SARS-CoV-2 RT-qPCR Ct values in saliva and nasopharyngeal swab samples for disease severity prediction.

Background: Comparison of clinical value of RT-qPCR-based SARS-CoV-2 tests performed on saliva samples (SSs) and nasopharyngeal swab samples (NPSs) for prediction of the COVID-19 disease severity. Methods: Three paired SSs and NPSs collected every 3 days from 100 hospitalised COVID-19 patients during 2020 Jul-2021 Jan were tested by RT-qPCR for the original SARS-CoV-2 virus and compared to 150 healthy controls. Cases were divided into mild+moderate (Cohort I, N = 47) and severe disease (Cohort II, N = 53) cohorts and compared. Results: SARS-CoV-2 was detected in 65% (91/140) vs. 53% (82/156) of NPSs and 49% (68/139) vs. 48% (75/157) of SSs collected from Cohort I and II, respectively, resulting in the total respective detection rates of 58% (173/296) vs. 48% (143/296) (P = 0.017). Ct values of SSs were lower than those of NPSs (mean Ct = 28.01 vs. 30.07, P = 0.002). Although Ct values of the first SSs were significantly lower in Cohort I than in Cohort II (P = 0.04), it became negative earlier (mean 11.7 vs. 14.8 days, P = 0.005). Multivariate Cox proportional hazards regression analysis showed that Ct value ≤30 from SSs was the independent predictor for severe COVID-19 (HR = 10.06, 95% CI: 1.84-55.14, P = 0.008). Conclusion: Salivary RT-qPCR testing is suitable for SARS-CoV-2 infection control, while simple measurement of Ct values can assist in prediction of COVID-19 severity.

Association between the overall burden of comorbidity and Ct values among the older patients with Omicron infection: Mediated by inflammation.

Objectives: To investigate the associations between the overall burden of comorbidity, inflammatory indicators in plasma and Ct values among the elderly with COVID-19. Methods: We conducted a retrospective observational study. The results of each nucleic acid test of during hospitalization were obtained. Linear regression models assessed the associations between the overall burden of comorbidity, inflammatory indicators in plasma and Ct values among the elderly. A causal mediation analysis was performed to assess the mediation effects of inflammatory indicators on the association between the overall burden of comorbidity and Ct values. Results: A total of 767 COVID-19 patients aged ≥ 60 years were included between April 2022 and May 2022. Patients with a high burden of comorbidity had significantly lower Ct values of the ORF gene than subjects with a low burden of comorbidity (median, 24.81 VS 26.58, P < 0.05). Linear regression models showed that a high burden of comorbidity was significantly associated with higher inflammatory responses, including white blood cell count, neutrophil count and C-reactive protein. Also, white blood cell count, neutrophil count, C-reactive protein and the overall burden of comorbidity assessed by age-adjusted Charlson comorbidity index were independent risk factors for the Ct values. A mediation analysis detected the mediation effect of white blood cells on the association between the burden of comorbidity and Ct values, with the indirect effect estimates of 0.381 (95% CI: 0.166, 0.632, P < 0.001). Similarly, the indirect effect of C-reactive protein was -0.307 (95% CI: -0.645, -0.064, P = 0.034). White blood cells and C-reactive protein significantly mediated the relationship between the burden of comorbidity and Ct values by 29.56% and 18.13% of the total effect size, respectively. Conclusions: Inflammation mediated the association between the overall burden of comorbidity and Ct values among elderly with COVID-19, which suggests that combined immunomodulatory therapies could reduce the Ct values for such patients with a high burden of comorbidity.

A follow up study of cycle threshold values of SARS-CoV-2 in Hunan Province, China.

Since the epidemic of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), many governments have used reverse transcription polymerase chain reaction (RT-PCR) to detect the virus. However, there are fewer measures of CT values information based on RT-PCR results, and the relationship between CT values and factors from consecutive tests is not clear enough. So in this study, we analyzed the connection between CT values and the factors based on cohort data from Delta variant of SARS-CoV-2 in Hunan Province. Previous studies have showed that the mean age of the cases was 33.34 years (±18.72 years), with a female predominance (55.03%, n = 71), and the greatest proportion of clinical symptoms were of the common type (60.47%, n = 78). There were statistical differences between the N and ORF1ab genes in the CT values for the cases. Based on the analysis of the association between CT values and the factors, the lowest CT values were obtained for the unvaccinated, older and clinically symptomatic group at 3-10 days, the maximum peak of viral load occurred. Therefore, it is recommended to use patient information to focus on older, clinically symptomatic, unvaccinated patients and to intervene promptly upon admission.

Increased risk of COVID-19 mortality rate in IFITM3 rs6598045 G allele carriers infected by SARS-CoV-2 delta variant.

BACKGROUND: The interferon-induced transmembrane-protein 3 (IFITM3) is a vital component of the immune system's defense against viral infection. Variants in the IFITM3 gene have been linked to changes in expression and the risk of severe Coronavirus disease 2019 (COVID-19). This study aimed to investigate whether IFITM3 rs6598045, quantitative polymerase chain reaction (qPCR) cycle threshold (Ct) values, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are associated with an increased mortality rate of COVID-19. METHODS: The genotyping of IFITM3 rs6598045 polymorphism was analyzed using the amplification refractory mutation system-polymerase chain reaction in 1342 recovered and 1149 deceased patients positive for SARS-CoV-2. RESULTS: In this study, IFITM3 rs6598045 G allele as minor allele frequency was significantly more common in the deceased patients than in the recovered ones. Furthermore, the highest mortality rates were observed in Delta variant and lowest qPCR Ct values. COVID-19 mortality was associated with IFITM3 rs6598045 GG and AG in Delta variant and IFITM3 rs6598045 AG in Alpha variant. A statistically significant difference was observed in the qPCR Ct values between individuals with GG and AG genotypes and those with an AA genotype. CONCLUSION: A possible correlation was observed between the mortality rate of COVID-19, the G allele of IFITM3 rs6598045, and SARS-CoV-2 variants. However, large-scale research is still required to validate our results.

SARS-CoV-2 nasopharyngeal viral load in individuals infected with BA.2, compared to Alpha, Gamma, Delta and BA.1 variants: A single-center comparative analysis.

BACKGROUND: SARS-CoV-2 has evolved, leading to the emergence of new Variants Of Concern (VOCs) with significant impact on transmissibility. Although the transmission process is complex, higher nasopharyngeal viral load (NP-VL) can be considered as a proxy for greater transmissibility. OBJECTIVES: The aim of this analysis was to compare NP-VL across a set of representative VOCs observed in mildly symptomatic patients. STUDY DESIGN: Observational single-center comparative analysis of patients with early mild-to-moderate COVID-19, enrolled within the early treatment access program of Lazzaro Spallanzani Institute (March 2021-March 2022). NP-VL before drug administration was estimated through RT-PCR, based on cycle threshold values (CTs); VOCs were identified by Sanger sequencing. VOCs' average treatment effect (ATE) was estimated on the CTs fitted in the log2 scale, controlling for potential confounders. RESULTS: A total of 707 patients were included. VOCs were: 10% Alpha, 3% Gamma, 34% Delta, 34% BA.1, 19% BA.2. Mean CTs for BA.1 and BA.2 were lower than Delta and BA.1, respectively. After adjusting for calendar time, age, immunodeficiency and vaccination, CTs for Gamma were lower than those seen for Alpha and higher than Delta, for Delta were similar to BA.1, for BA.2 were lower than Delta and BA.1. CONCLUSIONS: Our analysis shows higher NP-VL of BA.2 compared to previously circulating VOCs, even after controlling for factors potentially contributing to the amount of nasopharyngeal viral RNA, included vaccination, supporting the increased transmissibility of BA.2. Further studies are necessary to clarify this mechanism and to provide guidance for public health measures.

DYNAMICS OF COVID-19 SYMPTOMS AND CHANGES IN CT VALUES OF RDRP, N AND E GENES IN 1044 PATIENTS POSITIVE FOR SARS-COV-2

Purpose: To describe clinical characteristics of patients positive simultaneously for RdRp, N and E genes of SARS-CoV-2 and to analyse dynamics of symptoms and Ct values in the interval from day 0 to day 10 after symptoms onset. Materials and methods: Retrospective analysis of data obtained on the day of specimen collection from 1044 individuals was carried out. Detection of RdRp, E and N genes of SARS-CoV-2 was conducted by RT-PCR. Only patients positive for all three genes were included. Results: Out of all patients, 47.8% were female, and 52.2% were male with a median age of 60 years, and the elder (>50 years) population constituted 71.5%. The most common comorbidities were cardiovascular disease (44.5%), diabetes mellitus (11.0%), and chronic pulmonary disease (8.6%). The prevalent symptoms at the time of specimen collection were fever (74.7%), cough (67.1%), and dyspnea (39.6%). Fever and cough were leading symptoms in the time interval between zero and the tenth day since the onset of COVID-19. A linear trend for dry cough and dyspnea, with a daily increase of 2.2% and 2.3%, respectively, was observed. Dry cough was the primary discriminator in distinguishing mild and moderate infection. Gradual increase of Ct values of all genes was observed from day 0 to day 10, and day 3 was essential for separating two time intervals. Conclusions: Flu-like symptoms were leading over the study period. Male sex, older age, cardiovascular disease, diabetes mellitus, and chronic pulmonary disease were risk factors for infection. Cough, age over 65 years and male sex in the group 33-63 years were predictors of more severe disease.

Weekly Nowcasting of New COVID-19 Cases Using Past Viral Load Measurements.

The rapid spread of the coronavirus disease COVID-19 has imposed clinical and financial burdens on hospitals and governments attempting to provide patients with medical care and implement disease-controlling policies. The transmissibility of the disease was shown to be correlated with the patient's viral load, which can be measured during testing using the cycle threshold (Ct). Previous models have utilized Ct to forecast the trajectory of the spread, which can provide valuable information to better allocate resources and change policies. However, these models combined other variables specific to medical institutions or came in the form of compartmental models that rely on epidemiological assumptions, all of which could impose prediction uncertainties. In this study, we overcome these limitations using data-driven modeling that utilizes Ct and previous number of cases, two institution-independent variables. We collected three groups of patients (n = 6296, n = 3228, and n = 12,096) from different time periods to train, validate, and independently validate the models. We used three machine learning algorithms and three deep learning algorithms that can model the temporal dynamic behavior of the number of cases. The endpoint was 7-week forward number of cases, and the prediction was evaluated using mean square error (MSE). The sequence-to-sequence model showed the best prediction during validation (MSE = 0.025), while polynomial regression (OLS) and support vector machine regression (SVR) had better performance during independent validation (MSE = 0.1596, and MSE = 0.16754, respectively), which exhibited better generalizability of the latter. The OLS and SVR models were used on a dataset from an external institution and showed promise in predicting COVID-19 incidences across institutions. These models may support clinical and logistic decision-making after prospective validation.

The Matrix Effect in the RT-PCR Detection of SARS-CoV-2 Using Saliva without RNA Extraction.

The present work focuses on the detection of SARS-CoV-2 in saliva, contributing to understanding the inhibition effect of the matrix and its influence on the results. Detection of viral genes ORF1ab, N, and E was performed by RT-PCR using saliva directly in the reaction without RNA extraction. Different amounts of saliva were spiked with increasing amounts of viral RNA from COVID-19 patients and subjected to RT-PCR detection. In parallel, 64 saliva samples from confirmed COVID-19 patients were used in two different amounts directly in the RT-PCR reaction and their results compared. The presence of saliva in the RT-PCR always causes a positive shift of the Ct values, but a very high between-person variability of its magnitude was obtained, with increases ranging from 0.93 to 11.36. Viral targets are also affected differently depending on the initial number of viral particles. Due to inhibitors present in saliva, the duplication of sample volume causes only 48 to 61% of the expected Ct value decrease depending on the viral target gene. The use of saliva has advantages, but also limitations, due to potential inhibitors present in the matrix. However, the choice of the target and the right amount of sample may significantly influence the results.

Which criteria should we use to end isolation in hemodialysis patients with COVID-19?

Safe and timely discontinuation of quarantine of in-center hemodialysis (HD) patients with a previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a challenging issue for the nephrological community because current guidelines for ending isolation do not mention dialysis patients. To prevent potentially fatal outbreaks of coronavirus disease 2019 (COVID-19), a cautionary approach has been adopted by most dialysis units. The criteria for ending the isolation in the HD population generally coincide with those recommended for immunocompromised people. Thus, a test-based strategy relying on two consecutive negative reverse transcriptase-polymerase chain reaction (RT-PCR) nasopharyngeal swabs has been adopted to terminate quarantine. This strategy has the disadvantage of prolonging isolation as RT-PCR positivity does not equate to SARS-CoV-2 infectivity. Consequentially, prolonged positivity of SARS-CoV-2 results in excessive workload for the HD staff who must face an increasing number of COVID-19 patients requiring isolation. This condition leads also to serious implications for the patients and their households including work productivity loss, postponement of health-care appointments and an increased risk of COVID-19 reinfection. To counteract this problem, other diagnostic tests should be used to provide the best care to HD patients. Recent results seem to encourage the use of RT-PCR cycle threshold (Ct) values and rapid antigen tests given their better correlation with cell culture for SARS-CoV-2 than RT-PCR testing. Here, we provide an overview of the current scientific evidence on the tests used to verify the infectiousness of the virus in order to stimulate the nephrological community to adopt a streamlined and pragmatic procedure to end isolation in COVID-19 patients on HD.

Correlation between real-time PCR cycle threshold and clinical classification of COVID-19

Background: The cycle threshold (Ct) of real-time reverse transcription PCR (RT-qPCR) indicates the relative concentration of an RNA sequence, this value has been related to clinical profile in viral infections. Aim: To determine the correlation between the Ct value and the clinical classification of COVID-19. Method: A correlational cross-sectional study was carried out, the Ct values were obtained by RT-qPCR directed to the N gene of SARS-CoV-2, grouping them by means of a central robust estimator and related to the clinical classification of COVID-19. Results: Of the 718 cases included in the study;77.7% (558) were mild;21.3% (153) moderate and 1% (7) severe. The Ct value was grouped into levels: low Ct <= 18.83;medium Ct> 18.83- 30.10 and high Ct> 30.10. There was a weak inverse significant correlation (p = 0.002;Spearman's rho = -0.117) between the Ct value and the clinical classification. The characteristics: sex, age under 65 years, fever, chills, diarrhea, anosmia, and overweight-obesity were associated with the Ct value. Conclusion: The lower the Ct value, a classification of greater severity of COVID-19 is expected, however, because the correlation is weak, its usefulness as a severity predictor is limited.

Can a quantitative assessment of SARS-CoV-2 PCR predict degree of severity and outcomes in critical care patients with COVID-19?

Real-Time polymerase chain reaction (qPCR) is the gold standard diagnostic method for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cycle threshold (Ct) is defined as the number of heating and cooling cycles required during the PCR process. Ct-values are inversely proportional to the amount of target nucleic acid in a sample. Our aim, in this retrospective study, was to determine the impact of serial SARS-CoV-2 qPCR Ct-values on: mortality, need for mechanical ventilation (MV) and development of acute kidney injury (AKI) in patients admitted to the intensive care unit (ICU) with COVID-19. Ct values were evaluated during the time points from pre-ICU admission to week 1, week 2 and week 3 during ICU stay; impact on mortality, need for MV and AKI was determined. There was a continuous increment in Ct-values over the ICU stay from 1st week through to 3rd week. Although not significant, lower ICU 1st week Ct-values were associated with Black ethnicity, increased need for MV and mortality. However, patients who had developed AKI at any stage of their illness had significantly lower Ct-values compared to those with normal renal function. When ICU 1st-week Ct-values are subcategorised as <20, 20-30 and >30 the 28-day survival probability was less for patients with Ct-values of <20. This report shows that the impact of Ct-values and outcomes, especially AKI, among patients at different time points prior to and during ICU stay, larger studies are required to confirm out findings.

Comparison of FTD SARS-CoV-2 Assay and RealStar RT-PCR kit 1.0 for the detection of SARS-CoV-2.

The aim of the study was to evaluate the clinical performance of FTD SARS-CoV-2 compared to the RealStar RT-PCR kit 1.0. The analysis of 100 nasopharyngeal swabs showed an overall agreement of 88 %. The positive percentage agreement was 85.6 % and the negative percentage agreement was 91 %. In conclusion we observed a substantial agreement among the two methods, with discrepancies mainly observed in specimens with relatively low amount of viral RNA.

Acute onset olfactory/taste disorders are associated with a high viral burden in mild or asymptomatic SARS-CoV-2 infections.

This study investigated, using cycle threshold (Ct) qPCR values, the association between symptoms and viral clearance in 57 patients with asymptomatic/mild SARS-CoV-2 infection. Patients with olfactory/taste disorders (OTDs) exhibited lower qPCR Ct values and longer time to negative qPCR than those without OTDs, suggesting an association between OTDs and high viral burden.

Viral Dynamics and Real-Time RT-PCR Ct Values Correlation with Disease Severity in COVID-19.

Real-time RT-PCR is considered the gold standard confirmatory test for coronavirus disease 2019 (COVID-19). However, many scientists disagree, and it is essential to understand that several factors and variables can cause a false-negative test. In this context, cycle threshold (Ct) values are being utilized to diagnose or predict SARS-CoV-2 infection. This practice has a significant clinical utility as Ct values can be correlated with the viral load. In addition, Ct values have a strong correlation with multiple haematological and biochemical markers. However, it is essential to consider that Ct values might be affected by pre-analytic, analytic, and post-analytical variables such as collection technique, specimen type, sampling time, viral kinetics, transport and storage conditions, nucleic acid extraction, viral RNA load, primer designing, real-time PCR efficiency, and Ct value determination method. Therefore, understanding the interpretation of Ct values and other influential factors could play a crucial role in interpreting viral load and disease severity. In several clinical studies consisting of small or large sample sizes, several discrepancies exist regarding a significant positive correlation between the Ct value and disease severity in COVID-19. In this context, a revised review of the literature has been conducted to fill the knowledge gaps regarding the correlations between Ct values and severity/fatality rates of patients with COVID-19. Various databases such as PubMed, Science Direct, Medline, Scopus, and Google Scholar were searched up to April 2021 by using keywords including "RT-PCR or viral load", "SARS-CoV-2 and RT-PCR", "Ct value and viral load", "Ct value or COVID-19". Research articles were extracted and selected independently by the authors and included in the present review based on their relevance to the study. The current narrative review explores the correlation of Ct values with mortality, disease progression, severity, and infectivity. We also discuss the factors that can affect these values, such as collection technique, type of swab, sampling method, etc.

S-Variant SARS-CoV-2 Lineage B1.1.7 Is Associated With Significantly Higher Viral Load in Samples Tested by TaqPath Polymerase Chain Reaction.

A SARS-CoV-2 variant B1.1.7 containing mutation Δ69/70 has spread rapidly in the United Kingdom and shows an identifiable profile in ThermoFisher TaqPath RT-qPCR, S gene target failure (SGTF). We analyzed recent test data for trends and significance. Linked cycle threshold (Ct) values for respiratory samples showed that a low Ct for ORF1ab and N were clearly associated with SGTF. Significantly more SGTF samples had higher inferred viral loads between 1×107 and 1×108. Our conclusion is that patients whose samples exhibit the SGTF profile are more likely to have high viral loads, which may explain higher infectivity and rapidity of spread.

CRISPR/Cas12a-Based Versatile Method for Checking Quantitative Polymerase Chain Reaction Samples with Cycles of Threshold Values in the Gray Zone.

Quantitative polymerase chain reaction (qPCR) is widely applied in foodborne pathogen detection and diagnosis. According to the cycles of threshold (Ct) values of qPCR testing, samples are judged as positive or negative. However, samples with Ct values in the gray zone are classified as "possibly positive" and required to be tested again. Repetitive qPCR may not eliminate the uncertain results but increase the workload of detection. CRISPR/Cas12a can specifically recognize the nucleic acid of the nM level and then indiscriminately slash the single-strand DNA with multiple turnovers. In this way, the detection signals can be greatly amplified. Here, we propose a CRISPR-based checking method to solve gray zone problems. After qPCR testing, the screening gray zone samples can be successfully checked by the CRISPR/Cas12a method. Furthermore, to conduct CRISPR reaction assay more conveniently and prevent possible aerosol contamination in the operational process, a gray zone checking cassette is designed. African swine fever virus (ASFV) is selected as an example to demonstrate the feasibility of the CRISPR-based checking method. Of 28 real swine blood samples, 6 ASFV qPCR gray zone samples are successfully checked. The CRISPR-based checking method provides a novel solution to eliminate gray zone sample problems with no additional effects on the PCR, which is operable and applicable in practical detection. The entire process can be completed within 10-15 min. This method will be a good supplementary and assistance for qPCR-based detection, especially in the diagnosis of diseases such as COVID-19.

Comparative evaluation of four SARS-CoV-2 antigen tests in hospitalized patients.

OBJECTIVES: Rapid identification of infected subjects is a cornerstone for controlling a pandemic like the current one with the SARS-CoV-2. Easy to handle antigen tests can provide timely results, which is of particular importance in a primary care setting. However, concerns exist regarding their sensitivity, which led us to evaluate four commercially available tests in patients hospitalized for COVID-19. METHODS: We analyzed in parallel nasopharyngeal/oropharyngeal swabs from 154 consecutive patients admitted to our department with moderate to severe COVID-19, using quantitative RT-PCR (Cobas, Roche) and up to four antigen tests from different distributors. Antigen test results were linked to Ct (cycle threshold) values as markers for patients' infectivity. RESULTS: We found that two out of four antigen tests correctly identified subjects with high viral loads (Ct≤25), and three out of four tests detected more than 80% of subjects with a Ct≤30, which is considered the threshold for infectivity. However, one test investigated had a poor clinical performance. When investigating subjects with Ct values >30, we found that the antigen test was still positive in up to 45% of those cases. CONCLUSION: Most antigen tests had a sufficient sensitivity to identify symptomatic subjects infected with SARS-CoV-2 and with transmissible infection. On the other hand, antigen testing may not be suitable to identify loss of infectivity in COVID-19 subjects during follow-up. Newly introduced antigen tests need to be validated in a clinical or primary care setting to define their clinical usefulness.

Misinterpretation of viral load in COVID-19 clinical outcomes.

Knowledge of viral load is essential to formulate strategies for antiviral treatment, vaccination, and epidemiological control of COVID-19. Moreover, identification of patients with high viral loads can also be useful to understand risk factors such as age, comorbidities, severity of symptoms and hypoxia, to decide on the need for hospitalization. Several ongoing studies are analyzing viral load in different types of samples and evaluating its relationship with clinical outcomes and viral transmission pathways. However, in a great number of emerging studies, cycle threshold (Ct) values alone are often used as viral load indicators, which may be a mistake. In this study, we compared tracheal aspirate with nasopharyngeal swab samples obtained from critically ill COVID-19 patients and here we report how the raw Ct can lead to misinterpretation of results. Furthermore, based on analysis of nasopharyngeal swab samples we propose a method to reduce evaluation errors that could occur from using raw Ct data. Based on these findings, we show the impact that normalization of Ct values has on interpretation of SARS-CoV-2 viral load from different biological samples.

Significance of liver dysfunction associated with decreased hepatic CT attenuation values in Japanese patients with severe COVID-19.

BACKGROUND: COVID-19 has emerged as a threat to human health. Liver dysfunction has been reported to occur frequently in patients with COVID-19, although its significance has not yet been elucidated. METHODS: The subjects were 35 patients with COVID-19, and clinical characteristics were retrospectively analyzed. COVID-19 patients requiring ventilator were classified as having severe COVID-19. RESULTS: All 35 patients were diagnosed as having mild-to-moderate COVID-19 at admission, but the severity aggravated to severe in 8 patients (22.9%) in hospital. Hepatocellular-type liver injury, defined as elevation of the serum AST and/or ALT levels to ≥ 3 times the ULN, was seen in 2 patients (5.7%), and cholestasis-type liver injury, defined as elevation of the serum ALP, γ-GTP and/or total bilirubin levels to ≥ twice the ULN, was seen in 4 patients (11.4%). A total of 9 patients (25.7%) fulfilled the criteria for liver injury. The percentage of patients with liver injury was higher in patients with severe COVID-19 than in the remaining patients (P = 0.001). Both the hepatic CT attenuation values and the liver-to-spleen attenuation (L/S) ratios at admission were lower in the former patients than in the latter patients (P < 0.001). ROC curve revealed the optimal cut-off value of the L/S ratio of 1.03 for discriminating between patients with severe and non-severe diseases. The hepatic CT attenuation values increased at the remission phase of the disease as compared to the values at admission (P = 0.012). CONCLUSION: Liver dysfunction associated with reduced hepatic CT attenuation values correlated with the disease severity in patients with COVID-19.

SARS-CoV-2-IgG response is different in COVID-19 outpatients and asymptomatic contact persons.

Commercially available immunoassays have been developed for sensitive and specific detection of antibodies against SARS-CoV-2. While a fast and reliable IgG response has been reported for samples from hospitalized COVID-19 patients, less is known about ambulatory patients. We evaluated the SARS-CoV-2-IgG response by the Anti-SARS-CoV-2-ELISA IgG (Euroimmun) in a defined cohort of SARS-CoV-2-PCR-confirmed outpatients and asymptomatic contact persons including 137 serum samples from PCR-confirmed outpatients (n = 111) and asymptomatic but PCR-positive contact persons (n = 26) sent to our laboratory as part of routine diagnostics for determination of SARS-CoV-2-IgG. Overall positivity rate for SARS-CoV-2-IgG was 81.1 % in outpatients (irrespective of sampling before or after day 21 after onset of symptoms) but significantly lower in asymptomatic contact persons (15.4 %, p < 0.0001). In contact persons without symptoms the ct values of the PCR assays were significantly higher (5-7 threshold cycles) than in outpatients, and ct values were significantly negative correlated to the SARS-CoV-2-IgG ratio, suggesting a lower viral load as a possible explanation for lower rate of seropositivity. In summary, our study shows that serological response to SARS-CoV-2 in outpatients including asymptomatic persons is less pronounced than in hospitalized patients. Further controlled studies are urgently needed to determine serological response in outpatients and asymptomatic persons since this is the main target population for seroepidemiological investigations.