Dataset Information

Less severe course of COVID-19 is associated with elevated levels of antibodies against seasonal human coronaviruses OC43 and HKU1 (HCoV OC43, HCoV HKU1).

ABSTRACT: The clinical course of COVID-19 is very heterogeneous: most infected individuals can be managed in an outpatient setting, but a substantial proportion of patients requires intensive care, resulting in a high rate of fatalities. We performed a biomarker study to assess the impact of prior infections with seasonal coronaviruses on COVID-19 severity. Sixty patients with confirmed COVID-19 infections were included (age 30-82; 52 males, 8 females): 19 inpatients with critical disease, 16 inpatients with severe or moderate disease, and 25 outpatients. Patients with critical disease had significantly lower levels of anti-HCoV OC43-NP (P = 0.016) and HCoV HKU1-NP (P = 0.023) antibodies at the first encounter compared to other COVID-19 patients. Our results indicate that prior infections with seasonal coronaviruses might protect against a severe course of disease.

SUBMITTER: Dugas M

PROVIDER: S-EPMC7901274 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Less severe course of COVID-19 is associated with elevated levels of antibodies against seasonal human coronaviruses OC43 and HKU1 (HCoV OC43, HCoV HKU1).

Dugas Martin M Grote-Westrick Tanja T Vollenberg Richard R Lorentzen Eva E Brix Tobias T Schmidt Hartmut H Tepasse Phil-Robin PR Kühn Joachim J

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 20210223

The clinical course of COVID-19 is very heterogeneous: most infected individuals can be managed in an outpatient setting, but a substantial proportion of patients requires intensive care, resulting in a high rate of fatalities. We performed a biomarker study to assess the impact of prior infections with seasonal coronaviruses on COVID-19 severity. Sixty patients with confirmed COVID-19 infections were included (age 30-82; 52 males, 8 females): 19 inpatients with critical disease, 16 inpatients w ...[more]

PMID: 33636357

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Project description:Human seasonal coronaviruses (hCoVs) are a group of viruses that affect the upper respiratory tract. While seasonal patterns and the annual variability of predominant hCoV species are well-documented, their genetic and species diversity in St. Petersburg and across Russia remains largely unexplored. In this study, we developed a two-pool, long-amplicon (900-1100 bp) PCR primer panel for the whole-genome sequencing of four seasonal hCoV species. The panel was validated using nasopharyngeal swab samples collected within the Global Influenza Hospital Surveillance Network (GIHSN) project. Over a period of six epidemiological seasons from 2017 to 2023, we retrospectively analyzed 14,704 nasopharyngeal swabs collected from patients hospitalized in St. Petersburg clinics. Of these samples, 5010 (34.07%) tested positive for respiratory viruses, with 424 (2.88% of all samples) identified as seasonal human coronaviruses. The assessment of species diversity showed that predominant hCoV species alternate between seasons. Whole-genome sequences for 85 seasonal human coronaviruses (hCoVs) with >70% genome coverage were obtained, including 23 hCoV-OC43, 6 hCoV-HKU1, 39 hCoV-229E, and 17 hCoV-NL63. These represent the first near-complete genomes of seasonal hCoVs from the Russian Federation, addressing a significant gap in the genomic epidemiology of these viruses. A detailed phylogenetic analysis of the sequenced genomes was conducted, highlighting the emergence of hCoV-229E subclades 7b.1 and 7b.2, which carry numerous substitutions in the Spike protein. Additionally, we sequenced a historical hCoV-229E isolate collected in the USSR in 1979, the oldest sequenced 229E virus from Eurasia, and demonstrated that it belongs to Genotype 2. The newly developed PCR-based sequencing protocol for seasonal hCoVs is straightforward and well-suited for genomic surveillance, providing a valuable tool to enhance our understanding of the genetic diversity of human seasonal coronaviruses.

Project description:Four coronaviruses (HCoV-OC43, HCoV-HKU1, HCoV-NL63, and HCoV-229E) are endemic in human populations. All these viruses are seasonal and generate short-term immunity. Like the highly pathogenic coronaviruses, the endemic coronaviruses have zoonotic origins. Thus, understanding the evolutionary dynamics of these human viruses might provide insight into the future trajectories of SARS-CoV-2 evolution. Because the zoonotic sources of HCoV-OC43 and HCoV-229E are known, we applied a population genetics-phylogenetic approach to investigate which selective events accompanied the divergence of these viruses from the animal ones. Results indicated that positive selection drove the evolution of some accessory proteins, as well as of the membrane proteins. However, the spike proteins of both viruses and the hemagglutinin-esterase (HE) of HCoV-OC43 represented the major selection targets. Specifically, for both viruses, most positively selected sites map to the receptor-binding domains (RBDs) and are polymorphic. Molecular dating for the HCoV-229E spike protein indicated that RBD Classes I, II, III, and IV emerged 3-9 years apart. However, since the appearance of Class V (with much higher binding affinity), around 25 years ago, limited genetic diversity accumulated in the RBD. These different time intervals are not fully consistent with the hypothesis that HCoV-229E spike evolution was driven by antigenic drift. An alternative, not mutually exclusive possibility is that strains with higher affinity for the cellular receptor have out-competed strains with lower affinity. The evolution of the HCoV-OC43 spike protein was also suggested to undergo antigenic drift. However, we also found abundant signals of positive selection in HE. Whereas such signals might result from antigenic drift, as well, previous data showing co-evolution of the spike protein with HE suggest that optimization for human cell infection also drove the evolution of this virus. These data provide insight into the possible trajectories of SARS-CoV-2 evolution, especially in case the virus should become endemic.

Project description:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has renewed interest in human coronaviruses that cause the common cold, particularly as research with them at biosafety level (BSL)-2 avoids the added costs and biosafety concerns that accompany work with SARS-CoV-2, BSL-3 research. One of these, human coronavirus OC43 (HCoV-OC43), is a well-matched surrogate for SARS-CoV-2 because it is also a Betacoronavirus, targets the human respiratory system, is transmitted via respiratory aerosols and droplets and is relatively resistant to disinfectants. Unfortunately, growth of HCoV-OC43 in the recommended human colon cancer (HRT-18) cells does not produce obvious cytopathic effect (CPE) and its titration in these cells requires expensive antibody-based detection. Consequently, multiple quantification approaches for HCoV-OC43 using alternative cell lines exist, which complicates comparison of research results. Hence, we investigated the basic growth parameters of HCoV-OC43 infection in three of these cell lines (HRT-18, human lung fibroblasts (MRC-5) and African green monkey kidney (Vero E6) cells) including the differential development of cytopathic effect (CPE) and explored reducing the cost, time and complexity of antibody-based detection assay. Multi-step growth curves were conducted in each cell type in triplicate at a multiplicity of infection of 0.1 with daily sampling for seven days. Samples were quantified by tissue culture infectious dose50(TCID50)/mL or plaque assay (cell line dependent) and additionally analyzed on the Sartorius Virus Counter 3100 (VC), which uses flow virometry to count the total number of intact virus particles in a sample. We improved the reproducibility of a previously described antibody-based detection based TCID50 assay by identifying commercial sources for antibodies, decreasing antibody concentrations and simplifying the detection process. The growth curves demonstrated that HCoV-O43 grown in MRC-5 cells reached a peak titer of ˜107 plaque forming units/mL at two days post infection (dpi). In contrast, HCoV-OC43 grown on HRT-18 cells required six days to reach a peak titer of ˜106.5 TCID50/mL. HCoV-OC43 produced CPE in Vero E6 cells but these growth curve samples failed to produce CPE in a plaque assay after four days. Analysis of the VC data in combination with plaque and TCID50 assays together revealed that the defective:infectious virion ratio of MRC-5 propagated HCoV-OC43 was less than 3:1 for 1-6 dpi while HCoV-OC43 propagated in HRT-18 cells varied from 41:1 at 1 dpi, to 329:4 at 4 dpi to 94:1 at 7 dpi. These results should enable better comparison of extant HCoV-OC43 study results and prompt further standardization efforts.

Dataset Information

Less severe course of COVID-19 is associated with elevated levels of antibodies against seasonal human coronaviruses OC43 and HKU1 (HCoV OC43, HCoV HKU1).

Publications

Less severe course of COVID-19 is associated with elevated levels of antibodies against seasonal human coronaviruses OC43 and HKU1 (HCoV OC43, HCoV HKU1).

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