One of the immune characteristics of coronavirus disease 2019 (COVID-19) is a massive fall in lymphocyte count in which magnitude associates with mortality. 1,2 Recent monitoring of COVID-19 intensive care units (ICU) patients confirmed the profound lymphopenia and its remarkable stability over time. 3,4 While most immunomodulation approaches proposed so far in COVID-19 focused on inhibiting inflammatory cytokine response; mounting evidence indicates that this viral-induced defective lymphocyte response may play a central role in COVID-19 pathophysiology. 5 Interestingly, recombinant human interleukin-7 (IL-7) therapy, known to efficiently restore lymphocyte count in several viral infections was safely administered in septic shock patients 6 who present with similar lymphocyte alterations as observed in COVID-19. 3 We report here the case of a 74-year-old patient without any comorbidity. He was admitted to our university hospital ICU (Hospices Civils de Lyon, France) for COVID-19 ARDS requiring high flow oxygen. ICU admission (thereafter corresponding to day 0) occurred 9 days after first symptom onset. SARS-COV-2 PCR was positive (nasal swab) and CT scan was highly suspect of severe COVID-19. He was intubated 24 h after admission and ventilation was set according to guidelines for ARDS including prone positioning. PEEP was around 8-10 cm H 2 O for the whole ICU stay. Antibiotics were initiated at admission until bacterial samples were negative. On day 10, as the patient was still presenting with severe ARDS without any infection criteria, steroids were initiated at 1 mg/kg/day (equivalent prednisolone) but stopped 5 days later (i.e., day 15) due to ventilator associated pneumonia (VAP, Morganella morganii and Aspergillus fumigatus were identified in BALF). Antibiotics and antifungal therapies were started immediately. At day 20, an additional VAP was suspected (without any bacterial documentation) treated with meropenem. After admission, SARS-CoV-2 PCR remained positive at D10 and D16. From day 0 to day 24, the patient remained deeply lymphopenic and presented with markedly decreased monocytic expression of HLA-DR (Fig. 1) reflecting deep immunocompromised state. Therefore, at day 24, while the patient did not show any improvement in pulmonary function, presented with several intercurrent infections, absence of negativation of SARS-CoV-2 PCR, and marked and persisting lymphopenia, compassionate use of IL-7 was initiated in order to improve immunity and consequently allow viral clearance. After inaugural injection

BACKGROUND SARS-Cov-2 (COVID-19) has become a major worldwide health concern since its appearance in China at the end of 2019.OBJECTIVE To evaluate the intrinsic mortality and burden of COVID-19 and seasonal influenza pneumonia in ICUs in the city of Lyon, France.DESIGN A retrospective study.SETTING Six ICUs in a single institution in Lyon, France.PATIENTS Consecutive patients admitted to an ICU with SARS-CoV-2 pneumonia from 27 February to 4 April 2020 (COVID-19 group) and seasonal influenza pneumonia from 1 November 2015 to 30 April 2019 (influenza group). A total of 350 patients were included in the COVID-19 group (18 refused to consent) and 325 in the influenza group (one refused to consent). Diagnosis was confirmed by RT-PCR. Follow-up was completed on 1 April 2021. MAIN OUTCOME(S) AND MEASURE(S)Differences in 90day adjusted-mortality between the COVID-19 and influenza groups were evaluated using a multivariable Cox proportional hazards model.RESULTS COVID-19 patients were younger, mostly men and had a higher median BMI, and comorbidities, including immunosuppressive condition or respiratory history were less frequent. In univariate analysis, no significant differences were observed between the two groups regarding in-ICU mortality, 30, 60 and 90-day mortality. After Cox modelling adjusted on age, sex, BMI, cancer, sepsis-related organ failure assessment (SOFA) score, simplified acute physiology score SAPS II score, chronic obstructive pulmonary disease and myocardial infarction, the probability of death associated with COVID-19 was significantly higher in comparison to seasonal influenza [hazard ratio 1.57, 95% CI (1.14 to 2.17); P ¼ 0.006]. The clinical course and morbidity profile of both groups was markedly different; COVID-19 patients had less severe illness at admission (SAPS II score, 37 [28 to 48] vs. 48 [39 to 61], P < 0.001 and SOFA score, 4 [2 to 8] vs. 8 [5 to 11], P < 0.001), but the disease was more severe considering ICU length of stay, duration of mechanical ventilation, PEEP level and prone positioning requirement.CONCLUSION After ICU admission, COVID-19 was associated with an increased risk of death compared with seasonal influenza. Patient characteristics, clinical course and morbidity profile of these diseases is markedly different.