SARS-CoV-2 Omicron variant BA.2 neutralisation in sera of people with Comirnaty or CoronaVac vaccination, infection or breakthrough infection, Hong Kong, 2020 to 2022.

BackgroundOmicron subvariant BA.2 circulation is rapidly increasing globally.AimWe evaluated the neutralising antibody response from vaccination or prior SARS-CoV-2 infection against symptomatic infection by BA.2 or other variants.MethodsUsing 50% plaque reduction neutralisation tests (PRNT50), we assessed neutralising antibody titres to BA.2, wild type (WT) SARS-CoV-2 and other variants in Comirnaty or CoronaVac vaccinees, with or without prior WT-SARS-CoV-2 infection. Titres were also measured for non-vaccinees convalescing from a WT-SARS-CoV-2 infection. Neutralising antibodies in BA.2 and BA.1 breakthrough infections and in BA.2 infections affecting non-vaccinees were additionally studied.ResultsIn vaccinees or prior WT-SARS-CoV-2-infected people, BA.2 and BA.1 PRNT50 titres were comparable but significantly (p < 10 - 5) lower than WT. In each group of 20 vaccinees with (i) three-doses of Comirnaty, (ii) two CoronaVac followed by one Comirnaty dose, or (iii) one dose of either vaccine after a WT-SARS-CoV-2 infection, ≥ 19 individuals developed detectable (PRNT50 titre ≥ 10) antibodies to BA.2, while only 15 of 20 vaccinated with three doses of CoronaVac did. Comirnaty vaccination elicited higher titres to BA.2 than CoronaVac. In people convalescing from a WT-SARS-CoV-2 infection, a single vaccine dose induced higher BA.2 titres than three Comirnaty (p = 0.02) or CoronaVac (p = 0.00001) doses in infection-naïve individuals. BA.2 infections in previously uninfected and unvaccinated individuals elicited low (PRNT50 titre ≤ 80) responses with little cross-neutralisation of other variants. However, vaccinees with BA.1 or BA.2 breakthrough infections had broad cross-neutralising antibodies to WT viruses, and BA.1, BA.2, Beta and Delta variants.ConclusionsExisting vaccines can be of help against the BA.2 subvariant.

Waning antibody levels after COVID-19 vaccination with mRNA Comirnaty and inactivated CoronaVac vaccines in blood donors, Hong Kong, April 2020 to October 2021.

The mRNA vaccine Comirnaty and the inactivated vaccine CoronaVac are both available in Hong Kong's COVID-19 vaccination programme. We observed waning antibody levels in 850 fully vaccinated (at least 14 days passed after second dose) blood donors using ELISA and surrogate virus neutralisation test. The Comirnaty-vaccinated group's (n = 593) antibody levels remained over the ELISA and sVNT positive cut-offs within the first 6 months. The CoronaVac-vaccinated group's (n = 257) median antibody levels began to fall below the cut-offs 4 months after vaccination.

Long-term persistence of SARS-CoV-2 neutralizing antibody responses after infection and estimates of the duration of protection.

BACKGROUND: The duration of immunity in SARS-CoV-2 infected people remains unclear. Neutralizing antibody responses are the best available correlate of protection against re-infection. Recent studies estimated that the correlate of 50% protection from re-infection was 20% of the mean convalescent neutralizing antibody titre. METHODS: We collected sera from a cohort of 124 individuals with RT-PCR confirmed SARS-CoV-2 infections from Prince of Wales Hospital, Princess Margaret Hospital, Queen Elizabeth Hospital and Queen Mary Hospitals of the Hospital Authority of Hong Kong, for periods up to 386 days after symptom onset and tested these for antibody to SARS-CoV-2 using 50% virus plaque reduction neutralization tests (PRNT50), surrogate neutralization tests and spike receptor binding domain (RBD) binding antibody. Patients were recruited from 21 January 2020 to 16 February 2021 and follow-up samples were collected until 9th March 2021. FINDINGS: Because the rate of antibody waning slows with time, we fitted lines of decay to 115 sera from 62 patients collected beyond 90 days after symptom onset and estimate that PRNT50 antibody will remain detectable for around 1,717 days after symptom onset and that levels conferring 50% protection will be maintained for around 990 days post-symptom onset, in symptomatic patients. This would potentially be affected by emerging virus variants. PRNT titres wane faster in children. There was a high level of correlation between PRNT50 antibody titers and the % of inhibition in surrogate virus neutralization tests. INTERPRETATION: The data suggest that symptomatic COVID-19 disease is followed by relatively long-lived protection from re-infection by antigenically similar viruses. FUNDING: Health and Medical Research Fund, Commissioned research on Novel Coronavirus Disease (COVID-19) (Reference Nos. COVID190126 and COVID1903003) from the Food and Health Bureau and the Theme-based Research Scheme project no. T11-712/19-N, the University Grants Committee of the Hong Kong SAR Government.

The SARS-CoV-2 antibody landscape is lower in magnitude for structural proteins, diversified for accessory proteins and stable long-term in children.

Background: Children are less clinically affected by SARS-CoV-2 infection than adults with the majority of cases being mild or asymptomatic and the differences in infection outcomes are poorly understood. The kinetics, magnitude and landscape of the antibody response may impact the clinical severity and serological diagnosis of COVID-19. Thus, a comprehensive investigation of the antibody landscape in children and adults is needed. Methods: We tested 254 plasma from 122 children with symptomatic and asymptomatic SARS-CoV-2 infections in Hong Kong up to 206 days post symptom onset, including 146 longitudinal samples from 58 children. Adult COVID-19 patients and pre-pandemic controls were included for comparison. We assessed antibodies to a 14-wide panel of SARS-CoV-2 structural and accessory proteins by Luciferase Immunoprecipitation System (LIPS). Findings: Children have lower levels of Spike and Nucleocapsid antibodies than adults, and their cumulative humoral response is more expanded to accessory proteins (NSP1 and Open Reading Frames (ORFs)). Sensitive serology using the three N, ORF3b, ORF8 antibodies can discriminate COVID-19 in children. Principal component analysis revealed distinct serological signatures in children and the highest contribution to variance were responses to non-structural proteins ORF3b, NSP1, ORF7a and ORF8. Longitudinal sampling revealed maintenance or increase of antibodies for at least 6 months, except for ORF7b antibodies which showed decline. It was interesting to note that children have higher antibody responses towards known IFN antagonists: ORF3b, ORF6 and ORF7a. The diversified SARS-CoV-2 antibody response in children may be an important factor in driving control of SARS-CoV-2 infection.

SARS-CoV-2 specific T cell responses are lower in children and increase with age and time after infection.

SARS-CoV-2 infection of children leads to a mild illness and the immunological differences with adults remains unclear. We quantified the SARS-CoV-2 specific T cell responses in adults and children (<13 years of age) with RT-PCR confirmed asymptomatic and symptomatic infection for long-term memory, phenotype and polyfunctional cytokines. Acute and memory CD4+ T cell responses to structural SARS-CoV-2 proteins significantly increased with age, whilst CD8+ T cell responses increased with time post infection. Infected children had significantly lower CD4+ and CD8+ T cell responses to SARS-CoV-2 structural and ORF1ab proteins compared to infected adults. SARS-CoV-2-specific CD8+ T cell responses were comparable in magnitude to uninfected negative adult controls. In infected adults CD4+ T cell specificity was skewed towards structural peptides, whilst children had increased contribution of ORF1ab responses. This may reflect differing T cell compartmentalisation for antigen processing during antigen exposure or lower recruitment of memory populations. T cell polyfunctional cytokine production was comparable between children and adults, but children had a lower proportion of SARS-CoV-2 CD4+ T cell effector memory. Compared to adults, children had significantly lower levels of antibodies to ß-coronaviruses, indicating differing baseline immunity. Total T follicular helper responses was increased in children during acute infection indicating rapid co-ordination of the T and B cell responses. However total monocyte responses were reduced in children which may be reflective of differing levels of inflammation between children and adults. Therefore, reduced prior ß-coronavirus immunity and reduced activation and recruitment of de novo responses in children may drive milder COVID-19 pathogenesis.

Lack of serological evidence of Middle East respiratory syndrome coronavirus infection in virus exposed camel abattoir workers in Nigeria, 2016.

BackgroundMiddle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic threat of global public health concern and dromedary camels are the source of zoonotic infection. Although MERS-CoV is enzootic in dromedaries in Africa as well as the Middle East, zoonotic disease has not been reported in Africa. Methods: In an abattoir in Kano, Nigeria, we tested nasal swabs from camels and investigated 261 humans with repeated occupational exposure to camels, many of whom also reported drinking fresh camel milk (n = 138) or urine (n = 94) or using camel urine for medicinal purposes (n = 96). Results: Weekly MERS-CoV RNA detection in January-February 2016 ranged from 0-8.4% of camels sampled. None of the abattoir workers with exposure to camels had evidence of neutralising antibody to MERS-CoV. Conclusion: There is a need for more studies to investigate whether or not zoonotic transmission of MERS-CoV does take place in Africa.