RNAemia Corresponds to Disease Severity and Antibody Response in Hospitalized COVID-19 Patients

Eberhardt, Kirsten Alexandra; Meyer‐Schwickerath, Charlotte; Heger, Eva; Knops, Elena; Lehmann, Clara; Rybniker, Jan; Schommers, Philipp; Eichenauer, Dennis A.; Kurth, Florian; Ramharter, Michael; Kaiser, Rolf; Holtick, Udo; Klein, Florian; Jung, Norma; Cristanziano, Veronica Di

doi:10.3390/v12091045

Cited by 59 publications

(66 citation statements)

References 36 publications

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“…In patients with fatal COVID-19 disease, approximately 60-70% have viremia, with detectable SARS-CoV-2 in the plasma by PCR [3,4], consistent with our observation that 73% of the patients had detectable SARS-CoV-2 in the myocardium at autopsy. In addition to the heart, previous studies utilizing RT-PCR on fresh tissue have shown similar levels of SARS-CoV-2 RNA in other organs throughout the Fig.…”

Section: Discussionsupporting

confidence: 90%

“…While coronavirus disease 2019 (COVID- 19), as caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), primarily affects the lungs [1,2], systemic viremia can occur in critically ill patients with COVID-19 [3,4]. Potential cardiac involvement by SARS-CoV-2 as indicated by dysrhythmias and acute heart failure with reduced ejection fraction has been reported [5,6].…”

Section: Introductionmentioning

confidence: 99%

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Factors associated with myocardial SARS-CoV-2 infection, myocarditis, and cardiac inflammation in patients with COVID-19

et al. 2021

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COVID-19 has been associated with cardiac injury and dysfunction. While both myocardial inflammatory cell infiltration and myocarditis with myocyte injury have been reported in patients with fatal COVID-19, clinical-pathologic correlations remain limited. The objective was to determine the relationships between cardiac pathological changes in patients dying from COVID-19 and cardiac infection by SARS-CoV-2, laboratory measurements, clinical features, and treatments. In a retrospective study, 41 consecutive autopsies of patients with fatal COVID-19 were analyzed for the associations between cardiac inflammation, myocarditis, cardiac infection by SARS-CoV-2, clinical features, laboratory measurements, and treatments. Cardiac infection was assessed by in situ hybridization and NanoString transcriptomic profiling. Cardiac infection by SARS-CoV-2 was present in 30/41 cases: virus + with myocarditis (n = 4), virus + without myocarditis (n = 26), and viruswithout myocarditis (n = 11). In the cases with cardiac infection, SARS-CoV-2 + cells in the myocardium were rare, with a median density of 1 cell/cm 2. Virus + cases showed higher densities of myocardial CD68 + macrophages and CD3 + lymphocytes, as well as more electrocardiographic changes (23/27 vs 4/10; P = 0.01). Myocarditis was more prevalent with IL-6 blockade than with nonbiologic immunosuppression, primarily glucocorticoids (2/3 vs 0/14; P = 0.02). Overall, SARS-CoV-2 cardiac infection was less prevalent in patients treated with nonbiologic immunosuppression (7/14 vs 21/24; P = 0.02). Myocardial macrophage and lymphocyte densities overall were positively correlated with the duration of symptoms but not with underlying comorbidities. In summary, cardiac infection with SARS-CoV-2 is common among patients dying from COVID-19 but often with only rare infected cells. Cardiac infection by SARS-CoV-2 is associated with more cardiac inflammation and electrocardiographic changes. Nonbiologic immunosuppression is associated with lower incidences of myocarditis and cardiac infection by SARS-CoV-2.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Factors associated with myocardial SARS-CoV-2 infection, myocarditis, and cardiac inflammation in patients with COVID-19

et al. 2021

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“…SARS-CoV2 RNAemia has been associated with more severe COVID-19, including a higher probability of ICU admission and mechanical ventilation. However, in these studies disease severity was either heterogenous [ 27 ] and ARDS severity remained undefined, respectively [ 28 ]. Only a minority of patients enrolled in these studies actually required intensive care, whereas our study only included critically ill ICU patients.…”

Section: Discussionmentioning

confidence: 99%

“…Cycle thresholds of positive samples differed between survivors and non-survivors: Median cycles of oropharyngeal swabs were 35 (30)(31)(32)(33)(34)(35)(36)(37) in survivors and 30 (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32) in non-survivors (p = 0.003). However, no significant difference was observed in tracheal swabs with 31 (25)(26)(27)(28)(29)(30)(31)(32)(33)(34) in survivors and 27 (24)(25)(26)(27)(28)(29)(30)(31)(32) in non-survivors (p = 0.11). Median cycles (IQR) in blood samples were equal in survivors and non-survivors (p = 0.613).…”

Section: Plos Onementioning

confidence: 99%

Biodistribution and serologic response in SARS-CoV-2 induced ARDS: A cohort study

et al. 2020

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Background The viral load and tissue distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain important questions. The current study investigated SARS-CoV-2 viral load, biodistribution and anti-SARS-CoV-2 antibody formation in patients suffering from severe corona virus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). Methods This is a retrospective single-center study in 23 patients with COVID-19-induced ARDS. Data were collected within routine intensive care. SARS-CoV-2 viral load was assessed via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Overall, 478 virology samples were taken. Anti-SARS-CoV-2-Spike-receptor binding domain (RBD) antibody detection of blood samples was performed with an enzyme-linked immunosorbent assay. Results Most patients (91%) suffered from severe ARDS during ICU treatment with a 30-day mortality of 30%. None of the patients received antiviral treatment. Tracheal aspirates tested positive for SARS-CoV-2 in 100% of the cases, oropharyngeal swabs only in 77%. Blood samples were positive in 26% of the patients. No difference of viral load was found in tracheal or blood samples with regard to 30-day survival or disease severity. SARS-CoV-2 was never found in dialysate. Serologic testing revealed significantly lower concentrations of SARS-CoV-2 neutralizing IgM and IgA antibodies in survivors compared to non-survivors (p = 0.009). Conclusions COVID-19 induced ARDS is accompanied by a high viral load of SARS-CoV-2 in tracheal aspirates, which remained detectable in the majority throughout intensive care treatment. Remarkably, SARS-CoV-2 RNA was never detected in dialysate even in patients with RNAemia. Viral load or the buildup of neutralizing antibodies was not associated with 30-day survival or disease severity.

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“…The correlation between the level of IgG titers and disease severity during the acute phase of COVID-19 is well described, as patients with a severe course of COVID-19 show higher levels of anti-spike 1 (S1) IgA and IgG than patients with mild course [36][37][38] is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint…”

Section: Discussionmentioning

confidence: 99%

Recovered not restored: Long-term health consequences after mild COVID-19 in non-hospitalized patients

Schommers

Stecher

Dewald

et al. 2021

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Background While the leading symptoms during coronavirus disease 2019 (COVID-19) are acute and the majority of patients fully recover, a significant fraction of patients now increasingly experience long-term health consequences. However, most data available focus on health-related events after severe infection and hospitalization. We present a longitudinal, prospective analysis of health consequences in patients who initially presented with no or minor symptoms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. Hence we focus on mild COVID-19 in non-hospitalized patients. Methods We included 958 patients with confirmed SARS-CoV-2 infection in this study. Patients were observed for seven months from April 6th to December 2nd 2020 for long-term symptoms and SARS-CoV-2 antibodies. We identified anosmia, ageusia, fatigue or shortness of breath as most common, persisting symptoms at month 4 and 7 and summarized presence of such long-term health consequences as post-COVID syndrome (PCS). Predictors of long-term symptoms were assessed using an uni- and multivariable logistic regression model. Findings We observed 442 and 353 patients over four and seven months after symptom onset, respectively. Four months post SARS-CoV-2 infection, 8.6% (38/442) of patients presented with shortness of breath, 12.4% (55/442) with anosmia, 11.1% (49/442) with ageusia and 9.7% (43/442) with fatigue. At least one of these characteristic symptoms was present in 27.8% (123/442) and 34.8% (123/353) at month 4 and 7 post-infection, respectively. This corresponds to 12.8% patients with long-lasting symptoms relative to the initial total cohort (123/958). A lower baseline level of SARS-CoV-2 IgG, anosmia and diarrhea during acute COVID-19 were associated with higher risk to develop long-term symptoms. Interpretation The on-going presence of either shortness of breath, anosmia, ageusia or fatigue as long-lasting symptoms even in non-hospitalized patients was observed at four and seven months post-infection and summarized as post-COVID syndrome (PCS). The continued assessment of patients with PCS will become a major task to define and mitigate the socioeconomic and medical long-term effects of COVID-19.

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RNAemia Corresponds to Disease Severity and Antibody Response in Hospitalized COVID-19 Patients

Cited by 59 publications

References 36 publications

Factors associated with myocardial SARS-CoV-2 infection, myocarditis, and cardiac inflammation in patients with COVID-19

Factors associated with myocardial SARS-CoV-2 infection, myocarditis, and cardiac inflammation in patients with COVID-19

Biodistribution and serologic response in SARS-CoV-2 induced ARDS: A cohort study

Recovered not restored: Long-term health consequences after mild COVID-19 in non-hospitalized patients

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