Correction: "Acute kidney injury in critically ill patients with COVID-19: The AKICOV multicenter study in Catalonia".

[This corrects the article DOI: 10.1371/journal.pone.0284248.].

"Acute kidney injury in critically ill patients with COVID-19: The AKICOV multicenter study in Catalonia".

This study describes the incidence, evolution and prognosis of acute kidney injury (AKI) in critical COVID-19 during the first pandemic wave. We performed a prospective, observational, multicenter study of confirmed COVID-19 patients admitted to 19 intensive care units (ICUs) in Catalonia (Spain). Data regarding demographics, comorbidities, drug and medical treatment, physiological and laboratory results, AKI development, need for renal replacement therapy (RRT) and clinical outcomes were collected. Descriptive statistics and logistic regression analysis for AKI development and mortality were used. A total of 1,642 patients were enrolled (mean age 63 (15.95) years, 67.5% male). Mechanical ventilation (MV) was required for 80.8% and 64.4% of these patients, who were in prone position, while 67.7% received vasopressors. AKI at ICU admission was 28.4% and increased to 40.1% during ICU stay. A total of 172 (10.9%) patients required RRT, which represents 27.8% of the patients who developed AKI. AKI was more frequent in severe acute respiratory distress syndrome (ARDS) ARDS patients (68% vs 53.6%, p<0.001) and in MV patients (91.9% vs 77.7%, p<0.001), who required the prone position more frequently (74.8 vs 61%, p<0.001) and developed more infections. ICU and hospital mortality were increased in AKI patients (48.2% vs 17.7% and 51.1% vs 19%, p <0.001) respectively). AKI was an independent factor associated with mortality (IC 1.587-3.190). Mortality was higher in AKI patients who required RRT (55.8% vs 48.2%, p <0.04). Conclusions There is a high incidence of AKI in critically ill patients with COVID-19 disease and it is associated with higher mortality, increased organ failure, nosocomial infections and prolonged ICU stay.

Genetic screening for TLR7 variants in young and previously healthy men with severe COVID-19: a case series

Advanced age, male sex and chronic comorbidities are associated with severe COVID-19. However, these general risk factors cannot explain why critical illness occurs in young and apparently healthy individuals. In the past months, several publications have identified susceptibility loci and genes using comprehensive GWAS studies or genome, exome or candidate genes analysis. A recent study reported rare, loss-of-function TLR7 variants in otherwise healthy young brother pairs from two families with severe COVID-19. We aimed to prospectively study the prevalence of rare X-chromosomal TLR7 genetic variants in our cohort of young male patients with severe COVID-19. We recruited 13 patients [≤]50 years who had no risk factors known to be associated with severe disease. We studied the entire TLR7 coding region and identified two missense variants (p.Asn215Ser, c.644A>G and p.Trp933Arg, c.2797T>C) in two out of 13 cases (15.4%). These variants were not previously reported in population control databases (gnomAD) and were predicted to be damaging by all in silico predictors. The male index patients were between 25 and 30 years old and had no apparent comorbidities. The TLR7 p.Asn215Ser co-segregated in 2 first-degree relatives severely affected by COVID-19, in a younger previously healthy the variant was found in hemizygous state, and in an older than 60 was in heterozygous state. No family members were available for testing the segregation of the p.Trp933Arg variant. These results further support that susceptibility to severe COVID-19 could be determined by inherited rare genetic variants in TLR7. Understanding the causes and mechanisms of life-threatening COVID-19 is crucial and could lead to novel preventive and therapeutic options. This study supports a rationale for the genetic screening for TLR7 variants in young men with severe COVID-19 in the absence of other relevant risk factors. A diagnosis of TLR7 deficiency could not only inform on treatment options for the patient, but it also enables for pre-symptomatic testing of at-risk male relatives with the possibility of instituting early preventive and therapeutic interventions.

Pragmatic, open-label, single-center, randomized, phase II clinical trial to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus in patients with severe pneumonia secondary to COVID-19: the TACROVID trial protocol

IntroductionSome COVID-19 patients evolve to severe lung injury and systemic hyperinflammatory syndrome triggered by both the coronavirus infection and the subsequent host-immune response. Accordingly, the use of immunomodulatory agents has been suggested but still remains controversial. Our working hypothesis is that methylprednisolone pulses and tacrolimus may be an effective and safety drug combination for treating severe COVID-19 patients. Methods and analysisTACROVID is a randomized, open-label, single-center, phase II trial to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) versus SoC alone, in patients at advanced stage of COVID-19 disease with lung injury and systemic hyperinflammatory response. Patients are randomly assigned (1:1) to one of two arms (42 patients in each group). The primary aim is to assess the time to clinical stability after initiating randomization. Clinical stability is defined as body temperature [≤] 37.5{degrees}C, and PaO2/FiO2 > 400 and/or SatO2/FiO2 > 300, and respiratory rate [≤]24 rpm; for 48 consecutive hours. DiscussionMethylprednisolone and tacrolimus might be beneficial to treat those COVID-19 patients progressing into severe pulmonary failure and systemic hyperinflammatory syndrome. The rationale for its use is the fast effect of methylprednisolone pulses and the ability of tacrolimus to inhibit both the CoV-2 replication and the secondary cytokine storm. Interestingly, both drugs are low-cost and can be manufactured on a large scale; thus, if effective and safe, a large number of patients could be treated in developed and developing countries. Trial registration numberNCT04341038 / EudraCT: 2020-001445-39

Beneficial Effect of Corticosteroids in Preventing Mortality in Patients Receiving Tocilizumab to Treat Severe COVID-19 Illness

IntroductionOn the basis of the preliminary report from the RECOVERY trial, the use of dexamethasone or alternative corticosteroids (CS) is currently recommended in severe COVID-19 patients requiring supplemental oxygen. However, last updated recommendations have not taken a position either for or against the use of other immunomodulators such as tocilizumab (TCZ), with or without CS, since results are still limited. MethodsFrom March 17 to April 7, 2020, a real-world observational retrospective analysis was conducted at our 750-bed university hospital to study the characteristics and risk factors for mortality in patients with severe COVID-19 treated with TCZ +/-CS, in addition to standard of care (SOC). Data were obtained from routine clinical practice, stored in electronic medical records. The main outcome was all-cause in-hospital mortality. ResultsA total of 1,092 COVID-19 patients were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186, 155 (83.3 %) patients were receiving non-invasive ventilation when TCZ +/-CS was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 ({+/-} 4.3) and 4.3 days ({+/-} 3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR=1.09, p<0.001), chronic heart failure (HR=4.4, p=0.003), and chronic liver disease (HR=4.69, p=0.004). The use of CS, in combination with TCZ, was the main protective factor against mortality (HR=0.26, p<0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. ConclusionsIn severe COVID-19 patients receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in addition to TCZ therapy, showed beneficial effect in preventing in-hospital mortality.