Prevalence of post-acute coronavirus disease 2019 symptoms twelve months after hospitalization in participants retained in follow-up: analyses stratified by gender from a large prospective cohort.

OBJECTIVES: Persistent post-acute coronavirus disease 2019 (COVID-19) symptoms (PACSs) have been reported up to 6 months after hospital discharge. Herein we assessed the symptoms that persisted 12 months (M12) after admission for COVID-19 in the longitudinal prospective national French coronavirus disease cohort. METHODS: Hospitalized patients with a confirmed virological diagnosis of COVID-19 were enrolled. Follow-up was planned until M12 after admission. Associations between persistence of ≥3 PACSs at M12 and clinical characteristics at admission were assessed through logistic regression according to gender. RESULTS: We focused on participants enrolled between 24 January 2020 and 15 July 2020, to allow M12 follow-up. The M12 data were available for 737 participants. Median age was 61 years, 475 (64%) were men and 242/647 (37%) were admitted to intensive care units during the acute phase. At M12, 27% (194/710) of the participants had ≥3 persistent PACS, mostly fatigue, dyspnoea and joint pain. Among those who had a professional occupation before the acute phase, 91 out of 339 (27%) were still on sick leave at M12. Presence of ≥3 persistent PACS was associated with female gender, both anxiety and depression, impaired health-related quality of life and Medical Muscle Research Council Scale <57. Compared with men, women more often reported presence of ≥3 persistent PACSs (98/253, 39% vs. 96/457, 21%), depression and anxiety (18/152, 12% vs. 17/268, 6% and 33/156, 21% vs. 26/264, 10%, respectively), impaired physical health-related quality of life (76/141, 54% vs. 120/261, 46%). Women had less often returned to work than men (77/116, 66% vs. 171/223, 77%). CONCLUSIONS: One fourth of the individuals admitted to hospital for COVID-19 still had ≥3 persistent PACSs at M12 post-discharge. Women reported more often ≥3 persistent PACSs, suffered more from anxiety and depression and had less often returned to work than men.

Prevalence of post-acute COVID-19 symptoms twelve months after hospitalisation in participants retained in follow-up: analyses stratified by gender from a large prospective cohort

Objectives Persistent post-acute COVID-19 symptom (PACS) have been reported up to 6-months (M6) after hospital discharge. Here we assessed, in the longitudinal prospective national French COVID cohort, symptoms that persisted 12-months (M12) after admission for COVID-19. Methods Hospitalized patients with a virologically-confirmed COVID-19 were enrolled. Follow-up was planned until M12 post-admission. Associations between persistence of ≥3 PACS at M12 and clinical characteristics at admission were assessed through logistic regression according to gender. Results We focused on participants enrolled between January 24th and July 15th 2020, in order to allow M12 follow-up. M12 data were available for 737 participants. Median age was 61 years, 475 (64%) were men and 242/647 (37%) were admitted to ICU during the acute phase. At M12, 194/710 (27%) of participants had ≥3 persistent PACS, mostly fatigue, dyspnea and joint pain. Among those who had a professional occupation before the acute phase 91/339 (27%) were still on sick leave at M12. Presence of ≥3 persistent PACS was associated with female gender, both anxiety and depression, impaired health-related quality of life (HRQL) and mMRC scale <57. Compared to men, women more often reported presence of >3 persistent PACS (98/253, 39% vs 96/457, 21%), depression and anxiety (18/152, 12% vs 17/268, 6% and 33/156, 21% vs 26/264, 10%, respectively), impaired physical HRQL (76/141, 54% vs 120/261, 46%). Women had less often returned to work than men (77/116, 66% vs 171/223, 77%). Conclusions A fourth of individuals admitted to hospital for COVID-19 still had ≥3 persistent PACS at M12 post-discharge. Women reported more often ≥3 persistent PACS, suffered more from anxiety and depression, and had less often returned to work than men.

Acquired decrease of the C3b/C4b receptor (CR1, CD35) and increased C4d deposits on erythrocytes from ICU COVID-19 patients.

In order to study the mechanisms of COVID-19 damage following the complement activation phase occurring during the innate immune response to SARS-CoV-2, CR1 (the regulating complement activation factor, CD35, the C3b/C4b receptor), C4d deposits on Erythrocytes (E), and the products of complement activation C3b/C3bi, were assessed in 52 COVID-19 patients undergoing O2 therapy or assisted ventilation in ICU units in Rheims France. An acquired decrease of CR1 density on E from COVID-19 patients was observed (Mean = 418, SD = 162, N = 52) versus healthy individuals (Mean = 592, SD = 287, N = 400), Student's t-test p < 10-6, particularly among fatal cases, and in parallel with several parameters of clinical severity. Large deposits of C4d on E in patients were well above values observed in normal individuals, mostly without concomitant C3 deposits, in more than 80% of the patients. This finding is reminiscent of the increased C4d deposits on E previously observed to correlate with sub endothelial pericapillary deposits in organ transplant rejection, and with clinical SLE flares. Conversely, significant C3 deposits on E were only observed among » of the patients. The decrease of CR1/E density, deposits of C4 fragments on E and previously reported detection of virus spikes or C3 on E among COVID-19 patients, suggest that the handling and clearance of immune complex or complement fragment coated cell debris may play an important role in the pathophysiology of SARS-CoV-2. Measurement of C4d deposits on E might represent a surrogate marker for assessing inflammation and complement activation occurring in organ capillaries and CR1/E decrease might represent a cumulative index of complement activation in COVID-19 patients. Taken together, these original findings highlight the participation of complement regulatory proteins and indicate that E are important in immune pathophysiology of COVID-19 patients. Besides a potential role for monitoring the course of disease, these observations suggest that novel therapies such as the use of CR1, or CR1-like molecules, in order to down regulate complement activation and inflammation, should be considered.

Severe acute respiratory syndrome coronavirus 2 vaccination for patients with solid cancer: Review and point of view of a French oncology intergroup (GCO, TNCD, UNICANCER).

The impacts of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on cancer care are multiple, entailing a high risk of death from coronavirus disease 2019 (COVID-19) in patients with cancer treated by chemotherapy. SARS-CoV-2 vaccines represent an opportunity to decrease the rate of severe COVID-19 cases in patients with cancer and also to restore normal cancer care. Patients with cancer to be targeted for vaccination are difficult to define owing to the limited contribution of these patients in the phase III trials testing the different vaccines. It seems appropriate to vaccinate not only patients with cancer with ongoing treatment or with a treatment having been completed less than 3 years ago but also household and close contacts. High-risk patients with cancer who are candidates for priority access to vaccination are those treated by chemotherapy. The very high-priority population includes patients with curative treatment and palliative first- or second-line chemotherapy, as well as patients requiring surgery or radiotherapy involving a large volume of lung, lymph node and/or haematopoietic tissue. When possible, vaccination should be carried out before cancer treatment begins. SARS-CoV-2 vaccination can be performed during chemotherapy while avoiding periods of neutropenia and lymphopenia. For organisational reasons, vaccination should be performed in cancer care centres with messenger RNA vaccines (or non-replicating adenoviral vaccines in non-immunocompromised patients). Considering the current state of knowledge, the benefit-risk ratio strongly favours SARS-CoV-2 vaccination of all patients with cancer. To obtain more data concerning the safety and effectiveness of vaccines, it is necessary to implement cohorts of vaccinated patients with cancer.

[Vaccination against COVID-19 in patients with solid cancer: Review and point of view from a French oncology inter-group (CGO, TNCD, UNICANCER)]. / Vaccination contre la COVID-19 des patients atteints de cancer solide : revue et préconisations d'un inter-groupe oncologique français (CGO, TNCD, UNICANCER).

The COVID-19 pandemic has a major impact at all stages of cancer treatment. Risk of death from COVID-19 in patients treated for a cancer is high. COVID-19 vaccines represent a major issue to decrease the rate of severe forms of the COVID-19 cases and to maintain a normal cancer care. It is difficult to define the target population for vaccination due to the limited data available and the lack of vaccine doses available. It appears theoretically important to vaccinate patients with active cancer treatment or treated since less than three years, as well as their family circle. In France, patients actually defined at "high risk" for priority access to vaccination are those with a cancer treated by chemotherapy. A panel of experts recently defined another "very high-priority" population, which includes patients with curative or palliative first or second-line chemotherapy, as well as patients requiring surgery or radiotherapy involving a large lung volume, lymph nodes and/or of hematopoietic tissue. Ideally, it is best to vaccinate before cancer treatment. Despite the lack of published data, COVID-19 vaccines can also be performed during chemotherapy by avoiding periods of bone marrow aplasia and if possible, to do it in cancer care centers. It is necessary to implement cohorts with immunological and clinical monitoring of vaccinated cancer patients. To conclude, considering the current state of knowledge, the benefit-risk ratio strongly favours COVID-19 vaccination of all cancer patients.

Corticosteroids in patients hospitalized for COVID-19 pneumonia who require oxygen: observational comparative study using routine care data.

OBJECTIVE: To assess the effectiveness of corticosteroids on outcomes of patients with coronavirus disease 2019 (COVID-19) pneumonia requiring oxygen without mechanical ventilation. METHODS: We used routine care data from 51 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids at 0.8 mg/kg/day eq. prednisone (CTC group) versus standard of care (no-CTC group) among adults 18-80 years old with confirmed COVID-19 pneumonia requiring oxygen without mechanical ventilation. The primary outcome was intubation or death by day 28. In our main analysis, characteristics of patients at baseline (i.e. time when patients met all inclusion criteria) were balanced by using propensity-score inverse probability of treatment weighting. RESULTS: Among the 891 patients included in the analysis, 203 were assigned to the CTC group. Use of corticosteroids was not significantly associated with risk of intubation or death by day 28 (weighted hazard ratio (wHR) 0.92, 95%CI 0.61-1.39) nor cumulative death rate (wHR 1.03, 95%CI 0.54-1.98). However, use of corticosteroids was associated with reduced risk of intubation or death by day 28 in the prespecified subgroups of patients requiring oxygen ≥3 L/min (wHR 0.50, 95%CI 0.30-0.85) or C-reactive protein level ≥100 mg/L (wHR 0.44, 95%CI 0.23-0.85). The number of hyperglycaemia events was higher for patients with corticosteroids than for those without, but the number of infections was similar. CONCLUSIONS: We found no association between the use of corticosteroids and intubation or death in the broad population of patients 18-80 years old, with COVID-19, hospitalized in settings non intensive care units. However, the treatment was associated with a reduced risk of intubation or death for patients with ≥3 L/min oxygen or C-reactive protein level ≥100 mg/L at baseline. Further research is needed to confirm the right timing for corticosteroids in patients with COVID-19 requiring oxygen only.

Corticosteroid therapy for patients with COVID-19 pneumonia: a before-after study.

Anti-inflammatory drugs such as corticosteroids may beneficially modulate the host inflammatory response to coronavirus disease 2019 (COVID-19) pneumonia. The aim of this study was to evaluate the impact of addition of corticosteroids to the hospital protocol for treatment of suspected or confirmed COVID-19 pneumonia on rates of death or intensive care unit (ICU) admission. A before-after study was performed to evaluate the effect of addition of corticosteroids to our institution's COVID-19 treatment protocol on hospital mortality. A total of 257 patients with a COVID-19 diagnosis were included in this study between 3 March 2020 and 14 April 2020. As corticosteroids were widely used after 27 March 2020, two periods were considered for the purposes of this study: the 'before' period from 3-20 March 2020 (n = 85); and the 'after' period from 26 March-14 April 2020 (n = 172). The 'after' period was associated with a lower risk of death [adjusted hazard ratio (aHR) = 0.47, 95% confidence interval (CI) 0.23-0.97; P = 0.04] and a lower risk of ICU admission or of death before ICU admission (aHR = 0.37, 95% CI 0.21-0.64; P = 0.0005) by multivariate analysis adjusted for age, National Early Warning score and institutionalisation status. In conclusion, addition of corticosteroids to our institution's COVID-19 treatment protocol was associated with a significant reduction in hospital mortality in the 'after' period.