Immune Profile and Clinical Outcome of Breakthrough Cases After Vaccination With an Inactivated SARS-CoV-2 Vaccine

Constant efforts to prevent infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are actively carried out around the world. Several vaccines are currently approved for emergency use in the population, while ongoing studies continue to provide information on their safety and effectiveness. CoronaVac is an inactivated SARS-CoV-2 vaccine with a good safety and immunogenicity profile as seen in phase 1, 2, and 3 clinical trials around the world, with an effectiveness of 65.9% for symptomatic cases. Although vaccination reduces the risk of disease, infections can still occur during or after completion of the vaccination schedule (breakthrough cases). This report describes the clinical and immunological profile of vaccine breakthrough cases reported in a clinical trial in progress in Chile that is evaluating the safety, immunogenicity, and efficacy of two vaccination schedules of CoronaVac (clinicaltrials.gov NCT04651790). Out of the 2,263 fully vaccinated subjects, at end of June 2021, 45 have reported symptomatic SARS-CoV-2 infection 14 or more days after the second dose (1.99% of fully vaccinated subjects). Of the 45 breakthrough cases, 96% developed mild disease; one case developed a moderate disease; and one developed a severe disease and required mechanical ventilation. Both cases that developed moderate and severe disease were adults over 60 years old and presented comorbidities. The immune response before and after SARS-CoV-2 infection was analyzed in nine vaccine breakthrough cases, revealing that six of them exhibited circulating anti-S1-RBD IgG antibodies with neutralizing capacities after immunization, which showed a significant increase 2 and 4 weeks after symptoms onset. Two cases exhibited low circulating anti-S1-RBD IgG and almost non-existing neutralizing capacity after either vaccination or infection, although they developed a mild disease. An increase in the number of interferon-γ-secreting T cells specific for SARS-CoV-2 was detected 2 weeks after the second dose in seven cases and after symptoms onset. In conclusion, breakthrough cases were mostly mild and did not necessarily correlate with a lack of vaccine-induced immunity, suggesting that other factors, to be defined in future studies, could lead to symptomatic infection after vaccination with CoronaVac.

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1329 Can One Size Fit All: Is Laparoscopic Roux-En-Y Gastric Bypass the Best Bariatric Procedure for Treating Type 2 Diabetes Mellitus (T2DM)?

British Journal of Surgery ◽

10.1093/bjs/znab259.194 ◽

2021 ◽

Vol 108 (Supplement_6) ◽

Author(s):

V Mahendran ◽

P Ricart ◽

S Robinson ◽

A Perry ◽

M Wadley

Keyword(s):

Bariatric Surgery ◽

Gastric Bypass ◽

Retrospective Cohort ◽

Severe Disease ◽

Morbidly Obese ◽

Disease Remission ◽

Mild Disease ◽

Moderate Disease ◽

Remission Rates

Abstract Introduction Bariatric surgery produces superior weight loss and reversal of comorbidities in morbidly obese individuals compared to medical therapy alone. Laparoscopic Roux-en-Y gastric bypass (LRYGB) was traditionally considered to prolonged remission of T2DM compared to other procedures such as Laparoscopic Sleeve-Gastrectomy (LSG). But recently published studies seek to disprove this by emphasising on duration and severity of T2DM before surgery rather than the type of procedure. We aim to verify if the severity of T2DM and type of operation (LRYGB Vs LSG) influence remission rates. Method In this retrospective cohort study, 204 patients were diagnosed with T2DM pre-operatively and had undergone either LRYGB or LSG. We used the Individualised Metabolic Surgery Score (IMSS) tool to divide patients into mild, moderate, and severe categories. Results Results showed that of the 204 patients 15% (n = 31) had mild disease, 62%( n = 127) had moderate disease and 23% (n = 46) had severe disease. Remission rates in each category were as follows: Conclusions We agree that patients with longstanding and severe T2DM have low remission rates after bariatric surgery, probably due to diminished beta-cell reserve. It is in contrary to recent publications which recommend LSG over LRYGB in patients with severe disease. This evidence necessitates further prospective studies before deciding which is the best procedure for patients with severe and longstanding T2DM.

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Some Clinical and Immunological Features of Imported COVID-19 Cases in Mongolia

10.1101/2021.03.17.21253849 ◽

2021 ◽

Author(s):

Tsogtsaikhan Sandag ◽

Enkhsaikhan Lkhagvasuren ◽

Munkhundrakh Batmunkh ◽

Oyungerel Ravjir

Keyword(s):

Immune Response ◽

Severe Disease ◽

Lower Percentage ◽

Enzyme Linked Immunosorbent Assay ◽

P Value ◽

Mild Disease ◽

Pulmonary Infiltrates ◽

Cytokines And Chemokines ◽

Moderate Disease ◽

Serum Crp

SARS-CoV-2 disturbs the normal immune responses causing an uncontrolled inflammatory response in patients with severe COVID-19. The pattern of the immune response to the SARS-CoV-2 in individuals may fluctuate. Some have a virus-dependent protective immune response resulting in asymptomatic or mild disease with elimination of the virus within 7-10 days after onset of infection. Others develop virus non-dependent uncontrolled hyper-inflammation in the later period, leading to severe disease with cytokine storm, acute respiratory distress syndrome, disseminated intravascular coagulation and multi-organ failure. Methods: The serum of 72 patients was investigated for titers of 15 cytokines and chemokines using Enzyme-linked immunosorbent assay (ELISA) kits in the serum of peripheral blood samples. The means of groups were compared using ANOVA followed by Tukey multiple post hoc comparisons if the ANOVA p-value was <0.05. Results: Patients with pulmonary infiltrates on CT demonstrated a lower percentage of eosinophils (1.38±1.46%) and elevated level of serum CRP (8.57±19.10 mg/dL) compared to patients without pulmonary infiltrates (2.52±1.47% and 1.96±3.02 mg/dL respectively; p<0.05). ROC analysis for patients aged ≥35 years showed patients with mild disease (n=3) had a significantly higher titer of IL-1α and MCP-1 (AUC, 0.958 and 0.917 respectively, p<0.05) compared to patients with moderate disease (n=7).

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Epidemic process of COVID-19 in the Russian Federation: interim results. 2nd report

Infekcionnye bolezni ◽

10.20953/1729-9225-2021-1-10-15 ◽

2021 ◽

pp. 10-15

Author(s):

N.Yu. Pshenichnaya ◽

◽

I.A. Lizinfeld ◽

G.Yu. Zhuravlev ◽

A.A. Ploskireva ◽

...

Keyword(s):

Russian Federation ◽

Severe Disease ◽

Age Groups ◽

Social Institutions ◽

Age Group ◽

Epidemic Process ◽

Mild Disease ◽

Household Contacts ◽

Moderate Disease ◽

The Russian Federation

Objective. To perform an interim analysis of epidemiological parameters of COVID-19 related to contacts and secondary cases of infection in the Russian Federation. Materials and methods. We analyzed 190,856 primary COVID-19 cases and 146,996 people who had been in contact with them. We used some data of monitoring performed by the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing in January–June 2020. We characterized the foci of infection and people who had contacts with primary COVID-19 cases and secondary cases of infection. Results. Just over half (50.02%) of study participants who had contacts with COVID-19 contacted with primary patients with mild disease, whereas 45.40% of individuals contacted with patients with moderate disease and 4.58% of individuals had contacts with patients with severe disease. Patients with mild COVID-19 interacted with more people, which resulted in a greater number of secondary cases of infection. The highest proportion of both primary COVID-19 patients and people who had contact with COVID-19 was observed in the age group of 41–64 years (44.42% and 44.51%, respectively). Approximately one third of COVID-19 patients and people who had contact with COVID-19 were 18 to 40 years old (30.20% and 34.21% respectively). The proportions of children aged 0–6 years and 7–17 years among COVID-19 patients were 2.70% and 4.02%, respectively; the same proportions among those who had contact with COVID-19 cases were 1.94 and 3.13%, respectively. Household contacts were the most common ways of COVID-19 transmission in all age groups. Patients aged between 40 and 64 years played the most significant role in the transmission of this infection in different foci. Individuals from this age group comprised 42.02% of patients infected in social institutions, 43.40% of those who had household contacts, and 47.70% of those infected at work. Conclusion. Patients with mild and moderate disease aged 18 to 64 years had the highest number of contacts and, therefore, caused the highest number of secondary cases of infection. Household contacts played the most important role in COVID-19 transmission in all age groups. Among people aged 18 to 64 years, COVID-19 transmission at work was also important. In all foci of infection, the majority of patients were in the age group of 40–64 years. Our findings can be used to optimize the preventive measures for COVID-19. Key words: epidemic process, age groups, severity, contacts, COVID-19, Russia, household contacts

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Ulcerative colitis

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0307 ◽

2020 ◽

pp. 2937-2950

Author(s):

Jeremy Sanderson ◽

Peter Irving

Keyword(s):

Ulcerative Colitis ◽

Severe Disease ◽

Stool Culture ◽

Volume Depletion ◽

Mild Disease ◽

Gradual Onset ◽

Moderate Disease ◽

Variable Extent ◽

Maintenance Of Remission ◽

Intravenous Steroids

Ulcerative colitis is a chronic relapsing and remitting disease in which chronic inflammation affects the rectum and extends proximally to a variable extent. The precise aetiology remains unknown but involves an interplay between reduced diversity in the gut microbiota and a genetically dysregulated gut immune system and epithelial barrier. Typical presentation of mild or moderate disease is with a gradual onset of symptoms including diarrhoea, rectal bleeding, and the passage of mucus. Severe disease is characterized by anorexia, nausea, weight loss, and severe diarrhoea, with the patient likely to look unwell with fever, tachycardia, and other signs of volume depletion, and the abdomen may be distended and tympanitic, with reduced bowel sounds and marked colonic tenderness. Diagnosis is usually made on the basis of exclusion of infective colitis by stool culture and the finding of typical diffuse inflammation in the rectum and above at sigmoidoscopy. Management requires rapid control of symptoms with induction therapy followed by maintenance of remission. Mild disease is typically treated with 5-aminosalicyclic acid delivered both orally and by enema, and moderate disease by 5-aminosalicyclic acid and steroids. Patients with severe disease require hospital admission, intravenous steroids, and daily review by both a physician and a surgeon experienced in the management of ulcerative colitis. Ciclosporin or infliximab are used as rescue therapies for steroid-resistant acute severe ulcerative colitis, but colectomy should not be delayed when this is required. Maintenance therapy with immunomodulators and biological therapies are both effective at maintaining remission, and several new biologicals are in clinical trials.

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Avian influenza: our current understanding

Animal Health Research Reviews ◽

10.1017/s1466252310000095 ◽

2010 ◽

Vol 11 (1) ◽

pp. 19-33 ◽

Cited By ~ 36

Author(s):

David L. Suarez

Keyword(s):

Avian Influenza ◽

Severe Disease ◽

Case Fatality ◽

Broad Host Range ◽

Highly Pathogenic ◽

Mild Disease ◽

Mucosal Surfaces ◽

The World ◽

Major Exception ◽

Asian Lineage

AbstractAvian influenza (AI) virus is one of the most important diseases of the poultry industry around the world. The virus has a broad host range in birds and mammals, although the natural reservoir is wild birds where it typically causes an asymptomatic to mild infection. The virus in poultry can cause a range of clinical diseases and is defined either as low pathogenic AI (LPAI) or highly pathogenic AI (HPAI) depending on the type of disease it causes in chickens. Viruses that replicate primarily on mucosal surfaces and cause mild disease with low mortality are termed LPAI. Viruses that replicate on mucosal surfaces and systemically and cause severe disease with a mortality rate of 75% or greater in experimentally infected chickens are referred to as HPAI. A virus that is highly pathogenic in chickens may infect but result in a completely different disease and replication pattern in other host species. Outbreaks of HPAI have been relatively uncommon around the world in the last 50 years and have had limited spread within a country or region with one major exception, Asian lineage H5N1 that was first identified in 1996. This lineage of virus has spread to over 60 countries and has become endemic in poultry in at least four countries. AI virus also represents a public health threat, with some infected humans having severe disease and with a high case fatality rate. AI remains a difficult disease to control because of the highly infectious nature of the virus and the interface of domestic and wild animals. A better understanding of the disease and its transmission is important for control.

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COVID-19 Severity and Neonatal BCG Vaccination among Young Population in Taiwan

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18084303 ◽

2021 ◽

Vol 18 (8) ◽

pp. 4303

Author(s):

Wei-Ju Su ◽

Chia-Hsuin Chang ◽

Jiun-Ling Wang ◽

Shu-Fong Chen ◽

Chin-Hui Yang

Keyword(s):

Severe Disease ◽

Clinical Syndrome ◽

Vaccination Status ◽

World Health ◽

Age Group ◽

Young Population ◽

Individual Patient Level ◽

Bcg Vaccination ◽

Mild Disease ◽

Moderate Disease

Background: Data have not been reported to explore the relation between COVID-19 severity and BCG vaccination status at the individual patient level. Methods: Taiwan has a nationwide neonatal BCG vaccination program that was launched in 1965. The Taiwan Centers for Disease Control established a web-based National Immunization Information System (NISS) in 2003 and included all citizens’ BCG vaccination records in NISS for those born after 1985. We identified COVID-19 Taiwanese patients born after 1985 between 21 January and 19 March 2021. Study participants were further classified into ages 4–24 years (birth year 1996–2016) and 25–33 years (birth year 1986–1995). We described their clinical syndrome defined by the World Health Organization and examined the relation between the COVID-19 severity and BCG vaccination status. Results: In the 4–24 age group, among 138 BCG vaccinated individuals, 80.4% were asymptomatic or had mild disease, while 17.4% had moderate disease, 1.5% had severe disease, and 0.7% had acute respiratory distress syndrome but none of them died. In contrast, all 6 BCG unvaccinated individuals in this age group experienced mild illness. In the 25–33 age group, moderate disease occurred in 14.2% and severe disease occurred in 0.9% of the 106 patients without neonatal BCG vaccination records, as compared to 19.2% had moderate disease and none had severe or critical disease of the 78 patients with neonatal BCG vaccination records. Conclusions: Our finding indicated that BCG immunization might not relate to COVID-19 severity in the young population.

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Serum β2-microglobulin levels in Coronavirus disease 2019 (Covid-19): Another prognosticator of disease severity?

PLoS ONE ◽

10.1371/journal.pone.0247758 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0247758

Author(s):

Walter Conca ◽

Mayyadah Alabdely ◽

Faisal Albaiz ◽

Michael Warren Foster ◽

Maha Alamri ◽

...

Keyword(s):

Disease Severity ◽

Viral Infections ◽

Linear Trend ◽

Severe Disease ◽

Tertiary Care ◽

Care Hospital ◽

Mhc I ◽

Mild Disease ◽

Moderate Disease ◽

Single Center Study

β2-microglobulin (β2-m), a 11.8 kDa protein, pairs non-covalently with the α3 domain of the major histocompatibility class (MHC) I α-chain and is essential for the conformation of the MHC class I protein complex. Shed β2-m is measurable in circulation, and various disorders are accompanied by increases in β2-m levels, including several viral infections. Therefore, we explored whether β2-m levels could also be elevated in Coronavirus disease 2019 (Covid-19) and whether they predict disease severity. Serum β2-m levels were measured in a cohort of 34 patients infected with SARS-CoV-2 on admission to a tertiary care hospital in Riyadh, Saudi Arabia, as well as in an approximately age-sex matched group of 34 uninfected controls. Mean β2-m level was 3.25±1.68 mg/l (reference range 0.8–2.2 mg/l) in patients (mean age 48.2±21.6) and 1.98±0.61 mg/l in controls (mean age 48.2±21.6). 17 patients (mean age 36.9± 18.0) with mean β2-m levels of 2.27±0.64 mg/l had mild disease by WHO severity categorization, 12 patients (mean age 53.3±18.1) with mean β2-m levels of 3.57±1.39 mg/l had moderate disease, and five patients (of whom 2 died; mean age 74.4±13.8) with mean β2-m levels of 5.85±1.85 mg/l had severe disease (P < = 0.001, by ANOVA test for linear trend). In multivariate ordinal regression β2-m levels were the only significant predictor of disease severity. Our findings suggest that higher β2-m levels could be an early indicator of severity of disease and predict outcome of Covid-19. As the main limitations of the study are a single-center study, sample size and ethnicity, these results need confirmation in larger cohorts outside the Arabian Peninsula in order to delineate the value of β2-m measurements. The role of β2-m in the etiology and pathogenesis of severe Covid-19 remains to be elucidated.

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Low Sensitivity of Admission Lung US Compared to Chest CT for Diagnosis of Lung Involvement in a Cohort of 82 Patients with COVID-19 Pneumonia

Medicina ◽

10.3390/medicina57030236 ◽

2021 ◽

Vol 57 (3) ◽

pp. 236

Author(s):

Carla Maria Irene Quarato ◽

Antonio Mirijello ◽

Donato Lacedonia ◽

Raffaele Russo ◽

Michele Maria Maggi ◽

...

Keyword(s):

Severe Disease ◽

Chest Ct ◽

Nasopharyngeal Swab ◽

Lung Involvement ◽

Reference Standard ◽

Mild Disease ◽

Imaging Tool ◽

Moderate Disease ◽

Low Sensitivity

Background and Objectives: The potential role of lung ultrasound (LUS) in characterizing lung involvement in Coronavirus disease 2019 (COVID-19) is still debated. The aim of the study was to estimate sensitivity of admission LUS for the detection of SARS-CoV-2 lung involvement using Chest-CT (Computed Tomography) as reference standard in order to assess LUS usefulness in ruling out COVID-19 pneumonia in the Emergency Department (ED). Methods: Eighty-two patients with confirmed COVID-19 and signs of lung involvement on Chest-CT were consecutively admitted to our hospital and recruited in the study. Chest-CT and LUS examination were concurrently performed within the first 6–12h from admission. Sensitivity of LUS was calculated using CT findings as a reference standard. Results: Global LUS sensitivity in detecting COVID-19 pulmonary lesions was 52%. LUS sensitivity ranged from 8% in case of focal and sporadic ground-glass opacities (mild disease), to 52% for a crazy-paving pattern (moderate disease) and up to 100% in case of extensive subpleural consolidations (severe disease), although LUS was not always able to detect all the consolidations assessed at Chest-CT. LUS sensitivity was higher in detecting a typical Chest-CT pattern (60%) and abnormalities showing a middle-lower zone predominance (79%). Conclusions: As admission LUS may result falsely negative in most cases, it should not be considered as a reliable imaging tool in ruling out COVID-19 pneumonia in patients presenting in ED. It may at least represent an expanded clinical evaluation that needs integration with other diagnostic tests (e.g., nasopharyngeal swab, Chest-CT).

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Hepatic lesions associated with iron accumulation in captive kori bustards (Ardeotis kori)

Veterinary Pathology ◽

10.1177/03009858211035386 ◽

2021 ◽

pp. 030098582110353

Author(s):

Sarah K. Cudd ◽

Michael M. Garner ◽

Andrew N. Cartoceti ◽

Elise E. B. LaDouceur

Keyword(s):

Severe Disease ◽

Iron Accumulation ◽

Iron Storage ◽

Mild Disease ◽

Tissue Sections ◽

Moderate Disease ◽

Hematoxylin And Eosin ◽

Hepatic Lesions ◽

Age Range ◽

Ardeotis Kori

There are anecdotal reports of iron storage disease in captive kori bustards ( Ardeotis kori), but detailed descriptions of this disease have not been reported. The goals of this retrospective, multi-institutional study were to (1) describe microscopic findings associated with iron accumulation in postmortem tissues of kori bustards and (2) use an adapted grading scale to score iron accumulation and associated hepatic lesions. Tissue sections from 19 adult captive kori bustards (age range 3–28 years; 12 males and 7 females) were evaluated histologically with hematoxylin and eosin, Masson’s trichrome, and Prussian blue stains, and scored for iron accumulation. Hemochromatosis was diagnosed in cases with iron storage (in hepatocytes and/or Kupffer cells) and concurrent parenchymal damage (defined as having both necrosis and fibrosis). Hemosiderosis was diagnosed in animals with evidence of iron storage without necrosis or fibrosis. Ten of the 19 cases (age range 8–27 years; 7 males and 3 females) were diagnosed with hemochromatosis, including 6 with mild disease, 3 with moderate disease, and 1 with severe disease. Histologic evidence of iron accumulation was also identified in kidney, intestinal tract, adrenal gland, and spleen, but there were no associations between severity of iron accumulation in the liver and accumulation in other organs.

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Definition of fibromyalgia severity: findings from a cross-sectional survey of 2339 Italian patients

Rheumatology ◽

10.1093/rheumatology/keaa355 ◽

2020 ◽

Cited By ~ 1

Author(s):

Fausto Salaffi ◽

Marco Di Carlo ◽

Laura Bazzichi ◽

Fabiola Atzeni ◽

Marcello Govoni ◽

...

Keyword(s):

Disease Severity ◽

Severe Disease ◽

Fibromyalgia Impact Questionnaire ◽

Cross Sectional Survey ◽

External Criterion ◽

Cross Sectional ◽

Mild Disease ◽

Moderate Disease ◽

Definition Of ◽

Distress Scale

Abstract Objective To establish optimal cut-off values for the scores of the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromialgia Assessment Scale (FAS 2019mod), and the Polysymptomatic Distress Scale (PDS) in order to distinguish five levels of FM disease severity. Methods Consecutive FM patients were evaluated with the three clinimetric indices, and each patient was required to answer the anchor question: ‘In general, would you say your health is 1 = very good, 2 = good, 3 = fair, 4 = poor, or 5 = very poor?’—which represented the external criterion. Cut-off points were established through the interquartile reconciliation approach. Results The study sample consisted of 2181 women (93.2%) and 158 men (6.8%), with a mean age of 51.9 (11.5) years, and mean disease duration was 7.3 (6.9) years. The overall median FIQR, FAS 2019 mod and PDS scores (25th–75th percentiles) were respectively 61.16 (41.16–77.00), 27.00 (19.00–32.00) and 19.0 (13.00–24.00). Reconciliation of the mean 75th and 25th percentiles of adjacent categories defined the severity states for FIQR: 0–23 for remission, 24–40 for mild disease, 41–63 for moderate disease, 64–82 for severe disease and >83 for very severe disease; FAS 2019 mod: 0–12 for remission, 13–20 for mild disease, 21–28 for moderate disease, 29–33 for severe disease and >33 for very severe disease; PDS: 0–5 for remission, 6–15 for mild disease, 16–20 for moderate disease, 21–25 for severe disease and >25 for very severe disease. Conclusions Disease severity cut-offs can represent an important improvement in interpreting FM.

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