Is coagulation-protein consumption upon admission linked to COVID-19 severity and mortality?

The link between coagulation system disorders and COVID-19 has not yet been fully elucidated. With the aim of evaluating the association of several coagulation proteins with COVID-19 severity and mortality, we performed a cross-sectional study in 134 patients classified according to the highest disease severity reached during the disease. We found higher levels of antithrombin, prothrombin, factor XI, factor XII and factor XIII in asymptomatic/mild and moderate COVID-19 patients than healthy individuals. Interestingly, decreased levels of antithrombin, factor XI, XII and XIII were observed in those patients who eventually developed severe illness. Additionally, survival models showed us that patients with lower levels of these coagulation proteins had an increased risk of death. In conclusion, COVID-19 provokes early increments of some specific coagulation proteins in most patients. However, lower levels of these proteins at diagnosis might "paradoxically" imply a higher risk of progression to severe disease and COVID-19-related mortality.

Absent or insufficient anti-SARS-CoV-2 S antibodies at ICU admission are associated to higher viral loads in plasma, antigenemia and mortality in COVID-19 patients

Purposeto evaluate the association between anti-SARS-CoV-2 S IgM and IgG antibodies with viral RNA load in plasma, the frequency of antigenemia and with the risk of mortality in critically ill patients with COVID-19. Methodsanti-SARS-CoV-2 S antibodies levels, viral RNA load and antigenemia were profiled in plasma of 92 adult patients in the first 24 hours following ICU admission. The impact of these variables on 30-day mortality was assessed by using Kaplan-Meier curves and multivariate Cox regression analysis. Resultsnon survivors showed more frequently absence of anti-SARS-CoV-2 S IgG and IgM antibodies than survivors (26.3% vs 5.6% for IgM and 18.4% vs 5.6% for IgG), and a higher frequency of antigenemia (47.4% vs 22.2%) (p <0.05). Non survivors showed lower concentrations of anti-S IgG and IgM and higher viral RNA loads in plasma, which were associated to increased 30-day mortality and decreased survival mean time. [Adjusted HR (CI95%), p]: [S IgM (AUC [≥]60): 0.48 (0.24; 0.97), 0.040]; [S IgG (AUC [≥]237): 0.47 (0.23; 0.97), 0.042]; [Antigenemia (+): 2.45 (1.27; 4.71), 0.007]; [N1 viral load ([≥] 2.156 copies/mL): 2.21 (1.11; 4.39),0.024]; [N2 viral load ([≥] 3.035 copies/mL): 2.32 (1.16; 4.63), 0.017]. Frequency of antigenemia was >2.5-fold higher in patients with absence of antibodies. Levels of anti-SARS-CoV-2 S antibodies correlated inversely with viral RNA load. Conclusionabsence / insufficient levels of anti-SARS-CoV-2 S antibodies following ICU admission is associated to poor viral control, evidenced by increased viral RNA loads in plasma, higher frequency of antigenemia, and also to increased 30-day mortality. Take-home messageabsent or low levels of antibodies against the S protein of SARS-CoV- 2 at ICU admission is associated to an increased risk of mortality, higher frequency of antigenemia and higher viral RNA loads in plasma. Profiling anti-SARS-CoV-2 s antibodies at ICU admission could help to predict outcome and to better identify those patients potentially deserving replacement treatment with monoclonal or polyclonal antibodies.

Panbio antigen rapid test is reliable to diagnose SARS-CoV-2 infection in the first 7 days after the onset of symptoms

BackgroundReal-time reverse transcription polymerase chain reaction (RT-qPCR) is the current recommended laboratory method to diagnose SARS-CoV-2 acute infection, several factors such as requirement of special equipment, time consuming, high cost and skilled staff limit the use of these molecular techniques. A more rapid and high-throughput method is in growing demand. MethodsEvaluate the performances of the Panbio COVID-19 AG Rapid Test Device (Nasopharyngeal), a rapid immunochromatographic test for the detection of SARS-CoV-2 antigen, in comparison to RT-qPCR. ResultsThe RDT evaluated in this study showed a high sensitivity and specificity in samples mainly obtained during the first week of symptoms and with high viral loads. ConclusionsThis assay seems to be an effective strategy for controlling the COVID-19 pandemic for the rapid identification and isolation of SARS-CoV-2 infected patients.

Comparative evaluation of six immunoassays for the detection of antibodies against SARS-CoV-2

ObjectivesSerologic techniques can serve as a complement to diagnose SARS-CoV-2 infection. The objective of our study was to compare the diagnostic performance of six immunoassays to detect antibodies against SARS-CoV-2: three lateral flow immunoassays (LFAs), one ELISA and two chemiluminescence assays (CLIAs). MethodsWe evaluated three LFAs (Alltest, One Step and SeroFlash), one ELISA (Dia.Pro) and 34 two CLIAs (Elecsys and COV2T). To assess the specificity, 60 pre-pandemic sera were 35 used. To evaluate the sensitivity, we used 80 serum samples from patients with 36 positive PCR for SARS-CoV-2. Agreement between techniques was evaluated using the kappa score (k). ResultsAll immunoassays showed a specificity of 100% except for SeroFlash (96.7%). Overall sensitivity was 61.3%, 73.8%, 67.5%, 85.9%, 88.0% and 92.0% for Alltest, One Step, SeroFlash, Dia.Pro, Elecsys and COV2T, respectively. Sensitivity increased throughout the first two weeks from the onset of symptoms, reaching sensitivities over 85% from 14 days for all LFAs, being One Step the most sensitive (97.6%), followed by SeroFlash (95.1%). Dia.Pro, Elecsys and COV2T showed sensitivities over 97% from 14 days, being 100% for COV2T. One Step showed the best agreement results among LFAs, showing excellent agreement with Dia.Pro (agreement=94.2%, k=0.884), COV2T (99.1%, k=0.981) and Elecsys (97.3%, k=0.943). Dia.Pro, COV2T and Elecsys also showed excellent agreement between them. ConclusionOne Step, Dia.Pro, Elecsys and COV2T obtained the best diagnostic performanc e results. All these techniques showed a specificity of 100% and sensitivities over 97% from 14 days after the onset of symptoms, as well as excellent levels of agreement.

SARS-CoV-2-RNA viremia is associated to hypercytokinemia and critical illness in COVID-19

BackgroundSevere COVID-19 is characterized by clinical and biological manifestations typically observed in sepsis. SARS-CoV-2 RNA is commonly detected in nasopharyngeal swabs, however viral RNA can be found also in peripheral blood and other tissues. Whether systemic spreading of the virus or viral components plays a role in the pathogenesis of the sepsis-like disease observed in severe COVID-19 is currently unknown. MethodsWe determined the association of plasma SARS-CoV-2 RNA with the biological responses and the clinical severity of patients with COVID-19. 250 patients with confirmed COVID-19 infection were recruited (50 outpatients, 100 hospitalised ward patients, and 100 critically ill). The association between plasma SARS-CoV-2 RNA and laboratory parameters was evaluated using multivariate GLM with a gamma distribution. The association between plasma SARS-CoV-2 RNA and severity was evaluated using multivariate ordinal logistic regression analysis and Generalized Linear Model (GLM) analysis with a binomial distribution. ResultsThe presence of SARS-CoV-2-RNA viremia was independently associated with a number of features consistently identified in sepsis: 1) high levels of cytokines (including CXCL10, CCL-2, IL-10, IL-1ra, IL-15, and G-CSF); 2) higher levels of ferritin and LDH; 3) low lymphocyte and monocyte counts 4) and low platelet counts. In hospitalised patients, the presence of SARS-CoV-2-RNA viremia was independently associated with critical illness: (adjusted OR= 8.30 [CI95%=4.21 - 16.34], p < 0.001). CXCL10 was the most accurate identifier of SARS-CoV-2-RNA viremia in plasma (area under the curve (AUC), [CI95%], p) = 0.85 [0.80 - 0.89), <0.001]), suggesting its potential role as a surrogate biomarker of viremia. The cytokine IL-15 most accurately differentiated clinical ward patients from ICU patients (AUC: 0.82 [0.76 - 0.88], <0.001). Conclusionssystemic dissemination of genomic material of SARS-CoV-2 is associated with a sepsis-like biological response and critical illness in patients with COVID-19. RNA viremia could represent an important link between SARS-CoV-2 infection, host response dysfunction and the transition from moderate illness to severe, sepsis-like COVID-19 disease.

Prevalence and risk factors for mortality related to COVID-19 in a severely affected area of Madrid, Spain

BACKGROUNDThe coronavius disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reached Spain by 31 January 2020, in April 2020, the Comunidad de Madrid suffered one of the worlds highest crude mortality rate ratios. This study aimed to detect risk factors for mortality in patients with COVID-19. METHODSOur cohort were all consecutive adult patients ([≥]18 years) with laboratory-confirmed COVID-19 at a secondary hospital in Madrid, March 3-16, 2020. Clinical and laboratory data came from electronic clinical records and were compared between survivors and non-survivors, with outcomes followed up until April 4. Univariable and multivariable logistic regression methods allowed us to explore risk factors associated with in-hospital death. FINDINGSThe cohort comprised 562 patients with COVID-19. Clinical records were available for evaluation for 392 patients attended at the emergency department of our hospital, of whom 199 were discharged, 85 remained hospitalized and 108 died during hospitalization. Among 311 of the hospitalized patients, 34.7% died. Of the 392 patients with records, the median age was 71.5 years (50.6-80.7); 52.6% were men. 252 (64.3%) patients had a comorbidity, hypertension being the most common: 175 (44.6%), followed by other cardiovascular disease: 102 (26.0%) and diabetes: 97 (24.7%). Multivariable regression showed increasing odds of in-hospital death associated with age over 65 (odds ratio 8.32, 95% CI 3.01-22.96; p<0.001), coronary heart disease (2.76, 1.44-5.30; 0.002), and both lower lymphocyte count (0.34, 0.17-0.68; 0.002) and higher LDH (1.25, 1.05-1.50; 0.012) per 1-unit increase and per 100 units respectively. INTERPRETATIONCOVID-19 was associated in our hospital at the peak of the pandemic with a crude mortality ratio of 19.2% and a mortality ratio of 34.7% in admitted patients, considerably above most of the ratios described in the Chinese series. These results leave open the question as to which factors, epidemiological or intrinsically viral, apart from age and comorbidities, can explain this difference in excess mortality. FUNDINGNone.

Rapid diagnosis of SARS-CoV-2 infection by detecting IgG and IgM antibodies with an immunochromatographic device: a prospective single-center study

ObjectivesSARS-CoV-2 infection diagnosis is challenging in patients from 2-3 weeks after the onset of symptoms, due to the low positivity rate of the PCR. Serologic tests could be complementary to PCR in these situations. The aim of our study was to analyze the diagnostic performance of one serologic rapid test in COVID-19 patients. MethodsWe evaluated an immunochromatographic test (AllTest COVID-19 IgG / IgM) which detects IgG and IgM antibodies. We validated the serologic test using serum samples from 45 negative patients (group 1) and 55 patients with COVID-19 confirmed by PCR (group 2). Then, we prospectively evaluated the test in 63 patients with clinical diagnosis of pneumonia of unknown etiology that were COVID-19 negative by PCR (group 3). ResultsAll 45 patients from group 1 were negative for the serologic test (specificity = 100%). Regarding group 2 (PCR-positive), the median time from their symptom onset until testing was 11 days. For these 55 group-2 patients, the test was positive for either IgM or IgG in 26 (overall sensitivity = 47%), and in patients tested 14 days or more after the onset of symptoms, the sensitivity was 74%. Regarding the 63 group-3 patients, median time after symptom onset was 17 days, and the test was positive in 56 (89% positivity). ConclusionsOur study shows that serologic rapid tests could be used as a complement of PCR to diagnose SARS-CoV-2 infection after 14 days from the onset of symptoms and in patients with pneumonia and negative PCR for SARS-CoV-2.