jul 7, 2021 IgM: 1.695(+);
IgG: 11.139(+)Aug 17, 2021 IgM: 2.426(+);
IgG: 5.001(+)* C1=confirmed COVID-19 case 1; C2=confirmed COVID-19 case 2; P1=probable case 1, P2=probable case 2.
† The COVID-19 vaccine they received has only one dose.Table 1. Characteristics of the two confirmed COVID-19 cases and two probable cases in Ruili City, Yunnan Province, China, July–September 2021.
Characteristics Total (n=238), n (%) C1* (n=85), n (%) C2† (n=153), n (%) Age (years) Mean±SD 31.2±13.5 30.7±17.7 31.4±10.4 <18 22/234 (9.4) 19/84 (22.6) 3/150 (2.0) ≥18 to <45 173/234 (73.9) 49/84 (58.3) 124/150 (82.7) ≥45 to <65 37/234 (15.8) 14/84 (16.7) 23/150 (15.3) ≥65 2/234 (0.9) 2/84 (2.4) 0/150 (0.0) Sex Male 164/236 (69.5) 35/84 (41.7) 129/152 (84.9) Female 72/236 (30.5) 49/84 (58.3) 23/152 (15.1) Nationality China 193 (81.1) 42 (49.4) 151 (98.7) Myanmar 45 (18.9) 43 (50.6) 2 (1.3) COVID-19 vaccination Yes 179 (75.2) 60 (70.6) 119 (77.8) No 59 (24.8) 25 (29.4) 34 (22.2) Infection status Confirmed COVID-19 case 3 (1.3) 3 (3.5) 0 (0) Probable case 53 (22.3) 21 (24.7) 32 (20.9) Non-case close contact 150 (63.0) 58 (68.2) 92 (60.1) Unknown status 32 (13.4) 3 (3.5) 29 (19.0) * C1=confirmed COVID-19 case 1.
† C2=confirmed COVID-19 case 2.Table 2. Characteristics of close contacts of the two confirmed COVID-19 cases in Ruili City, Yunnan Province, China, July–September 2021.
P1 (a 34-year-old man from Myanmar) and P2 (a 25-year-old Chinese man) were two close contacts of the two patients. P1 was a close contact of C1, and P2 was a close contact of P1 and C2. All four patients had been vaccinated against COVID-19 before (Table 1, Figure 1). The detailed transmission chain was described in the following three stages (Figure 1).
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P1 had sustained environmental exposure to C1 due to sharing stairs until July 4, 2021. He had a high-level IgG value of 21.139 S/CO tested on July 5, 2021. The quarantine began on July 4, 2020, and he was repatriated to Myanmar on August 2, 2021. C1 also had extremely high antibody values tested on the same day (July 5, 2021), of which IgM value was 11.773 S/CO, and IgG value was 64.768 S/CO (Table 1). The potential transmission path might exist between the two cases (Figure 1).
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P2 had contact with P1 through shopping on June 27, 2021, and the quarantine period lasted from July 6 to 20, 2021. He had a positive IgM test result, and a relatively high IgG value of 11.552 S/CO tested on July 7, 2021. Considering that the infection of P1 occurred earlier (IgM negative and IgG positive) at the same period, there was a high probability that the virus transmitted from P1 to P2. (Table 1, Figure 1)
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After P2 left the first quarantine on July 20, 2021, he was quarantined a second time on August 3, 2021 because he had work and daily life contact with C2. The last contact between P2 and C2 was on August 2, 2021. C2 was diagnosed as a confirmed COVID-19 case on August 2, 2021, and the first antibody test results were negative for both IgM and IgG tested on August 3, 2021, but then both were revealed to be positive in subsequent tests. The three antibodies test results of P2 during this quarantine were all double-positive for IgM and IgG until August 17, 2021. It was possible that P2’s latent infection status continued from July to August after the contact with P1, in which the virus was transmitted to C2. (Table 1, Figure 1)
In the ongoing outbreak of COVID-19 in Ruili, antibody tests were carried out among almost all of the close contacts to identify potential probable cases. The epidemiological investigation and case tracing was carried out using the clue of probable cases. In addition, serological antibody monitoring and follow-up were strengthened for the probable cases.
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Stage 1: P1’s contact with C1
Stage 2: P2’s contact with P1
Stage 3: C2’s contact with P2
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