SARS-Cov-2 Natural Infection in a Symptomatic Cat: Diagnostic, Clinical and Medical Management in a One Health Vision

Despite the reported increase in SARS-CoV-2-infected pets, the description of the clinical features from natural infection and the medical follow up in symptomatic pets is still not sufficiently documented. This study reports the case of an indoor cat that displayed respiratory signs and a gastrointestinal syndrome, following the COVID-19 diagnosis of his owners. Thoracic radiographies were suggestive of bronchial pneumonia, while blood tests were indicative of a mild inflammatory process. Nasal and oropharyngeal swabs tested positive through RT-qPCR assays targeting SARS-CoV-2 genes 14 days after his owners tested positive for the virus. Nasal swabs persisted to be RT-qPCR positive after 31 days. Serology confirmed the presence of antibodies through ELISA, electrochemiluminescence analysis and plaque reduction neutralization test, recording a high antibody titre after 31 days. The cat improved after medical treatment and clinically recovered. This study suggests that exposure to SARS-CoV-2 could lead to a natural infection with bronchial pneumonia in cats along with a possible prolonged persistence of SARS-CoV-2 RNA in the upper airways, albeit at a low level. The cat developed neutralizing antibodies, reaching a high titre after 31 days. Further descriptions of SARS-CoV-2 naturally infected pets, their medical management and diagnostic findings would be useful to enhance knowledge about COVID-19 in susceptible animals.

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A localized outbreak of dengue fever in Kuala Lumpur: serological aspects

Journal of Hygiene ◽

10.1017/s0022172400037116 ◽

1957 ◽

Vol 55 (2) ◽

pp. 207-223 ◽

Cited By ~ 6

Author(s):

C. E. Gordon Smith

Keyword(s):

Dengue Fever ◽

Neutralizing Antibodies ◽

Complement Fixation Test ◽

Complement Fixation ◽

Neutralization Test ◽

High Titre ◽

Inhibition Test ◽

Kuala Lumpur ◽

Clear Identification ◽

Serial Serum

1. Sera from an outbreak of about forty cases of dengue fever due to dengue-1 virus have been studied using the neutralization, haemagglutinin-inhibition, and complement-fixation tests.2. The neutralization test was the most specific and the complement-fixation test the least so.3. The neutralization test is essential for clear identification of the causal virus by serological means, and serial serum specimens from each patient must be examined.4. The haemagglutinin-inhibition test can be used to screen patients in outbreaks where some cases have been fully identified by neutralization tests.5. Homologous neutralizing antibodies persist in high titre for at least 30 weeks after infection, while heterologous antibodies have disappeared by that time.6. Both haemagglutinin-inhibiting and complement-fixing antibodies to homologous and heterologous viruses usually persist for at least 30 weeks, although the homologous titres tend to be highest.7. The implications of these findings in serological surveys are discussed.8. Some evidence suggesting the occurrence of inapparent infections during the epidemic is presented.I am greatly indebted to my staff for help with this work: especially to my senior technician, Che Ali bin Mohamed Amin, and to Che Mohamed bin Omar who drew the figures.

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Function is more reliable than quantity to follow up the humoral response to the Receptor Binding Domain of SARS- CoV-2 Spike Protein after Natural Infection or COVID-19 vaccination

10.1101/2021.06.02.21257975 ◽

2021 ◽

Author(s):

Carlos A Sariol ◽

Petraleigh Pantoja ◽

Crisanta Serrano-Collazo ◽

Tiffant Rosa-Arocho ◽

Albersy Armina ◽

...

Keyword(s):

Immune Response ◽

Neutralizing Antibodies ◽

Natural Infection ◽

Vaccine Dose ◽

Humoral Response ◽

Neutralizing Antibody ◽

Viral Neutralization ◽

Neutralizing Activity ◽

Robust Immune Response

On this work we report that despite of a decline in the total anti-Spike antibodies the neutralizing antibodies remains at a similar level for an average of 98 days in a longitudinal cohort of 59 Hispanic/Latino exposed to SARS-CoV-2. We are also reporting that the percentage of neutralization correlates with the IgG titers and that in the first collected samples, IgG1 was the predominant isotype (62.71%), followed by IgG4 (15.25%), IgG3 (13.56%), and IgG2 (8.47%) during the tested period. The IgA was detectable in 28.81% of subjects. Only 62.71% of all subjects have detectable IgM in the first sample despite of confirmed infection by a molecular method. Our data suggests that 100% that seroconvert make detectable neutralizing antibody responses measured by a surrogate viral neutralization test. We also found that the IgG titers and neutralizing activity were higher after the first dose in 10 vaccinated subjects out of the 59 with prior infection compare to a subgroup of 21 subjects naive to SARS-CoV-2. One dose was enough but two were necessary to reach the maximum percentage of neutralization in subjects with previous natural infection or naive to SARS-CoV-2 respectively. Like the pattern seen after the natural infection, after the second vaccine dose, the total anti-S antibodies and titers declined but not the neutralizing activity which remains at same levels for more than 80 days after the first vaccine dose. That decline, however, was significantly lower in pre-exposed individuals which denotes the contribution of the natural infection priming a more robust immune response to the vaccine. Also, our data indicates that the natural infection induces a more robust humoral immune response than the first vaccine dose in unexposed subjects. However, the difference was significant only when the neutralization was measured but not by assessing the total anti-S antibodies or the IgG titers. This work is an important contribution to understand the natural immune response to the novel coronavirus in a population severely hit by the virus. Also provide an invaluable data by comparing the dynamic of the immune response after the natural infection vs. the vaccination and suggesting that a functional test is a better marker than the presence or not of antibodies. On this context our results are also highly relevant to consider standardizing methods that in addition to serve as a tool to follow up the immune response to the vaccines may also provide a correlate of protection.

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Neutralizing Antibodies against SARS-CoV-2, Anti-Ad5 Antibodies, and Reactogenicity in Response to Ad5-nCoV (CanSino Biologics) Vaccine in Individuals with and without Prior SARS-CoV-2

Vaccines ◽

10.3390/vaccines9091047 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1047

Author(s):

Jorge Hernández-Bello ◽

José Javier Morales-Núñez ◽

Andrea Carolina Machado-Sulbarán ◽

Saúl Alberto Díaz-Pérez ◽

Paola Carolina Torres-Hernández ◽

...

Keyword(s):

Clinical Trials ◽

Adverse Effects ◽

Phase I ◽

Neutralizing Antibodies ◽

Booster Dose ◽

Neutralization Test ◽

Natural Infection ◽

Post Vaccination ◽

Factors Associated ◽

History Of

This is the first study outside of clinical trials (phase I–III) evaluating the ability of the Ad5-nCoV vaccine to generate neutralizing antibodies and the factors associated with optimal or suboptimal response. In a longitudinal assay, 346 people (117 with prior COVID-19 and 229 without prior COVID-19) vaccinated with Ad5-nCoV were recruited. The percentage of neutralizing antibodies against SARS-CoV-2 (Surrogate Virus Neutralization Test) and antibodies against Ad5 (ADV-Ad5 IgG ELISA) were quantified pre and post-vaccination effects. The Ad5-nCoV vaccine induces higher neutralizing antibodies percentage in individuals with prior COVID-19 than those without prior COVID-19 (median [IQR]: 98% [97–98.1] vs. 72% [54–90], respectively; p < 0.0001). Furthermore, a natural infection (before vaccination) induces more neutralizing antibodies percentage than immunized individuals without prior COVID-19 (p < 0.01). No patient had vaccine-severe adverse effects. The age, antidepressant, and immunosuppressive treatments, reactogenicity, and history of COVID-19 are associated with impaired antibody production. The anti-Ad5 antibodies increased after 21 days of post-vaccination in all groups (p < 0.01). We recommend the application of a booster dose of Ad5-nCoV, especially for those individuals without previous COVID-19 infection. Finally, the induction of anti-Ad5 antibodies after vaccination should be considered if a booster with the same vaccine is planned.

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Validation and clinical evaluation of a SARS-CoV-2 Surrogate Virus Neutralization Test (sVNT)

10.1101/2020.09.21.20191288 ◽

2020 ◽

Author(s):

Benjamin Meyer ◽

Johan Reimerink ◽

Giulia Torriani ◽

Fion Brouwer ◽

Gert-Jan Godeke ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Neutralization Test ◽

Natural Infection ◽

High Specificity ◽

Analytical Sensitivity ◽

Wild Type ◽

Clinical Sensitivity ◽

Neutralization Capacity ◽

Specificity And Sensitivity ◽

Independent Evaluation

To understand SARS-CoV-2 immunity after natural infection or vaccination, functional assays such as virus neutralizing assays are needed. So far, assays to determine SARS-CoV-2 neutralizing antibodies rely on cell-culture based infection assays either using wild type SARS-CoV-2 or pseudotyped viruses. Such assays are labour-intensive, require appropriate biosafety facilities and are difficult to standardize. Recently, a new surrogate virus neutralisation assay (sVNT) was described that uses the principle of an ELISA to measure the neutralization capacity of anti-SARS-CoV-2 antibodies directed against the receptor binding domain. Here, we performed an independent evaluation of the robustness, specificity and sensitivity on an extensive panel of sera from 269 PCR-confirmed COVID-19 cases and 259 unmatched samples collected before 2020 and compared it to cell-based neutralization assays. We found a high specificity of 99.2 (95%CI: 96.9-99.9) and overall sensitivity of 80.3 (95%CI: 74.9-84.8) for the sVNT. Clinical sensitivity increased between early (<14 days post symptom onset or post diagnosis, dpos/dpd) and late sera (>14 dpos/dpd) from 75.0 (64.7-83.2) to 83.1 (76.5-88.1). Also, higher severity was associated with an increase in clinical sensitivity. Upon comparison with cell-based neutralisation assays we determined an analytical sensitivity of 74.3 (56.4-86.9) and 98.2 (89.4-99.9) for titres ≥10 to <40 and ≥40 to <160, respectively. Only samples with a titre ≥160 were always positive in the sVNT. In conclusion, the sVNT can be used as an additional assay to determine the immune status of COVID-19 infected of vaccinated individuals but its value needs to be assessed for the specific context of use.

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Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies

10.1101/2021.02.12.430472 ◽

2021 ◽

Author(s):

Delphine Planas ◽

Timothée Bruel ◽

Ludivine Grzelak ◽

Florence Guivel-Benhassine ◽

Isabelle Staropoli ◽

...

Keyword(s):

South Africa ◽

Humoral Immunity ◽

Partial Resistance ◽

Neutralizing Antibodies ◽

Natural Infection ◽

Neutralization Assay ◽

Fold Reduction ◽

Nasal Swabs ◽

Reference Virus ◽

Antibody Levels

AbstractSARS-CoV-2 B.1.1.7 and B.1.351 variants emerged respectively in United Kingdom and South Africa and spread in many countries. Here, we isolated infectious B.1.1.7 and B.1.351 strains and examined their sensitivity to anti-SARS-CoV-2 antibodies present in sera and nasal swabs, in comparison with a D614G reference virus. We established a novel rapid neutralization assay, based on reporter cells that become GFP+ after overnight infection. B.1.1.7 was neutralized by 79/83 sera from convalescent patients collected up to 9 months post symptoms, almost similar to D614G. There was a mean 6-fold reduction in titers and even loss of activity against B.1.351 in 40% of convalescent sera after 9 months. Early sera from 19 vaccinated individuals were almost as potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Nasal swabs from vaccine recipients were not neutralizing, except in individuals who were diagnosed COVID-19+ before vaccination. Thus, faster-spreading variants acquired a partial resistance to humoral immunity generated by natural infection or vaccination, mostly visible in individuals with low antibody levels.

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Coronary artery aneurysms: outcomes following medical, percutaneous interventional and surgical management

Open Heart ◽

10.1136/openhrt-2020-001440 ◽

2021 ◽

Vol 8 (1) ◽

pp. e001440

Author(s):

Shameer Khubber ◽

Rajdeep Chana ◽

Chandramohan Meenakshisundaram ◽

Kamal Dhaliwal ◽

Mohomed Gad ◽

...

Keyword(s):

Coronary Artery ◽

Surgical Management ◽

Medical Management ◽

Cox Regression ◽

Artery Bypass ◽

Management Strategies ◽

Coronary Artery Aneurysms ◽

Kaplan Meier

BackgroundCoronary artery aneurysms (CAAs) are increasingly diagnosed on coronary angiography; however, controversies persist regarding their optimal management. In the present study, we analysed the long-term outcomes of patients with CAAs following three different management strategies.MethodsWe performed a retrospective review of patient records with documented CAA diagnosis between 2000 and 2005. Patients were divided into three groups: medical management versus percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG). We analysed the rate of major cardiovascular and cerebrovascular events (MACCEs) over a period of 10 years.ResultsWe identified 458 patients with CAAs (mean age 78±10.5 years, 74.5% men) who received medical therapy (N=230) or underwent PCI (N=52) or CABG (N=176). The incidence of CAAs was 0.7% of the total catheterisation reports. The left anterior descending was the most common coronary artery involved (38%). The median follow-up time was 62 months. The total number of MACCE during follow-up was 155 (33.8%); 91 (39.6%) in the medical management group vs 46 (26.1%) in the CABG group vs 18 (34.6%) in the PCI group (p=0.02). Kaplan-Meier survival analysis showed that CABG was associated with better MACCE-free survival (p log-rank=0.03) than medical management. These results were confirmed on univariate Cox regression, but not multivariate regression (OR 0.773 (0.526 to 1.136); p=0.19). Both Kaplan-Meier survival and regression analyses showed that dual antiplatelet therapy (DAPT) and anticoagulation were not associated with significant improvement in MACCE rates.ConclusionOur analysis showed similar long-term MACCE risks in patients with CAA undergoing medical, percutaneous and surgical management. Further, DAPT and anticoagulation were not associated with significant benefits in terms of MACCE rates. These results should be interpreted with caution considering the small size and potential for selection bias and should be confirmed in large, randomised trials.

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Severe Referred Shoulder Pain Following Revision Fundoplication From a Stich on the Diaphragm

The American Surgeon ◽

10.1177/00031348211011110 ◽

2021 ◽

pp. 000313482110111

Author(s):

Kevin J. Gale ◽

Santana Sanchez ◽

Thomas J. Sorenson ◽

Todd D. Elftmann

Keyword(s):

Hiatal Hernia ◽

Shoulder Pain ◽

Medical Management ◽

Nissen Fundoplication ◽

Left Shoulder ◽

Toupet Fundoplication

Complications following fundoplication surgery for hiatal hernias are rare. Herein, we present the case of a 61-year-old woman who underwent a Nissen fundoplication, complicated by dysphagia, and a revision modified Toupet fundoplication for a hiatal hernia, after which she began to experience severe prandial referred left shoulder pain that was refractory to medical management. We hypothesized that a diaphragmatic suture placed during the revision fundoplication could be the source of the pain, and we elected to remove the suture, resulting in resolution of the pain. This pain remained resolved at the most recent follow-up on postoperative week six, and the patient had no further concerns.

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Upper airways after mandibular advancement orthognathic surgery: A 4-year follow-up

American Journal of Orthodontics and Dentofacial Orthopedics ◽

10.1016/j.ajodo.2020.02.018 ◽

2021 ◽

Author(s):

Paula Kirzner Nogueira Pereira ◽

Vanessa Álvares de Castro Rocha ◽

Viviane Veroni Degan ◽

Daniela Gamba Garib ◽

Silvia A.S. Vedovello ◽

...

Keyword(s):

Orthognathic Surgery ◽

Mandibular Advancement ◽

Upper Airways

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Five Commercial Immunoassays for SARS-CoV-2 Antibody Determination and Their Comparison and Correlation with the Virus Neutralization Test

Diagnostics ◽

10.3390/diagnostics11040593 ◽

2021 ◽

Vol 11 (4) ◽

pp. 593

Author(s):

Václav Šimánek ◽

Ladislav Pecen ◽

Zuzana Krátká ◽

Tomáš Fürst ◽

Hana Řezáčková ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Neutralization Test ◽

Young Patients ◽

Virus Neutralization Test ◽

Virus Neutralization ◽

Age Dependent ◽

Previous Contact ◽

Dependent Elderly ◽

Protein Assays ◽

Antibody Determination

There is an ongoing debate as to whether SARS-CoV-2 antibodies can be found in patients who have recovered from COVID-19 disease. Currently, there is no consensus on whether the antibodies, if present, are protective. Our regular measurements of SARS-CoV-2 antibodies, starting in July 2020, have provided us with the opportunity of becoming acquainted with the five different immunoassays. A total of 149 patients were enrolled in our study. We measured the samples using each immunoassay, then performing a virus neutralization test and comparing the results of SARS-CoV-2 antibodies with this test. We observed that the production of neutralizing antibodies is age-dependent. Elderly patients have a higher proportion of high neutralizing titers than young patients. Based on our results, and in combination with the literature findings, we can conclude that the serological SARS-CoV-2 antibody measurement is a helpful tool in the fight against COVID-19. The assays can provide information about the patient’s previous contact with the virus. Anti-spike protein assays correlate well with the virus neutralization test and can be used in the screening of potential convalescent plasma donors.

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Endogenously Produced SARS-CoV-2 Specific IgG Antibodies May Have a Limited Impact on Clearing Nasal Shedding of Virus during Primary Infection in Humans

Viruses ◽

10.3390/v13030516 ◽

2021 ◽

Vol 13 (3) ◽

pp. 516

Author(s):

Shuyi Yang ◽

Keith R. Jerome ◽

Alexander L. Greninger ◽

Joshua T. Schiffer ◽

Ashish Goyal

Keyword(s):

Production Rate ◽

Neutralizing Antibodies ◽

Primary Infection ◽

Natural Infection ◽

Viral Clearance ◽

Clinical Severity ◽

Igg Antibodies ◽

Igm Antibodies ◽

Specific Igg ◽

Specific Igg Antibodies

While SARS-CoV-2 specific neutralizing antibodies have been developed for therapeutic purposes, the specific viral triggers that drive the generation of SARS-CoV-2 specific IgG and IgM antibodies remain only partially characterized. Moreover, it is unknown whether endogenously derived antibodies drive viral clearance that might result in mitigation of clinical severity during natural infection. We developed a series of non-linear mathematical models to investigate whether SARS-CoV-2 viral and antibody kinetics are coupled or governed by separate processes. Patients with severe disease had a higher production rate of IgG but not IgM antibodies. Maximal levels of both isotypes were governed by their production rate rather than different saturation levels between people. Our results suggest that an exponential surge in IgG levels occurs approximately 5–10 days after symptom onset with no requirement for continual antigenic stimulation. SARS-CoV-2 specific IgG antibodies appear to have limited to no effect on viral dynamics but may enhance viral clearance late during primary infection resulting from the binding effect of antibody to virus, rather than neutralization. In conclusion, SARS-CoV-2 specific IgG antibodies may play only a limited role in clearing infection from the nasal passages despite providing long-term immunity against infection following vaccination or prior infection.

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