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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread within the human population. Although SARS-CoV-2 is a novel coronavirus, most humans had been previously exposed to other antigenically distinct common seasonal human coronaviruses (hCoVs) before the COVID-19 pandemic. Here, we quantified levels of SARS-CoV-2-reactive a...
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread within the human population. Although SARS-CoV-2 is a novel coronavirus, most humans had been previously exposed to other antigenically distinct common seasonal human coronaviruses (hCoVs) before the COVID-19 pandemic. Here, we quantified levels of SARS-CoV-2-reactive a...
Citations
... This evidence, suggestive of a positive interaction between influenza and SARS-CoV-2, is consistent with the findings from a mathematical modeling study [94]. Although a retrospective cohort study reported that prior infection with endemic human coronaviruses (hCoVs) was associated with protection against COVID-19-related ICU admission (OR: 0.1, 95% CI: 0.1 to 0.9) [91], a case-control study on serum samples from hospitalized COVID-19 patients found that hCoVs antibodies were not associated with protection against SARS-CoV-2 infections nor hospitalizations [92]. Regarding the impact of upper respiratory infections (URIs), a retrospective cohort study found lower risk (OR: 0.76, 95% CI: 0.75, 0.77) of testing positive for SARS-CoV-2 among individuals with URI diagnosed in the preceding year [93], while a case-control study found higher risk among individuals diagnosed with URI in the preceding 1 to 14 days (OR: 6.95, 95% CI: 6.38 to 7.58) and 1 to 90 days (OR: 2.70, 95% CI: 2.55 to 2.86) [90]. ...
... In summary, the evidence available from human population health data indicates that coinfection prevalence is largely variable, that influenza vaccines and PCVs may be associated with reduced risk of SARS-CoV-2, and that earlier influenza infection may be associated with increased risk of SARS-CoV-2 infection and disease severity. However, our review also highlighted the limitations in the current epidemiological literature, as many studies were prone to multiple biases, including confounding, and only very few [90][91][92][93][94] were designed to infer interaction. ...
Despite the availability of effective vaccines, the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggests that cocirculation with other pathogens and resulting multiepidemics (of, for example, COVID-19 and influenza) may become increasingly frequent. To better forecast and control the risk of such multiepidemics, it is essential to elucidate the potential interactions of SARS-CoV-2 with other pathogens; these interactions, however, remain poorly defined. Here, we aimed to review the current body of evidence about SARS-CoV-2 interactions. Our review is structured in four parts. To study pathogen interactions in a systematic and comprehensive way, we first developed a general framework to capture their major components: sign (either negative for antagonistic interactions or positive for synergistic interactions), strength (i.e., magnitude of the interaction), symmetry (describing whether the interaction depends on the order of infection of interacting pathogens), duration (describing whether the interaction is short-lived or long-lived), and mechanism (e.g., whether interaction modifies susceptibility to infection, transmissibility of infection, or severity of disease). Second, we reviewed the experimental evidence from animal models about SARS-CoV-2 interactions. Of the 14 studies identified, 11 focused on the outcomes of coinfection with nonattenuated influenza A viruses (IAVs), and 3 with other pathogens. The 11 studies on IAV used different designs and animal models (ferrets, hamsters, and mice) but generally demonstrated that coinfection increased disease severity compared with either monoinfection. By contrast, the effect of coinfection on the viral load of either virus was variable and inconsistent across studies. Third, we reviewed the epidemiological evidence about SARS-CoV-2 interactions in human populations. Although numerous studies were identified, only a few were specifically designed to infer interaction, and many were prone to multiple biases, including confounding. Nevertheless, their results suggested that influenza and pneumococcal conjugate vaccinations were associated with a reduced risk of SARS-CoV-2 infection. Finally, fourth, we formulated simple transmission models of SARS-CoV-2 cocirculation with an epidemic viral pathogen or an endemic bacterial pathogen, showing how they can naturally incorporate the proposed framework. More generally, we argue that such models, when designed with an integrative and multidisciplinary perspective, will be invaluable tools to resolve the substantial uncertainties that remain about SARS-CoV-2 interactions.
... RBD-bound B cells with a wide range of heavy chain and light chain V genes can produce such neutralizing antibodies (Robbiani et al., 2020). These neutralizing antibodies come not from preexisting cross-reactive B cells but from immature B cells (Anderson et al., 2020). Therefore, the neutralizing epitopes in the SARS-CoV-2 RBD domain have relatively strong immunogenicity and are easily recognized by antibodies. ...
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has been prominent around the world since it was first discovered, affecting more than 100 million people. Although the symptoms of most infected patients are not serious, there is still a considerable proportion of patients who need hospitalization and even develop fatal symptoms such as cytokine storms, acute respiratory distress syndrome and so on. Cytokine storm is usually described as a collection of clinical manifestations caused by overactivation of the immune system, which plays an important role in tissue injury and multiorgan failure. The immune system of healthy individuals is composed of two interrelated parts, the innate immune system and the adaptive immune system. Innate immunity is the body’s first line of defense against viruses; it can quickly perceive viruses through pattern recognition receptors and activate related inflammatory pathways to clear pathogens. The adaptive immune system is activated by specific antigens and is mainly composed of CD4+ T cells, CD8+ T cells and B cells, which play different roles in viral infection. Here, we discuss the immune response after SARS-CoV-2 infection. In-depth study of the recognition of and response of innate immunity and adaptive immunity to SARS-CoV-2 will help to prevent the development of critical cases and aid the exploration of more targeted treatments.
... Cross-neutralizing antibodies across the clade have also been identified (48). However, a longitudinal study showed that, while cross-reactive HCoV antibodies are boosted following SARS-CoV-2 infection, this does not correlate with protection against infection or hospitalization (49), and a lack of antibodymediated neutralizing cross-protection has been noted between sera from SARS-CoV-1 patients and SARS-CoV-2 (50). In addition, it has been postulated that the small variety in circulating human coronaviruses may have resulted due to competition between coronaviruses filtering out potential emergent coronaviruses (51). ...
Significance
Cross-protection from seasonal epidemics of human coronaviruses (HCoVs) has been hypothesized to contribute to the relative sparing of children during the early phase of the pandemic. Testing this relies on understanding the prepandemic age distribution of recent HCoV infections, but little is known about their dynamics. Using England and Wales as a case study, we use a transmission model to estimate the duration of immunity to seasonal coronaviruses, and show how cross-protection could have affected the age distribution of susceptibility during the first wave, and could alter SARS-CoV-2 transmission patterns over the coming decade.
... Some scholars suggest and illustrate that exposure to Human coronaviruses induces the formation of antibodies either monoclonal or mixed that crossreact with antigens present on the SARS-CoV-2 virus, especially the N and the S2 proteins to neutralize the virus lessening disease development and mortality rate , Khan et al., 2020, Mveang Nzoghe et al., 2020. Other studies suggest otherwise that previous exposure to human coronaviruses may lead to the development of Abs but without immunity to the SARS-CoV-2 virus (Guo et al., 2020, Shrock et al., 2020, Anderson et al., 2020, Nguyen-Contant et al., 2020. Overall, SARS-CoV-2-unexposed individuals demonstrate the presence of Abs that cross-react with to SARS-CoV-2 Ags to trigger a weak to moderate immune response in the population. ...
... Overall, SARS-CoV-2-unexposed individuals demonstrate the presence of Abs that cross-react with to SARS-CoV-2 Ags to trigger a weak to moderate immune response in the population. Contrastingly, other evidence has shown that individuals exposed to SARS-CoV-2 illustrated enhanced responses towards common cold human coronaviruses infections (HCoVs) (Nguyen-Contant et al., 2020, Anderson et al., 2020, Shrock et al., 2020, Yonker et al., 2020, Song et al., 2021. This upregulation of the response is attributed to the cross-reactivity of the SARS-CoV-2 antibodies with the HCoVs and again the antigenic determinants in play here are the S2 and N. Altogether, exposure to the HCoVs or SARS-CoV-2 results in the formation of Abs that cross-react with antigens present on either virus and in particular the S2 and the N protein. ...
Common cold is an upper respiratory infection with relatively high mortality and infection rate. This is especially true among immunosuppressed individuals. The infection can be caused by human coronaviruses of which common cold coronaviruses-229E, -NL63, -OC43, and -HKU1 are the major etiological agents. These viruses also belong to the same family as the SARS-CoV-2 virus that cause the COVID-19 pandemic. The pandemic has led to the development of the various COVID-19 vaccines. The coronaviruses all express similar types of proteins, the membrane, spike, envelope protein, and the nucleocapsid. The spike protein is the main antigenic determinant and also induces an endoplasmic reticulum stress response. Cross-reactivity on the antigenic determinants between both groups of coronaviruses exists due to similar main antigenic orientation. Studies on the strength of the immune responses evoked by either SARS-CoV-2 or the human common cold coronaviruses towards each other is inconclusive; averagely demonstrating that antibodies (Abs) against SARS-CoV-2 can neutralize antigens (Ags) on common cold coronaviruses. Due to cross-reactivity, theoretically vaccines against SARS-CoV-2 can be used to fight common cold coronavirus infections due to the two expressing similar antigenic determinants that elicit an immune response for the homologous antigen.
... These previous studies mainly investigated the effects of the positivity of other pathogens 8,18 or the positivity of influenza-specific IgM 19 on the coinfection of SARS-CoV-2. However, a serum antibody test study demonstrated that although approximately 23% of COVID-19 patients had SARS-CoV-2 cross-reactive antibodies during the prepandemic period, these antibodies were not neutralizing antibodies for SARS-CoV-2 and were not related to reducing COVID-19 susceptibility and hospitalization 20 . A cross-sectional study reported different contracting patterns of influenza viruses and SARS-CoV-2 21 . ...
We aimed to investigate the associations of previous influenza/URI with the susceptibility of COVID-19 patients compared to that of non-COVID-19 participants. A nationwide COVID-19 cohort database was collected by the Korea National Health Insurance Corporation. A total of 8,070 COVID-19 patients (1 January 2020 through 4 June 2020) were matched with 32,280 control participants. Severe COVID-19 morbidity was defined based on the treatment histories of the intensive care unit, invasive ventilation, and extracorporeal membrane oxygenation and death. The susceptibility/morbidity/mortality associated with prior histories of 1–14, 1–30, 1–90, 15–45, 15–90, and 31–90 days before COVID-19 onset were analyzed using conditional/unconditional logistic regression. Prior influenza infection was related to increased susceptibility to COVID-19 (adjusted odds ratio [95% confidence interval] = 3.07 [1.61–5.85] for 1–14 days and 1.91 [1.54–2.37] for 1–90 days). Prior URI was also associated with increased susceptibility to COVID-19 (6.95 [6.38–7.58] for 1–14 days, 4.99 [4.64–5.37] for 1–30 days, and 2.70 [2.55–2.86] for 1–90 days). COVID-19 morbidity was positively associated with influenza (3.64 [1.55–9.21] and 3.59 [1.42–9.05]) and URI (1.40 [1.11–1.78] and 1.28 [1.02–1.61]) at 1–14 days and 1–30 days, respectively. Overall, previous influenza/URI did not show an association with COVID-19 mortality. Previous influenza/URI histories were associated with increased COVID-19 susceptibility and morbidity. Our findings indicate why controlling influenza/URI is important during the COVID-19 pandemic.
... Regions within N and S antigens with high amino acid homology between SARS-CoV-2 and HCoV are potential targets of cross-reactive antibodies [33][34][35][36] , and could exert cross-protective effects against SARS-CoV-2 infection and/or disease. Prior studies have not found protection against infection, as participants with recent documented infection with an endemic HCoV had similar rates of SARS-CoV-2 acquisition than those without recent HCoV infection [37][38][39] . Regarding anti-disease protection, COVID-19 patients with a recent HCoV diagnosis had statistically significant lower odds for COVID-19 intensive care unit admission and death 39 , but other studies did not find any association between confirmed prior history of seasonal HCoVs and COVID-19 severity 37,38 . ...
... Prior studies have not found protection against infection, as participants with recent documented infection with an endemic HCoV had similar rates of SARS-CoV-2 acquisition than those without recent HCoV infection [37][38][39] . Regarding anti-disease protection, COVID-19 patients with a recent HCoV diagnosis had statistically significant lower odds for COVID-19 intensive care unit admission and death 39 , but other studies did not find any association between confirmed prior history of seasonal HCoVs and COVID-19 severity 37,38 . Some recent studies have suggested that this pre-existing immunity would not confer cross-protection but, rather, be responsible for an immunological imprinting or 'original antigenic sin', a phenomenon well studied for influenza virus infections. ...
... Combined with the observation that higher baseline anti-HCoV N antibody levels correlated with less de novo anti-SARS-CoV-2 N antibody production, we propose a protective effect of previous exposure to HCoVs, which could be the result of a diminished exposure (decreased viral load) due to the suggested protective role of anti-HCoV antibodies. Other studies have reported a lack of antidisease cross-protection [37][38][39] ; and some studies have associated severe COVID-19 with a back-boosting of antibodies against S2 from betacoronaviruses 32 , and N and S from OC43 31 . However, these studies included only hospitalized patients, as opposed to our cohort that included mainly asymptomatic and participants with mild/moderate symptoms. ...
Unraveling the long-term kinetics of antibodies to SARS-CoV-2 and the individual characteristics influencing it, including the impact of pre-existing antibodies to human coronaviruses causing common cold (HCoVs), is essential to understand protective immunity to COVID-19 and devise effective surveillance strategies. IgM, IgA and IgG levels against six SARS-CoV-2 antigens and the nucleocapsid antigen of the four HCoV (229E, NL63, OC43 and HKU1) were quantified by Luminex, and antibody neutralization capacity was assessed by flow cytometry, in a cohort of health care workers followed up to 7 months ( N = 578). Seroprevalence increases over time from 13.5% (month 0) and 15.6% (month 1) to 16.4% (month 6). Levels of antibodies, including those with neutralizing capacity, are stable over time, except IgG to nucleocapsid antigen and IgM levels that wane. After the peak response, anti-spike antibody levels increase from ~150 days post-symptom onset in all individuals (73% for IgG), in the absence of any evidence of re-exposure. IgG and IgA to HCoV are significantly higher in asymptomatic than symptomatic seropositive individuals. Thus, pre-existing cross-reactive HCoVs antibodies could have a protective effect against SARS-CoV-2 infection and COVID-19 disease.
... With further regard to cross-reactive Ab responses, it has been reported that a small proportion of individuals recently infected with endemic (seasonal) coronaviruses (CoVs), such as OC43, 229E, NL63 and HKU1 (or SARS-CoV), show anti-SARS-CoV-2 S reactivity and neutralizing ability at the polyclonal serum level, indicating that some anti-S binding modes may be cross-reactive between related CoVs [24]. Another study reported convergent clonotypes between SARS-CoV and SARS-CoV-2 [83], and relatedly, a back-boost of antibodies specific to seasonal CoVs was reported in individuals recently infected with SARS-CoV [84] and SARS-CoV-2 [25,85]. This supports that different SARS-CoV-2 S epitopes can trigger memory B cells generated by related viruses in a subset of individuals previously infected, although the extent to which they (and Ab cross-reactivity between alpha and beta coronaviruses [86,87]) shape population-level outcomes remains to be established. ...
Adaptive immune responses play critical roles in viral clearance and protection against re-infection, and SARS-CoV-2 is no exception. What is exceptional, is the rapid characterization of the immune response to the virus performed by researchers during the first 20 months of the pandemic. This has given us a more detailed understanding about SARS-CoV-2 than we have about many viruses that have been with us for a long time. Furthermore, effective COVID-19 vaccines were developed in record time, and their rollout worldwide is already making a significant difference, although major challenges remain in terms of equal access. The pandemic has engaged scientists and the public alike, and terms such as seroprevalence, neutralizing antibodies, antibody escape and vaccine certificates have become familiar to a broad community. Here, we review key findings concerning B cell and antibody (Ab) responses to SARS-CoV-2, focusing on non-severe cases and anti-spike (S) Ab responses in particular, the latter being central to protective immunity induced by infection or vaccination. The emergence of viral variants that have acquired mutations in S acutely highlights the need for continued characterization of both emerging variants and Ab responses against these during the evolving pathogen-immune system arms race.
Abstract
... Given that many individuals have been exposed to common cold HCoV and have generated HCoV-specific B cell and T cell responses [46,47], a pertinent question is whether common cold HCoV-specific antibodies and T cells cross-react with SARS-CoV-2. Research has yielded variable results [17,[47][48][49][50][51][52][53][54][55]. ...
... Anderson et al. [46] suggested that pre-pandemic SARS-CoV-2 cross-reactive antibodies were not associated with reducing SARS-CoV-2 infections. This conclusion was based on the finding that groups of SARS-CoV-2-infected and uninfected persons had similar SARS-CoV-2-specific IgG levels when their banked pre-pandemic samples were tested. ...
While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes serious morbidity and mortality in humans (coronavirus disease 2019, COVID-19), there is an enormous range of disease outcomes following virus exposures. Some individuals are asymptomatic while others succumb to virus infection within days. Presently, the factors responsible for disease severity are not fully understood. One factor that may influence virus control is pre-existing immunity conferred by an individual’s past exposures to common cold human coronaviruses (HCoVs). Here, we describe previous literature and a new, murine study designed to examine cross-reactive immune responses between SARS-CoV-2 and common cold HCoVs (represented by prototypes OC43, HKU1, 229E, and NL63). Experimental results have been mixed. In SARS-CoV-2-unexposed humans, cross-reactive serum antibodies were identified toward nucleocapsid (N) and the spike subunit S2. S2-specific antibodies were in some cases associated with neutralization. SARS-CoV-2-unexposed humans rarely exhibited antibody responses to the SARS-CoV-2 spike subunit S1, and when naïve mice were immunized with adjuvanted S1 from either SARS-CoV-2 or common cold HCoVs, S1-specific antibodies were poorly cross-reactive. When humans were naturally infected with SARS-CoV-2, cross-reactive antibodies that recognized common cold HCoV antigens increased in magnitude. Cross-reactive T cells, like antibodies, were present in humans prior to SARS-CoV-2 exposures and increased following SARS-CoV-2 infections. Some studies suggested that human infections with common cold HCoVs afforded protection against disease caused by subsequent exposures to SARS-CoV-2. Small animal models are now available for the testing of controlled SARS-CoV-2 infections. Additionally, in the United Kingdom, a program of SARS-CoV-2 human challenge experiments has received regulatory approval. Future, controlled experimental challenge studies may better define how pre-existing, cross-reactive immune responses influence SARS-CoV-2 infection outcomes.
... Quantification of pre-pandemic antibody levels in human serum samples revealed the presence of antibodies against HCoV virus and the same got amplified post-COVID-19 infection. A decent percentage of these antibodies cross-reacted with SARS-CoV-2 spike and nucleocapsid proteins but were not found to be associated with protection against SARS-CoV-2 hospitalizations or infections [68]. All these studies emphasize the overlapping of structural protein residues in different coronaviruses strains to some extent. ...
With increasing global cases and mortality rates due to COVID-19 infection, finding effective therapeutic interventions has become a top priority. Marine resources are not explored much and to be taken into consideration for exploring antiviral potential. Chitosan (carbohydrate polymer) is one such bioactive glycan found ubiquitously in marine organisms. The presence of reactive amine/hydroxyl groups, with low toxicity/allergenicity, compels us to explore it against SARS-CoV-2. We have screened a library of chitosan derivatives by site-specific docking at not only spike protein Receptor Binding Domain (RBD) of wild type SARS-CoV-2 but also on RBD of B.1.1.7 (UK) and P.1 (Brazil) SARS-CoV-2 variants. The obtained result was very interesting and ranks N-benzyl-O-acetyl-chitosan, Imino-chitosan, Sulfated-chitosan oligosaccharides derivatives as a potent antiviral candidate due to its high binding affinity of the ligands (-6.0 to -6.6 kcal/mol) with SARS-CoV-2 spike protein RBD and they critically interacting with amino acid residues Tyr 449, Asn 501, Tyr 501, Gln 493, Gln 498 and some other site-specific residues associated with higher transmissibility and severe infection. Further ADMET analysis was done and found significant for exploration of the future therapeutic potential of these three ligands. The obtained results are highly encouraging in support for consideration and exploration in further clinical studies of these chitosan derivatives as anti-SARS-CoV-2 therapeutics.
... Antibody responses to seasonal coronaviruses are temporarily boosted without worsening disease progression. Pre-existing antibody responses to other beta coronaviruses have been proposed to potentially have either a detrimental or beneficial role in COVID-19 20,21 . Testing of IgG to S2 of HCoV-OC43 and -HKU1 in samples collected during the first weeks from symptoms onset did not correlate with either time to a negative swab test or death ( Supplementary Fig. 5). ...
... Interestingly, our data concerning a pre-existing immunity to seasonal HCoVs suggest it not to be detrimental to the development of SARS-CoV-2 responses. Indeed, in contrast with Aydillo et al. and in agreement with Anderson et al. 20,21 , who analyzed smaller cohorts over a shorter time span, we found no correlation between the expansion of IgG to HCoVs and a delayed development of SARS-CoV-2 specific antibodies. Our patients exhibited a backboosting of antibodies to OC43 and HKU1 S2, which is not surprising in light of the structural and partial sequence homology (approximately 40%) between SARS-CoV-2 and HCoVs S2 domains. ...
Understanding how antibody responses to SARS-CoV-2 evolve during infection may provide important insight into therapeutic approaches and vaccination for COVID-19. Here we profile the antibody responses of 162 COVID-19 symptomatic patients in the COVID-BioB cohort followed longitudinally for up to eight months from symptom onset to find SARS-CoV-2 neutralization, as well as antibodies either recognizing SARS-CoV-2 spike antigens and nucleoprotein, or specific for S2 antigen of seasonal beta-coronaviruses and hemagglutinin of the H1N1 flu virus. The presence of neutralizing antibodies within the first weeks from symptoms onset correlates with time to a negative swab result (p = 0.002), while the lack of neutralizing capacity correlates with an increased risk of a fatal outcome (p = 0.008). Neutralizing antibody titers progressively drop after 5–8 weeks but are still detectable up to 8 months in the majority of recovered patients regardless of age or co-morbidities, with IgG to spike antigens providing the best correlate of neutralization. Antibody responses to seasonal coronaviruses are temporarily boosted, and parallel those to SARS-CoV-2 without dampening the specific response or worsening disease progression. Our results thus suggest compromised immune responses to the SARS-CoV-2 spike to be a major trait of COVID-19 patients with critical conditions, and thereby inform on the planning of COVID-19 patient care and therapy prioritization. Antibody responses are critical for protection from developing severe COVID-19 following SARS-CoV-2 infection. Here the authors show that antibody responses against SARS-CoV-2 spike protein correlate with neutralizing capacity and protection, are not affected by heterologous boosting of influenza or common cold immunity, and can last up to 8 months.
