SARS-CoV-2 Seroprevalence Among First Responders in Northeastern Ohio, 2020.

OBJECTIVES: First responders, including firefighters, emergency medical technicians (EMTs), paramedics, and law enforcement officers, are working on the front lines to fight the COVID-19 pandemic and facing an increased risk of infection. This study assessed the seroprevalence of SARS-CoV-2 infection among first responders in northeastern Ohio. METHODS: A survey and immunoglobulin G antibody test against SARS-CoV-2 nucleocapsid protein were offered to University Hospitals Health System-affiliated first-responder departments during May to September 2020. The survey contained questions about demographic characteristics and history of SARS-CoV-2 infection. A total of 3080 first responders with diverse job assignments from more than 400 fire and police departments participated in the study. RESULTS: Of 3080 participants, 73 (2.4%) were seropositive and 26 (0.8%) had previously positive real-time polymerase chain reaction results. Asymptomatic infection accounted for 46.6% (34 of 73) of seropositivity. By occupation, rates of seropositivity were highest among administration/support staff (3.8%), followed by paramedics (3.0%), EMTs (2.6%), firefighters (2.2%), and law enforcement officers (0.8%). Work-associated exposure rates to COVID-19 patients were: paramedics (48.2%), firefighters (37.1%), EMTs (32.3%), law enforcement officers (7.7%), and administration/support staff (4.4%). Self-reported community exposure was positively correlated with self-reported work-associated exposure rate (correlation coefficient = 0.99). Neither self-reported community nor work-associated exposure was correlated with SARS-CoV-2 seroprevalence. We found no significant difference in seroprevalence among sex/gender or age groups; however, Black participants had a higher positivity rate than participants of other racial groups despite reporting lower exposure. CONCLUSIONS: Despite the high work-associated exposure rate to SARS-CoV-2 infection, first responders with various roles demonstrated seroprevalence no higher than their administrative/supportive colleagues, which suggests infection control measures are effective in preventing work-related infection.

Performance Evaluation of RapiSure (EDGC) COVID-19 S1 RBD IgG/Neutralizing Ab Test for the Rapid Detection of SARS-CoV-2 Antibodies.

The accurate detection of anti-neutralizing SARS-CoV-2 antibodies can aid in the understanding of the development of protective immunity against COVID-19. This study evaluated the diagnostic performance of the RapiSure (EDGC) COVID-19 S1 RBD IgG/Neutralizing Ab Test. Using the 90% plaque reduction neutralization test (PRNT90) as a reference, 200 serum samples collected from 78 COVID-19-positive and 122 COVID-19-negative patients were divided into 76 PRNT90-positive and 124 PRNT90-negative groups. The ability of the RapiSure test to detect antibodies was compared to that of the STANDARD Q COVID-19 IgM/IgG Plus test and that of PRNT90. The positive, negative, and overall percent agreement between the RapiSure and STANDARD Q test was 95.7%, 89.3%, and 91.5%, respectively, with a Cohen's kappa of 0.82. The RapiSure neutralizing antibody test results revealed a sensitivity of 93.4% and a specificity of 100% compared to the PRNT results, with an overall percent agreement of 97.5% and Cohen's kappa of 0.95. The diagnostic performance of the RapiSure test was in good agreement with the STANDARD Q COVID-19 IgM/IgG Plus test and comparable to that of the PRNT. The RapiSure S1 RBD IgG/Neutralizing Ab Test was found to be convenient and reliable and, thus, can provide valuable information for rapid clinical decisions during the COVID-19 pandemic.

Evaluating Johnson and Johnson COVID-19 Vaccination Outcomes in a Low-Income Hispanic Population.

BACKGROUND: A pilot study was performed at a low-income emergency care clinic to assess the humoral immune response to the Johnson & Johnson (J&J) COVID-19 vaccine (Ad26.COV2.S) to better understand how to evaluate the COVID-19 health status of its Hispanic patient population following vaccination. METHODS: This study used the Clungene® SARS-CoV-2 IgG/IgM Rapid Test Cassette to determine the presence of binding antibodies resulting from the J&J COVID-19 vaccine. The Clungene test principle is based on the receptor-binding domain (RBD) of the spike protein. Antibodies targeting the spike protein are considered an appropriate measure of humoral response from spike-based vaccines. RESULTS: The study confirmed previous research that antibodies wane over time, and results are consistent with reported vaccine efficacy. There was a statistically significant relationship between the humoral immune response and demographic and health status variables. CONCLUSIONS: COVID-19 negative patients can be easily and efficiently monitored to determine the success and durability of COVID-19 vaccines in low-income minority populations. The use of simple low-cost spike targeted COVID-19 antibody lateral flow devices may serve as a useful adjunct to assist community-based physicians on the COVID-19 health status of its patients. Further research is needed to confirm the utility of this approach.

The Seroprevalence of SARS-CoV-2 in Children During Early COVID-19 Pandemic in Korea: A Nationwide, Population-Based Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is often asymptomatic and associated with mild clinical symptoms in children. Social distancing measures have led to a relatively small number of confirmed COVID-19 cases in Korea than in other countries in the earlier pandemic phase. Previous seroprevalence studies in Korean adults before the introduction of COVID-19 vaccination campaign have shown a low antibody positivity rate. However, data on COVID-19 seroprevalence in Korean children remained scarce. In this study, we assessed the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children in Korea. METHODS: Between December 2020 and March 2021, stratified serum samples were collected from children aged 0-18 years in 17 different regions across the country. The SARS-CoV-2 antibody test was conducted using an electro-chemiluminescence immunoassay (ECLIA) to detect the antibodies against nucleocapsid antigens of SARS-CoV-2. Samples that tested positive using the ECLIA were reflexed to an additional plaque reduction neutralization test (PRNT) for SARS-CoV-2. RESULTS: A total of 1,887 samples were collected. Excluding 21 samples collected from regional medical centers, 1,866 samples were included in the final analysis. Two samples (0.11%) were positive for the antibodies against nucleocapsid antigens of SARS-CoV-2. Both samples were shown to have neutralizing antibodies for SARS-CoV-2 via PRNT. CONCLUSION: After 1 year since the start of COVID-19 pandemic, the seroprevalence of SARS-CoV-2 among Korean children was 0.11%, which was lower than the adults (0.52%) in another study conducted during a similar period. In the early stages of the COVID-19 pandemic, the seroprevalence of SARS-CoV-2 in Korea was lower than those of other countries, which was presumed to be the consequence of a very strong social distancing measures.

Ultrarapid and ultrasensitive detection of SARS-CoV-2 antibodies in COVID-19 patients via a 3D-printed nanomaterial-based biosensing platform.

Rapid detection of antibodies during infection and after vaccination is critical for the control of infectious outbreaks, understanding immune response, and evaluating vaccine efficacy. In this manuscript, we evaluate a simple ultrarapid test for SARS-CoV-2 antibodies in COVID-19 patients, which gives quantitative results (i.e., antibody concentration) in 10-12 s using a previously reported nanomaterial-based three-dimensional (3D)-printed biosensing platform. This platform consists of a micropillar array electrode fabricated via 3D printing of aerosolized gold nanoparticles and coated with nanoflakes of graphene and specific SARS-CoV-2 antigens, including spike S1, S1 receptor-binding domain (RBD) and nucleocapsid (N). The sensor works on the principle of electrochemical transduction, where the change of sensor impedance is realized by the interactions between the viral proteins attached to the sensor electrode surface and the antibodies. The three sensors were used to test samples from 17 COVID-19 patients and 3 patients without COVID-19. Unlike other serological tests, the 3D sensors quantitatively detected antibodies at a concentration as low as picomole within 10-12 s in human plasma samples. We found that the studied COVID-19 patients had higher concentrations of antibodies to spike proteins (RBD and S1) than to the N protein. These results demonstrate the enormous potential of the rapid antibody test platform for understanding patients' immunity, disease epidemiology and vaccine efficacy, and facilitating the control and prevention of infectious epidemics.

Therapeutic Use of Convalescent Plasma in COVID-19 Infected Patients with Concomitant Hematological Disorders.

The use of convalescent plasma (CP) from individuals recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a promising therapeutic modality for the coronavirus disease 2019 (COVID-19). CP has been in use for at least a century to provide passive immunity against a number of diseases, and was recently proposed by the World Health Organization for human Ebola virus infection. Only a few small studies have so far been published on patients with COVID-19 and concomitant hematological malignancies (HM). The Italian Hematology Alliance on HM and COVID-19 has found that HM patients with COVID-19 clinically perform more poorly than those with either HM or COVID-19 alone. A COVID-19 infection in patients with B-cell lymphoma is associated with impaired generation of neutralizing antibody titers and lowered clearance of SARS-CoV-2. Treatment with CP was seen to increase antibody titers in all patients and to improve clinical response in 80% of patients examined. However, a recent study has reported impaired production of SARS-CoV-2-neutralizing antibodies in an immunosuppressed individual treated with CP, possibly supporting the notion of virus escape, particularly in immunocompromised individuals where prolonged viral replication occurs. This may limit the efficacy of CP treatment in at least some HM patients. More recently, it has been shown that CP may provide a neutralising effect against B.1.1.7 and other SARS-CoV-2 variants, thus expanding its application in clinical practice. More extensive studies are needed to further assess the use of CP in COVID-19-infected HM patients.

Characteristics of coronavirus disease 19 convalescent plasma donors and donations in the New York metropolitan area.

BACKGROUND: Convalescent plasma (CP) is an important initial treatment in pandemics and the New York (NY) metropolitan area is likely to remain a hotspot for collection and distribution of such units. This study reports characteristics of coronavirus disease 19 CP (CCP) donors and their donations to the New York Blood Center (NYBC). STUDY DESIGN AND METHODS: All CCP data from our first day of collection on March 26th through July 7th, 2020 are included in this retrospective analysis. Donor and donation data were extracted from NYBC electronic databases. SARS-CoV-2 antibody testing was initially performed by the NY State Department of Health, and later by NYBC using Ortho and Abbott platforms. RESULTS: CCP donor age and ABO distributions were consistent with reported lower COVID-19 susceptibility in O blood types. CCP versus whole blood donors had similar on-site deferrals, but higher post-donation deferral rates. CCP versus routine plasmapheresis donations had higher vasovagal reactions but similar product rejection rates. Changes in antibody (Ab) test platforms resulted in significant changes in the percent of donors regarded as antibody positive. Donor correlates with higher anti-spike total Ig S/CO ratios were Hispanic ethnicity, overweight body mass index, and longer symptom duration; and with higher anti-nucleocapsid IgG S/CO ratios were male gender, older age, Hispanic ethnicity, and fewer days between symptom onset and first donation. DISCUSSION: We identify donor characteristics not previously reported to correlate with Ab titer. Our analysis should assist with donor outreach strategies, blood center operating logistics, and recruitment of high titer donors.

Screen-Printed Graphene/Carbon Electrodes on Paper Substrates as Impedance Sensors for Detection of Coronavirus in Nasopharyngeal Fluid Samples.

Severe acute respiratory syndrome (SARS-CoV-2), the causative agent of the global pandemic, which has resulted in more than one million deaths with tens of millions reported cases, requires a fast, accurate, and portable testing mechanism operable in the field environment. Electrochemical sensors, based on paper substrates with portable electrochemical devices, can prove an excellent alternative in mitigating the economic and public health effects of the disease. Herein, we present an impedance biosensor for the detection of the SARS-CoV-2 spike protein utilizing the IgG anti-SARS-CoV-2 spike antibody. This label-free platform utilizing screen-printed electrodes works on the principle of redox reaction impedance of a probe and can detect antigen spikes directly in nasopharyngeal fluid as well as virus samples collected in the universal transport medium (UTM). High conductivity graphene/carbon ink is used for this purpose so as to have a small background impedance that leads to a wider dynamic range of detection. Antibody immobilization onto the electrode surface was conducted through a chemical entity or a biological entity to see their effect; where a biological immobilization can enhance the antibody loading and thereby the sensitivity. In both cases, we were able to have a very low limit of quantification (i.e., 0.25 fg/mL), however, the linear range was 3 orders of magnitude wider for the biological entity-based immobilization. The specificity of the sensor was also tested against high concentrations of H1N1 flu antigens with no appreciable response. The most optimized sensors are used to identify negative and positive COVID-19 samples with great accuracy and precision.

Symptoms, antibody levels and vaccination attitude after asymptomatic to moderate COVID-19 infection in 200 healthcare workers.

Aim: In Germany, the willingness to be vaccinated against COVID-19 is rather low among medical staff. We collected data on symptoms, antibody titers and vaccination readiness from clinic employees at a municipal clinic who had already been through a COVID-19 infection (asymptomatic to moderate). We also examined the antibody titers for their possible importance as an individual decision-making aid with regard to vaccination. Method: 200 employees of our municipal clinics were included in the study. COVID-19 antibody determination was performed using an ELISA (EUROIMMUN™, PerkinElmer, Inc. Company). The participants were given an anonymous questionnaire containing anthropometrical issues, symptoms of the infection and questions concerning the vaccination decision. Finally, the antibody levels were reported to the participants and the attitude towards a vaccination was reevaluated. Results: In all 200 participants who had already gone through a COVID-19 infection, 75 employees were in favor of a vaccination (37.5%), 96 were opposed to vaccination (48%), and 29 were undecided (14.5%). In the different occupational groups, the positive trend in terms of willingness to be vaccinated was highest among physicians and is least among nurses. The antibody results showed considerable variation in titer levels and therefore did not correlate with disease severity in asymptomatic to moderately ill persons. We also observed a pro-vaccination trend with increasing age of the participants. The specifically-asked symptom of cutaneous hyperesthesia during COVID-19 infection occurred in 5% of the participants. Conclusion: In medical personnel who had already suffered from a COVID-19 infection, the willingness to receive a vaccination tends to be highest among physicians, and lowest in nurses, and increases with age. For the vast majority of those affected, knowledge of the antibody titers only reinforces the vaccination decision made beforehand and thus does not contribute to a change in vaccination decision. The specifically-requested symptom of cutaneous hyperesthesia during COVID-19 infection was unexpectedly frequent.

The presence of SARS-CoV2 antibodies in MS patients.

BACKGROUND: The COVID-19 pandemic has raised novel concerns for people living with MS regarding their safety. METHODS: Observational study of patients at a single comprehensive community MS center. RESULTS: 48 patients with MS were suspected of developing COVID-19 March to May 2020; 2 died. Of the remainder, 17 were tested for COVID-19 antibodies as part of routine care. Average age of this subgroup was 49.8y ± 11.3 (age range 32-67), 76% female. 65% were treated with an anti-CD20 drug, 12% untreated, and 6% each received glatiramer acetate, interferon, natalizumab, or teriflunomide. 59% of patients were antibody negative. CONCLUSIONS: The low incidence of SARS CoV2 antibodies following infection suggests that certain DMTs may alter SARS CoV2-Ab response or persistence.

COVID-19 therapy with mesenchymal stromal cells (MSC) and convalescent plasma must consider exosome involvement: Do the exosomes in convalescent plasma antagonize the weak immune antibodies?

Exosome extracellular vesicles as biologic therapy for COVID-19 are discussed for two areas. The first involves the growing use of mesenchymal stromal cells (MSCs) for the profound clinical cytokine storm and severe pneumonia in COVID-19 patients. Instead, it is recommended to treat alternatively with their MSC-released exosomes. This is because many reports in the literature and our data have shown that the release of exosomes from the in vivo administered MSC is actually responsible for their beneficial effects. Further, the exosomes are superior, simpler and clinically more convenient compared to their parental MSC. Additionally, in the context of COVID-19, the known tendency of MSC to intravascularly aggregate causing lung dysfunction might synergize with the pneumonia aspects, and the tendency of MSC peripheral vascular micro aggregates might synergize with the vascular clots of the COVID-19 disease process, causing significant central or peripheral vascular insufficiency. The second exosome therapeutic area for severe COVID-19 involves use of convalescent plasma for its content of acquired immune antibodies that must consider the role in this therapy of contained nearly trillions of exosomes. Many of these derive from activated immune modulating cells and likely can function to transfer miRNAs that acting epigenetically to also influence the convalescent plasma recipient response to the virus. There is sufficient evidence, like recovery of patients with antibody deficiencies, to postulate that the antibodies actually have little effect and that immune resistance is principally due to T cell mechanisms. Further, COVID-19 convalescent plasma has remarkably weak beneficial effects if compared to what was expected from many prior studies. This may be due to the dysfunctional immune response to the infection and resulting weak Ab that may be impaired further by antagonistic exosomes in the convalescent plasma. At the least, pre selection of plasma for the best antibodies and relevant exosomes would produce the most optimum therapy for very severely affected COVID-19 patients.