ABSTRACT
Since the emergence of SARS-CoV-2, different variants and subvariants successively emerged to dominate global virus circulation as a result of immune evasion, replication fitness or both. COVID-19 vaccines continue to be updated in response to the emergence of antigenically divergent viruses, the first being the bivalent RNA vaccines that encodes for both the Wuhan-like and Omicron BA.5 subvariant spike proteins. Repeated infections and vaccine breakthrough infections have led to complex immune landscapes in populations making it increasingly difficult to assess the intrinsic neutralizing antibody responses elicited by the vaccines. Hong Kong’s intensive COVID-19 containment policy through 2020–2021 permitted us to identify sera from a small number of infection naïve individuals who received 3 doses RNA vaccine BNT162b2 of vaccines encoding the Wuhan-like spike who were boosted with a fourth dose monovalent Wuhan-like (WT) vaccine or the bivalent Wuhan-like and BA.4/5 spike (WT + BA.4/5) expressing vaccine. While neutralizing antibody to wild-type virus was comparable in both vaccine groups, BNT162b2 bivalent vaccine elicited significantly higher plaque neutralizing antibodies to Omicron subvariants BA.5, XBB.1.5, XBB.1.16, XBB.1.9.1, XBB.2.3.2, EG.5.1, HK.3, BA.2.86 and JN.1, compared to BNT162b2 monovalent vaccine. The single amino acid substitution that differentiates the spike of JN.1 from BA.2.86 resulted in a profound antigenic change.
Subject(s)
Breakthrough Pain , COVID-19 , SeizuresABSTRACT
After keeping infections at bay for two years, Hong Kong experienced a surge of Omicron BA.2 infections in early 2022 that overwhelmed the health care system, isolation facilities, and contact tracing capacity, leading to one of the highest per-capita death rates of COVID-19 in early 2022. The outbreak occurred against a backdrop of a dense population with low immunity towards natural SARS-CoV-2 infection, high vaccine hesitancy in vulnerable populations, comprehensive disease surveillance and the capacity for stringent public health and social measures. Using genome sequences and epidemiological data from this time, we reconstruct the epidemic trajectory of the BA.2 wave, estimate transmission and incidence rates, and evaluate the effectiveness of policy changes. We identify an increase in the effective reproductive rate (Re) to 9.5 in mid-January 2022, which preceded real-time estimates of transmission (Rt), revealing that BA.2 community transmission was under-ascertained weeks before the epidemic appeared to surge in mid-February 2022. Due to this, public health measures were relaxed in early February (Spring Festival) while Re increased and remained > 1 throughout February. An independent estimation of point prevalence and incidence using phylodynamics also indicates extensive superspreading at this time, which likely contributed to the rapid expansion of the epidemic. This study demonstrates that relying on Rt estimation methods dependent on case reporting can misinform epidemic response planning, sometimes with substantial consequences. There is a need for future research and implementation of improved estimates of epidemic growth in near real-time that combine multiple disparate data sources to better inform outbreak response policy.
Subject(s)
COVID-19ABSTRACT
Viral and host factors can shape SARS-CoV-2 within-host viral diversity and virus evolution. However, little is known about lineage-specific and vaccination-specific mutations that occur within individuals. Here we analysed deep sequencing data from 2,146 SARS-CoV-2 samples with different viral lineages to describe the patterns of within-host diversity in different conditions, including vaccine-breakthrough infections. Variant of Concern (VOC) Alpha, Delta, and Omicron samples were found to have higher within-host nucleotide diversity while being under weaker purifying selection at full genome level compared to non-VOC SARS-CoV-2 viruses. Breakthrough Delta and Omicron infections in Comirnaty and CoronaVac vaccinated individuals appeared to have higher within-host purifying selection at the full-genome and/or Spike gene levels. Vaccine-induced antibody or T cell responses did not appear to have significant impact on within-host SARS-CoV-2 evolution. Our findings suggest that vaccination does not increase SARS-CoV-2 protein sequence space and may not facilitate emergence of more viral variants.
ABSTRACT
Background: On-arrival quarantine has been one of the primary measures used to prevent the introduction of COVID-19 into Hong Kong since the start of the pandemic. Most on-arrival quarantines have been done in hotels, with the duration of quarantine and testing frequency during quarantine varying throughout the pandemic for various reasons. However, hotels are not necessarily designed with infection control in mind. We aimed to study the potential risk of transmission between persons in on-arrival quarantine. Methods: We examined data on each laboratory-confirmed COVID-19 case identified in on-arrival quarantine in a hotel in Hong Kong between 1 May 2020 and 31 January 2022. We sequenced the full genomes of viruses from cases that overlapped with other confirmed cases in terms of the hotel of stay, date of arrival and date of testing positive. A combination of epidemiological information and sequence information was then used to identify probable transmission events. Findings: Among 221 imported cases that overlapped with other quarantined cases, phylogenetic analysis identified eight suspected clusters comprising 20 cases in total. Only three of these clusters had been recognised as hotel transmission events. Interpretation: We have identified potential occurrences of COVID-19 transmission within hotel quarantine in Hong Kong demonstrating the underlying low but non-zero risk associated with sequestering arrivals within hotels. In future pandemics, on-arrival quarantine in hotels could be used to delay the introduction of infection, but the construction of purpose-built facilities for on-arrival quarantine might be necessary to minimize importation risk.
Subject(s)
COVID-19ABSTRACT
Vaccines that are broadly cross-protective against current and future SARS-CoV-2 variants of concern (VOC) or across the sarbecoviruses subgenus remain a priority for public health. Virus neutralization is the best available correlate of protection. We used sera from cohorts of individuals vaccinated with two or three doses of RNA (BNT162b2) or inactivated SARS-CoV-2 (Coronavac or Sinopharm) vaccines with or without a history of previous SARS-CoV-2 or SARS-CoV-1 (in 2003) infection, to define the magnitude and breath of cross-neutralization in a multiplex surrogate neutralization assay based on virus spike receptor binding domain of multiple SARS-CoV-2 variants of concern (VOC), SARS-CoV-2 related bat and pangolin viruses, SARS-CoV-1 and related bat sarbecoviruses. SARS-CoV-2 or SARS-CoV-1 infection followed by BNT162b2 vaccine, Omicron BA.2 breakthrough infection following BNT162b2 vaccine or a third dose of BNT162b2 following two doses of BNT162b2 or CoronaVac elicited the highest and broadest neutralization across VOCs. Considering breadth and magnitude of neutralization across all sarbecoviruses, those infected with SARS-CoV-1 immunized with BNT162b2 outperformed all other combinations of infection and/or vaccination. These data may inform vaccine design strategies for generating broadly neutralizing antibodies to SARS-CoV-2 variants or across the sarbecovirus subgenus.
ABSTRACT
We studied SARS-CoV-2 genomes from travelers arriving in Hong Kong from November-2021 to February-2022. Apart from detecting Omicron (BA.1, BA1.1. and BA.2) and Delta variants, we detected a BA.1/BA.2 recombinant in two epidemiologically linked cases. This recombinant has a breakpoint near the 5 end of Spike gene (nucleotide position 20055-21618).
ABSTRACT
Emergence of SARS-CoV-2 variants of concern (VOC) with progressively increased transmissibility between humans is a threat to global public health. Omicron variant also evades immunity from natural infection or vaccines 1 . It is unclear whether its exceptional transmissibility is due to immune evasion or inherent virological properties.We compared the replication competence and cellular tropism of the wild type (WT) virus, D614G, Alpha, Beta, Delta and Omicron variants in ex vivo explant cultures of human bronchus and lung. Dependence on TMPRSS2 for infection was also evaluated. We show that Omicron replicated faster than all other SARS-CoV-2 in the bronchus but less efficiently in the lung parenchyma. All VOCs had similar cellular tropism as the WT. Delta was more dependent on serine protease than other VOCs tested.Our findings demonstrate that Omicron is inherently able to replicate faster than other variants known to date and this likely contributes to its inherently higher transmissibility, irrespective of its ability to evade antibody immunity. The lower replication competence of Omicron in human lung may be compatible with reduced severity but the determinants of severe disease are multifactorial. These findings provide important biological clues to the transmissibility and pathogenesis of SARS-CoV-2 VOCs.
Subject(s)
Lung DiseasesABSTRACT
Background. A large cluster of 59 cases were linked to a single flight with 146 passengers from New Delhi to Hong Kong in April 2021. This outbreak coincided with early reports of exponential pandemic growth in New Delhi, which reached a peak of >400,000 newly confirmed cases on 7 May 2021. Methods. Epidemiological information including date of symptom onset, date of positive-sample detection, and travel and contact history for individual cases from this flight were collected. Whole genome sequencing was performed, and sequences were classified based on the dynamic Pango nomenclature system. Maximum-likelihood phylogenetic analysis compared sequences from this flight alongside other cases imported from India to Hong Kong on 26 flights between June 2020 and April 2021, as well as sequences from India or associated with India-related travel from February to April 2021, and 1,217 reference sequences. Results. Sequence analysis identified six lineages of SARS-CoV-2 belonging to two variants of concern (Alpha and Delta) and one variant of public health interest (Kappa) involved in this outbreak. Phylogenetic analysis confirmed at least three independent sub-lineages of Alpha with limited onward transmission, a superspreading event comprising 37 cases of Kappa, and transmission of Delta to only one passenger. Additional analysis of another 26 flights from India to Hong Kong confirmed widespread circulation of all three variants in India since early March 2021. Conclusions. The broad spectrum of disease severity and long incubation period of SARS-CoV-2 pose a challenge for surveillance and control. As illustrated by this particular outbreak, opportunistic infections of SARS-CoV-2 can occur irrespective of variant lineage, and requiring a nucleic acid test within 72 hours of departure may be insufficient to prevent importation or in-flight transmission.
Subject(s)
Opportunistic Infections , Severe Acute Respiratory Syndrome , Addison DiseaseABSTRACT
Hong Kong utilized an elimination strategy with intermittent use of public health and social measures and increasingly stringent travel regulations to control SARS-CoV-2 transmission. By analyzing >1700 genome sequences representing 17% of confirmed cases from 23-January-2020 to 26-January-2021, we reveal the effects of fluctuating control measures on the evolution and epidemiology of SARS-CoV-2 lineages in Hong Kong. Despite numerous importations, only three introductions were responsible for 90% of locally-acquired cases, two of which circulated cryptically for weeks while less stringent measures were in place. We found that SARS-CoV-2 within-host diversity was most similar among transmission pairs and epidemiological clusters due to a strong transmission bottleneck through which similar genetic background generates similar within-host diversity.
ABSTRACT
BackgroundChildren 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. MethodsWe 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). FindingsChildren 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.
Subject(s)
COVID-19ABSTRACT
Coronavirus disease 2019 (COVID-19) is a global health concern as it continues to spread within China and beyond. The causative agent of this disease, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belongs to the genus Betacoronavirus which also includes severe acute respiratory syndrome related coronavirus (SARSr-CoV) and Middle East respiratory syndrome related coronavirus (MERSr-CoV). Codon usage of viral genes are believed to be subjected to different selection pressures in different host environments. Previous studies on codon usage of influenza A viruses can help identify viral host origins and evolution trends, however, similar studies on coronaviruses are lacking. In this study, global correspondence analysis (CA), within-group correspondence analysis (WCA) and between-group correspondence analysis (BCA) were performed among different genes in coronavirus viral sequences. The amino acid usage pattern of SARS-CoV-2 was generally found similar to bat and human SARSr-CoVs. However, we found greater synonymous codon usage differences between SARS-CoV-2 and its phylogenetic relatives on spike and membrane genes, suggesting these two genes of SARS-CoV-2 are subjected to different evolutionary pressures.