COVID-19, circadian rhythms and sleep: from virology to chronobiology

Various aspects of our physiology and immune response to pathogens are under 24 h circadian control and its role in clinical and research practice is becoming increasingly recognized. Severe acute respiratory syndrome coronavirus-2, the causative agent of Coronavirus disease 2019 (COVID-19) has affected millions of people to date. Cross-disciplinary approaches and collaborative efforts have led to an unprecedented speed in developing novel therapies and vaccines to tackle the COVID-19 pandemic. Circadian misalignment and sleep disruption have a profound impact on immune function and subsequently on the ability of individuals to combat infections. This review summarizes the evidence on the interplay between circadian biology, sleep and COVID-19 with the aim to identify areas of translational potentials that may inform diagnostic and therapeutic strategies in this pandemic.

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COVID-19: Unmasking Emerging SARS-CoV-2 Variants, Vaccines and Therapeutic Strategies

Biomolecules ◽

10.3390/biom11070993 ◽

2021 ◽

Vol 11 (7) ◽

pp. 993

Author(s):

Renuka Raman ◽

Krishna J. Patel ◽

Kishu Ranjan

Keyword(s):

Immune Response ◽

Monoclonal Antibodies ◽

Severe Acute Respiratory Syndrome ◽

Small Molecules ◽

Viral Vector ◽

Therapeutic Strategies ◽

Convincing Evidence ◽

Plasma Therapy ◽

Therapeutic Monoclonal Antibodies ◽

Increased Susceptibility

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, which has been a topic of major concern for global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta), which show increased transmissibility and resistance towards vaccines and therapies. Importantly, there is convincing evidence of increased susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response and comorbidities. Herein, we provide a comprehensive perspective regarding vulnerability of SARS-CoV-2 infection in patients with underlying medical comorbidities. We discuss ongoing vaccine (mRNA, protein-based, viral vector-based, etc.) and therapeutic (monoclonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail, the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.

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COVID-19: Unmasking Emerging SARS-CoV-2 Variants, Vaccines and Therapeutic Strategies

10.20944/preprints202106.0060.v1 ◽

2021 ◽

Author(s):

Renuka Raman ◽

Krishna J. Patel ◽

Kishu Ranjan

Keyword(s):

Immune Response ◽

Severe Acute Respiratory Syndrome ◽

Small Molecules ◽

Human Health ◽

Viral Vector ◽

Therapeutic Strategies ◽

Etiological Agent ◽

Plasma Therapy

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic which has been a topic of major concern to global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7, B.1.351, P1 and, B.1.617., which show in-creased transmissibility and resistance towards vaccines and therapies. Importantly, the likelihood of susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response or comorbidities needs greater attention. Herein, we provide a comprehensive perspective regarding ongoing vaccine (mRNA, protein-based, viral vector based etc.) and therapeutic (mono-clonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.

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Is Immune Response Relevant in Interstitial Lung Disease?

Current Immunology Reviews ◽

10.2174/1573395516999200914143054 ◽

2020 ◽

Vol 16 (1) ◽

pp. 18-27

Author(s):

Manzoor M. Khan

Keyword(s):

Immune Response ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Lung Fibrosis ◽

Lymphocytic Infiltration ◽

Therapeutic Strategies ◽

Mediators Of Inflammation ◽

Acquired Immune Responses ◽

Novel Therapeutic Strategies

Interstitial lung disease, a term for a group of disorders, causes lung fibrosis, is mostly refractory to treatments and has a high death rate. After diagnosis the survival is up to 3 years but in some cases the patients live much longer. It involves a heterogenous group of lung diseases that exhibit progressive and irreversible destruction of the lung due to the formation of scars. This results in lung malfunction, disruption of gas exchange, and eventual death because of respiratory failure. The etiology of lung fibrosis is mostly unknown with a few exceptions. The major characteristics of the disease are comprised of injury of epithelial type II cells, increased apoptosis, chronic inflammation, monocytic and lymphocytic infiltration, accumulation of myofibroblasts, and inability to repair damaged tissue properly. These events result in abnormal collagen deposition and scarring. The inflammation process is mild, and the disease is primarily fibrotic driven. Immunosuppressants do not treat the disease but the evidence is evolving that both innate and acquired immune responses a well as the cytokines contribute to at least early progression of the disease. Furthermore, mediators of inflammation including cytokines are involved throughout the process of lung fibrosis. The diverse clinical outcome of the disease is due to different pattern of inflammatory markers. Nonetheless, the development of novel therapeutic strategies requires better understanding of the role of the immune response. This review highlights the role of the immune response in interstitial lung disease and considers the therapeutic strategies based on these observations. For this review several literature data sources were used to assess the role of the immune response in interstitial lung disease and to evaluate the possible therapeutic strategies for the disease.

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COVID-19: a review of current knowledge regarding exposure, quarantine, isolation and other preventive measures

Therapeutic Advances in Infectious Disease ◽

10.1177/20499361211032039 ◽

2021 ◽

Vol 8 ◽

pp. 204993612110320

Author(s):

Robert Rosolanka ◽

Andres F. Henao-Martinez ◽

Larissa Pisney ◽

Carlos Franco-Paredes ◽

Martin Krsak

Keyword(s):

Immune Response ◽

Severe Acute Respiratory Syndrome ◽

Clinical Response ◽

Preventive Measures ◽

Current Knowledge ◽

Therapeutic Options ◽

Exposure Control ◽

Knowledge Gaps ◽

Vaccination Strategies ◽

Speed Up

Deeper understanding of the spread, morbidity, fatality, and development of immune response associated with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is necessary in order to establish an appropriate epidemiological and clinical response. Exposure control represents a key part of the combat against COVID-19, as the effectiveness of current therapeutic options remains partial. Since the preventive measures have not been sufficiently able to slow down this pandemic, in this article we explore some of the pertinent knowledge gaps, while overall looking to effective vaccination strategies as a way out. Early on, such strategies may need to rely on counting the convalescents as protected in order to speed up the immunization of the whole population.

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Immunological imprinting of the antibody response in COVID-19 patients

Nature Communications ◽

10.1038/s41467-021-23977-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Teresa Aydillo ◽

Alexander Rombauts ◽

Daniel Stadlbauer ◽

Sadaf Aslam ◽

Gabriela Abelenda-Alonso ◽

...

Keyword(s):

Immune Response ◽

Severe Acute Respiratory Syndrome ◽

Antibody Response ◽

Humoral Immune Response ◽

Nucleocapsid Protein ◽

Spike Protein ◽

Ongoing Research ◽

Variable Regions ◽

Humoral Immune ◽

Human Coronaviruses

AbstractIn addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.

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Two‐Year Prospective Study of the Humoral Immune Response of Patients with Severe Acute Respiratory Syndrome

The Journal of Infectious Diseases ◽

10.1086/500469 ◽

2006 ◽

Vol 193 (6) ◽

pp. 792-795 ◽

Cited By ~ 133

Author(s):

Wei Liu ◽

Arnaud Fontanet ◽

Pan‐He Zhang ◽

Lin Zhan ◽

Zhong‐Tao Xin ◽

...

Keyword(s):

Immune Response ◽

Severe Acute Respiratory Syndrome ◽

Prospective Study ◽

Humoral Immune Response ◽

Humoral Immune

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POS1229 ANTI-MDA5 AND ANTISYNTHETASE ANTIBODIES SCREENING IN SEVERE SARS-COV-2 PNEUMONIA. BE AWARE OF FALSE POSITIVE RESULTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3019 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 898.1-898

Author(s):

A. Gil-Vila ◽

J. Perurena-Prieto ◽

C. Nolla-Fontana ◽

O. Orozco-Galvez ◽

M. Miarons-Font ◽

...

Keyword(s):

Intensive Care Unit ◽

Immune Response ◽

Severe Acute Respiratory Syndrome ◽

Chest Ct ◽

Antisynthetase Syndrome ◽

Antisynthetase Antibodies ◽

Group A ◽

Group B ◽

Positive Results ◽

Glass Pattern

Background:Several reports have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may trigger a vigorous immune response that could lead to the appearance of various autoantibodies such as antinuclear antibodies, antiphospholipid antibodies or anti-neutrophil cytoplasmic antibodies, among others. Moreover, the pulmonary involvement in SARS-CoV-2 may resemble that of patients with anti-MDA5 positive syndrome or acute form of antisynthetase syndrome.Objectives:Our aim was to analyse the presence of anti-MDA5 and other myositis-specific autoantibodies such as the antisynthetase antibodies in patients diagnosed with severe acute respiratory syndrome caused by SARS-CoV-2.Methods:Retrospective observational study performed in a tertiary care center. We included 28 patients admitted to the intensive care unit with severe acute respiratory syndrome, 14 at the onset of the disease (group A) and 14 after 30 days of being treated in an intensive care unit (group B). Chest CT was performed at the admission. We analyzed the presence of anti-MDA5 and antisynthetase antibodies by immunoblot (Euroimmune®) and in those who were positive we performed a confirmatory test by immunoprecipitation.Results:All chest CT showed bilateral ground glass pattern. Three out of 14 patients of group A (12 males, 86%, mean ± SD age 67.1 ± 12.2) were positive for antisynthetase antibodies (2 anti-PL7, 1 anti-Jo1), and 6 out of 14 patients of the group B (6 males, 48%, mean ± SD age 68.7 ± 8.1) were positive to antisynthetase antibodies (2 anti-PL7, 2 anti-PL-12, 1 anti-EJ, 1 anti-OJ+PL7). Immunoblots also show positivity for other myositis-specific or associated antibodies, such as anti-TIF1g, anti-PM75, anti-SAE and anti-SRP. All of these results found by immunoblotting were negative by immunoprecipitation. None of the 28 patients were positive for anti-MDA5 antibodies.Conclusion:Severe SARS-CoV-2 pneumonia is characterized by ground glass pattern in chest CT, as it is found in anti-MDA5 or antisynthetase syndrome. The positivity of several myositis related autoantibodies showed in immunoblot appears to be more related to the vigorous immune response producing polyclonal immunoglobulins than triggering a real myositis-associated interstitial lung disease. Clinicians must be aware about these false positive results in patients with severe COVID-19 acute respiratory syndrome.References:[1]Xu Q. MDA5 should be detected in severe COVID-19 patients. Med Hypotheses. 2020; 143:109890.[2]Giannini M, Ohana M, Nespola B, Zanframundo G, Geny B, Meyer A. Similarities between COVID-19 and anti-MDA5 syndrome: what can we learn for better care? Eur Respir J. 2020; 56:2001618.[3]Vlachoyiannopoulos PG, Magira E, Alexopoulos H, Jahaj E, Theophilopoulou K, Kotanidou A, Tzioufas AG. Autoantibodies related to systemic autoimmune rheumatic diseases in severely ill patients with COVID-19. Ann Rheum Dis. 2020 Dec;79(12):1661-1663Disclosure of Interests:None declared

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Genetic polymorphisms mediating behavioural and immune response to pathogens may moderate the impact of the COVID-19 pandemic: a pilot study

10.1101/2020.06.03.20120998 ◽

2020 ◽

Author(s):

Ravi Philip Rajkumar

Keyword(s):

Immune Response ◽

Pilot Study ◽

Immune Responses ◽

Genetic Variants ◽

Mortality Rates ◽

Therapeutic Strategies ◽

Published Data ◽

Entire World ◽

S Allele ◽

The Impact

AbstractBackgroundThe COVID-19 pandemic has affected the entire world, but there are wide variations in prevalence and mortality across nations. Genetic variants which influence behavioural or immune responses to pathogens, selected for by pathogen pressure, may influence this variability. Two relevant polymorphisms in this context are the s allele of the serotonin transporter promoter (5-HTTLPR) and the G allele of the interleukin-6 gene (IL-6 rs1800795).MethodsThe frequencies of the 5-HTTLPR s allele and IL-6 rs1800795 G allele were obtained from published data. The correlations between these allele frequencies and the prevalence and mortality rates of COVID-19 were examined across 44 nations.ResultsThe IL-6 rs1800795 G allele was negatively correlated with COVID-19 prevalence (ρ = −0.466, p < 0.01) and mortality (ρ = −0.591, p<0.001) across nations. The 5-HTTLPR s allele was negatively correlated with COVID-19 mortality rates (ρ = −0.437, p = 0.023).ConclusionsThese results suggest that a significant relationship exists between genetic variants that influence behavioural and immune responses to pathogens and indices of the impact of COVID-19 across nations. Further investigation of these variants and their correlates may permit the development of better preventive or therapeutic strategies in the management of the COVID-19 pandemic.

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Integrative multi-omics landscape of non-structural protein 3 of severe acute respiratory syndrome coronaviruses

10.1101/2021.07.19.452910 ◽

2021 ◽

Author(s):

Ruona Shi ◽

Zhenhuan Feng ◽

Xiaofei Zhang

Keyword(s):

Mass Spectrometry ◽

Signal Transduction ◽

Immune Response ◽

Severe Acute Respiratory Syndrome ◽

Ribosomal Proteins ◽

Structural Protein ◽

Cellular Functions ◽

Cellular Effects ◽

Cellular Changes ◽

Global Pandemic

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently a global pandemic. Extensive investigations have been performed to study the clinical and cellular effects of SARS-CoV-2 infection. Mass spectrometry-based proteomics studies have revealed the cellular changes due to the infection and identified a plethora of interactors for all SARS-CoV-2 components, except for the longest non-structural protein 3 (NSP3). Here, we expressed the full-length NSP3 proteins of SARS-CoV and SARS-CoV-2 to investigate their unique and shared functions using multi-omics methods. We conducted interactome, phosphoproteome, ubiquitylome, transcriptome, and proteome analyses of NSP3-expressing cells. We found that NSP3 plays essential roles in cellular functions such as RNA metabolism and immune response such as NF-kB signal transduction. Interestingly, we showed that SARS-CoV-2 NSP3 has both endoplasmic reticulum and mitochondrial localizations. In addition, SARS-CoV-2 NSP3 is more closely related to mitochondrial ribosomal proteins, whereas SARS-CoV NSP3 is related to the cytosolic ribosomal proteins. In summary, our multi-omics studies of NSP3 enhance our understanding of the functions of NSP3 and offer valuable insights for the development of anti-SARS strategies.

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Non-Coding RNAs in COVID-19: Emerging Insights and Current Questions

Non-Coding RNA ◽

10.3390/ncrna7030054 ◽

2021 ◽

Vol 7 (3) ◽

pp. 54

Author(s):

Tobias Plowman ◽

Dimitris Lagos

Keyword(s):

Immune Response ◽

Severe Acute Respiratory Syndrome ◽

Immune Cell ◽

Cytokine Storm ◽

Cell Recruitment ◽

Vascular Dysregulation ◽

Virus Rna ◽

Growing Body ◽

Non Coding Rnas ◽

Immune Cell Recruitment

The highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as the causative agent of coronavirus disease 2019 (COVID-19) in late 2019, igniting an unprecedented pandemic. A mechanistic picture characterising the acute immunopathological disease in severe COVID-19 is developing. Non-coding RNAs (ncRNAs) constitute the transcribed but un-translated portion of the genome and, until recent decades, have been undiscovered or overlooked. A growing body of research continues to demonstrate their interconnected involvement in the immune response to SARS-CoV-2 and COVID-19 development by regulating several of its pathological hallmarks: cytokine storm syndrome, haemostatic alterations, immune cell recruitment, and vascular dysregulation. There is also keen interest in exploring the possibility of host–virus RNA–RNA and RNA–RBP interactions. Here, we discuss and evaluate evidence demonstrating the involvement of short and long ncRNAs in COVID-19 and use this information to propose hypotheses for future mechanistic and clinical studies.

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