Paper-based electrochemical biosensor for diagnosing COVID-19: Detection of SARS-CoV-2 antibodies and antigen.

Here we report a case where the manifestations of insulin-dependent diabetes occurred following SARS-CoV-2 infection in a young individual in the absence of autoantibodies typical for type 1 diabetes mellitus. Specifically, a 19-year-old white male presented at our emergency department with diabetic ketoacidosis, C-peptide level of 0.62 µg l–1, blood glucose concentration of 30.6 mmol l–1 (552 mg dl–1) and haemoglobin A1c of 16.8%. The patient´s case history revealed probable COVID-19 infection 5–7 weeks before admission, based on a positive test for antibodies against SARS-CoV-2 proteins as determined by enzyme-linked immunosorbent assay. Interestingly, the patient carried a human leukocyte antigen genotype (HLA DR1-DR3-DQ2) considered to provide only a slightly elevated risk of developing autoimmune type 1 diabetes mellitus. However, as noted, no serum autoantibodies were observed against islet cells, glutamic acid decarboxylase, tyrosine phosphatase, insulin and zinc-transporter 8. Although our report cannot fully establish causality between COVID-19 and the development of diabetes in this patient, considering that SARS-CoV-2 entry receptors, including angiotensin-converting enzyme 2, are expressed on pancreatic β-cells and, given the circumstances of this case, we suggest that SARS-CoV-2 infection, or COVID-19, might negatively affect pancreatic function, perhaps through direct cytolytic effects of the virus on β-cells. The authors report the case of a young patient who displayed insulin-dependent diabetes after SARS-CoV-2 infection in the absence of autoantibodies indicative of autoimmune type 1 diabetes.

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Autoantibody-negative insulin-dependent diabetes mellitus after SARS-CoV-2 infection: a case report.

Antibody titers against SARS-CoV-2 decline, but do not disappear for several months

Diagnostic testing plays a critical role in addressing the coronavirus disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Rapid and accurate diagnostic tests are imperative for identifying and managing infected individuals, contact tracing, epidemiologic characterization, and public health decision making. Laboratory testing may be performed based on symptomatic presentation or for screening of asymptomatic people. Confirmation of SARS-CoV-2 infection is typically by nucleic acid amplification tests (NAAT), which requires specialized equipment and training and may be particularly challenging in resource-limited settings. NAAT may give false-negative results due to timing of sample collection relative to infection, improper sampling of respiratory specimens, inadequate preservation of samples, and technical limitations; false-positives may occur due to technical errors, particularly contamination during the manual real-time polymerase chain reaction (RT-PCR) process. Thus, clinical presentation, contact history and contemporary phyloepidemiology must be considered when interpreting results. Several sample-to-answer platforms, including high-throughput systems and Point of Care (PoC) assays, have been developed to increase testing capacity and decrease technical errors. Alternatives to RT-PCR assay, such as other RNA detection methods and antigen tests may be appropriate for certain situations, such as resource-limited settings. While sequencing is important to monitor on-going evolution of the SARS-CoV-2 genome, antibody assays are useful for epidemiologic purposes. The ever-expanding assortment of tests, with varying clinical utility, performance requirements, and limitations, merits comparative evaluation. We herein provide a comprehensive review of currently available COVID-19 diagnostics, exploring their pros and cons as well as appropriate indications. Strategies to further optimize safety, speed, and ease of SARS-CoV-2 testing without compromising accuracy are suggested. Access to scalable diagnostic tools and continued technologic advances, including machine learning and smartphone integration, will facilitate control of the current pandemic as well as preparedness for the next one.

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Review of Current COVID-19 Diagnostics and Opportunities for Further Development

COVID-19 (SARS-CoV-2) disease severity and stages varies from asymptomatic, mild flu-like symptoms, moderate, severe, critical, and chronic disease. COVID-19 disease progression include lymphopenia, elevated proinflammatory cytokines and chemokines, accumulation of macrophages and neutrophils in lungs, immune dysregulation, cytokine storms, acute respiratory distress syndrome (ARDS), etc. Development of vaccines to severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome coronavirus (MERS-CoV), and other coronavirus has been difficult to create due to vaccine induced enhanced disease responses in animal models. Multiple betacoronaviruses including SARS-CoV-2 and SARS-CoV-1 expand cellular tropism by infecting some phagocytic cells (immature macrophages and dendritic cells) via antibody bound Fc receptor uptake of virus. Antibody-dependent enhancement (ADE) may be involved in the clinical observation of increased severity of symptoms associated with early high levels of SARS-CoV-2 antibodies in patients. Infants with multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 may also have ADE caused by maternally acquired SARS-CoV-2 antibodies bound to mast cells. ADE risks associated with SARS-CoV-2 has implications for COVID-19 and MIS-C treatments, B-cell vaccines, SARS-CoV-2 antibody therapy, and convalescent plasma therapy for patients. SARS-CoV-2 antibodies bound to mast cells may be involved in MIS-C and multisystem inflammatory syndrome in adults (MIS-A) following initial COVID-19 infection. SARS-CoV-2 antibodies bound to Fc receptors on macrophages and mast cells may represent two different mechanisms for ADE in patients. These two different ADE risks have possible implications for SARS-CoV-2 B-cell vaccines for subsets of populations based on age, cross-reactive antibodies, variabilities in antibody levels over time, and pregnancy. These models place increased emphasis on the importance of developing safe SARS-CoV-2 T cell vaccines that are not dependent upon antibodies.

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Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies.

Coronavirus disease 2019 (COVID-19), which emerged in Wuhan, China in December 2019, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has become a major global public h...

https://www.tandfonline.com/doi/pdf/10.1080/22221751.2020.1773324

Patterns of IgG and IgM antibody response in COVID-19 patients.

The most appropriate alternative to induction therapy for HIV-associated cryptococcal meningitis (CM) remains unclear when standard treatment is unavailable, inaccessible, intolerable, or ineffective.A prospective, multi-centre cohort study was conducted to analyze the data of 156 HIV-infected patients with CM who were treated with amphotericin B deoxycholate (AmB-D) + flucytosine (5FC), voriconazole (VCZ) + 5FC, or AmB-D + Fluconazole (Flu) as induction regimens. Clinical efficacy, cumulative mortality, and adverse effects were compared among the three treatment groups.Fewer deaths occurred by week 4 and week 10 among patients receiving AmB-D + 5FC than among those receiving AmB-D + Flu [4 (5.1%) vs. 8 (16.0%) deaths by week 4; hazard ratio, 1.8; 95% confidence interval [CI], 1.0 to 3.3; p = 0.039; and 8 (10.3%) vs. 14 (28.0%) deaths by week 10; hazard ratio, 1.8; 95% CI, 1.1 to 2.7; p = 0.008, respectively]. AmB-D plus 5FC was found to result in significantly higher rates of cerebrospinal fluid (CSF) culture sterility (57.6% vs. 34% by week 2; 87.9% vs. 70% by week 10; p < 0.05 for both comparisons). However, the differences in CSF culture sterility and mortality between the VCZ + 5FC group and the AmB-D + 5FC group were not statistically significant. VCZ plus 5FC had a significantly advantageous effect on the incidence of new AIDS-defining illness and length of hospital stay, compared with AmB-D plus 5FC. Laboratory adverse events (grade 3 or 4), such as severe anemia, were less frequent with VCZ + 5FC use than with AmB-D combined with 5FC or Flu use.Our results suggest that AmB-D combined with 5FC remains the more efficacious induction regimen compared to AmB-D plus Flu, and that VCZ + 5FC might be a potential alternative when the standard regimen is not readily available, accessible, tolerated, or effective.Registration number, ChiCTR1900021195. Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 . 

https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-022-07665-z

Comparison of amphotericin B deoxycholate in combination with either flucytosine or fluconazole, and voriconazole plus flucytosine for the treatment of HIV-associated cryptococcal meningitis: a prospective multicenter study in China

Abstract Objective This study aimed to evaluate the effectiveness of therapeutic lumbar drainage (LD) compared to therapeutic lumbar puncture (LP) for the management of intracranial hypertension (ICH) among HIV-positive patients with cryptococcal meningitis (CM). Methods The study was a multicenter prospective non-randomized interventional clinical trial. One hundred and sixteen HIV-associated CM patients were identified who presented with ICH (≥250 mmH2O). The LP group comprised 76 cases, while the LD group consisted of 40 cases. We compared mortality, intracranial pressure (ICP) normalization rate, and clinical symptom remission at 10 weeks, between the two groups. Results The cumulative mortality at week 10 was 22.4% in the LP group and 20% in the LD group (p = .927), without any significant difference in mortality between the two groups. Improvement after treatment at 2-weeks, ICP normalization, and headache reversal event occurrence in the two groups showed no significant difference (p > .05). The incidence of CSF Cryptococcus clearance at two weeks in the LD group was significantly higher than in the LP group (p < .05). The frequency of invasive lumbar therapeutic procedures in the LP group during the first week was higher than that of the LD group (p < .05). Localized infection at the puncture site occurred more frequently in the LD group than in the LP group (p < .05). Conclusion For HIV-positive CM patients with an elevated ICP, LD and LP are comparably effective and safe options to normalize ICP. LP increases the frequency of invasive lumbar therapeutic procedures but does not incur more risk of infection events at the puncture site, while LD may accelerate CSF Cryptococcus clearance but may induce more frequent localized infection. Trial registration This study was registered as one of 12 trials under a general project at the Chinese Clinical Trial Registry (ChiCTR1900021195).

Therapeutic lumbar puncture and lumbar drainage: which is more effective for the management of intracranial hypertension in HIV patients with cryptococcal meningitis? Results of a prospective non-randomized interventional study in China

Xiaolei Xu

Papers

Patterns of IgG and IgM antibody response in COVID-19 patients.

Comparison of amphotericin B deoxycholate in combination with either flucytosine or fluconazole, and voriconazole plus flucytosine for the treatment of HIV-associated cryptococcal meningitis: a prospective multicenter study in China

Therapeutic lumbar puncture and lumbar drainage: which is more effective for the management of intracranial hypertension in HIV patients with cryptococcal meningitis? Results of a prospective non-randomized interventional study in China