Dynamics of circulating calprotectin accurately predict the outcome of moderate COVID-19 patients.

BACKGROUND: Severe COVID-19 is associated with a high circulating level of calprotectin, the S100A8/S100A9 alarmin heterodimer. Baseline calprotectin amount measured in peripheral blood at diagnosis correlates with disease severity. The optimal use of this biomarker along COVID-19 course remains to be delineated. METHODS: We focused on patients with a WHO-defined moderate COVID-19 requiring hospitalization in a medical ward. We collected plasma and serum from three independent cohorts (N = 626 patients) and measured calprotectin amount at admission. We performed longitudinal measures of calprotectin in 457 of these patients (1461 samples) and used a joint latent class mixture model in which classes were defined by age, body mass index and comorbidities to identify calprotectin trajectories predicting the risk of transfer into an intensive care unit or death. FINDINGS: After adjustment for age, sex, body mass index and comorbidities, the predictive value of baseline calprotectin in patients with moderate COVID19 could be refined by serial monitoring of the biomarker. We discriminated three calprotectin trajectories associated with low, moderate, and high risk of poor outcome, and we designed an algorithm available as online software (https://calpla.gustaveroussy.fr:8443/) to monitor the probability of a poor outcome in individual patients with moderate COVID-19. INTERPRETATION: These results emphasize the clinical interest of serial monitoring of calprotectin amount in the peripheral blood to anticipate the risk of poor outcomes in patients with moderate COVID-19 hospitalized in a standard care unit. FUNDING: The study received support (research grants) from ThermoFisher immunodiagnostics (France) and Gustave Roussy Foundation.

Outcomes of Patients With Active Cancer and COVID-19 in the Intensive-Care Unit: A Multicenter Ambispective Study.

Background: Several studies report an increased susceptibility to SARS-CoV-2 infection in cancer patients. However, data in the intensive care unit (ICU) are scarce. Research Question: We aimed to investigate the association between active cancer and mortality among patients requiring organ support in the ICU. Study Design and Methods: In this ambispective study encompassing 17 hospitals in France, we included all adult active cancer patients with SARS-CoV-2 infection requiring organ support and admitted in ICU. For each cancer patient, we included 3 non cancer patients as controls. Patients were matched at the same ratio using the inverse probability weighting approach based on a propensity score assessing the probability of cancer at admission. Mortality at day 60 after ICU admission was compared between cancer patients and non-cancer patients using primary logistic regression analysis and secondary multivariable analyses. Results: Between March 12, 2020 and March 8, 2021, 2608 patients were admitted with SARS-CoV-2 infection in our study, accounting for 2.8% of the total population of patients with SARS-CoV-2 admitted in all French ICUs within the same period. Among them, 105 (n=4%) presented with cancer (51 patients had hematological malignancy and 54 patients had solid tumors). 409 of 420 patients were included in the propensity score matching process, of whom 307 patients in the non-cancer group and 102 patients in the cancer group. 145 patients (35%) died in the ICU at day 60, 59 (56%) with cancer and 86 (27%) without cancer. In the primary logistic regression analysis, the odds ratio for death associated to cancer was 2.3 (95%CI 1.24 - 4.28, p=0.0082) higher for cancer patients than for a non-cancer patient at ICU admission. Exploratory multivariable analyses showed that solid tumor (OR: 2.344 (0.87-6.31), p=0.062) and hematological malignancies (OR: 4.144 (1.24-13.83), p=0.062) were independently associated with mortality. Interpretation: Patients with cancer and requiring ICU admission for SARS-CoV-2 infection had an increased mortality, hematological malignancy harboring the higher risk in comparison to solid tumors.

Screening for SARS-CoV-2 by RT-PCR: Saliva or nasopharyngeal swab? Rapid review and meta-analysis.

BACKGROUND: Diagnosis of COVID-19 in symptomatic patients and screening of populations for SARS-CoV-2 infection require access to straightforward, low-cost and high-throughput testing. The recommended nasopharyngeal swab tests are limited by the need of trained professionals and specific consumables and this procedure is poorly accepted as a screening method In contrast, saliva sampling can be self-administered. METHODS: In order to compare saliva and nasopharyngeal/oropharyngeal samples for the detection of SARS-CoV-2, we designed a meta-analysis searching in PubMed up to December 29th, 2020 with the key words "(SARS-CoV-2 OR COVID-19 OR COVID19) AND (salivary OR saliva OR oral fluid)) NOT (review[Publication Type]) NOT (PrePrint[Publication Type])" applying the following criteria: records published in peer reviewed scientific journals, in English, with at least 15 nasopharyngeal/orapharyngeal swabs and saliva paired samples tested by RT-PCR, studies with available raw data including numbers of positive and negative tests with the two sampling methods. For all studies, concordance and sensitivity were calculated and then pooled in a random-effects model. FINDINGS: A total of 377 studies were retrieved, of which 50 were eligible, reporting on 16,473 pairs of nasopharyngeal/oropharyngeal and saliva samples. Meta-analysis showed high concordance, 92.5% (95%CI: 89.5-94.7), across studies and pooled sensitivities of 86.5% (95%CI: 83.4-89.1) and 92.0% (95%CI: 89.1-94.2) from saliva and nasopharyngeal/oropharyngeal swabs respectively. Heterogeneity across studies was 72.0% for saliva and 85.0% for nasopharyngeal/oropharyngeal swabs. INTERPRETATION: Our meta-analysis strongly suggests that saliva could be used for frequent testing of COVID-19 patients and "en masse" screening of populations.