COVID-19 in hospitalized solid organ transplant recipients in a nationwide registry study.

OBJECTIVES: Underlying immunodeficiency has been associated with worse clinical presentation and increased mortality in patients with COVID-19. We evaluated the mortality of solid organ transplant (SOT) recipients (SOTR) hospitalized in Spain due to COVID-19. METHODS: Nationwide, retrospective, observational analysis of all adults hospitalized because of COVID-19 in Spain during 2020. Stratification was made according to SOT status. The National Registry of Hospital Discharges was used, using the International Classification of Diseases, 10th revision coding list. RESULTS: Of the 117,694 adults hospitalized during this period, 491 were SOTR: kidney 390 (79.4%), liver 59 (12%), lung 27 (5.5%), and heart 19 (3.9%). Overall, the mortality of SOTR was 13.8%. After adjustment for baseline characteristics, SOTR was not associated with higher mortality risk (odds ratio [OR] = 0.79, 95% confidence interval [CI] 0.60-1.03). However, lung transplantation was an independent factor related to mortality (OR = 3.26, 95% CI 1.33-7.43), while kidney, liver, and heart transplantation were not. Being a lung transplant recipient was the strongest prognostic factor in SOT patients (OR = 5.12, 95% CI 1.88-13.98). CONCLUSION: This nationwide study supports that the COVID-19 mortality rate in SOTR in Spain during 2020 did not differ from the general population, except for lung transplant recipients, who presented worse outcomes. Efforts should be focused on the optimal management of lung transplant recipients with COVID-19.

Increased incidence of giant cell arteritis and associated stroke during the COVID-19 pandemic in Spain: A nation-wide population study.

INTRODUCTION: SARS-CoV-2 infection and COVID-19 vaccines might have increased the incidence of giant-cell arteritis (GCA) and the risk of associated stroke in Spain. METHODS: Retrospective nation-wide observational analysis of all adults hospitalized with GCA in Spain during 5 years (Jan-2016 and Dec-2021). The incidence and proportion of admissions with or because of GCA and GCA-associated stroke were compared between pre-pandemic (2016-2019) and pandemic (2020 and 2021) years. Sensitivity analyses were conducted for the different COVID-19 waves and vaccine timing schedules. RESULTS: A total of 17,268 hospital admissions in patients diagnosed with GCA were identified. During 2020 there were 79.3 and 8.1 per 100,000 admissions of GCA and GCA-associated stroke, respectively. During 2021 these figures were 80.8 and 7.7 per 100,00 admissions, respectively. As comparison, yearly admissions due to GCA and GCA-associated stroke were 72.4 and 5.7 per 100,00, respectively, during the pre-pandemic period (p < 0.05). Coincident with the third wave of COVID-19 (and first vaccine dosing), the rate of GCA-associated stroke admissions increased significantly (from 6.7 to 12%; p < 0.001). Likewise, there was an increase in GCA-associated stroke (6.6% vs 4.1%, p = 0.016) coincident with the third dose vaccination (booster) in patients older than 70 at the end of 2021. In multivariate analysis, only patients admitted during the third COVID-19 wave (and first vaccine dosing) (OR = 1.89, 95% CI 1.22-2.93), and during the third vaccination dosing in patients older than 70 (booster) (OR = 1.66, CI 1.11-2.49), presented a higher GCA-associated stroke risk than the same months of previous years after adjustment by age, sex, classical cardiovascular risk factors and COVID-19 diagnosis. CONCLUSIONS: The COVID-19 pandemic led to an increased incidence of GCA during 2020 and 2021. Moreover, the risk of associated stroke significantly risen accompanying times of COVID-19 vaccine dosing, hypothetically linked to an increased thrombotic risk of mRNA-SARS-CoV-2 vaccines. Hence, forthcoming vaccine policies and indications must weigh the risk of severe COVID-19 with the risk of flare or stroke in patients with GCA.

Predictors of in-hospital mortality in HIV-infected patients with COVID-19.

BACKGROUND: Underlying immunodeficiency is associated with severe COVID-19, but the prognosis of persons with HIV (PWH) with COVID-19 is under debate. METHODS: Nationwide, retrospective, observational analysis of all hospitalizations with COVID-19 during year 2020 in Spain. Stratification was made according to HIV status. The National Registry of Hospital Discharges was used with the ICD-10 coding list. RESULTS: A total of 117,694 adults were hospitalized with COVID-19 during 2020. Only 234 (0.2%) were HIV-positives. More than 95% were on antiretroviral therapy. Compared to HIV-negatives, PWH were younger (mean age 53.2 vs 66.5 years-old; p < 0.001) and more frequently male (74.8% vs 56.6%; p < 0.001). Most co-morbidities predisposing to severe COVID-19 (diabetes, hypertension, dementia, cardiovascular disease) were more frequent in HIV-negatives. In contrast, the rate of baseline liver disease was over 6-fold higher in PWH (27.4% vs 4.4%; p < 0.001). In-hospital mortality was lower in PWH (9.4% vs 16%; p = 0.004). In multivariate analysis, older age, dementia and especially advanced liver disease (RR: 7.6) were the major determinants of death in PWH hospitalized with COVID-19. CONCLUSION: HIV-infected patients hospitalized in Spain with COVID-19 during 2020 had better survival than HIV-negatives, most likely explained by younger age and lower rate of co-morbidities. However, advanced liver disease was a major predictor of death in PWH hospitalized with COVID-19.

Use of Monoclonal Antibodies in Immunocompromised Patients Hospitalized with Severe COVID-19: A Retrospective Multicenter Cohort.

OBJECTIVE: We aim to describe the safety and efficacy of sotrovimab in severe cases of COVID-19 in immunocompromised hosts. METHODS: We used a retrospective multicenter cohort including immunocompromised hospitalized patients with severe COVID-19 treated with sotrovimab between October 2021 and December 2021. RESULTS: We included 32 patients. The main immunocompromising conditions were solid organ transplantation (46.9%) and hematological malignancy (37.5%). Seven patients (21.9%) had respiratory progression: 12.5% died and 9.4% required mechanical ventilation. Patients treated within the first 14 days of their symptoms had a lower progression rate: 12.0% vs. 57.1%, p = 0.029. No adverse event was attributed to sotrovimab. CONCLUSIONS: Sotrovimab was safe and may be effective in its use for immunocompromised patients with severe COVID-19. More studies are needed to confirm these preliminary data.

Systemic Autoimmune Diseases in Patients Hospitalized with COVID-19 in Spain: A Nation-Wide Registry Study.

We aimed to evaluate the clinical outcome of Systemic Autoimmune Diseases (SADs) patients hospitalized with COVID-19 in Spain, before the introduction of SARS-CoV-2 vaccines. A nationwide, retrospective and observational analysis of the patients admitted during 2020, based on the ICD10 codes in the National Registry of Hospital Discharges, was performed. Among 117,694 patients, only 892 (0.8%) presented any type of SAD before COVID-19-related admission: Sjogren's Syndrome constituted 25%, Systemic Vasculitides 21%, Systemic Lupus Erythematosus 19%, Sarcoidosis 17%, Systemic Sclerosis 11%, Mixed and Undifferentiated Connective Tissue Disease 4%, Behçet's Disease 4% and Inflammatory Myopathies 2%. The in-hospital mortality rate was higher in SAD individuals (20% vs. 16%, p < 0.001). After adjustment by baseline conditions, SADs were not associated with a higher mortality risk (OR = 0.93, 95% CI 0.78-1.11). Mortality in the SADs patients was determined by age (OR = 1.05, 95% CI 1.04-1.07), heart failure (OR = 1.67, 95% CI 1.10-2.49), chronic kidney disease (OR = 1.29, 95% CI 1.05-1.59) and liver disease (OR = 1.97, 95% CI 1.13-3.44). In conclusion, the higher COVID-19 mortality rate seen in SADs patients hospitalized in Spain in 2020 was related to the higher burden of comorbidities, secondary to direct organ damage and sequelae of their condition. Whilst further studies should evaluate the impact of baseline immunosuppression on COVID-19 outcomes in this population, efforts should be focused on the optimal management of SAD to minimize the impact of the organ damage that has been shown to determine COVID-19 prognosis.

Impact of the COVID-19 Pandemic on the Clinical Profile of Candidemia and the Incidence of Fungemia Due to Fluconazole-Resistant Candida parapsilosis.

Severely ill COVID-19 patients are at high risk of nosocomial infections. The aim of the study was to describe the characteristics of candidemia during the pre-pandemic period (January 2019-February 2020) compared to the pandemic period (March 2020-September 2021). Antifungal susceptibilities were assessed using the EUCAST E.Def 7.3.2 broth dilution method. Fluconazole-resistant C. parapsilosis isolates (FRCP) were studied for sequencing of the ERG11 gene. The incidence of candidemia and C. parapsilosis bloodstream infection increased significantly in the pandemic period (p = 0.021). ICU admission, mechanical ventilation, parenteral nutrition and corticosteroids administration were more frequent in patients with candidemia who had been admitted due to COVID-19. Fifteen cases of FRCP fungemia were detected. The first case was recorded 10 months before the pandemic in a patient transferred from another hospital. The incidence of FRCP in patients admitted for COVID-19 was 1.34 and 0.16 in all other patients (p < 0.001). ICU admission, previous Candida spp. colonization, arterial catheter use, parenteral nutrition and renal function replacement therapy were more frequent in patients with candidemia due to FRCP. All FRCP isolates showed the Y132F mutation. In conclusion, the incidence of candidemia experienced an increase during the COVID-19 pandemic and FRCP fungemia was more frequent in patients admitted due to COVID-19.

COVID-19-associated pulmonary aspergillosis (CAPA): Risk factors and development of a predictive score for critically ill COVID-19 patients.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) is a major complication of critically ill COVID-19 patients, with a high mortality rate and potentially preventable. Thus, identifying patients at high risk of CAPA would be of great interest. We intended to develop a clinical prediction score capable of stratifying patients according to the risk for CAPA at ICU admission. METHODS: Single centre retrospective case-control study. A case was defined as a patient diagnosed with CAPA according to 2020 ECMM/ISHAM consensus criteria. 2 controls were selected for each case among critically ill COVID-19 patients. RESULTS: 28 CAPA patients and 56-matched controls were included. Factors associated with CAPA included old age (68 years vs. 62, p = .033), active smoking (17.9% vs. 1.8%, p = .014), chronic respiratory diseases (48.1% vs. 26.3%, p = .043), chronic renal failure (25.0% vs. 3.6%, p = .005), chronic corticosteroid treatment (28.6% vs. 1.8%, p < .001), tocilizumab therapy (92.9% vs. 66.1%, p = .008) and high APACHE II at ICU admission (median 13 vs. 10 points, p = .026). A score was created including these variables, which showed an area under the receiver operator curve of 0.854 (95% CI 0.77-0.92). A punctuation below 6 had a negative predictive value of 99.6%. A punctuation of 10 or higher had a positive predictive value of 27.9%. CONCLUSION: We present a clinical prediction score that allowed to stratify critically ill COVID-19 patients according to the risk for developing CAPA. This CAPA score would allow to target preventive measures. Further evaluation of the score, as well as the utility of these targeted preventive measures, is needed.

Incidence, Clinical Presentation, Relapses and Outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Patients Treated With Anti-CD20 Monoclonal Antibodies.

BACKGROUND: Our objective is to describe the presentation and complications, including relapses, of coronavirus disease 2019 (COVID-19) in patients under anti-CD20 treatments. In addition, to describe viral clearance and determine the safety of reintroducing anti-CD20 treatment. METHODS: Retrospective cohort study of 422 patients under anti-CD20 treatment that was administered from 1 January 2019 to 31 December 2020. RESULTS: Fifty-seven patients were diagnosed with COVID-19 (13.5%). Twenty-five patients (43.9%) required hospital admission. Five patients died (8.8%), and 10 developed severe COVID-19 and acute respiratory distress syndrome. Mortality rate was higher among patients infected during the first 3 months following the last dose of anti-CD20 (14.7% vs 0%, P = .046). The median time of persistence of positive reverse transcription polymerase chain reaction (RT-PCR) was 22 days (IQR 13-40).Nine out of 52 survivors (17.3%) presented relapses. All of them received the last dose of anti-CD20 less than 6 months before the COVID-19 episode. Clinical presentation was fever (n = 8; 88.9%), dyspnea (n = 7; 77.8%), cough (n = 7; 77.8%), worsening of previous infiltrates (n = 5; 55.6%) and new pulmonary infiltrates (n = 8; 88.9%). An increase in lymphocytes with CD4/CD8 ratio inversion was observed in all cases. Among the 25 patients who resumed anti-CD20 drug, 4 (16.0%) presented relapses vs 5/28 among those who did not (17.9%), (P = .857). CONCLUSIONS: Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the 6 months after anti-CD20 administration had a worse outcome and a higher mortality rate. The duration of infectivity may be longer. Relapses of COVID-19 occurred in more than 15% and were associated with viral replication. Once the infection is resolved, it is safe to restart treatment with anti-CD20.

Association of COVID-19-Associated Pulmonary Aspergillosis with Cytomegalovirus Replication: A Case-Control Study.

Introduction: Cytomegalovirus (CMV) infection is a well-known factor associated with invasive aspergillosis in immunocompromised hosts. However, its association with COVID-19-associated pulmonary aspergillosis (CAPA) has not been described. We aimed to examine the possible link between CMV replication and CAPA occurrence. Methods: A single-center, retrospective case-control study was conducted. A case was defined as a patient diagnosed with CAPA according to 2020 ECMM/ISHAM consensus criteria. Two controls were selected for each case among critically ill COVID-19 patients. Results: In total, 24 CAPA cases were included, comprising 14 possible CAPA and 10 probable CAPA. Additionally, 48 matched controls were selected. CMV replication was detected more frequently in CAPA than in controls (75.0% vs. 35.4%, p = 0.002). Probable CMV end-organ disease was more prevalent in CAPA (20.8% vs. 4.2%, p = 0.037). After adjusting for possible confounding factors, CMV replication persisted strongly associated with CAPA (OR 8.28 95% CI 1.90-36.13, p = 0.005). Among 11 CAPA cases with CMV PCR available prior to CAPA, in 9 (81.8%) cases, CMV replication was observed prior to CAPA diagnosis. Conclusions: Among critically ill COVID-19 patients, CMV replication was associated with CAPA and could potentially be considered a harbinger of CAPA. Further studies are needed to confirm this association.

Mortality by COVID-19 Before Vaccination - One Year Experience of Hospitalized Patients in Madrid.

OBJECTIVES: The aim of the study was to analyze the mortality and characteristics of deceased patients with COVID-19 during the first year of the pandemic. METHODS: All admissions owing to COVID-19 at a tertiary hospital in Madrid were analyzed. Three waves were considered: March 2020 to June 2020, July 2020 to November 2020, and December 2020 to April 2021. RESULTS: A total of 3,676 patients were identified. Among inpatients, no differences regarding age, sex, length of admission, or mortality were found between the 3 waves (p >0.05). The overall mortality rate was 12.9%. Among deceased patients, the median age was 82 years and the median Charlson Comorbidity Index was 6. Considering the main predictors for mortality by COVID-19 (age, sex, and concomitant comorbidities), only patients with previous lung disease were more prevalent in the third period (p <0.01). Finally, higher intensive care unit admission rates, a lower rate of patients coming from nursing homes, and a lower rate of patients with dementia were noted in the third period (p <0.05) among deceased patients. CONCLUSION: One year after the onset of the pandemic, the mortality rate of hospitalized patients and the profile of non-survivors have not changed significantly. In the absence of vaccine benefits, advanced age and multiple pathologies are uniform characteristics of non-survivors.

Influence of chronic use of corticosteroids and calcineurin inhibitors on COVID-19 clinical outcomes: analysis of a nationwide registry.

OBJECTIVES: The aim of this study was to analyze whether subgroups of immunosuppressive (IS) medications conferred different outcomes in COVID-19. METHODS: The study involved a multicenter retrospective cohort of consecutive immunosuppressed patients (ISPs) hospitalized with COVID-19 from March to July, 2020. The primary outcome was in-hospital mortality. A propensity score-matched (PSM) model comparing ISP and non-ISP was planned, as well as specific PSM models comparing individual IS medications associated with mortality. RESULTS: Out of 16 647 patients, 868 (5.2%) were on chronic IS therapy prior to admission and were considered ISPs. In the PSM model, ISPs had greater in-hospital mortality (OR 1.25, 95% CI 0.99-1.62), which was related to a worse outcome associated with chronic corticoids (OR 1.89, 95% CI 1.43-2.49). Other IS drugs had no repercussions with regard to mortality risk (including calcineurin inhibitors (CNI); OR 1.19, 95% CI 0.65-2.20). In the pre-planned specific PSM model involving patients on chronic IS treatment before admission, corticosteroids were associated with an increased risk of mortality (OR 2.34, 95% CI 1.43-3.82). CONCLUSIONS: Chronic IS therapies comprise a heterogeneous group of drugs with different risk profiles for severe COVID-19 and death. Chronic systemic corticosteroid therapy is associated with increased mortality. On the contrary, CNI and other IS treatments prior to admission do not seem to convey different outcomes.

A multicenter randomized open-label clinical trial for convalescent plasma in patients hospitalized with COVID-19 pneumonia.

BACKGROUNDPassive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19. Evidence from controlled clinical trials is inconclusive.METHODSWe conducted a randomized, open-label, controlled clinical trial at 27 hospitals in Spain. Patients had to be admitted for COVID-19 pneumonia within 7 days from symptom onset and not on mechanical ventilation or high-flow oxygen devices. Patients were randomized 1:1 to treatment with CP in addition to standard of care (SOC) or to the control arm receiving only SOC. The primary endpoint was the proportion of patients in categories 5 (noninvasive ventilation or high-flow oxygen), 6 (invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), or 7 (death) at 14 days. Primary analysis was performed in the intention-to-treat population.RESULTSBetween April 4, 2020, and February 5, 2021, 350 patients were randomly assigned to either CP (n = 179) or SOC (n = 171). At 14 days, proportion of patients in categories 5, 6, or 7 was 11.7% in the CP group versus 16.4% in the control group (P = 0.205). The difference was greater at 28 days, with 8.4% of patients in categories 5-7 in the CP group versus 17.0% in the control group (P = 0.021). The difference in overall survival did not reach statistical significance (HR 0.46, 95% CI 0.19-1.14, log-rank P = 0.087).CONCLUSIONCP showed a significant benefit in preventing progression to noninvasive ventilation or high-flow oxygen, invasive mechanical ventilation or ECMO, or death at 28 days. The effect on the predefined primary endpoint at 14 days and the effect on overall survival were not statistically significant.TRIAL REGISTRATIONClinicaltrials.gov, NCT04345523.FUNDINGGovernment of Spain, Instituto de Salud Carlos III.

Inadequate use of antibiotics in the covid-19 era: effectiveness of antibiotic therapy.

BACKGROUND: Since December 2019, the COVID-19 pandemic has changed the concept of medicine. This work aims to analyze the use of antibiotics in patients admitted to the hospital due to SARS-CoV-2 infection. METHODS: This work analyzes the use and effectiveness of antibiotics in hospitalized patients with COVID-19 based on data from the SEMI-COVID-19 registry, an initiative to generate knowledge about this disease using data from electronic medical records. Our primary endpoint was all-cause in-hospital mortality according to antibiotic use. The secondary endpoint was the effect of macrolides on mortality. RESULTS: Of 13,932 patients, antibiotics were used in 12,238. The overall death rate was 20.7% and higher among those taking antibiotics (87.8%). Higher mortality was observed with use of all antibiotics (OR 1.40, 95% CI 1.21-1.62; p < .001) except macrolides, which had a higher survival rate (OR 0.70, 95% CI 0.64-0.76; p < .001). The decision to start antibiotics was influenced by presence of increased inflammatory markers and any kind of infiltrate on an x-ray. Patients receiving antibiotics required respiratory support and were transferred to intensive care units more often. CONCLUSIONS: Bacterial co-infection was uncommon among COVID-19 patients, yet use of antibiotics was high. There is insufficient evidence to support widespread use of empiric antibiotics in these patients. Most may not require empiric treatment and if they do, there is promising evidence regarding azithromycin as a potential COVID-19 treatment.

Inappropriate antibiotic use in the COVID-19 era: Factors associated with inappropriate prescribing and secondary complications. Analysis of the registry SEMI-COVID.

BACKGROUND: Most patients with COVID-19 receive antibiotics despite the fact that bacterial co-infections are rare. This can lead to increased complications, including antibacterial resistance. We aim to analyze risk factors for inappropriate antibiotic prescription in these patients and describe possible complications arising from their use. METHODS: The SEMI-COVID-19 Registry is a multicenter, retrospective patient cohort. Patients with antibiotic were divided into two groups according to appropriate or inappropriate prescription, depending on whether the patient fulfill any criteria for its use. Comparison was made by means of multilevel logistic regression analysis. Possible complications of antibiotic use were also identified. RESULTS: Out of 13,932 patients, 3047 (21.6%) were prescribed no antibiotics, 6116 (43.9%) were appropriately prescribed antibiotics, and 4769 (34.2%) were inappropriately prescribed antibiotics. The following were independent factors of inappropriate prescription: February-March 2020 admission (OR 1.54, 95%CI 1.18-2.00), age (OR 0.98, 95%CI 0.97-0.99), absence of comorbidity (OR 1.43, 95%CI 1.05-1.94), dry cough (OR 2.51, 95%CI 1.94-3.26), fever (OR 1.33, 95%CI 1.13-1.56), dyspnea (OR 1.31, 95%CI 1.04-1.69), flu-like symptoms (OR 2.70, 95%CI 1.75-4.17), and elevated C-reactive protein levels (OR 1.01 for each mg/L increase, 95% CI 1.00-1.01). Adverse drug reactions were more frequent in patients who received ANTIBIOTIC (4.9% vs 2.7%, p < .001). CONCLUSION: The inappropriate use of antibiotics was very frequent in COVID-19 patients and entailed an increased risk of adverse reactions. It is crucial to define criteria for their use in these patients. Knowledge of the factors associated with inappropriate prescribing can be helpful.

Risk factors for unfavorable outcome and impact of early post-transplant infection in solid organ recipients with COVID-19: A prospective multicenter cohort study.

The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of 210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (24.5%). Thirty-seven (17.6%) patients required ICU admission, 12 (5.7%) suffered graft dysfunction, and 45 (21.4%) died. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis. Four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. In summary, this study presents comprehensive information on characteristics and complications of COVID-19 in hospitalized SOTRs and provides indicators available upon hospital admission for the identification of SOTRs at risk of critical disease or death, underlining the need for stringent preventative measures in the early post-transplant period.