Severe Acute Respiratory Syndrome Coronavirus 2 Nucleocapsid Antigen in Urine of Hospitalized Patients With Coronavirus Disease 2019.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid antigen (N-Ag) can be detected in the blood of patients with coronavirus disease 2019 (COVID-19). We used a highly sensitive and specific assay to explore the presence of N-Ag in urine during the course of COVID-19 and its relationship with the severity of disease. METHODS: We studied urinary and plasma N-Ag using a highly sensitive immunoassay in 82 patients with SARS-CoV-2 infection proved by polymerase chain reaction. RESULTS: In the first and second weeks of COVID-19, hospitalized patients tested positive for urinary N-Ag (81.25% and 71.79%, respectively) and plasma N-Ag (93.75% and 94.87%, respectively). High urinary N-Ag levels were associated with the absence of SARS-CoV-2 nucleocapsid antibodies, admission in intensive care units, high C-reactive protein levels, lymphopenia, eosinopenia, and high lactate dehydrogenase levels. Higher accuracy was observed for urinary N-Ag as a predictor of severe COVID-19 than for plasma N-Ag. CONCLUSIONS: Our study demonstrates that N-Ag is present in the urine of patients hospitalized in the early phase of COVID-19. As a direct marker of SARS-CoV-2, urinary N-Ag reflects the dissemination of viral compounds in the body. Urinary N-Ag may be a useful marker for disease severity in SARS-CoV-2 infections.

Efficacy of approved vaccines to prevent COVID-19: a systematic review and network meta-analysis of reconstructed individual patient data from randomized trials.

Aim: To optimize vaccination strategy, evidence on vaccine efficacy against COVID-19 is needed. Method: The present network meta-analysis uses reconstructed individual patient data from phase III trials on vaccine efficacy (VE), identified through MEDLINE, EMBASE, and Cochrane library (CENTRAL) peer-reviewed and published in English before August 31, 2021. The primary outcome was the VE against confirmed COVID-19 at any time after the first dose as defined in each study. VE was re-estimated using the two-stage approach. Poisson regression models were applied to each trial at the first stage, and the incidence risk ratio (IRR) and their 95% CI were aggregated to allow random-effects network meta-analysis (NMA) at the second stage. VE was expressed as: (1-IRR) × 100. The study protocol is registered in PROSPERO (CRD42020200012). Results: A total of eight studies, evaluating nine different vaccines were identified and analyzed. Between April 23, 2020 and January 05, 2021, 210,418 participants were recruited in 354 sites worldwide. During a median (IQR) follow-up duration of 69.8 (69.7-70.3) days, 2131 confirmed COVID-19 cases occurred (604; 26.0 per 1000 person-years in vaccine recipients and 1527; 85.9 per 1000 person-years in the control group). The mRNA-1273 vaccine was the most effective (P-score 0.99); at any time after dose 1, incidence reduction for mRNA-1273 ranged from 78% to 98% compared to the other vaccines. Conclusion: Our results provide evidence for the short-term superiority of mRNA vaccines, especially the mRNA-1273 vaccine in prevention of COVID-19 in different populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-022-01707-1.

Inhaled ciclesonide for outpatient treatment of COVID-19 in adults at risk of adverse outcomes: a randomised controlled trial (COVERAGE).

OBJECTIVES: To assess the efficacy of inhaled ciclesonide in reducing the risk of adverse outcomes in COVID-19 outpatients at risk of developing severe illness. METHODS: COVERAGE is an open-label, randomized controlled trial. Outpatients with documented COVID-19, risk factors for aggravation, symptoms for ≤7 days, and absence of criteria for hospitalization are randomly allocated to either a control arm or one of several experimental arms, including inhaled ciclesonide. The primary efficacy endpoint is COVID-19 worsening (hospitalization, oxygen therapy at home, or death) by Day 14. Other endpoints are adverse events, maximal follow-up score on the WHO Ordinal Scale for Clinical Improvement, sustained alleviation of symptoms, cure, and RT-PCR and blood parameter evolution at Day 7. The trial's Safety Monitoring Board reviewed the first interim analysis of the ciclesonide arm and recommended halting it for futility. The results of this analysis are reported here. RESULTS: The analysis involved 217 participants (control 107, ciclesonide 110), including 111 women and 106 men. Their median age was 63 years (interquartile range 59-68), and 157 of 217 (72.4%) had at least one comorbidity. The median time since first symptom was 4 days (interquartile range 3-5). During the 28-day follow-up, 2 participants died (control 2/107 [1.9%], ciclesonide 0), 4 received oxygen therapy at home and were not hospitalized (control 2/107 [1.9%], ciclesonide 2/110 [1.8%]), and 24 were hospitalized (control 10/107 [9.3%], ciclesonide 14/110 [12.7%]). In intent-to-treat analysis of observed data, 26 participants reached the composite primary endpoint by Day 14, including 12 of 106 (11.3%, 95% CI: 6.0%-18.9%) in the control arm and 14 of 106 (13.2%; 95% CI: 7.4-21.2%) in the ciclesonide arm. Secondary outcomes were similar for both arms. DISCUSSION: Our findings are consistent with the European Medicines Agency's COVID-19 task force statement that there is currently insufficient evidence that inhaled corticosteroids are beneficial for patients with COVID-19.

Performances of rapid and connected salivary RT-LAMP diagnostic test for SARS-CoV-2 infection in ambulatory screening.

In the context of social events reopening and economic relaunch, sanitary surveillance of SARS-CoV-2 infection is still required. Here, we evaluated the diagnostic performances of a rapid, extraction-free and connected reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay on saliva. Nasopharyngeal (NP) swabs and saliva from 443 outpatients were collected simultaneously and tested by reverse-transcription quantitative PCR (RT-qPCR) as reference standard test. Seventy-one individuals (16.0%) were positive by NP and/or salivary RT-qPCR. Sensitivity and specificity of salivary RT-LAMP were 85.9% (95%CI 77.8-94.0%) and 99.5% (98.7-100%), respectively. Performances were similar for symptomatic and asymptomatic participants. Moreover, SARS-CoV-2 genetic variants were analyzed and no dominant mutation in RT-LAMP primer region was observed during the period of the study. We demonstrated that this RT-LAMP test on self-collected saliva is reliable for SARS-CoV-2 detection. This simple connected test with optional automatic results transfer to health authorities is unique and opens the way to secure professional and social events in actual context of economics restart.

An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-ß-1a and hydroxychloroquine in hospitalized patients with COVID-19.

OBJECTIVES: We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-ß-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support. METHODS: We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely. RESULTS: The intention-to-treat population included 583 participants-lopinavir/ritonavir (n = 145), lopinavir/ritonavir-IFN-ß-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)-among whom 418 (71.7%) were male, the median age was 63 years (IQR 54-71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55-1.26, p 0.39), lopinavir/ritonavir-IFN-ß-1a versus control, aOR 0.69 (95%CI 0.45-1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62-1.41, p 0.75). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of serious adverse events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms. CONCLUSION: In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir-IFN-ß-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens.

Diagnosis value of SARS-CoV-2 antigen/antibody combined testing using rapid diagnostic tests at hospital admission.

The implementation of rapid diagnostic tests (RDTs) may enhance the efficiency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, as RDTs are widely accessible and easy to use. The aim of this study was to evaluate the performance of a diagnosis strategy based on a combination of antigen and immunoglobulin M (IgM) or immunoglobulin G (IgG) serological RDTs. Plasma and nasopharyngeal samples were collected between 14 March and 11 April 2020 at hospital admission from 45 patients with reverse transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 and 20 negative controls. SARS-CoV-2 antigen (Ag) was assessed in nasopharyngeal swabs using the Coris Respi-Strip. For IgM/IgG detection, SureScreen Diagnostics and Szybio Biotech RDTs were used in addition to laboratory assays (Abbott Alinity i SARS-CoV-2 IgG and Theradiag COVID-19 IgM enzyme-linked immunosorbent assay). Using the Ag RDT, 13 out of 45 (29.0%) specimens tested positive, the sensitivity was 87.0% for cycle threshold (Ct ) values ≤25% and 0% for Ct values greater than 25. IgG detection was associated with high Ct values and the amount of time after the onset of symptoms. The profile of isolated IgM on RDTs was more frequently observed during the first and second week after the onset of symptoms. The combination of Ag and IgM/IgG RDTs enabled the detection of up to 84.0% of COVID-19 confirmed cases at hospital admission. Antigen and antibody-based RDTs showed suboptimal performances when used alone. However when used in combination, they are able to identify most COVID-19 patients admitted in an emergency department.

Monocyte CD169 Expression as a Biomarker in the Early Diagnosis of Coronavirus Disease 2019.

We assessed the expression of CD169, a type I interferon-inducible receptor, on monocytes (monocyte CD169 [mCD169]) in 53 adult patients admitted to the hospital during the coronavirus disease 2019 (COVID-19) outbreak for a suspicion of severe acute respiratory syndrome coronavirus 2 infection. Monocyte CD169 was strongly overexpressed in 30 of 32 (93.7%) confirmed COVID-19 cases, compared with 3 of 21 (14.3%) patients in whom the diagnosis of COVID-19 was finally ruled out. Monocyte CD169 was associated with the plasma interferon-alpha level and thrombocytopenia. Monocyte CD169 testing may be helpful for the rapid triage of suspected COVID-19 patients during an outbreak.

Diagnostic Value of Patient-Reported and Clinically Tested Olfactory Dysfunction in a Population Screened for COVID-19.

Importance: Recent studies have suggested that olfactory dysfunction and gustatory dysfunction are associated with coronavirus disease 2019 (COVID-19). However, olfaction has been evaluated solely on reported symptoms, after COVID-19 diagnosis, and in both mild and severe COVID-19 cases, but rarely has it been assessed in prospectively unselected populations. Objective: To evaluate the diagnostic value of a semiobjective olfactory test developed to assess patient-reported chemosensory dysfunction prior to testing for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients attending a COVID-19 screening facility. Design, Setting, and Participants: This prospective diagnostic study with participants and observers blinded to COVID-19 status was conducted in a COVID-19 screening center of a tertiary university hospital in France from March 23 to April 22, 2020. Participants were 854 consecutively included health care workers or outpatients with symptoms or with close contact with an index case. Exclusion criteria were prior chemosensory dysfunction, testing inability, or contraindications (n = 45). Main Outcomes and Measures: Participants were interviewed to ascertain their symptoms and then underwent Clinical Olfactory Dysfunction Assessment (CODA), an ad hoc test developed for a simple and fast evaluation of olfactory function. This assessment followed a standardized procedure in which participants identified and rated the intensity of 3 scents (lavender, lemongrass, and mint) to achieve a summed score ranging from 0 to 6. The COVID-19 status was assessed using reverse transcriptase-polymerase chain reaction to detect the presence of SARS-CoV-2 in samples collected via nasopharyngeal swab (reference standard) to calculate the diagnostic values of patient-reported chemosensory dysfunction and CODA. Results: Of 809 participants, the female to male sex ratio was 2.8, and the mean (SD) age was 41.8 (13.0) years (range, 18-94 years). All participants, if symptomatic, had mild disease at the time of testing, and 58 (7.2%) tested positive for SARS-CoV-2. Chemosensory dysfunction was reported by 20 of 58 participants (34.5%) with confirmed COVID-19 vs 29 of 751 participants (3.9%) who tested negative for COVID-19 (absolute difference, 30.6% [95% CI, 18.3%-42.9%]). Olfactory dysfunction, either self-reported or clinically ascertained (CODA score ≤3), yielded similar sensitivity (0.31 [95% CI, 0.20-0.45] vs 0.34 [95% CI, 0.22-0.48]) and specificity (0.97 [95% CI, 0.96-0.98) vs 0.98 [95% CI, 0.96-0.99]) for COVID-19 diagnosis. Concordance was high between reported and clinically tested olfactory dysfunction, with a Gwet AC1 of 0.95 (95% CI, 0.93-0.97). Of 19 participants, 15 (78.9%) with both reported olfactory dysfunction and a CODA score of 3 or lower were confirmed to have COVID-19. The CODA score also revealed 5 of 19 participants (26.3%) with confirmed COVID-19 who had previously unperceived olfactory dysfunction. Conclusions and Relevance: In this prospective diagnostic study of outpatients with asymptomatic or mild to moderate COVID-19, systematically assessed anamnesis and clinical testing with the newly developed CODA were complementary and specific for chemosensory dysfunction. Olfactory dysfunction was suggestive of COVID-19, particularly when clinical testing confirmed anamnesis. However, normal olfaction was most common among patients with COVID-19.

The Plasmatic Aldosterone and C-Reactive Protein Levels, and the Severity of Covid-19: The Dyhor-19 Study.

BACKGROUND: The new coronavirus SARS-CoV-2, responsible for the Covid-19 pandemic, uses the angiotensin converting enzyme type 2 (ACE2), a physiological inhibitor of the renin angiotensin aldosterone system (RAAS), as a cellular receptor to infect cells. Since the RAAS can induce and modulate pro-inflammatory responses, it could play a key role in the pathophysiology of Covid-19. Thus, we aimed to determine the levels of plasma renin and aldosterone as indicators of RAAS activation in a series of consecutively admitted patients for Covid-19 in our clinic. METHODS: Plasma renin and aldosterone levels were measured, among the miscellaneous investigations needed for Covid-19 management, early after admission in our clinic. Disease severity was assessed using a seven-category ordinal scale. Primary outcome of interest was the severity of patients' clinical courses. RESULTS: Forty-four patients were included. At inclusion, 12 patients had mild clinical status, 25 moderate clinical status and 7 severe clinical status. In univariate analyses, aldosterone and C-reactive protein (CRP) levels at inclusion were significantly higher in patients with severe clinical course as compared to those with mild or moderate course (p < 0.01 and p = 0.03, respectively). In multivariate analyses, only aldosterone and CRP levels remained positively associated with severity. We also observed a positive significant correlation between aldosterone and CRP levels among patients with an aldosterone level greater than 102.5 pmol/L. CONCLUSIONS: Both plasmatic aldosterone and CRP levels at inclusion are associated with the clinical course of Covid-19. Our findings may open new perspectives in the understanding of the possible role of RAAS for Covid-19 outcome.

Abnormal liver tests in patients hospitalized with Coronavirus disease 2019: Should we worry?

While several studies from China have reported COVID-19-related liver injury, there are currently no data on liver dysfunction in hospitalized COVID-19 patients in Europe. The aim of this study was to describe the prevalence and predictive value of abnormal liver function in patients hospitalized with COVID-19. This was a retrospective cohort study of confirmed COVID-19 patients hospitalized in two referral hospitals in France. Clinical, biological and radiological data were collected and analysed. In all, 234 patients confirmed to have COVID-19 by RT-PCR were included. Liver function was abnormal in 66.6% of patients on admission. In multivariate logistic regression, abnormal liver test on admission were associated with in-hospital aggravation (OR = 4.1, 95% CI 1.5-10.8; P = .004) and mortality (OR 3.3; 95% CI = 1.04-10.5; P = .04). This study of liver tests in a European COVID-19 population confirms a high prevalence of abnormal liver tests on admission that are predictive of severe disease course and higher in-hospital mortality.