Value of increased soluble suppressor tumorigenicity biomarker 2 (sST2) on admission as an indicator of severity in patients with COVID-19 / Valor del aumento del biomarcador supresor soluble de tumorigenicidad 2 (sST2) al ingreso como indicador de gravedad en pacientes con COVID-19

Background Soluble suppressor of tumorigenicity-2 (sST2) is a biomarker for heart failure and pulmonary injury. We hypothesize that sST2 could help predict severity of SARS-CoV-2 infections. Methods sST2 was analyzed in patients consecutively admitted for SARS-CoV-2 pneumonia. Other prognostic markers were also measured. In-hospital complications were registered, including death, ICU admission, and respiratory support requirements. Results 495 patients were studied (53% male, age: 57.6±17.6). At admission, median sST2 concentrations was 48.5ng/mL [IQR, 30.6–83.1ng/mL] and correlated with male gender, older age, comorbidities, other severity biomarkers, and respiratory support requirements. sST2 levels were higher in patients who died (n=45, 9.1%) (45.6 [28.0, 75.9]ng/mL vs. 144 [82.6, 319] ng/mL, p<0.001) and those admitted to ICU (n=46, 9.3%) (44.7 [27.5, 71.3] ng/mL vs. 125 [69.0, 262]ng/mL, p<0.001). sST2 levels>210ng/mL were a strong predictor of complicated in-hospital courses, with higher risk of death (OR, 39.3, CI95% 15.9, 103) and death/ICU (OR 38.3, CI95% 16.3–97.5) after adjusting for all other risk factors. The addition of sST2 enhanced the predictive capacity of mortality risk models. Conclusions sST2 represents a robust severity predictor in COVID-19 and could be an important tool for identifying at-risk patients who may benefit from closer follow-up and specific therapies (AU)

Antecedentes El supresor soluble de tumorigenicidad 2 (sST2) es un biomarcador de insuficiencia cardiaca y daño pulmonar. Nuestra hipótesis es que la determinación de sST2 al ingreso podría ayudar a predecir la gravedad de la infección por SARS-CoV-2. Métodos Se analizó la concentración de sST2 en pacientes ingresados por neumonía por SARS-CoV-2, junto con otros biomarcadores pronósticos conocidos. Asimismo, se registraron las complicaciones durante la estancia hospitalaria, incluidas la muerte, el ingreso en Unidad de Cuidados Intensivos (UCI) y los requerimientos de soporte respiratorio. Resultados Se estudiaron 495 pacientes (53% hombres, edad 57,6 ± 17,6). Al ingreso, la mediana de la concentración de sST2 fue 48,5 ng/mL (índice intercuartílico [IQR] 30,6-83,1 ng/mL) y correlacionó con el género masculino, una mayor edad, comorbilidades, otros biomarcadores de gravedad, así como necesidad de soporte respiratorio. Los niveles de sST2 fueron mayores en pacientes que fallecieron (n = 45, 9,1%) (45,6 [28,0, 75,9] ng/mL vs. 144 [82,6, 319] ng/mL, p < 0,001) y aquellos que requirieron ingreso en UCI (n = 46, 9,3%) (44,7 [27,5, 71,3] ng/mL vs. 125 [69,0, 262] ng/mL, p < 0,001). Así, los valores de sST2 > 210 ng/mL se han demostrado como un fuerte predictor de complicaciones, con un mayor riesgo de fallecimiento (odds ratio [OR], 39,3, intervalo de confianza [IC] 95% 15,9, 103) y fallecimiento o ingreso en UCI (OR 38,3, IC 95% 16,3-97,5), tras el ajuste por todos los demás factores de riesgo. La adición de la determinación de los niveles de sST2 mejoró la potencia predictiva de los modelos de riesgo desarrollados. Conclusiones El sST2 representa un predictor robusto de la gravedad en pacientes con COVID-19 y podría convertirse en una herramienta importante para la identificación de pacientes en riesgo que podrían beneficiarse de un mayor seguimiento y terapias específicas (AU)

High serum nitrates levels in non-survivor COVID-19 patients / Altas concentraciones séricas de nitratos en pacientes fallecidos por COVID-19

Objective: Higher blood nitrate and nitrite levels have been found in coronavirus disease 2019 (COVID-19) patients than in healthy subjects. The present study explores the potential association between serum nitrate levels and mortality in COVID-19 patients. Design: A prospective observation study was carried out. Setting: Eight Intensive Care Units (ICUs) from 6 hospitals in the Canary Islands (Spain). Patients: COVID-19 patients admitted to the ICU. Interventions: Determination of serum nitrate levels at ICU admission. Main variable of interest: Mortality at 30 days. Results: Non-surviving (n=11) compared to surviving patients (n=42) showed higher APACHE-II (p<0.001) and SOFA scores (p=0.004), and higher serum nitrate levels (p=0.001). Logistic regression analyses showed serum nitrate levels to be associated to 30-day mortality after controlling for SOFA (OR=1.021; 95%CI=1.006–1.036; p=0.01) or APACHE-II (OR=1.023; 95%CI=1.006–1.041; p=0.01). There were no differences in the area under the curve (AUC) for mortality prediction by serum nitrate levels (AUC=83%; 95%CI=73–92%; p<0.001), APACHE II (AUC=85%; 95%CI=75–96%; p<0.001) and SOFA (AUC=78%; 95%CI=63–92%; p=0.005) based on the DeLong method. The Kaplan–Meier analysis found patients with serum nitrates levels>68.4μmol/l to have a higher mortality rate (hazard ratio=138.8; 95%CI=22.3–863.9; p<0.001). Conclusions: The main novel finding was the association between serum nitrate levels and mortality in COVID-19 patients controlling for the SOFA or APACHE-II scores, though larger studies are needed to confirm this observation (AU)

Objetivo: Se han encontrado niveles más elevados de nitratos en la sangre de pacientes con enfermedad del coronavirus 2019 (COVID-19) que en sujetos sanos. Por lo tanto, el objetivo de estudio consistió en explorar la posible asociación entre los niveles séricos de nitratos y la mortalidad de pacientes por COVID-19. Diseño: Estudio observacional y prospectivo. Ámbito: Ocho unidades de cuidados intensivos (UCI) de 6 hospitales de las Islas Canarias (España). Pacientes: Pacientes COVID-19 ingresados en la UCI. Intervenciones: Se midieron los niveles séricos de nitratos al ingreso en la UCI. Variable de interés principal: Mortalidad a los 30 días. Resultados: Los pacientes fallecidos (n=11) comparados con los supervivientes (n=42) presentaron mayores APACHE-II (p<0,001), SOFA (p=0,004) y niveles séricos de nitratos (p=0,001). Los análisis de regresión logística mostraron una asociación entre los niveles séricos de nitratos al ingreso en la UCI y la mortalidad a los 30 días controlando por SOFA (OR:1.021; IC 95%:1.006-1.036; p=0,01) o APACHE-II (OR:1.023; IC 95%:1.006-1.041; p=0,01). No encontramos diferencias en el área bajo la curva (ABC) para la predicción de mortalidad entre los niveles séricos de nitratos (ABC:83%; IC 95%:73-92%; p<0,001), APACHE-II (ABC:85%; IC 95%:75-96%; p<0,001) y SOFA (ABC:78%; IC 95%:63-92%; p=0,005) con el método de DeLong. El análisis de Kaplan-Meier mostró que los pacientes que tenían niveles séricos de nitratos al ingreso en la UCI>68,4μmol/l presentaban mayor riesgo de fallecer (hazard ratio:138,8; IC 95%:22,3-863,9; p<0,001). Conclusiones: El principal nuevo hallazgo fue la asociación entre los niveles séricos de nitratos y la mortalidad de pacientes COVID-19 controlando por SOFA o APACHE-II; pero estudios de mayor tamaño muestral son necesarios para confirmar este resultado (AU)

Development of a Novel Double Antibody Sandwich ELISA for Quantitative Detection of Porcine Deltacoronavirus Antigen.

Porcine deltacoronavirus (PDCoV) can cause diarrhea and dehydration in newborn piglets. Here, we developed a double antibody sandwich quantitative enzyme-linked immunosorbent assay (DAS-ELISA) for detection of PDCoV by using a specific monoclonal antibody against the PDCoV N protein and an anti-PDCoV rabbit polyclonal antibody. Using DAS-ELISA, the detection limit of recombinant PDCoV N protein and virus titer were approximately 0.5 ng/mL and 103.0 TCID50/mL, respectively. A total of 59 intestinal and 205 fecal samples were screened for the presence of PDCoV by using DAS-ELISA and reverse transcriptase real-time PCR (RT-qPCR). The coincidence rate of the DAS-ELISA and RT-qPCR was 89.8%. DAS-ELISA had a sensitivity of 80.8% and specificity of 95.6%. More importantly, the DAS-ELISA could detect the antigen of PDCoV inactivated virus, and the viral antigen concentrations remained unchanged in the inactivated virus. These results suggest that DAS-ELISA could be used for antigen detection of clinical samples and inactivated vaccines. It is a novel method for detecting PDCoV infections and evaluating the PDCoV vaccine.

Independent infections of porcine deltacoronavirus among Haitian children.

Coronaviruses have caused three major epidemics since 2003, including the ongoing SARS-CoV-2 pandemic. In each case, the emergence of coronavirus in our species has been associated with zoonotic transmissions from animal reservoirs1,2, underscoring how prone such pathogens are to spill over and adapt to new species. Among the four recognized genera of the family Coronaviridae, human infections reported so far have been limited to alphacoronaviruses and betacoronaviruses3-5. Here we identify porcine deltacoronavirus strains in plasma samples of three Haitian children with acute undifferentiated febrile illness. Genomic and evolutionary analyses reveal that human infections were the result of at least two independent zoonoses of distinct viral lineages that acquired the same mutational signature in the genes encoding Nsp15 and the spike glycoprotein. In particular, structural analysis predicts that one of the changes in the spike S1 subunit, which contains the receptor-binding domain, may affect the flexibility of the protein and its binding to the host cell receptor. Our findings highlight the potential for evolutionary change and adaptation leading to human infections by coronaviruses outside of the previously recognized human-associated coronavirus groups, particularly in settings where there may be close human-animal contact.

Cytokine Drizzle-The Rationale for Abandoning "Cytokine Storm".

BACKGROUND: "Cytokine storm" has been used to implicate increased cytokine levels in the pathogenesis of serious clinical conditions. Similarities with Severe Acute Respiratory Syndrome Coronoavirus-2 (SARS CoV-2) and the 2012 Middle Eastern Respiratory Syndrome led early investigators to suspect a "cytokine storm" resulting in an unregulated inflammatory response associated with the significant morbidity and mortality induced by SARS CoV-2. The threshold of blood cytokines necessary to qualify as a "cytokine storm" has yet to be defined. METHODS: A literature review was conducted to identify cytokine levels released during 11 assorted clinical conditions or diseases. Weighted averages for various cytokines were calculated by multiplying the number of patients in the paper by the average concentration of each cytokine. Correlation between cytokine levels for individual conditions or diseases were assessed using Pearson correlation coefficient. RESULTS: The literature was reviewed to determine blood levels of cytokines in a wide variety of clinical conditions. These conditions ranged from exercise and autoimmune disease to septic shock and therapy with chimeric antigen receptor T cells. The most frequently measured cytokine was IL-6 which ranged from 24,123 pg/mL in septic shock to 11 pg/mL after exercise. In patients with severe SARS CoV-2 infections, blood levels of IL-6 were only 43 pg/mL, nearly three magnitudes lower than IL-6 levels in patients with septic shock. The clinical presentations of these different diseases do not correlate with blood levels of cytokines. Additionally, there is poor correlation between the concentrations of different cytokines among the different diseases. Specifically, blood levels of IL-6 did not correlate with levels of IL-8, IL-10, or TNF. Septic shock had the highest concentrations of cytokines, yet multiple cytokine inhibitors have failed to demonstrate improved outcomes in multiple clinical trials. Patients with autoimmune diseases have very low blood levels of cytokines (rheumatoid arthritis, IL-6 = 34 pg/mL; Crohn's disease, IL-6 = 5 pg/mL), yet respond dramatically to cytokine inhibitors. CONCLUSION: The misleading term "cytokine storm" implies increased blood levels of cytokines are responsible for a grave clinical condition. Not all inflammatory conditions resulting in worsened disease states are correlated with significantly elevated cytokine levels, despite an association with the term "cytokine storm". "Cytokine storm" should be removed from the medical lexicon since it does not reflect the mediators driving the disease nor does it predict which diseases will respond to cytokine inhibitors.

Pathogenic evaluation of a turkey coronavirus isolate (TCoV NC1743) in turkey poults for establishing a TCoV disease model.

Turkey coronavirus (TCoV) can cause a highly contagious enteric disease in turkeys with severe economic losses in the global turkey industry. To date, no commercial vaccines are available for control of the disease. In the present study, we isolated a field strain (NC1743) of TCoV and evaluated its pathogenicity in specific-pathogen-free (SPF) turkey poults to establish a TCoV disease model. The results showed that the TCoV NC1743 isolate was pathogenic to turkey poults with a minimal infectious dose at 106 EID50/bird. About 50 % of one-day-old SPF turkeys infected with the virus's minimal infectious dose exhibited typical enteric disease signs and lesions from 6 days post-infection (dpi) to the end of the experiment (21 dpi). In contrast, fewer than 20 % of older turkeys (1- or 2-week-old) infected with the same amount of TCoV displayed enteric disease signs, which disappeared after 15-18 dpi. Although all infected turkeys, regardless of age, shed TCoV, the older turkeys shed less virus than the younger birds, and 50 % of the 2-week-old birds even cleared the virus at 21 dpi. Furthermore, the viral infection caused day-old turkeys more body-weight-gain reduction than older birds. The overall data demonstrated that the TCoV NC1743 isolate is a highly pathogenic strain and younger turkeys are more susceptible to TCoV infection than older birds. Thus, one-day-old turkeys infected with the minimal infectious dose of TCoV NC1743 could be used as a TCoV disease model to study the disease pathogenesis, and the TCoV NC1743 strain could be used as a challenge virus to evaluate a vaccine protective efficacy.

Marcadores y seguimiento tras alta de urgencias en neumonías COVID-19 / Biological markers and follow-up after discharge home of patients with COVID-19 pneumonia

Objetivos: Analizar la evolución de los pacientes que fueron dados de alta del servicio de urgencias (SU) con neumonía compatible con COVID-19. Método: Se realiza el seguimiento de 102 pacientes dados de alta desde SU con diagnóstico de neumonía compatible con COVID-19 entre el 12 y el 21 de marzo de 2020 en un hospital del sur de Madrid. Se describen las principales variables utilizando mediana e intervalo intercuartil o usando frecuencias, según corresponda. La comparación entre tratamientos/pronóstico se realizó utilizando el test ji cuadrado, el test de Kruskal Wallis o el test de Mann-Whitney. Finalmente, se realizó un modelo de regresión logística. Resultados: La mayoría de los pacientes (74,5%) fueron tratados con hidroxicloroquina en monoterapia. La tasa de reingreso fue de 15,7% y de revisita a urgencias de 25,7%. El ingreso se relacionó con un LDL (lactato deshidrogena-sa) elevado (p = 0,011), creatincinasa (CK) elevada (p = 0,004) y linfopenia (p = 0,034). La hipertensión y la enferme-dad pulmonar obstructiva crónica se relacionaron con el ingreso, y la cardiopatía isquémica fue la comorbilidad que se asoció a mayor duración de la sintomatología. Conclusión: La linfopenia, LDH y CK pronosticaron mejor la necesidad de ingreso que otros marcadores clásicos en pacientes con clínica leve-moderada. El seguimiento telefónico demostró ser de utilidad ante la sobrecarga de recursos sanitarios. (AU)

Background and objective: We aimed to analyze the clinical course of patients discharged from our emergency departament (ED) with pneumonia symptoms compatible with a diagnosis of COVID-19. Methods: We followed 102 patients discharged home with a diagnosis of pneumonia compatible with COVID19 between March 12 and 21, 2020, in our hospital in the southern part of the autonomous community of Madrid. Descriptive statistics (medians and interquartile ranges or frequencies, as appropriate) were compiled for the main variables. Treatments and prognoses were compared with c2, Kruskal–Wallis, or Mann–Whitney tests. The data then underwent logistic regression analysis. Results: Most patients (accounting for 74.5% of the discharges) were treated with hydroxychloroquine alone. The readmission rate was 15.7%; the ED revisiting rate was 25.7%. Admission was associated with an elevated lactate dehydrogenase (LDH) level (P=.011), elevated creatine kinase (CK) (P=.004), and lymphopenia (P=.034). Hypertension and chronic obstructive pulmonary disease were also related to admission. Ischemic heart disease was associated with longer duration of symptoms. Conclusions: Lymphopenia, and elevated LDH and CK levels predicted the need for hospital admission better than other traditional biological markers in patients with mild to moderate symptoms. Telephone follow-up proved useful for dealing with the overloading of health care services. (AU)

COVID-19 serological survey using micro blood sampling.

During August 2020, we carried out a serological survey among students and employees at the Okinawa Institute of Science and Technology Graduate University (OIST), Japan, testing for the presence of antibodies against SARS-CoV-2, the causative agent of COVID-19. We used a FDA-authorized 2-step ELISA protocol in combination with at-home self-collection of blood samples using a custom low-cost finger prick-based capillary blood collection kit. Although our survey did not find any COVID-19 seropositive individuals among the OIST cohort, it reliably detected all positive control samples obtained from a local hospital and excluded all negatives controls. We found that high serum antibody titers can persist for more than 9 months post infection. Among our controls, we found strong cross-reactivity of antibodies in samples from a serum pool from two MERS patients in the anti-SARS-CoV-2-S ELISA. Here we show that a centralized ELISA in combination with patient-based capillary blood collection using as little as one drop of blood can reliably assess the seroprevalence among communities. Anonymous sample tracking and an integrated website created a stream-lined procedure. Major parts of the workflow were automated on a liquid handler, demonstrating scalability. We anticipate this concept to serve as a prototype for reliable serological testing among larger populations.

Aprendiendo sobre anticoagulación con la COVID-19 / Learning about anticoagulation with COVID-19

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Relación entre los niveles de interleucina 6 y depresión en pacientes afectados por Covid-19 / Interleukin 6 and depression in patients affected by Covid-19

Introducción: El incremento de citocinas centrales resultante de infecciones produce cambios neuronales. La Covid-19 permite estudiar los síntomas depresivos en un estrés sostenido y su relación con mecanismos moleculares.ObjetivosValorar la correlación entre niveles de IL-6, IL-1β y TNF-α y sintomatología depresiva. Caracterizar los cuadros depresivos presentes.MétodosEstudio observacional. Se incluyeron pacientes ingresados por Covid-19 mayores de 60años con una determinación de interleucinas. Se utilizó la Escala de depresión geriátrica de Yesavage (GDS), asociándose cada ítem con un neurotransmisor.ResultadosSe incluyeron 27 pacientes. No encontramos correlación entre los niveles de IL-6 y la puntuación de la escala GDS (rho=0,204; IC95% −0,192 a 0,543); ni con los niveles de IL-1β (rho=−0,126; IC95% −0,490 a 0,276); ni de TNF-α (rho=−0,033; IC95% −0,416 a 0,360). Tres pacientes (11,1%) presentaron una puntuación compatible con cuadro depresivo. Se asoció a déficit de noradrenalina y serotonina.ConclusionesNo hallamos correlación entre los niveles de IL-6, IL-1β y TNF-α con la puntuación en la GDS. La sintomatología depresiva presenta características similares a las depresiones vasculares. (AU)

Introduction: Rise of central cytokines resulting from infections produces neuronal changes. Covid-19 allows the study of depressive symptoms in sustained stress and its relationship with molecular mechanisms.ObjectivesTo assess correlation between IL-6, IL-1β and TNF-α and depressive symptoms. Characterize the depressive symptoms present.MethodsObservational study. Patients admitted for Covid-19 older than 60 years with a interleukin determination were included. The Yesavage Geriatric Depression Scale (GDS) was used, associating each item with a neurotransmitter.Results27 patients included. We did not find correlation between IL-6 levels and the GDS scale score (rho=0.204; 95% CI −0.192 to 0.543); with IL-1β levels (rho=−0.126; 95% CI −0.490 to 0.276); nor of TNF-α (rho=−0.033; 95% CI −0.416 to 0.360). 3 patients (11.1%) presented score compatible with depressive disorder. It was associated with a deficiency of noradrenaline and serotonin.ConclusionsWe found no correlation between the levels of IL-6, IL-1β, and TNF-α with the GDS score. Depressive symptomatology is similar to vascular depressions. (AU)

Presencia de anticuerpos antifosfolipidos IgA en pacientes con lesiones pernioticas asociadas a COVID 19 / Immunoglobulin A Antiphospholipid Antibodies in Patients With Chilblain-like Lesions During the COVID-19 Pandemic

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Relationship between leukocyte, neutrophil, lymphocyte, platelet counts, and neutrophil to lymphocyte ratio and polymerase chain reaction positivity.

BACKGROUND: Exposure to viral or bacterial pathogens increases the number of neutrophils with a relative decrease in lymphocytes, leading to elevated neutrophil to lymphocyte ratio (NLR). This study aimed to investigate whether differences in NLR among real-time polymerase chain reaction (PCR)-positive and -negative patients presenting with a prediagnosis of COVID-19 pneumonia could be useful in the differential diagnosis. METHODS: The study included 174 patients admitted because of suspected COVID-19 infection between March and April 2020. Patients were divided into two groups: PCR-negative and PCR-positive. Hemogram, NLR, urea, creatinine, aspartate aminotransferase, alanine aminotransferase, bilirubin, ferritin, D-dimer, C-reactive protein, procalcitonin, troponin, and coagulation parameters were analyzed. RESULTS: On comparison of laboratory parameters between both groups at presentation, PCR-positive patients were significantly more likely to have leukopenia (p < 0.001), thrombocytopenia (p = 0.006), neutropenia (p < 0.001), lymphopenia (p = 0.001), and increased NLR (p = 0.003). Furthermore, PCR-positive patients showed significant elevations of ferritin (p = 0.012) and procalcitonin (p = 0.038) and significant lower potassium levels (p = 0.05). CONCLUSION: COVID-19 pneumonia has become a major global health problem. Early diagnosis and treatment of these patients are crucial, as COVID-19 pneumonia shows a rapid progression in most cases. Thus, leukopenia, thrombocytopenia, elevated NLR, and elevated ferritin may be useful as supplementary diagnostic tests in these patients, which may allow early initiation of treatment and may contribute to preventing progression in patients with abnormal results.

Revisión sistemática sobre la utilidad pronóstica del dímero-D, coagulación intravascular diseminada y tratamiento anticoagulante en pacientes graves con COVID-19 / Systematic review of the prognostic utility of D-dimer, disseminated intravascular coagulation, and anticoagulant therapy in COVID-19 critically ill patient

Durante la nueva pandemia causada por SARS-CoV-2 existe poca evidencia con relación a varios aspectos de la enfermedad, como es el caso de la coagulopatía e interpretación de los niveles de dímero D, su asociación con la coagulación intravascular diseminada (CID) y la controversia en cuanto al beneficio de la anticoagulación. Por ello, se ha hecho una revisión sistemática para definir el rol del dímero D en la enfermedad, la prevalencia y valor pronóstico de la CID y la utilidad del tratamiento anticoagulante en dichos pacientes. Se abordó una búsqueda bibliográfica y análisis de la literatura sobre pacientes con COVID-19. Se elaboraron 4 recomendaciones basadas en la opinión de expertos y en el conocimiento científico, según el sistema Grading of Recommendations Assesment, Development and Evaluation (GRADE). La presente revisión en pacientes con COVID-19 indica la presencia de mayor nivel de dímero D en aquellos con peor pronóstico, que puede haber un sobrediagnóstico de CID en el curso de la enfermedad y que no existe evidencia sobre el beneficio de iniciar tratamiento anticoagulante basándose únicamente en datos aislados de laboratorio

During the new pandemic caused by SARS-CoV-2, there is short knowledge regarding the management of different disease areas, such as coagulopathy and interpretation of D-dimer levels, its association with disseminated intravascular coagulation (DIC) and controversy about the benefit of anticoagulation. Thus, a systematic review has been performed to define the role of D-dimer in the disease, the prevalence of DIC and the usefulness of anticoagulant treatment in these patients. A literature search was performed to analyze the studies of COVID-19 patients. Four recommendations were drawn based on expert opinion and scientific knowledge, according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The present review suggests the presence of higher levels of D-dimer in those with worse prognosis, there may be an overdiagnosis of DIC in the course of the disease and there is no evidence on the benefit of starting anticoagulant treatment based only on isolated laboratory data

Distinct antibody repertoires against endemic human coronaviruses in children and adults.

Four endemic human coronaviruses (HCoVs) are commonly associated with acute respiratory infection in humans. B cell responses to these "common cold" viruses remain incompletely understood. Here we report a comprehensive analysis of CoV-specific antibody repertoires in 231 children and 1168 adults using phage immunoprecipitation sequencing. Seroprevalence of antibodies against endemic HCoVs ranged between approximately 4% and 27% depending on the species and cohort. We identified at least 136 novel linear B cell epitopes. Antibody repertoires against endemic HCoVs were qualitatively different between children and adults in that anti-HCoV IgG specificities more frequently found among children targeted functionally important and structurally conserved regions of the spike, nucleocapsid, and matrix proteins. Moreover, antibody specificities targeting the highly conserved fusion peptide region and S2' cleavage site of the spike protein were broadly cross-reactive with peptides of epidemic human and nonhuman coronaviruses. In contrast, an acidic tandem repeat in the N-terminal region of the Nsp3 subdomain of the HCoV-HKU1 polyprotein was the predominant target of antibody responses in adult donors. Our findings shed light on the dominant species-specific and pan-CoV target sites of human antibody responses to coronavirus infection, thereby providing important insights for the development of prophylactic or therapeutic monoclonal antibodies and vaccine design.

Complement activation and coagulopathy - an ominous duo in COVID19.

INTRODUCTION: COVID-19 has similarities to the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, as severe patients and non-survivors have frequently shown abnormal coagulation profiles. Immune-mediated pathology is a key player in this disease; hence, the role of the complement system needs assessment. The complement system and the coagulation cascade share an intricate network, where multiple mediators maintain a balance between both pathways. Coagulopathy in COVID-19, showing mixed features of complement-mediated and consumption coagulopathy, creates a dilemma in diagnosis and management. AREAS COVERED: Pathophysiology of coagulopathy in COVID-19 patients, with a particular focus on D-dimer and its role in predicting the severity of COVID-19 has been discussed. A comprehensive search of the medical literature on PubMed was done till May 30th, 2020 with the keywords 'COVID-19', 'SARS-CoV-2', 'Coronavirus', 'Coagulopathy', and 'D-dimer'. Twenty-two studies were taken for weighted pooled analysis of D-dimer. EXPERT OPINION: A tailored anticoagulant regimen, including intensification of standard prophylactic regimens with low-molecular-weight heparin is advisable for COVID-19 patients. Atypical manifestations and varying D-dimer levels seen in different populations bring forth the futility of uniform recommendations for anticoagulant therapy. Further, direct thrombin inhibitors and platelet inhibitors in a patient-specific manner should also be considered.

Systemic and intestinal porcine epidemic diarrhea virus-specific antibody response and distribution of antibody-secreting cells in experimentally infected conventional pigs.

Porcine epidemic diarrhea (PED) is a coronavirus disease characterized by the rapid spread of severe diarrhea among pigs. PED virus (PEDV) infects and replicates mainly in the epithelial cells of the duodenum, jejunum, ileum and colon. Serum or mucosal IgA antibody levels have been used to predict both vaccine efficacy and the level of protective immunity to enteric infectious diseases in individuals or herds. Details of the B-cell immune response upon PEDV infection, such as the systemic and mucosal PEDV IgA antibody response, the distribution of IgA antibody-secreting cells (ASCs), and their role in virus clearance are not yet clear. In this experimental infection study, we observed similar fluctuations in PEDV IgA antibody levels in serum and intestinal contents of the upper and lower jejunum and ileum, but not fecal samples, over the 4-week experimental course. ASCs that actively secrete PEDV IgA antibody without in vitro stimulation were distributed mainly in the upper jejunum, whereas memory B cells that showed enhanced PEDV IgA antibody production upon in vitro stimulation were observed in mesenteric lymph nodes and the ileum. Our findings will contribute to the development of effective vaccines and diagnostic methods for PEDV.

Alpha-1 Antitrypsin Deficiency and COVID-19 Infection / Deficiencia de Alfa-1 antitripsina e infección por COVID-19

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The Value of C-Reactive Protein-to-Lymphocyte Ratio in Predicting the Severity of SARS-CoV-2 Pneumonia / Valor del ratio proteína C-reactiva-linfocitos para predecir la gravedad de la neumonía causada por SARS-CoV-2

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Two Opposing Roles of SARS-CoV-2 RBD-Reactive Antibodies in Pre-Pandemic Plasma Samples From Elderly People in ACE2-Mediated Pseudovirus Infection.

A novel coronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged and caused an outbreak of unusual viral pneumonia. Several reports have shown that cross-reactive antibodies against SARS-CoV-2 also exist in people unexposed to this virus. However, the neutralizing activity of cross-reactive antibodies is controversial. Here, we subjected plasma samples from SARS-CoV-2-unexposed elderly Korean people (n = 119) to bead-based IgG antibody analysis. SARS-CoV-2 S1 subunit-reactive IgG antibody analysis detected positive signals in some samples (59 of 119, 49.6%). SARS-CoV-2 receptor-binding domain (RBD)-reactive antibody levels were most significantly correlated with human coronavirus-HKU1 S1 subunit-reactive antibody levels. To check the neutralizing activity of plasma samples, the SARS-CoV-2 spike pseudotype neutralizing assay was used. However, the levels of cross-reactive antibodies did not correlate with neutralizing activity. Instead, SARS-CoV-2 pseudovirus infection was neutralized by some RBD-reactive plasma samples (n = 9, neutralization ≥ 25%, P ≤ 0.05), but enhanced by other RBD-reactive plasma samples (n = 4, neutralization ≤ -25%, P ≤ 0.05). Interestingly, the blood plasma groups with enhancing and neutralizing effects had high levels of SARS-CoV-2 RBD-reactive antibodies than the plasma group that had no effect. These results suggest that some SARS-CoV-2 RBD-reactive antibodies from pre-pandemic elderly people exert two opposing functions during SARS-CoV-2 pseudovirus infection. In conclusion, preformed RBD-reactive antibodies may have two opposing functions, namely, protecting against and enhancing viral infection. Analysis of the epitopes of preformed antibodies will be useful to elucidate the underlying mechanism.

Multiplexed detection and quantification of human antibody response to COVID-19 infection using a plasmon enhanced biosensor platform.

The 2019 SARS CoV-2 (COVID-19) pandemic has illustrated the need for rapid and accurate diagnostic tests. In this work, a multiplexed grating-coupled fluorescent plasmonics (GC-FP) biosensor platform was used to rapidly and accurately measure antibodies against COVID-19 in human blood serum and dried blood spot samples. The GC-FP platform measures antibody-antigen binding interactions for multiple targets in a single sample, and has 100% selectivity and sensitivity (n = 23) when measuring serum IgG levels against three COVID-19 antigens (spike S1, spike S1S2, and the nucleocapsid protein). The GC-FP platform yielded a quantitative, linear response for serum samples diluted to as low as 1:1600 dilution. Test results were highly correlated with two commercial COVID-19 antibody tests, including an enzyme linked immunosorbent assay (ELISA) and a Luminex-based microsphere immunoassay. To demonstrate test efficacy with other sample matrices, dried blood spot samples (n = 63) were obtained and evaluated with GC-FP, yielding 100% selectivity and 86.7% sensitivity for diagnosing prior COVID-19 infection. The test was also evaluated for detection of multiple immunoglobulin isotypes, with successful detection of IgM, IgG and IgA antibody-antigen interactions. Last, a machine learning approach was developed to accurately score patient samples for prior COVID-19 infection, using antibody binding data for all three COVID-19 antigens used in the test.