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Background: The novel coronavirus SARS-CoV- 2 has caused far-reaching consequences world-wide. Lack of immunity in human, severe airway disease based on a high virulence and its airborne transmission pointed to a significant role of the airways. To investigate immune responses and antibody seroconversion in nasal lining fluid and in serum we examined a cohort of health professionals at the university hospital Klinikum rechts der Isar in Munich. By long-term follow-up of infected and non-infected participants, we were able to investigate the development of local and systemic immunity against SARS-CoV- 2. Method(s): To learn about nasal antibody production we reached out for hospital staff with estimated high risk of a possible Covid19 infection due to their working conditions and staff members suffering from symptoms like fever, cough, loss of smell and taste or sore throat. To detect current infections, we performed SARS-CoV- 2 PCR testing at visit one (V1) and asked our participants to rate possible Covid19 symptoms by filling a questionnaire before every sampling. We eventually included participants, who had been tested positive for SARS-CoV- 2 before (n = 22), as well as people without detected infection, including high-risk contact persons of Covid19 patients and individuals with no Covid-19 infection so far (n = 85). The cohort included 107 hospital staff members, who were sampled six times overall between March and September 2020. Each of the six visits V1 -V6 contained the sampling of serum and nasal fluid to measure IgG, IgM, and IgA rates using immunoassay technique. Result(s): We were able to show the increase of IgA and IgG in the nasal mucosa after recent Covid19 infection. In infected individuals the levels of SARS-CoV- 2 specific nasal IgA increased until V2 with a mean of 4,81 +/- 1,92 mug/l compared to a mean of 0,13 mug/l in non-infected participants, followed by a plateau until V4 and decreased again until V6. Nasal IgG showed a similar trend, apart from a steeper decline after reaching a peak on V2 with a mean of 7,39 +/- 1,63 mug/l, which correlated to the antibody responses in serum. Non-infected individuals showed a mean level of 0,03 mug/l nasal IgG on V2. Serum IgA declined from V1 onwards and hereby showed a quicker drop of systemic antibody levels compared to the nasal lining fluid. Nasal antibody rates reached peaks of 40,00 mug/l (nasal IgA) and 25,74 mug/l (nasal IgG). However, these counts will need further confirmation by a vaccinated control group. Conclusion(s): Nasal measurement of SARS-CoV- 2 specific antibodies provides deeper understanding of mucosal processes while facing inflammation, which may pave the way to less invasive diagnostic possibilities in the future. Furthermore, nasal antibodies built-up after an infection with Covid19 may be protective features concerning a possible re-infection with the virus.
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Introduction : Functional follow-up of patients after Covid-19 pneumonia is essential, not only to adapt patient care but also to better understand the medium and long-term consequences of the virus on respiratory function. Among the respiratory function tests, DLCO allows to evaluate the sequelae on the quality of gas exchanges. Methods : The DLCO was measured as part of a respiratory function assessment, 3 months after recovery from Covid-19 pneumonia in a group of 469 patients. Result(s): Study population was composed of 262 males and 207 females. Mean age and body mass index (BMI) were respectively 59.45+/-12.85 years-old and 31.24+/-5.83 kg/m2. Smoking was reported in 32.9% of cases. Hospitalization was needed on 92.3%, oxygen supply in 91.8% and respiratory aid in 11.1% of cases. Mean DLCO was 74.24%+/-17.7 and was abnormal in 43% of cases whereas restriction and obstruction were found respectively in 14.8% and 4.9% of spirometry. DLCO was correlated with age (r=0.236;p<10-3), BMI (r=-0.097;p=0.036), dyspnea severity according to the mMRC score (r=-0.318;p<10-3), duration of hospitalization (r=-0.13;p=0.008), respiratory aid (r=-0.159;p=0.01), duration of oxygen need (-0.364;p<10-3), extension of pneumonia on the CT scan (r=-0.245;p<10-3), FVC (r=0.521;p<10-3), FEV1 (r=0.479;p<10-3) and TLC (r=0.290;p<10-3). Conclusions : DLCO seems to be one of the first functional parameters to be altered after Covid-19 pneumonia, which justifies its regular measurement in patient follow-up.
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Introduction: After Covid-19 pneumonia, regular respiratory function assessment is necessary for the subsequent management of patients, including resting respiratory function tests and assessment of submaximal exercise tolerance by six-minute walk (6MW) test. Method(s): Six-minute walk test was undergone for 326 patients about 3 months after Covid-19 pneumonia. Physiological cost of walking (PCW) defined as the difference between maximum heart rate reached at the 6MWT and resting heart rate divided by walking speed was calculated. Result(s): Median age and BMI were respectively 61 [18-95] years-old and 30,4 [18,5-65,2] kg/m2 with a sex-ratio at 1.26. Smoking was reported in 52.8% of cases (12,45 PY). Median 6MW distance was 528 meters [48-832], corresponding of 80% [7-113] of theoric. Median PCW was 0,379 beats/meter [-1.38-5.38]. Low 6MW distance and low saturation during the test were found respectively in 33.1% and 15.2% of cases and were both correlated with DLCO (r=-0.258;p<10-3 and r=-0.423;p<10-3). Chronotropic insufficiency and chronotropic intolerance were found in 13.8% and 7% of cases. PCW was correlated with BMI (r=0.463;p<10-3), FEV1 (r=-0.175;p=0.001), FVC (r=-0.167;p=0.002) and DLCO (r=-0.161;p=0.004). Conclusion(s): Six-minute walk test is an inexpensive, easy and reliable tool that tells us about the global response to submaximal exercise, especially after Covid-19 pneumonia. It is an interesting alternative for patients follow-up, especially when rehabilitation is considered.
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Declaration de liens d'interets: Les auteurs declarent ne pas avoir de liens d'interets. Copyright © 2022
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Introduction La pneumonie à Sars-CoV-2 est pourvoyeuse de séquelles respiratoires avec un retentissement fonctionnel respiratoire. L’objectif de notre étude est d’évaluer le retentissement fonctionnel respiratoire à 3 mois post pneumonie à Sars CoV-2. Méthodes Étude rétrospective longitudinale incluant 70 patients ayant présentaient une pneumonie à SARS CoV-2 confirmée par une RT-PCR et qui ont consulté à 3 mois (M3) post hospitalisation pour l’épisode aiguë. Ces patients ont été recrutés au sein de la consultation de suivi post Covid, au service de pneumologie D de l’hôpital Abderrahmen Mami de l’Ariana, durant une période allant de janvier 2020 à août 2021. Résultats L’âge moyen des patients était de 60,83 ans (28–85 ans) avec une prédominance masculine (58,6 %). Les comorbidités étaient dominées par l’hypertension artérielle (52,9 %) et le diabète (38,6 %). L’obésité a été notée chez 38,6 % des patients avec un IMC moyen à 30,43kg/m2 [20,99–63,4kg/m2]. La dyspnée d’effort à M3 était notée dans 34,28 % des patients. Les valeurs moyennes des paramètres fonctionnels aux explorations fonctionnelles respiratoires (EFR) à M3 étaient respectivement: CVF à 90,94 % (58 %–121,7 %), VEMS à 92,84 % (45 %–125 %), CPT à 88,4 % (64 %–118 %) et DLCO à 76,23 % (35 %–118 %) de la valeur prédite. L’EFR était normale dans 38,6 % des cas. Elle a montré un trouble ventilatoire restrictif chez (5,7 %), un ventilatoire obstructif (2,9 %) et un trouble de la diffusion (44,3 %). Le TM6 a montré une réduction du PM dans 27,1 % des cas. Les patients avec une atteinte sévère (au moins 50 %) au scanner initial avaient une valeur de VEMS moyen plus basses (87,4 versus 97,7 % de la valeur prédite;p=0,01). Cependant les valeurs de la CVF (p=0,2), CPT (p=0,2) et de la DLCO (p=0,16) étaient similaires quel que soit la sévérité de l’atteinte initiale. Conclusion La baisse de la DLCO constitue l’anomalie fonctionnelle la plus fréquente. Les anomalies fonctionnelles respiratoires persistantes à 3 mois d’une infection à SARS-CoV-2 justifient un suivi large et à long terme.
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Background: Monocytes and macrophages drive the inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) and they are a major source of eicosanoids in airway inflammation. Method: We used RNA sequencing and LC-MS/ MS analysis to determine transcriptional and lipid mediator profiles of monocyte-derived macrophages from convalescent COVID-19 patients 3-5 months post-SARS- CoV- 2 infection. Results: We found that monocyte-derived macrophages (MDM) from SARS-CoV- 2- infected individuals with mild disease show an inflammatory transcriptional and metabolic imprint several (3-5) months after SARS-CoV- 2 infection. MDM from convalescent SARS-CoV- 2- infected individuals showed higher expression of fatty acid-metabolic enzymes and increased production of pro-inflammatory eicosanoids, particularly neutrophil chemotactic leukotriene B4 (LTB4) and LTD4 a driver of airway remodeling. MDM from previously SARS-CoV- 2- infected subjects showed an exaggerated induction of inflammatory chemokines as well as T-cell suppressive enzymes and receptors following stimulation with spike protein or LPS. Corticosteroids reduced inflammatory cytokine-, but increased leukotriene production in macrophages. Conclusion: Thus, SARS-CoV- 2 infection leaves an inflammatory imprint in the monocyte/macrophage compartment that drives aberrant effector functions and eicosanoid metabolism, possibly explaining long-term effects in patients recovering from mild COVID-19.
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Background: Severe acute respiratory coronavirus 2 (SARS-CoV-2) is the infectious agent of the current COVID-19 pandemic and is responsible for more than 2 million deaths worldwide. The virus utilizes the surface receptor angiotensin-converting enzyme 2 (ACE2) to infiltrate its target cells. It has been postulated that ACE2 is a human interferon-stimulated gene (ISG) and is upregulated by interferon (IFN) and virus stimulation. However, previous studies showed that not ACE2, moreover a novel short isoform of the enzyme is mainly expressed after IFN stimulation. Method: In this study, we aimed to investigate the impact of IFN stimulation on ACE2 expression in human bronchial epithelial cells. We measured the expression levels of two ACE2 isoforms, namely the full-length isoform and the IFN-induced truncated isoform proposed by Onabajo et al. (truncACE2) at the transcription and protein level following stimulation of Calu-3 and primary human bronchial epithelial cells (NHBE) with type-I,-II and-III IFNs. Specific primers along the ACE2 coding sequence were used for quantitative and semi-quantitative analysis of the transcript isoforms. Induced ACE2 protein isoforms were additionally analyzed using immunoblotting. Results: In both, the Calu3 cell line and the NHBE, truncACE2 was dose-dependently upregulated at the transcription level after 6h of IFNγ stimulation, whereas the full-length transcript levels did not change. IFNs of type-I and type-III stimulation induced a dosedependent upregulation of both ACE2 versions at the mRNA level, although the truncACE2 showed a higher expression level. In the immunoblotting analysis, neither the full-length nor the truncated ACE2 version showed a difference after IFNγ stimulation of NHBE. Conclusion: This study is in line with previous findings that only a truncated ACE2 isoform acts as an ISG. However, our data additionally show that not only type-II, but also type-I and type-III interferons induce this truncated version of ACE2. This is especially important, as type-I and type-III IFNs are secreted during the initial epithelial host response to the virus. It remains to be uncovered whether SARS-CoV-2 can utilize also truncACE2 to enter cells thereby using the initial host response to increase truncACE2 and facilitate viral spread.
Subject(s)
Environmental Medicine , Nasal Polyps , Nasal Surgical Procedures , Sinusitis , Humans , OmalizumabABSTRACT
Innovative and effective vaccination strategies are the most important lever to address the global SARS-COV2 pandemic. Within months scientists all over the world have developed promising new vaccines, many of which use adenoviral vectors to incorporate immunogenic molecules of SARS-coronavirus in order to elicit effective immune responses. The Gamaleya institute developed the COVID-19 vaccine named Sputnik (Gam-COVID-Vac) using adenoviral vectors ad 26 and ad5 to incorporate a full SARS-Spike Protein for vaccination. Two differing vectors enable so called prime-boost, thus avoiding neutralizing effects against the vector itself, ensuring proper immunogenicity against the vaccine. Current available published evidence has raised controversy among small sample sizes in phase II and early endpoints in phase III studies with Sputnik and scientific community took notice that full study protocols and clinical data haven't been made available yet. Patient subgroups and vaccination efficacy in healthy vaccinated may be at risk in case of partial viral replication of Ad5 vectors or when batch to batch reproducibility is not warranted, as concerns from authorities in Brazil and Slovakia have recently been raised. Final approval by governing health authorities (e.âg. EMA) should therefore be awaited.
Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , Humans , RNA, Viral , Reproducibility of Results , SARS-CoV-2 , VaccinationABSTRACT
Allergic reactions against mRNA COVID-19 vaccine are yet uncommon, but due to the high number of people who get this vaccination anaphylaxis will be seen. This is especially so in people who are sensitized to components of the vaccine. This article focuses on practical aspects of diagnostic possibilities, prevention, recognition and therapy of anaphylactic reactions. High-risk population, who should not get vaccinated; as well as people who need allergy diagnostics before vaccinations are discussed. In opinion of allergy experts patients with atopic allergies or venom allergies do not have a higher risk regarding anaphylaxic reaction due to COVID vaccination.
Subject(s)
Anaphylaxis , COVID-19 , Vaccines , Anaphylaxis/diagnosis , Anaphylaxis/etiology , Anaphylaxis/prevention & control , BNT162 Vaccine , COVID-19 Vaccines , Humans , RNA, Messenger , SARS-CoV-2 , VaccinationABSTRACT
With BNT162b2 (approved in the EC on 27th of December 2020) and mRNA-1273 (approved in the EC on 6th of January 2021) for the first time ever two RNA-vaccines received conditional approval within the EC in order to effectively combat the SARS-COV2 pandemic. The emergence of sporadic cases of anaphylaxis following vaccination with these new compounds and the identification of PEGs (polyethylenglycols) as potential, widely used but yet usually unknown culprits have led to uncertainty among treating physicians and patients. The aim of this article series is to summarize current available pathophysiological and clinical information (part 1), to describe the characteristics of the vaccines (part 2) and to provide practical solutions for diagnosis and treatment of potential allergy against mRNACovid19 vaccines.
Subject(s)
COVID-19 , Hypersensitivity , Vaccines , BNT162 Vaccine , COVID-19 Vaccines , Humans , RNA, Messenger , RNA, Viral , SARS-CoV-2 , VaccinationABSTRACT
Vaccinations are the gold-standard in order to prevent dangerous infectious diseases. Within 12 months since the RNA sequence of SARS-COV2 has been published already two RNA vaccines against COVID-19 have been licensed and are broadly used in many relevant parts of the world. Matching the challenge of an unprecedented global pandemic unique collaborative approaches have made available several vaccines based on a variety of technological platforms that are under current development. This article explains the characteristics, biology and pharmacology of subunit-vaccines, inactivated and attenuated vaccines, Virus-like-Particle vaccines, recombinant strategies based on adenoviral vectors and newly developed and first time in human licensed RNA-vaccines that came into scope recently. Allergic reactions against the vaccine and its components have been reported but are yet uncommon, however need good documentation such as other side-effects and immune-phenomena. In rare cases where allergy against vaccine components such as PEGs is considered, such PEGs can be tested using a skin-prick test. Development of innovative vaccine technology and antiviral medication is of strategic relevance in the best sense of "pandemic preparedness" for the future.