The onset of late severe lung impairment in COVID-19 is associated with high inflammation markers at admission and metabolic syndrome markers (preprint)

Background: COVID-19 severity is mainly related to lung impairment. However, preexisting patient characteristics and biomarkers at admission associated with this event are not precisely known. Methods. We report 205 patients admitted for a proven COVID-19 in our institution between March 7 and April 22, 2020, particularly their comorbidities, respiratory severity, immune profile, and metabolic profile. Findings. Median age was 70 years [interquartile range (IQR) 25-75: 60;79]; 115 (56.1%) patients were men. Oxygen supplementation of >2L/min was required in 107 patients (52.2%) after a median time of 8 days [IQR: 6;10] after the first symptoms; 67 (32.7%) patients were admitted to the intensive care unit (ICU), almost exclusively due to severe hypoxia. Patients requiring >2L/min oxygen therapy and/or ICU admission were older and more frequently males, with a significantly higher body mass index (BMI), a significantly higher total cholesterol (TC) / HDL cholesterol ratio, and higher triglycerides. They also had higher plasma levels of C-reactive protein (CRP) and interleukin 6 (IL-6); IL-6 >20 ng/L and CRP >70 mg/L were significantly associated with ICU admission and/or (for patients with a decision of limitation of life-support therapy) death. Higher BMI and TC/HDL-c ratio were associated with higher CRP and IL-6 levels. Steroid therapy was performed in 61 patients; while its clinical impact was inconclusive due to heterogeneous situations, IL-6 levels decreased significantly more in these patients. Interpretation. Severe COVID-19 mostly relates to late-onset pneumonia associated with preexisting metabolic syndrome markers and a surge in inflammatory markers, allowing the early identification of at-risk patients.

Clinical and Microbiological Assessments of COVID-19 in Healthcare Workers: A Prospective Longitudinal Study (preprint)

Background: A comprehensive assessment of COVID-19 in healthcare workers (HCWs) including the investigation of viral shedding duration is critical.Methods: A longitudinal study including 319 HCWs was conducted. After SARS-CoV-2 screening with RT-PCR assay, other respiratory pathogens were tested with a multiplex molecular panel. For SARS-CoV-2 positive HCWs, the normalized viral load was determined weekly; viral culture and virus neutralization assay were also performed. For 190 HCWs tested negative for SARS-CoV-2, serological testing was performed one month after the inclusion.Findings: Of the 319 HCWs included, 67 (21.0%) were tested positive for SARS-CoV-2; two of them developed severe COVID-19. The proportion of smell and taste dysfunction was significantly higher in SARS-CoV-2 positive HCWs than in negative ones (38.8% vs 9.5% and 37.3% vs 10.7%, respectively, p<0.001). Of 67 positive patients, 9.1% were tested positive for at least another respiratory pathogen ( vs 19.5%, p=0.07). The proportion of HCWs with a viral load > 5.0 log 10 cp/ml (Ct value <25) was less than 15% at 8 days after symptom onset; 12% of them were still positive after 40 days (Ct >37). More than 90% of samples with cultivable virus had a viral load > 4.5 log 10 cp/ml (Ct < 26) and were collected within 10 days after symptom onset. From HCWs tested negative, 6/190 (3.2%) exhibited seroconversion for SARS-CoV-2 IgG antibodies.Interpretation: Our data suggest that the monitoring of normalized viral load (or its estimation through Ct values) can be useful for discontinuing isolation of HCWs and facilitating their safe return to work. HCWs presenting mild COVID-19 are unlikely infectious 10 days after symptom onset.Trial Registration: The clinical study registered on ClinicalTrial.gov (NCT04341142) has been fully detailed.Funding: Fondation des Hospices Civils de Lyon. bioMérieux provided diagnostic kits.Declaration of Interests: Several authors (KBP, FAF, GO, VC) are bioMérieux employees. AB has received a grant from bioMérieux and has served as consultant for bioMérieux. KBP, FAF, GO VC and AB were involved in data analysis, interpretation and wrote the article.Ethics Approval Statement: Written informed consent was obtained from all participants and approval was obtained from the national review board for biomedical research in April 2020 (Comité de Protection des Personnes Sud Méditerranée I, Marseille, France; ID RCB 2020-A00932-37).

Clinical and microbiological assessments of COVID-19 in healthcare workers: a prospective longitudinal study (preprint)

Background A comprehensive assessment of COVID-19 in healthcare workers (HCWs) including the investigation of viral shedding duration is critical. Methods A longitudinal study including 319 HCWs was conducted. After SARS-CoV-2 screening with RT-PCR assay, other respiratory pathogens were tested with a multiplex molecular panel. For SARS-CoV-2 positive HCWs, the normalized viral load was determined weekly; viral culture and virus neutralization assays were also performed. For 190 HCWs tested negative, SARS-CoV-2 serological testing was performed one month after the inclusion. Findings Of the 319 HCWs included, 67 (21.0%) were tested positive for SARS-CoV-2; two of them developed severe COVID-19. The proportion of smell and taste dysfunction was significantly higher in SARS-CoV-2 positive HCWs than in negative ones (38.8% vs 9.5% and 37.3% vs 10.7%, respectively, p<0.001). Of the 67 positive patients, 9.1% were tested positive for at least another respiratory pathogen (vs 19.5%, p=0.07). The proportion of HCWs with a viral load > 5.0 log10 cp/ml (Ct value <25) was less than 15% at 8 days after symptom onset; 12% of them were still positive after 40 days (Ct >37). More than 90% of culturable virus had a viral load > 4.5 log10 cp/ml (Ct < 26) and were collected within 10 days after symptom onset. From HCWs tested negative, 6/190 (3.2%) exhibited seroconversion for IgG antibodies. Interpretation Our data suggest that the determination of normalized viral load (or its estimation through Ct values) can be useful for discontinuing isolation of HCWs and facilitating their safe return to work. HCWs presenting mild COVID-19 are unlikely infectious 10 days after symptom onset.

Performance characteristics of the VIDAS(R) SARS-COV-2 IgM and IgG serological assays (preprint)

The COVID-19 pandemic, caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread worldwide. Serological testing for SARS-CoV-2-specific antibodies plays an important role in understanding and controlling the pandemics, notably through epidemiological surveillance. Well validated and highly specific SARS-CoV-2 serological assays are urgently needed. We describe here the analytical and clinical performance of VIDAS(R) SARS-CoV-2 IgM and VIDAS(R) SARS-CoV-2 IgG, two CE-marked, EUA-authorized, automated, qualitative assays for the detection of SARS-CoV-2-specific IgM and IgG, respectively. Both assays showed high within-run and within-laboratory precision (coefficients of variation < 11.0%) and very low cross-reactivity towards sera of patients with a past common coronavirus or respiratory virus infection. Clinical specificity determined on up to 989 pre-pandemic healthy donors was [≥] 99% with a narrow 95% confidence interval for both IgM and IgG assays. Clinical sensitivity was determined on up to 232 samples from 130 RT-PCR-confirmed SARS-CoV-2 patients. The positive percent agreement (PPA) with SARS-CoV-2 PCR reached 100% at [≥] 16 days (VIDAS(R) SARS-CoV-2 IgM) and [≥] 32 days (VIDAS(R) SARS-CoV-2 IgG) of symptom onset. Combined IgM/IgG test results improved the PPA compared to each test alone. SARS-CoV-2 IgG seroconversion followed closely that of SARS-CoV-2 IgM and remained stable over time, while SARS-CoV-2 IgM levels rapidly declined. Interestingly, SARS-CoV-2-specific IgM and IgG responses were significantly higher in COVID-19 hospitalized vs. non-hospitalized patients. Altogether, the VIDAS(R) SARS-CoV-2 IgM and IgG assays are highly specific and sensitive serological tests suitable for the reliable detection of past acute SARS-CoV-2 infections.