Seroprevalence of SARS-CoV-2-specific anti-spike IgM, IgG, and anti-nucleocapsid IgG antibodies during the second wave of the pandemic: A population-based cross-sectional survey across Kashmir, India.
Within Kashmir, which is one of the topographically distinct areas in the Himalayan belt of India, a total of 2,236 cumulative deaths occurred by the end of the second wave. We aimed to conduct this population-based study in the age group of 7 years and above to estimate the seropositivity and its attributes in Kashmir valley.
We conducted a community-based household-level cross-sectional study, with a multistage, population-stratified, probability-proportionate-to-size, cluster sampling method to select 400 participants from each of the 10 districts of Kashmir. We also selected a quota of healthcare workers, police personnel, and antenatal women from each of the districts. Households were selected from each cluster and all family members with age 7 years or more were invited to participate. Information was collected through a standardized questionnaire and entered into Epicollect 5 software. Trained healthcare personnel were assigned for collecting venous blood samples from each of the participants which were transferred and processed for immunological testing. Testing was done for the presence of SARS-CoV-2-specific anti-spike IgM, IgG antibodies, and anti-nucleocapsid IgG antibodies. Weighted seropositivity was estimated along with the adjustment done for the sensitivity and specificity of the test used.
The data were collected from a total of 4,229 participants from the general population within the 10 districts of Kashmir. Our results showed that 84.84% (95% CI 84.51-85.18%) of the participants were seropositive in the weighted imputed data among the general population. In multiple logistic regression, the variables significantly affecting the seroprevalence were the age group 45-59 years (odds ratio of 0.73; 95% CI 0.67-0.78), self-reported history of comorbidity (odds ratio of 1.47; 95% CI 1.33-1.61), and positive vaccination history (odds ratio of 0.85; 95% CI 0.79-0.90) for anti-nucleocapsid IgG antibodies. The entire assessed variables showed a significant role during multiple logistic regression analysis for affecting IgM anti-spike antibodies with an odds ratio of 1.45 (95% CI 1.32-1.57) for age more than 60 years, 1.21 (95% CI 1.15-1.27) for the female gender, 0.87 (95% CI 0.82-0.92) for urban residents, 0.86 (95% CI 0.76-0.92) for self-reported comorbidity, and an odds ratio of 1.16 (95% CI 1.08-1.24) for a positive history of vaccination. The estimated infection fatality ratio was 0.033% (95% CI: 0.034-0.032%) between 22 May and 31 July 2021 against the seropositivity for IgM antibodies.
During the second wave of the SARS-CoV-2 pandemic, 84.84% (95% CI 84.51-85.18%) of participants from this population-based cross-sectional sample were seropositive against SARS-CoV-2. Despite a comparatively lower number of cases reported and lower vaccination coverage in the region, our study found such high seropositivity across all age groups, which indicates the higher number of subclinical and less severe unnoticed caseload in the community.
Lone KS
，Khan SMS
，Qurieshi MA
，Majid S
，Pandit MI
，Haq I
，Ahmad J
，Bhat AA
，Bashir K
，Bilquees S
，Fazili AB
，Hassan M
，Jan Y
，Kaul RR
，Khan ZA
，Mushtaq B
，Nazir F
，Qureshi UA
，Raja MW
，Rasool M
，Asma A
，Bhat AA
，Chowdri IN
，Ismail S
，Jeelani A
，Kawoosa MF
，Khan MA
，Khan MS
，Kousar R
，Lone AA
，Nabi S
，Qazi TB
，Rather RH
，Sabah I
，Sumji IA
... -
《Frontiers in Public Health》
Antibody tests for identification of current and past infection with SARS-CoV-2.
The diagnostic challenges associated with the COVID-19 pandemic resulted in rapid development of diagnostic test methods for detecting SARS-CoV-2 infection. Serology tests to detect the presence of antibodies to SARS-CoV-2 enable detection of past infection and may detect cases of SARS-CoV-2 infection that were missed by earlier diagnostic tests. Understanding the diagnostic accuracy of serology tests for SARS-CoV-2 infection may enable development of effective diagnostic and management pathways, inform public health management decisions and understanding of SARS-CoV-2 epidemiology.
To assess the accuracy of antibody tests, firstly, to determine if a person presenting in the community, or in primary or secondary care has current SARS-CoV-2 infection according to time after onset of infection and, secondly, to determine if a person has previously been infected with SARS-CoV-2. Sources of heterogeneity investigated included: timing of test, test method, SARS-CoV-2 antigen used, test brand, and reference standard for non-SARS-CoV-2 cases.
The COVID-19 Open Access Project living evidence database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) was searched on 30 September 2020. We included additional publications from the Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre) 'COVID-19: Living map of the evidence' and the Norwegian Institute of Public Health 'NIPH systematic and living map on COVID-19 evidence'. We did not apply language restrictions.
We included test accuracy studies of any design that evaluated commercially produced serology tests, targeting IgG, IgM, IgA alone, or in combination. Studies must have provided data for sensitivity, that could be allocated to a predefined time period after onset of symptoms, or after a positive RT-PCR test. Small studies with fewer than 25 SARS-CoV-2 infection cases were excluded. We included any reference standard to define the presence or absence of SARS-CoV-2 (including reverse transcription polymerase chain reaction tests (RT-PCR), clinical diagnostic criteria, and pre-pandemic samples).
We use standard screening procedures with three reviewers. Quality assessment (using the QUADAS-2 tool) and numeric study results were extracted independently by two people. Other study characteristics were extracted by one reviewer and checked by a second. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test and, for meta-analysis, we fitted univariate random-effects logistic regression models for sensitivity by eligible time period and for specificity by reference standard group. Heterogeneity was investigated by including indicator variables in the random-effects logistic regression models. We tabulated results by test manufacturer and summarised results for tests that were evaluated in 200 or more samples and that met a modification of UK Medicines and Healthcare products Regulatory Agency (MHRA) target performance criteria.
We included 178 separate studies (described in 177 study reports, with 45 as pre-prints) providing 527 test evaluations. The studies included 64,688 samples including 25,724 from people with confirmed SARS-CoV-2; most compared the accuracy of two or more assays (102/178, 57%). Participants with confirmed SARS-CoV-2 infection were most commonly hospital inpatients (78/178, 44%), and pre-pandemic samples were used by 45% (81/178) to estimate specificity. Over two-thirds of studies recruited participants based on known SARS-CoV-2 infection status (123/178, 69%). All studies were conducted prior to the introduction of SARS-CoV-2 vaccines and present data for naturally acquired antibody responses. Seventy-nine percent (141/178) of studies reported sensitivity by week after symptom onset and 66% (117/178) for convalescent phase infection. Studies evaluated enzyme-linked immunosorbent assays (ELISA) (165/527; 31%), chemiluminescent assays (CLIA) (167/527; 32%) or lateral flow assays (LFA) (188/527; 36%). Risk of bias was high because of participant selection (172, 97%); application and interpretation of the index test (35, 20%); weaknesses in the reference standard (38, 21%); and issues related to participant flow and timing (148, 82%). We judged that there were high concerns about the applicability of the evidence related to participants in 170 (96%) studies, and about the applicability of the reference standard in 162 (91%) studies. Average sensitivities for current SARS-CoV-2 infection increased by week after onset for all target antibodies. Average sensitivity for the combination of either IgG or IgM was 41.1% in week one (95% CI 38.1 to 44.2; 103 evaluations; 3881 samples, 1593 cases), 74.9% in week two (95% CI 72.4 to 77.3; 96 evaluations, 3948 samples, 2904 cases) and 88.0% by week three after onset of symptoms (95% CI 86.3 to 89.5; 103 evaluations, 2929 samples, 2571 cases). Average sensitivity during the convalescent phase of infection (up to a maximum of 100 days since onset of symptoms, where reported) was 89.8% for IgG (95% CI 88.5 to 90.9; 253 evaluations, 16,846 samples, 14,183 cases), 92.9% for IgG or IgM combined (95% CI 91.0 to 94.4; 108 evaluations, 3571 samples, 3206 cases) and 94.3% for total antibodies (95% CI 92.8 to 95.5; 58 evaluations, 7063 samples, 6652 cases). Average sensitivities for IgM alone followed a similar pattern but were of a lower test accuracy in every time slot. Average specificities were consistently high and precise, particularly for pre-pandemic samples which provide the least biased estimates of specificity (ranging from 98.6% for IgM to 99.8% for total antibodies). Subgroup analyses suggested small differences in sensitivity and specificity by test technology however heterogeneity in study results, timing of sample collection, and smaller sample numbers in some groups made comparisons difficult. For IgG, CLIAs were the most sensitive (convalescent-phase infection) and specific (pre-pandemic samples) compared to both ELISAs and LFAs (P < 0.001 for differences across test methods). The antigen(s) used (whether from the Spike-protein or nucleocapsid) appeared to have some effect on average sensitivity in the first weeks after onset but there was no clear evidence of an effect during convalescent-phase infection. Investigations of test performance by brand showed considerable variation in sensitivity between tests, and in results between studies evaluating the same test. For tests that were evaluated in 200 or more samples, the lower bound of the 95% CI for sensitivity was 90% or more for only a small number of tests (IgG, n = 5; IgG or IgM, n = 1; total antibodies, n = 4). More test brands met the MHRA minimum criteria for specificity of 98% or above (IgG, n = 16; IgG or IgM, n = 5; total antibodies, n = 7). Seven assays met the specified criteria for both sensitivity and specificity. In a low-prevalence (2%) setting, where antibody testing is used to diagnose COVID-19 in people with symptoms but who have had a negative PCR test, we would anticipate that 1 (1 to 2) case would be missed and 8 (5 to 15) would be falsely positive in 1000 people undergoing IgG or IgM testing in week three after onset of SARS-CoV-2 infection. In a seroprevalence survey, where prevalence of prior infection is 50%, we would anticipate that 51 (46 to 58) cases would be missed and 6 (5 to 7) would be falsely positive in 1000 people having IgG tests during the convalescent phase (21 to 100 days post-symptom onset or post-positive PCR) of SARS-CoV-2 infection.
Some antibody tests could be a useful diagnostic tool for those in whom molecular- or antigen-based tests have failed to detect the SARS-CoV-2 virus, including in those with ongoing symptoms of acute infection (from week three onwards) or those presenting with post-acute sequelae of COVID-19. However, antibody tests have an increasing likelihood of detecting an immune response to infection as time since onset of infection progresses and have demonstrated adequate performance for detection of prior infection for sero-epidemiological purposes. The applicability of results for detection of vaccination-induced antibodies is uncertain.
Fox T
，Geppert J
，Dinnes J
，Scandrett K
，Bigio J
，Sulis G
，Hettiarachchi D
，Mathangasinghe Y
，Weeratunga P
，Wickramasinghe D
，Bergman H
，Buckley BS
，Probyn K
，Sguassero Y
，Davenport C
，Cunningham J
，Dittrich S
，Emperador D
，Hooft L
，Leeflang MM
，McInnes MD
，Spijker R
，Struyf T
，Van den Bruel A
，Verbakel JY
，Takwoingi Y
，Taylor-Phillips S
，Deeks JJ
，Cochrane COVID-19 Diagnostic Test Accuracy Group
... -
《Cochrane Database of Systematic Reviews》
Seroprevalence and humoral immune durability of anti-SARS-CoV-2 antibodies in Wuhan, China: a longitudinal, population-level, cross-sectional study.
Wuhan was the epicentre of the COVID-19 outbreak in China. We aimed to determine the seroprevalence and kinetics of anti-SARS-CoV-2 antibodies at population level in Wuhan to inform the development of vaccination strategies.
In this longitudinal cross-sectional study, we used a multistage, population-stratified, cluster random sampling method to systematically select 100 communities from the 13 districts of Wuhan. Households were systematically selected from each community and all family members were invited to community health-care centres to participate. Eligible individuals were those who had lived in Wuhan for at least 14 days since Dec 1, 2019. All eligible participants who consented to participate completed a standardised electronic questionnaire of demographic and clinical questions and self-reported any symptoms associated with COVID-19 or previous diagnosis of COVID-19. A venous blood sample was taken for immunological testing on April 14-15, 2020. Blood samples were tested for the presence of pan-immunoglobulins, IgM, IgA, and IgG antibodies against SARS-CoV-2 nucleocapsid protein and neutralising antibodies were assessed. We did two successive follow-ups between June 11 and June 13, and between Oct 9 and Dec 5, 2020, at which blood samples were taken.
Of 4600 households randomly selected, 3599 families (78·2%) with 9702 individuals attended the baseline visit. 9542 individuals from 3556 families had sufficient samples for analyses. 532 (5·6%) of 9542 participants were positive for pan-immunoglobulins against SARS-CoV-2, with a baseline adjusted seroprevalence of 6·92% (95% CI 6·41-7·43) in the population. 437 (82·1%) of 532 participants who were positive for pan-immunoglobulins were asymptomatic. 69 (13·0%) of 532 individuals were positive for IgM antibodies, 84 (15·8%) were positive for IgA antibodies, 532 (100%) were positive for IgG antibodies, and 212 (39·8%) were positive for neutralising antibodies at baseline. The proportion of individuals who were positive for pan-immunoglobulins who had neutralising antibodies in April remained stable for the two follow-up visits (162 [44·6%] of 363 in June, 2020, and 187 [41·2%] of 454 in October-December, 2020). On the basis of data from 335 individuals who attended all three follow-up visits and who were positive for pan-immunoglobulins, neutralising antibody levels did not significantly decrease over the study period (median 1/5·6 [IQR 1/2·0 to 1/14·0] at baseline vs 1/5·6 [1/4·0 to 1/11·2] at first follow-up [p=1·0] and 1/6·3 [1/2·0 to 1/12·6] at second follow-up [p=0·29]). However, neutralising antibody titres were lower in asymptomatic individuals than in confirmed cases and symptomatic individuals. Although titres of IgG decreased over time, the proportion of individuals who had IgG antibodies did not decrease substantially (from 30 [100%] of 30 at baseline to 26 [89·7%] of 29 at second follow-up among confirmed cases, 65 [100%] of 65 at baseline to 58 [92·1%] of 63 at second follow-up among symptomatic individuals, and 437 [100%] of 437 at baseline to 329 [90·9%] of 362 at second follow-up among asymptomatic individuals).
6·92% of a cross-sectional sample of the population of Wuhan developed antibodies against SARS-CoV-2, with 39·8% of this population seroconverting to have neutralising antibodies. Our durability data on humoral responses indicate that mass vaccination is needed to effect herd protection to prevent the resurgence of the epidemic.
Chinese Academy of Medical Sciences & Peking Union Medical College, National Natural Science Foundation, and Chinese Ministry of Science and Technology.
For the Chinese translation of the abstract see Supplementary Materials section.
He Z
，Ren L
，Yang J
，Guo L
，Feng L
，Ma C
，Wang X
，Leng Z
，Tong X
，Zhou W
，Wang G
，Zhang T
，Guo Y
，Wu C
，Wang Q
，Liu M
，Wang C
，Jia M
，Hu X
，Wang Y
，Zhang X
，Hu R
，Zhong J
，Yang J
，Dai J
，Chen L
，Zhou X
，Wang J
，Yang W
，Wang C
... -
《-》
High prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies among unvaccinated children of Chandigarh, Northwest India, in a household-based paediatric serosurvey post-second wave of pandemic (June to July 2021).
Current national severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination policy covers children aged >12 years. Unvaccinated, uninfected children remain susceptible to SARS-CoV-2 and play a role in community transmission, as paediatric infection is mostly mild or asymptomatic. To estimate the proportion of susceptible children in a community for public health measures, there is a need to assess the extent of natural infection.
We performed a cross-sectional household serosurvey of SARS-CoV-2 antibodies in unvaccinated children aged between 6 and 18 years after the second COVID-19 wave.
Anti-SARS-CoV-2 immunoglobin G (IgG) testing in serum was done using chemiluminescence immunoassay. We used a logistic regression model to investigate predicted factors of seropositivity.
We observed a high prevalence (weighted average: 68.3%) of anti-SARS-CoV-2 IgG in 2700 enrolled children. Logistic regression for predictors of IgG seropositivity showed lower odds in households with completely vaccinated adults (adjusted odds ratio [OR]: 0.43, 95% confidence interval [CI]: 0.26-0.71, P = 0.0011) compared with households with unvaccinated adults. Other factors for low seropositivity included frontline workers as family members (adjusted OR: 0.69, 95% CI: 0.52-0.91, P = 0.0091) and non-crowded households (adjusted OR: 0.74, 95% CI: 0.61-0.89, P = 0.0019).
A high SARS-CoV-2 IgG prevalence in unvaccinated children was indicative of previous exposure to potentially infected contacts. This implies in-person academic activities for children can be continued during future community transmission. Comparatively lower seropositivity in children of completely vaccinated households or frontline workers suggests decreased transmission due to vaccination-induced immunity of family members. Vaccination will still be required in these children to maintain protective IgG levels, particularly in low seroprevalence groups.
Ghosh A
，Goyal K
，Singh R
，Lakshmi PVM
，Kaur R
，Kumar V
，Muralidharan J
，Puri GD
，Ram J
，Singh MP
... -
《-》
ResearchGate
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钛学术
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