Early high antibody titre convalescent plasma for hospitalised COVID-19 patients: DAWn-plasma.

BACKGROUND: Several randomised clinical trials have studied convalescent plasma for coronavirus disease 2019 (COVID-19) using different protocols, with different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralising antibody titres, at different time-points and severities of illness. METHODS: In the prospective multicentre DAWn-plasma trial, adult patients hospitalised with COVID-19 were randomised to 4 units of open-label convalescent plasma combined with standard of care (intervention group) or standard of care alone (control group). Plasma from donors with neutralising antibody titres (50% neutralisation titre (NT50)) ≥1/320 was the product of choice for the study. RESULTS: Between 2 May 2020 and 26 January 2021, 320 patients were randomised to convalescent plasma and 163 patients to the control group according to a 2:1 allocation scheme. A median (interquartile range) volume of 884 (806-906) mL) convalescent plasma was administered and 80.68% of the units came from donors with neutralising antibody titres (NT50) ≥1/320. Median time from onset of symptoms to randomisation was 7 days. The proportion of patients alive and free of mechanical ventilation on day 15 was not different between both groups (convalescent plasma 83.74% (n=267) versus control 84.05% (n=137)) (OR 0.99, 95% CI 0.59-1.66; p=0.9772). The intervention did not change the natural course of antibody titres. The number of serious or severe adverse events was similar in both study arms and transfusion-related side-effects were reported in 19 out of 320 patients in the intervention group (5.94%). CONCLUSIONS: Transfusion of 4 units of convalescent plasma with high neutralising antibody titres early in hospitalised COVID-19 patients did not result in a significant improvement of clinical status or reduced mortality.

Efficacy of systematic coronavirus screening by PCR and viral cultures in addition to triage in limiting the spread of SARS-CoV-2 within a hemodialysis unit.

BACKGROUND: Patients with end-stage-renal-disease (ESRD) undergoing hemodialysis (HD) represent a vulnerable population for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, due to their intrinsic fragility and increased exposure to the virus. Therefore, applying effective screening strategies and infection control measures is essential to control the spread of the epidemic within hemodialysis centers. OBJECTIVE: Description and evaluation of the efficacy of systematic screening by rt-PCR and viral cultures, in addition to triage to limit the spread of the epidemic. Evaluation of the performance of these tests using "post-hoc" SARS-CoV-2 serology as a surrogate marker of infection. METHODS: One hundred and forty-four patients undergoing hemodialysis in the Nephrology-Hemodialysis center of CHU Brugmann, Brussels, benefited from systematic virological screening using viral cultures in asymptomatic patients, or molecular tests (rt-PCR) for symptomatic ones, in addition to general prevention measures. Post-hoc serology was performed in all patients. RESULTS: Thirty-eight (26.3%) individuals were infected with SARS-CoV-2. Seventeen infected patients (44.7%) were asymptomatic and thus detected by viral culture. Our strategy allowed us to detect and isolate 97.4% of the infected patients, as proven by post-hoc serology. Only one patient, missed by clinical screening and sequential viral cultures, had a positive serology. CONCLUSION: The implementation of a control and prevention strategy based on a systematic clinical and virological screening showed its effectiveness in limiting (and shortening) the spread of the SARS-CoV-2 epidemic within our hemodialysis unit.

Covid-19 and blood groups: ABO antibody levels may also matter.

BACKGROUND: Susceptibility to Covid-19 has been found to be associated with the ABO blood group, with O type individuals being at a lower risk. However, the underlying mechanism has not been elucidated. Here, we aimed to test the hypothesis that Covid-19 patients might have lower levels of ABO antibodies than non-infected individuals as they could offer some degree of protection. METHODS: After showing that the viral spike protein harbors the ABO glycan epitopes when produced by cells expressing the relevant glycosyltransferases, like upper respiratory tract epithelial cells, we enrolled 290 patients with Covid-19 and 276 asymptomatic controls to compare their levels of natural ABO blood group antibodies. RESULTS: We found significantly lower IgM anti-A + anti-B agglutination scores in blood group O patients (76.93 vs 88.29, P-value = 0.034) and lower levels of anti-B (24.93 vs 30.40, P-value = 0.028) and anti-A antibodies (28.56 vs 36.50, P-value = 0.048) in blood group A and blood group B patients, respectively, compared to controls. CONCLUSION: In this study, we showed that ABO antibody levels are significantly lower in Covid-19 patients compared to controls. These findings could indicate that patients with low levels of ABO antibodies are at higher risk of being infected.

Significance of Hypernatremia Due to SARS-CoV-2 Associated ARDS in Critically Ill Patients.

Background and Objectives: SARS-CoV-2-induced ARDS is a new entity that should be characterized as it appears to be different from standard ARDS. Hypernatremia is a biological alteration that seems to occur very often in this population without any clear cause. The present study aims to clarify the possible causes of hypernatremia and evaluate its impact on patient outcome. Patients and Methods: We conducted a retrospective one-day prevalence study in 2 intensive care units, which only treated COVID-19 patients with moderate to severe ARDS. We measured blood and urine electrolytes in all the patients. Patients with chronic renal failure or renal replacement therapy were excluded from the study. Hypernatremia was defined as plasma sodium levels above 145 mmol/L. Results: Inclusion criteria were met in 17 out of 24 patients. Hypernatremia was present in 52% patients. All had a natriuresis higher than 20 mmol/L and a urine osmolality above 600 mOsm/L. Hypernatremia was acquired in ICU as all the patients had a normal serum sodium level at admission. Conclusion: The incidence of hypernatremia was elevated and appears to be linked to significant insensible water losses. This should trigger us to optimize the maintenance fluid therapy in critically ill patients with SARS-CoV-2-induced ARDS.

COVID-19-Associated Fusobacterium nucleatum Bacteremia, Belgium.

We report 4 cases of Fusobacterium nucleatum bacteremia associated with coronavirus disease (COVID-19). Three cases occurred concomitantly with COVID-19 diagnosis; 1 occurred on day 15 of intensive care. None of the patients had known risk factors for F. nucleatum bacteremia. F. nucleatum infection could represent a possible complication of COVID-19.

Cytomegalovirus haemorrhagic colitis complicating COVID-19 in an immunocompetent critically ill patient: A case report.

Suspicion threshold for opportunistic coinfections should be lowered in severe COVID-19. Serum CMV polymerase chain reaction and colonoscopy should be discussed in presence of persistent digestive disturbances.

A score combining early detection of cytokines accurately predicts COVID-19 severity and intensive care unit transfer.

OBJECTIVES: We aimed to explore cytokine profile in patients as it relates to Coronavirus Disease 2019 (COVID-19) severity, and to establish a predictive cytokine score to discriminate severe from non-severe cases and provide a prognosis parameter for patients that will require intensive care unit (ICU) transfer. METHODS: Serum samples of 63 patients diagnosed with SARS-CoV-2 infection were collected early after hospital admission (day 0-3). Patients were categorized in five groups based on the clinical presentation, the PaO2/FiO2 ratio and the requirement of mechanical ventilation. RESULTS: Three cytokines, IL-6, IL-8 and IL-10, were markedly higher in severe forms (n = 44) than in non-severe forms (n = 19) (p < 0.005). A score combining levels of these three cytokines (IL-6*IL-8*IL-10) had the highest performance to predict severity: sensitivity of 86.4% (95% CI, 72.4-94.8) and specificity of 94.7% (95% CI, 74.0-99.9) for a cutoff value of 2068 pg/mL. Elevated levels of IL-6, IL-8 and IL-10 were also found in critically ill patients. The combination of IL-6*IL-10 serum levels allowed the highest predictability for ICU transfer: AUC of 0.898 (p < 0.0001). CONCLUSION: The combinatorial IL-6*IL-8*IL-10 score at presentation was highly predictive of the progression to a severe form of the disease, and could contribute to improve patient triage and to adapt therapeutic strategy within clinical trials more accurately and efficiently.