Innate and Adaptive Immune Responses in the Upper Respiratory Tract and the Infectivity of SARS-CoV-2

Ramasamy, Ranjan

doi:10.3390/v14050933

Cited by 21 publications

(42 citation statements)

References 96 publications

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“…This contrasts with HCoV-NL63, typically associated with the common cold and primarily upper respiratory symptoms, as well as SARS-CoV-2, which is known to cause a wide range of disease from asymptomatic infections to mild colds to severe pneumonia. It is plausible that HCoV-mediated cytotoxicity in the case of mild SARS-CoV-2 and HCoV-NL63 infections in the nasal epithelium may facilitate early viral clearance and limit the subsequent spread of viral infection to the lower airway (Ramasamy, 2022). Whereas limited cytotoxicity during MERS-CoV infection may allow for uninhibited spread to cause lower airway pathology.…”

Section: Discussionmentioning

confidence: 99%

Infection of primary nasal epithelial cells differentiates among lethal and seasonal human coronaviruses

Otter

Fausto

Tan

et al. 2022

Preprint

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The nasal epithelium is the initial entry portal and primary barrier to infection by all human coronaviruses (HCoVs). We utilize primary nasal epithelial cells grown at air-liquid interface, which recapitulate the heterogeneous cellular population as well as mucociliary clearance functions of the in vivo nasal epithelium, to compare lethal (SARS-CoV-2 and MERS-CoV) and seasonal (HCoV-NL63 and HCoV-229E) HCoVs. All four HCoVs replicate productively in nasal cultures but diverge significantly in terms of cytotoxicity induced following infection, as the seasonal HCoVs as well as SARS-CoV-2 cause cellular cytotoxicity as well as epithelial barrier disruption, while MERS-CoV does not. Treatment of nasal cultures with type 2 cytokine IL-13 to mimic asthmatic airways differentially impacts HCoV replication, enhancing MERS-CoV replication but reducing that of SARS-CoV-2 and HCoV-NL63. This study highlights diversity among HCoVs during infection of the nasal epithelium, which is likely to influence downstream infection outcomes such as disease severity and transmissibility.

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Section: Discussionmentioning

confidence: 99%

Infection of primary nasal epithelial cells differentiates among lethal and seasonal human coronaviruses

Otter

Fausto

Tan

et al. 2022

Preprint

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“…It is well known that when the response to respiratory viruses is inadequate the infection spreads to lower respiratory tract (LRT) 106 . An early and effective immune response in patients infected with SARS-CoV-2 can limit and eliminate the infection yet in the upper respiratory tract (URT) 107 . Genomic analyses shown that there is no tissue specific genetic adaptation of SARS-CoV-2 to the URT or LRT 108 .…”

Section: Discussionmentioning

confidence: 99%

Blood leukocyte transcriptional modules and differentially expressed genes associated with disease severity and age in COVID-19 patients

Bando

Bertonha

Vieira

et al. 2023

Sci Rep

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Since the molecular mechanisms determining COVID-19 severity are not yet well understood, there is a demand for biomarkers derived from comparative transcriptome analyses of mild and severe cases, combined with patients’ clinico-demographic and laboratory data. Here the transcriptomic response of human leukocytes to SARS-CoV-2 infection was investigated by focusing on the differences between mild and severe cases and between age subgroups (younger and older adults). Three transcriptional modules correlated with these traits were functionally characterized, as well as 23 differentially expressed genes (DEGs) associated to disease severity. One module, correlated with severe cases and older patients, had an overrepresentation of genes involved in innate immune response and in neutrophil activation, whereas two other modules, correlated with disease severity and younger patients, harbored genes involved in the innate immune response to viral infections, and in the regulation of this response. This transcriptomic mechanism could be related to the better outcome observed in younger COVID-19 patients. The DEGs, all hyper-expressed in the group of severe cases, were mostly involved in neutrophil activation and in the p53 pathway, therefore related to inflammation and lymphopenia. These biomarkers may be useful for getting a better stratification of risk factors in COVID-19.

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“…For controlling SARS-CoV-2, a primary goal of current vaccines is to prevent severe infection by reducing the viral load in the lower airways (vs. in both lower and upper airways to prevent mild disease). [25][26][27] The notion of mechanistic correlates of clinical protection is supported by a study in nonhuman primates showing that levels of neutralizing activity were inversely correlated with viral replication in the upper and lower airways after a SARS-CoV-2 challenge. Importantly, protection against lower versus upper respiratory tract disease was achieved at lower serum antibody concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…Conditions of immunosuppression provide a unique opportunity to dissect the different roles of immune elements and provide a novel avenue for the protection of at‐risk and general populations. For controlling SARS‐CoV‐2, a primary goal of current vaccines is to prevent severe infection by reducing the viral load in the lower airways (vs. in both lower and upper airways to prevent mild disease) 25–27 . The notion of mechanistic correlates of clinical protection is supported by a study in nonhuman primates showing that levels of neutralizing activity were inversely correlated with viral replication in the upper and lower airways after a SARS‐CoV‐2 challenge.…”

Section: Discussionmentioning

confidence: 99%

BNT162b2‐vaccine‐induced neutralization responses are immune correlates of clinical protection against SARS‐CoV‐2 in heart transplant recipients

Peled,

Patel,

Raanani

et al. 2023

Clinical Transplantation

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BackgroundDefining immune correlates of protection against COVID‐19 is pivotal for optimizing the use of COVID‐19 vaccines, predicting the impact of novel variants on clinical outcomes, and advancing the development of immunotherapies and next‐generation vaccines. We aimed to identify vaccine‐induced immune correlates of protection against COVID‐19‐related hospitalizations in a highly vaccinated heart transplant (HT) cohort.MethodsIn a case‐control study of HT recipients vaccinated with the BNT162b2 vaccine, patients were prospectively assessed for vaccine‐induced neutralization of the wild‐type virus, and the Delta and Omicron BA.1, BA.2, BA.4, and BA.5 variants. Comparative analyses with controls were conducted to identify correlates of protection against COVID‐19 hospitalization. ROC analyses were performed. Primary outcomes were COVID‐19 hospitalizations and severity of SARS‐CoV‐2 breakthrough infection.ResultsThe study cohort comprised 59 HT recipients aged 58 (49,65) years with breakthrough infections after three or four monovalent BNT162b2 doses; 41 (69.5%) were men. Thirty‐six (61%) patients with COVID‐19 were hospitalized; most cases were non‐severe (58, 98%). For hospitalized (vs. non‐hospitalized) COVID‐19 patients, vaccine‐induced neutralization titers were significantly lower against all SARS‐CoV‐2 variants (p < .005). Vaccine‐induced neutralization of the wild‐type virus and delta and omicron BA.1, BA.2, BA.4, and BA.5 variants was associated with a reduced risk for COVID‐19‐related hospitalization. The optimal neutralization titer thresholds that were predictive of COVID‐19 hospitalizations were 96 (wild‐type), 48 (delta), 12 (BA.1), 96 (BA.2), 96 (BA.4), and 48 (BA.5).ConclusionsBNT162b2‐vaccine‐induced neutralization responses are immune correlates of protection and confer clinical protection against COVID‐19 hospitalizations.

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Innate and Adaptive Immune Responses in the Upper Respiratory Tract and the Infectivity of SARS-CoV-2

Cited by 21 publications

References 96 publications

Infection of primary nasal epithelial cells differentiates among lethal and seasonal human coronaviruses

Infection of primary nasal epithelial cells differentiates among lethal and seasonal human coronaviruses

Blood leukocyte transcriptional modules and differentially expressed genes associated with disease severity and age in COVID-19 patients

BNT162b2‐vaccine‐induced neutralization responses are immune correlates of clinical protection against SARS‐CoV‐2 in heart transplant recipients

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