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1.
International Journal of Environmental Research and Public Health ; 19(24):17074, 2022.
Article in English | MDPI | ID: covidwho-2166578

ABSTRACT

SARS-CoV-2 RNA is frequently identified in patient rooms and it was speculated that the viral load quantified by PCR might correlate with infectivity of surfaces. To evaluate Ct values for the prediction of infectivity, we investigated contaminated surfaces and Ct-value changes after disinfection. Viral RNA was detected on 37 of 143 investigated surfaces of an ICU. However, virus isolation failed for surfaces with a high viral RNA load. Also, SARS-CoV-2 could not be cultivated from surfaces artificially contaminated with patient specimens. In order to evaluate the significance of Ct values more precisely, we used surrogate enveloped bacteriophage phi6. A strong reduction in phi6 was achieved by three different disinfection methods. Despite a strong reduction in viability almost no change in the Ct values was observed for UV-C and alcoholic surface disinfectant. Disinfection using ozone resulted in a lack of phi6 recovery as well as a detectable shift in Ct values indicating strong degradation of the viral RNA. The observed lack of significant effects on the detectable viral RNA after effective disinfection suggest that quantitative PCR is not suitable for predicting the infectivity of SARS-CoV-2 on inanimate surfaces. Ct values should therefore not be considered as markers for infectivity in this context.

2.
Ann Intern Med ; 173(4): 268-277, 2020 08 18.
Article in English | MEDLINE | ID: covidwho-2110835

ABSTRACT

BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19-positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. RESULTS: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION: Limited sample size. CONCLUSION: The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.


Subject(s)
Autopsy/methods , Coronavirus Infections/mortality , Pneumonia, Viral/mortality , Pulmonary Embolism/mortality , Venous Thromboembolism/mortality , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Cause of Death , Female , Germany/epidemiology , Humans , Male , Middle Aged , Pandemics , Prospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed
3.
Cell Rep Med ; 3(9): 100735, 2022 09 20.
Article in English | MEDLINE | ID: covidwho-1984242

ABSTRACT

We here investigate the impact of antiviral treatments such as remdesivir on intra-host genomic diversity and emergence of SARS-CoV2 variants in patients with a prolonged course of infection. Sequencing and variant analysis performed in 112 longitudinal respiratory samples from 14 SARS-CoV2-infected patients with severe disease progression show that major frequency variants do not generally arise during prolonged infection. However, remdesivir treatment can increase intra-host genomic diversity and result in the emergence of novel major variant species harboring fixed mutations. This is particularly evident in a patient with B cell depletion who rapidly developed mutations in the RNA-dependent RNA polymerase gene following remdesivir treatment. Remdesivir treatment-associated emergence of novel variants is of great interest in light of current treatment guidelines for hospitalized patients suffering from severe SARS-CoV2 disease, as well as the potential use of remdesivir to preventively treat non-hospitalized patients at high risk for severe disease progression.


Subject(s)
COVID-19 , Coronavirus Infections , Pneumonia, Viral , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/adverse effects , Betacoronavirus , COVID-19/drug therapy , Coronavirus Infections/drug therapy , Disease Progression , Humans , Pandemics , Pneumonia, Viral/chemically induced , RNA, Viral/therapeutic use , RNA-Dependent RNA Polymerase , SARS-CoV-2/genetics
4.
Emerg Infect Dis ; 28(9): 1765-1769, 2022 09.
Article in English | MEDLINE | ID: covidwho-1974607

ABSTRACT

Beginning in May 2022, a rising number of monkeypox cases were reported in non-monkeypox-endemic countries in the Northern Hemisphere. We adapted 2 published quantitative PCRs for use as a dual-target monkeypox virus test on widely used automated high-throughput PCR systems. We determined analytic performance by serial dilutions of monkeypox virus reference material, which we quantified by digital PCR. We found the lower limit of detection for the combined assays was 4.795 (95% CI 3.6-8.6) copies/mL. We compared clinical performance against a commercial manual orthopoxvirus research use only PCR kit by using clinical remnant swab samples. Our assay showed 100% positive (n = 11) and 100% negative (n = 56) agreement. Timely and scalable PCR tests are crucial for limiting further spread of monkeypox. The assay we provide streamlines high-throughput molecular testing for monkeypox virus on existing broadly established platforms used for SARS-CoV-2 diagnostic testing.


Subject(s)
COVID-19 , Monkeypox , Humans , Molecular Diagnostic Techniques , Monkeypox/diagnosis , Monkeypox/epidemiology , Monkeypox virus/genetics , SARS-CoV-2/genetics , Sensitivity and Specificity
5.
Pathologe ; 42(Suppl 1): 69-75, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1971683

ABSTRACT

BACKGROUND: Autopsy is an important tool for understanding the pathogenesis of diseases, including COVID-19. MATERIAL AND METHODS: On 15 April 2020, together with the German Society of Pathology and the Federal Association of German Pathologists, the German Registry of COVID-19 Autopsies (DeRegCOVID) was launched ( www.DeRegCOVID.ukaachen.de ). Building on this, the German Network for Autopsies in Pandemics (DEFEAT PANDEMIcs) was established on 1 September 2020. RESULTS: The main goal of DeRegCOVID is to collect and distribute de facto anonymized data on potentially all autopsies of people who have died from COVID-19 in Germany in order to meet the need for centralized, coordinated, and structured data collection and reporting during the pandemic. The success of the registry strongly depends on the willingness of the respective centers to report the data, which has developed very positively so far and requires special thanks to all participating centers. The rights to own data and biomaterials (stored decentrally) remain with each respective center. The DEFEAT PANDEMIcs network expands on this and aims to strengthen harmonization and standardization as well as nationwide implementation and cooperation in the field of pandemic autopsies. CONCLUSIONS: The extraordinary cooperation in the field of autopsies in Germany during the COVID-19 pandemic is impressively demonstrated by the establishment of DeRegCOVID, the merger of the registry of neuropathology (CNS-COVID19) with DeRegCOVID and the establishment of the autopsy network DEFEAT PANDEMIcs. It gives a strong signal for the necessity, readiness, and expertise to jointly help manage current and future pandemics by autopsy-derived knowledge.


Subject(s)
COVID-19 , Pandemics , Autopsy , Humans , Registries , SARS-CoV-2
6.
J Reprod Immunol ; 153: 103685, 2022 09.
Article in English | MEDLINE | ID: covidwho-1966885

ABSTRACT

Breast milk is a pivotal source to provide passive immunity in newborns over the first few months of life. Very little is known about the antibody transfer levels over the period of breastfeeding. We conducted a prospective study in which we evaluated concentrations of anti-SARS-CoV-2 Spike IgA and RBD IgG/M/A antibodies in maternal serum and breast milk over a duration of up to 6 months after delivery. We compared antibody levels in women with confirmed COVID-19 infection during pregnancy (n = 16) to women with prenatal SARS-CoV-2 vaccination (n = 5). Among the recovered women, n = 7 (44%) had been vaccinated during the lactation period as well. We observed intraindividual moderate positive correlations between antibody levels in maternal serum and breast milk (r = 0.73, p-value<0.0001), whereupon the median levels were generally higher in serum. Anti-RBD IgA/M/G transfer into breast milk was significantly higher in women recovered from COVID-19 and vaccinated during lactation (35.15 AU/ml; IQR 21.96-66.89 AU/ml) compared to the nonvaccinated recovered group (1.26 AU/ml; IQR 0.49-3.81 AU/ml), as well as in the vaccinated only group (4.52 AU/ml; IQR 3.19-6.23 AU/ml). Notably, the antibody level in breast milk post SARS-CoV-2 infection sharply increased following a single dose of vaccine. Breast milk antibodies in all groups showed neutralization capacities against an early pandemic SARS-CoV-2 isolate (HH-1) and moreover, also against the Omicron variant, although with lower antibody titer. Our findings highlight the importance of booster vaccinations especially after SARS-CoV-2 infection in pregnancy in order to optimize protection in mother and newborn.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Viral , Breast Feeding , COVID-19/prevention & control , COVID-19 Vaccines , Cohort Studies , Female , Humans , Immunoglobulin A , Immunoglobulin G , Infant, Newborn , Lactation , Milk, Human , Prospective Studies , SARS-CoV-2 , Vaccination
7.
Vaccines (Basel) ; 10(7)2022 Jul 06.
Article in English | MEDLINE | ID: covidwho-1917889

ABSTRACT

BACKGROUND: The immunogenicity of different COVID-19 vaccine regimens and combinations in naïve and convalescent individuals has not been formally tested in controlled studies, and real-life observational studies are scarce. METHODS: We assessed the SARS-CoV-2 infection and COVID-19 vaccination-induced immunity of 697 hospital workers at the University Medical Center Hamburg-Eppendorf between 17 and 31 January 2022. RESULTS: The overall prevalence of anti-NC-SARS-CoV-2 antibodies indicating prior infection was 9.8% (n = 68) and thus lower than the seroprevalence in the general population. All vaccinated individuals had detectable anti-S1-RBD-SARS-CoV-2 antibodies (median AU/mL [IQR]: 13,891 [8505-23,543]), indicating strong protection against severe COVID-19. Individuals who received three COVID-19 vaccine doses (median AU/mL [IQR]: 13,856 [8635-22,705]) and those who resolved a prior SARS-CoV-2 infection and had received two COVID-19 vaccine doses (median AU/mL [IQR] 13,409 [6934-25,000]) exhibited the strongest humoral immune responses. CONCLUSIONS: The current study indicates that three exposures to the viral spike protein by either SARS-CoV-2 infection or COVID-19 vaccination are necessary to elicit particularly strong humoral immune responses, which supports current vaccination recommendations.

8.
Clin Infect Dis ; 2022 Jun 19.
Article in English | MEDLINE | ID: covidwho-1901142

ABSTRACT

BACKGROUND: The ongoing COVID-19 pandemic significantly burdens hospitals and other healthcare facilities. Therefore, understanding the entry and transmission of SARS-CoV-2 is critical for effective prevention and preparedness measures. We performed surveillance and analysis of testing and transmission of SARS-CoV-2 infections in a tertiary-care hospital in Germany during the second and third pandemic waves in fall/winter 2020. METHODS: Between calendar weeks 41/2020 and 1/2021 40% of all positive patient and staff samples (284 total) were subjected to full-length viral genome sequencing. Clusters were defined based on similar genotypes indicating common sources of infection. We integrated phylogenetic, spatial, and temporal metadata to detect nosocomial infections and outbreaks, uncover transmission chains, and evaluate containment measures' effectiveness. RESULTS: Epidemiologic data and contact tracing readily recognize most healthcare-associated patient infections. However, sequencing data reveal that temporally preceding index cases and transmission routes can be missed using epidemiologic methods, resulting in delayed interventions and serially linked outbreaks being counted as independent events. While hospital-associated transmissions were significantly elevated at a moderate rate of community transmission during the second wave, systematic testing and high vaccination rates among staff have led to a substantial decrease in healthcare-associated infections at the end of the second/beginning of the third wave despite high community transmissions. CONCLUSIONS: While epidemiologic analysis is critical for immediate containment of healthcare-associated SARS-CoV-2 outbreaks, integration of genomic surveillance revealed weaknesses in identifying staff contacts. Our study underscores the importance of high testing frequency and genomic surveillance to detect, contain and prevent SARS-CoV-2-associated infections in healthcare settings.

9.
J Med Virol ; 94(10): 5038-5043, 2022 10.
Article in English | MEDLINE | ID: covidwho-1888757

ABSTRACT

We aimed to provide in vitro data on the neutralization capacity of different monoclonal antibody (mAb) preparations against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta and omicron variant, respectively, and describe the in vivo RNA kinetics of coronavirus disease 2019 (COVID-19) patients treated with the respective mAbs. Virus neutralization assays were performed to assess the neutralizing effect of the mAb formulations casirivimab/imdevimab and sotrovimab on the SARS-CoV-2 delta and omicron variant. Additionally, respiratory tract SARS-CoV-2 RNA kinetics are provided for 25 COVID-19 patients infected with either delta variant (n = 18) or omicron variant (n = 7) treated with the respective mAb formulations during their hospital stay. In the virus neutralization assay, sotrovimab exhibits neutralizing capacity at therapeutically achievable concentrations against the SARS-CoV-2 delta and omicron variant. In contrast, casivirimab/imdevimab had neutralizing capacity against the delta variant but failed neutralization against the omicron variant except for a very high concentration above the currently recommended therapeutic dosage. In patients with delta variant infections treated with casivirimab/imdevimab, we observed a rapid decrease of respiratory viral RNA at day 3 after mAb therapy. In contrast, no such prompt decline was observed in patients with delta variant or omicron variant infections receiving sotrovimab.


Subject(s)
Antineoplastic Agents, Immunological , COVID-19 , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/drug therapy , Humans , Membrane Glycoproteins/genetics , Neutralization Tests , RNA, Viral , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Treatment Outcome , Viral Envelope Proteins/genetics
10.
Eur Heart J ; 43(11): 1124-1137, 2022 03 14.
Article in English | MEDLINE | ID: covidwho-1853027

ABSTRACT

AIMS: Long-term sequelae may occur after SARS-CoV-2 infection. We comprehensively assessed organ-specific functions in individuals after mild to moderate SARS-CoV-2 infection compared with controls from the general population. METHODS AND RESULTS: Four hundred and forty-three mainly non-hospitalized individuals were examined in median 9.6 months after the first positive SARS-CoV-2 test and matched for age, sex, and education with 1328 controls from a population-based German cohort. We assessed pulmonary, cardiac, vascular, renal, and neurological status, as well as patient-related outcomes. Bodyplethysmography documented mildly lower total lung volume (regression coefficient -3.24, adjusted P = 0.014) and higher specific airway resistance (regression coefficient 8.11, adjusted P = 0.001) after SARS-CoV-2 infection. Cardiac assessment revealed slightly lower measures of left (regression coefficient for left ventricular ejection fraction on transthoracic echocardiography -0.93, adjusted P = 0.015) and right ventricular function and higher concentrations of cardiac biomarkers (factor 1.14 for high-sensitivity troponin, 1.41 for N-terminal pro-B-type natriuretic peptide, adjusted P ≤ 0.01) in post-SARS-CoV-2 patients compared with matched controls, but no significant differences in cardiac magnetic resonance imaging findings. Sonographically non-compressible femoral veins, suggesting deep vein thrombosis, were substantially more frequent after SARS-CoV-2 infection (odds ratio 2.68, adjusted P < 0.001). Glomerular filtration rate (regression coefficient -2.35, adjusted P = 0.019) was lower in post-SARS-CoV-2 cases. Relative brain volume, prevalence of cerebral microbleeds, and infarct residuals were similar, while the mean cortical thickness was higher in post-SARS-CoV-2 cases. Cognitive function was not impaired. Similarly, patient-related outcomes did not differ. CONCLUSION: Subjects who apparently recovered from mild to moderate SARS-CoV-2 infection show signs of subclinical multi-organ affection related to pulmonary, cardiac, thrombotic, and renal function without signs of structural brain damage, neurocognitive, or quality-of-life impairment. Respective screening may guide further patient management.


Subject(s)
COVID-19 , COVID-19/diagnosis , COVID-19/epidemiology , Cohort Studies , Humans , SARS-CoV-2 , Stroke Volume , Ventricular Function, Left
11.
Virchows Arch ; 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1787815

ABSTRACT

The use of autopsies in medicine has been declining. The COVID-19 pandemic has documented and rejuvenated the importance of autopsies as a tool of modern medicine. In this review, we discuss the various autopsy techniques, the applicability of modern analytical methods to understand the pathophysiology of COVID-19, the major pathological organ findings, limitations or current studies, and open questions. This article summarizes published literature and the consented experience of the nationwide network of clinical, neuro-, and forensic pathologists from 27 German autopsy centers with more than 1200 COVID-19 autopsies. The autopsy tissues revealed that SARS-CoV-2 can be found in virtually all human organs and tissues, and the majority of cells. Autopsies have revealed the organ and tissue tropism of SARS-CoV-2, and the morphological features of COVID-19. This is characterized by diffuse alveolar damage, combined with angiocentric disease, which in turn is characterized by endothelial dysfunction, vascular inflammation, (micro-) thrombosis, vasoconstriction, and intussusceptive angiogenesis. These findings explained the increased pulmonary resistance in COVID-19 and supported the recommendations for antithrombotic treatment in COVID-19. In contrast, in extra-respiratory organs, pathological changes are often nonspecific and unclear to which extent these changes are due to direct infection vs. indirect/secondary mechanisms of organ injury, or a combination thereof. Ongoing research using autopsies aims at answering questions on disease mechanisms, e.g., focusing on variants of concern, and future challenges, such as post-COVID conditions. Autopsies are an invaluable tool in medicine and national and international interdisciplinary collaborative autopsy-based research initiatives are essential.

12.
Nat Metab ; 4(3): 310-319, 2022 03.
Article in English | MEDLINE | ID: covidwho-1764213

ABSTRACT

Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae1. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displays tropism towards several organs, including the heart and kidney. Whether it also directly affects the liver has been debated2,3. Here we provide clinical, histopathological, molecular and bioinformatic evidence for the hepatic tropism of SARS-CoV-2. We find that liver injury, indicated by a high frequency of abnormal liver function tests, is a common clinical feature of COVID-19 in two independent cohorts of patients with COVID-19 requiring hospitalization. Using autopsy samples obtained from a third patient cohort, we provide multiple levels of evidence for SARS-CoV-2 liver tropism, including viral RNA detection in 69% of autopsy liver specimens, and successful isolation of infectious SARS-CoV-2 from liver tissue postmortem. Furthermore, we identify transcription-, proteomic- and transcription factor-based activity profiles in hepatic autopsy samples, revealing similarities to the signatures associated with multiple other viral infections of the human liver. Together, we provide a comprehensive multimodal analysis of SARS-CoV-2 liver tropism, which increases our understanding of the molecular consequences of severe COVID-19 and could be useful for the identification of organ-specific pharmacological targets.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Liver , Proteomics , Tropism
13.
Viruses ; 14(3)2022 03 15.
Article in English | MEDLINE | ID: covidwho-1742730

ABSTRACT

BACKGROUND: The recently emerged SARS-CoV-2 B.1.1.529 lineage and its sublineages (Omicron variant) pose a new challenge to healthcare systems worldwide due to its ability to efficiently spread in immunized populations and its resistance to currently available monoclonal antibody therapies. RT-PCR-based variant tests can be used to screen large sample-sets rapidly and accurately for relevant variants of concern (VOC). The aim of this study was to establish and validate a multiplex assay on the cobas 6800/8800 systems to allow discrimination between the two currently circulating VOCs, Omicron and Delta, in clinical samples. METHODS: Primers and probes were evaluated for multiplex compatibility. Analytic performance was assessed using cell culture supernatant of an Omicron variant isolate and a clinical Delta variant sample, normalized to WHO-Standard. Clinical performance of the multiplex assay was benchmarked against NGS results. RESULTS: In silico testing of all oligos showed no interactions with a high risk of primer-dimer formation or amplification of human DNA/RNA. Over 99.9% of all currently available Omicron variant sequences are a perfect match for at least one of the three Omicron targets included in the multiplex. Analytic sensitivity was determined as 19.0 IU/mL (CI95%: 12.9-132.2 IU/mL) for the A67V + del-HV69-70 target, 193.9 IU/mL (CI95%: 144.7-334.7 IU/mL) for the E484A target, 35.5 IU/mL (CI95%: 23.3-158.0 IU/mL) for the N679K + P681H target and 105.0 IU/mL (CI95%: 80.7-129.3 IU/mL) for the P681R target. All sequence variances were correctly detected in the clinical sample set (225/225 Targets). CONCLUSION: RT-PCR-based variant screening compared to whole genome sequencing is both rapid and reliable in detecting relevant sequence variations in SARS-CoV-2 positive samples to exclude or verify relevant VOCs. This allows short-term decision-making, e.g., for patient treatment or public health measures.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , DNA Primers/genetics , High-Throughput Screening Assays , Humans , SARS-CoV-2/genetics
14.
Int J Hyg Environ Health ; 240: 113928, 2022 03.
Article in English | MEDLINE | ID: covidwho-1648655

ABSTRACT

We describe two outbreaks of SARS-CoV-2 in daycare centers in the metropolitan area of Hamburg, Germany. The outbreaks occurred in rapid chronological succession, in neighborhoods with a very similar sociodemographic structure, thus allowing for cross-comparison of these events. We combined classical and molecular epidemiologic investigation methods to study infection entry, spread within the facilities, and subsequent transmission of infections to households. Epidemiologic and molecular evidence suggests a superspreading event with a non-variant of concern (non-VOC) SARS CoV-2 strain at the root of the first outbreak. The second outbreak involved two childcare facilities experiencing infection activity with the variant of concern (VOC) B.1.1.7 (Alpha). We show that the index cases in all outbreaks had been childcare workers, and that children contributed substantially to secondary transmission of SARS-CoV-2 infection from childcare facilities to households. The frequency of secondary transmissions in households originating from B.1.1.7-infected children was increased compared to children with non-VOC infections. Self-reported symptoms, particularly cough and rhinitis, occurred more frequently in B.1.1.7-infected children. Especially in light of the rapidly spreading VOC B.1.617.2 (Delta), our data underline the notion that rigorous SARS-CoV-2 testing in combination with screening of contacts regardless of symptoms is an important measure to prevent SARS-CoV-2 infection of unvaccinated individuals in daycare centers and associated households.


Subject(s)
COVID-19 , Child Day Care Centers , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/virology , COVID-19 Testing , Child , Disease Outbreaks , Germany/epidemiology , Humans
15.
Open Forum Infect Dis ; 8(11): ofab509, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1526187

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA loads in patient specimens may act as a clinical outcome predictor in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: We evaluated the predictive value of viral RNA loads and courses in the blood compared with the upper and lower respiratory tract loads of critically ill COVID-19 patients. Daily specimen collection and viral RNA quantification by reverse transcription quantitative polymerase chain reaction were performed in all consecutive 170 COVID-19 patients between March 2020 and February 2021 during the entire intensive care unit (ICU) stay (4145 samples analyzed). Patients were grouped according to their 90-day outcome as survivors (n=100) or nonsurvivors (n=70). RESULTS: In nonsurvivors, blood SARS-CoV-2 RNA loads were significantly higher at the time of admission to the ICU (P=.0009). Failure of blood RNA clearance was observed in 33/50 (66%) of the nonsurvivors compared with 12/64 (19%) survivors (P<.0001). As determined by multivariate analysis, taking sociodemographic and clinical parameters into account, blood SARS-CoV-2 RNA load represents a valid and independent predictor of outcome in critically ill COVID-19 patients (odds ratio [OR; log10], 0.23; 95% CI, 0.12-0.42; P<.0001), with a significantly higher effect for survival compared with respiratory tract SARS-CoV-2 RNA loads (OR [log10], 0.75; 95% CI, 0.66-0.85; P<.0001). Blood RNA loads exceeding 2.51×103 SARS-CoV-2 RNA copies/mL were found to indicate a 50% probability of death. Consistently, 29/33 (88%) nonsurvivors with failure of virus clearance exceeded this cutoff value constantly. CONCLUSIONS: Blood SARS-CoV-2 load is an important independent outcome predictor and should be further evaluated for treatment allocation and patient monitoring.

16.
Emerg Infect Dis ; 28(1): 244-247, 2022 01.
Article in English | MEDLINE | ID: covidwho-1496968

ABSTRACT

We investigated the infectivity of 128 severe acute respiratory disease coronavirus 2-associated deaths and evaluated predictive values of standard diagnostic procedures. Maintained infectivity (20%) did not correlate with viral RNA loads but correlated well with anti-S antibody levels. Sensitivity >90% for antigen-detecting rapid diagnostic tests supports their usefulness for assessment.


Subject(s)
COVID-19 , SARS-CoV-2 , Autopsy , Diagnostic Tests, Routine , Humans , Sensitivity and Specificity , Viral Load
17.
Int J Hyg Environ Health ; 238: 113851, 2021 09.
Article in English | MEDLINE | ID: covidwho-1479610

ABSTRACT

In this longitudinal cohort study, we assessed the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) seroconversion rates and analyzed the coronavirus disease 2019 (COVID-19) vaccine-induced immunity of 872 hospital workers at the University Medical Center Hamburg-Eppendorf between May 11 and May 31, 2021. The overall seroprevalence of anti-NC-SARS-CoV-2 antibodies was 4.7% (n = 41), indicating low SARS-CoV-2 infection rates and persistent effectiveness of hospital-wide infection control interventions during the second and third wave of the pandemic. In total, 92.7% (n = 808) out of the entire study cohort, 98.2% (n = 325) of those who had been vaccinated once and all 393 individuals who had been vaccinated twice had detectable anti-S1-RBD-SARS-CoV-2 antibody titers and no significant differences in vaccine-induced immune response were detected between male and female individuals and between different age groups. Vaccinated study participants with detectable anti-NC-SARS-CoV-2 antibody titers (n = 30) developed generally higher anti-S1-RBD-SARS-CoV-2 antibody titers compared to anti-NC-SARS-CoV-2 negative individuals (n = 694) (median titer: 7812 vs. 345 BAU/ml, p < 0.0001). Furthermore, study participants who received heterologous vaccination with AZD1222 followed by an mRNA vaccine showed markedly higher anti-S1-RBD-SARS-CoV-2 antibody titers than individuals who received two doses of an mRNA vaccine or two doses of AZD1222 (median titer: AZD1222/AZD1222: 1069 BAU/ml, mRNA/mRNA: 1388 BAU/ml, AZD1222/mRNA: 9450 BAU/ml; p < 0.0001). Our results indicate that infection control interventions were generally effective in preventing nosocomial transmission of SARS-CoV-2 and that COVID-19 vaccines can elicit strong humoral responses in the majority of a real-world cohort of hospital workers.


Subject(s)
COVID-19 , Vaccines , Antibodies, Viral , COVID-19 Vaccines , Female , Health Personnel , Humans , Longitudinal Studies , Male , Pandemics , SARS-CoV-2 , Seroepidemiologic Studies
18.
Diagnostics (Basel) ; 11(10)2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-1444133

ABSTRACT

BACKGROUND: The recent emergence of distinct and highly successful SARS-CoV-2 lineages has substantial implications for individual patients and public health measures. While next-generation-sequencing is routinely performed for surveillance purposes, RT-qPCR can be used to rapidly rule-in or rule-out relevant variants, e.g., in outbreak scenarios. The objective of this study was to create an adaptable and comprehensive toolset for multiplexed Spike-gene SNP detection, which was applied to screen for SARS-CoV-2 B.1.617 lineage variants. METHODS: We created a broad set of single nucleotide polymorphism (SNP)-assays including del-Y144/145, E484K, E484Q, P681H, P681R, L452R, and V1176F based on a highly specific multi-LNA (locked nucleic acid)-probe design to maximize mismatch discrimination. As proof-of-concept, a multiplex-test was compiled and validated (SCOV2-617VOC-UCT) including SNP-detection for L452R, P681R, E484K, and E484Q to provide rapid screening capabilities for the novel B.1.617 lineages. RESULTS: For the multiplex-test (SCOV2-617VOC-UCT), the analytic lower limit of detection was determined as 182 IU/mL for L452R, 144 IU/mL for P681R, and 79 IU/mL for E484Q. A total of 233 clinical samples were tested with the assay, including various on-target and off-target sequences. All SNPs (179/179 positive) were correctly identified as determined by SARS-CoV-2 whole genome sequencing. CONCLUSION: The recurrence of SNP locations and flexibility of methodology presented in this study allows for rapid adaptation to current and future variants. Furthermore, the ability to multiplex various SNP-assays into screening panels improves speed and efficiency for variant testing. We show 100% concordance with whole genome sequencing for a B.1.617.2 screening assay on the cobas6800 high-throughput system.

19.
Sci Rep ; 11(1): 19342, 2021 09 29.
Article in English | MEDLINE | ID: covidwho-1442803

ABSTRACT

Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic with significant mortality. Accurate information on the specific circumstances of death and whether patients died from or with SARS-CoV-2 is scarce. To distinguish COVID-19 from non-COVID-19 deaths, we performed a systematic review of 735 SARS-CoV-2-associated deaths in Hamburg, Germany, from March to December 2020, using conventional autopsy, ultrasound-guided minimally invasive autopsy, postmortem computed tomography and medical records. Statistical analyses including multiple logistic regression were used to compare both cohorts. 84.1% (n = 618) were classified as COVID-19 deaths, 6.4% (n = 47) as non-COVID-19 deaths, 9.5% (n = 70) remained unclear. Median age of COVID-19 deaths was 83.0 years, 54.4% were male. In the autopsy group (n = 283), the majority died of pneumonia and/or diffuse alveolar damage (73.6%; n = 187). Thromboses were found in 39.2% (n = 62/158 cases), pulmonary embolism in 22.1% (n = 56/253 cases). In 2020, annual mortality in Hamburg was about 5.5% higher than in the previous 20 years, of which 3.4% (n = 618) represented COVID-19 deaths. Our study highlights the need for mortality surveillance and postmortem examinations. The vast majority of individuals who died directly from SARS-CoV-2 infection were of advanced age and had multiple comorbidities.


Subject(s)
Autopsy , COVID-19 , Comorbidity , Adult , Age Factors , Aged , Aged, 80 and over , Alveolar Epithelial Cells/pathology , Alveolar Epithelial Cells/virology , COVID-19/diagnosis , COVID-19/epidemiology , Female , Germany/epidemiology , Humans , Lung/pathology , Male , Middle Aged , Mortality , Pneumonia , Prospective Studies , Pulmonary Embolism , SARS-CoV-2 , Thrombosis
20.
J Infect ; 83(5): 589-593, 2021 11.
Article in English | MEDLINE | ID: covidwho-1401632

ABSTRACT

INTRODUCTION: The large number of asymptomatic SARS-CoV-2 infections necessitates general screening of employees. We evaluate the performance of a SARS-CoV-2 screening program in asymptomatic healthcare-workers (HCW), utilizing self-sampled gargling-solution and sample pooling for RT-qPCR. METHODS: We conducted a cross-sectional retrospective study to collect real-life data on the performance of a screening-workflow based on automated-pooling and high-throughput qPCR testing over a 3-month-period at the University Hospital Hamburg. RESULTS: Matrix validation reveals that lower limit of detection for SARS-CoV-2 RNA in gargling-solution was 180 copies/mL (5-sample-pool). A total of 55,122 self-collected gargle samples (= 7513 HCWs) was analyzed. The median time to result was 8.5 hours (IQR 7.2-10.8). Of 11,192 pools analyzed, 11,041 (98.7%) were negative, 69 (0.6%) were positive and 82 (0.7%) were invalid. Individual testing of pool participants revealed 57 SARS-CoV-2 previously unrecognized infections. All 57 HCWs were either pre-symptomatic or asymptomatic (prevalence 0.76%,CI95%0.58-0.98%). Accuracy based on HCWs with gargle-solution and NP-swab available within 3-day-interval (N = 521) was 99.5% (CI95%98.3-99.9%), sensitivity 88.9% (CI95%65.3-98.6%) while specificity 99.8% (CI95%98.9-99.9). CONCLUSION: This workflow was highly effective in identifying SARS-CoV-2 positive HCWs, thereby lowering the potential of inter-HCW and HCW-patient transmissions. Automated-sample-pooling helped to conserve qPCR reagents and represents a promising alternative strategy to antigen testing in mass-screening programs.


Subject(s)
COVID-19 , SARS-CoV-2 , Cross-Sectional Studies , Delivery of Health Care , Humans , RNA, Viral , Retrospective Studies , Workflow
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