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.

Coronavirus and other airborne agents with pandemic potential.

The recent emergence of a novel coronavirus (severe acute respiratory syndrome coronavirus 2) has caused a pandemic, which is the most severe infectious disease outbreak in many decades. Other infective agents such as influenza as well as other neglected viruses such as Lassa virus, Nipah virus or poxviruses are also a cause for concern owing to their attack rate and potential for global spread. Drug-resistant bacteria, such as Mycobacterium tuberculosis, are already a significant public health issue in many countries, and it is expected that they will be expanding in the near future. Finally, airborne bioterrorism agents have high morbidity and mortality rates and should be looked with concern in the current international unrest.

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.

Is SARS-CoV-2 the only cause of long-COVID?

Around 10% of adults infected with SARS-CoV-2 that survive a first episode of COVID-19 appear to experience long-term clinical manifestations. The signs and symptoms of this post-acute COVID-19 syndrome (PACS) include fatigue, dyspnea, joint pain, myalgia, chest pain, cough, anosmia, dysgeusia, headache, depression, anxiety, memory loss, concentration difficulties, and insomnia. These sequelae remind the constellation of clinical manifestations previously recognized as myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS). This condition has been described following distinct infectious events, mostly acute viral illnesses. In this way, the pathophysiology of PACS might overlap with mechanisms involved in other post-infectious fatigue syndromes. The risk of PACS is more frequent in women than men. Additional host genetic factors could be involved. There is a dysregulation of multiple body organs and systems, involving the immune system, the coagulation cascade, endocrine organs, autonomic nervous system, microbiota-gut-brain axis, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-thyroid axis, etc. Hypothetically, an abnormal response to certain infectious agents could trigger the development of postinfectious fatigue syndromes.

Pre-Exposure Prophylaxis for viral infections other than HIV

SUMMARY The battle against human viral infections has historically relied on two medical strategies, namely vaccines to protect from contagion and antivirals to treat infected patients. In the absence of vaccines, antivirals have occasionally been used as peri-exposure prophylaxis, given either before (pre-exposure prophylaxis) or right after (post-exposure prophylaxis). In an unprecedented way, the use of antiretrovirals as chemoprophylaxis has triumphed in the HIV field. Indeed, oral antiretrovirals given either daily or at demand to HIV-uninfected individuals engaged in high-risk behaviors protect from contagion. More recently, the advent of long-acting formulations has allowed HIV protection following intramuscular injections every three months. Can we envision a similar prophylactic strategy for other human viral infections? The advent of such ‘chemical vaccines’ would fill an unmet need when classical vaccines do not exist, cannot be recommended, immune responses are suboptimal, escape mutants emerge or immunity wanes. In this review, we discuss the opportunities for antiviral chemoprophylaxis for viral hepatitis B and C, retroviruses HTLV-1 and HIV-2, and respiratory viruses influenza and SARS-CoV-2, among others.

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.

Impact of scaling up SARS-CoV-2 vaccination on COVID-19 hospitalizations in Spain.

BACKGROUND: The advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has been associated with a significant decline in coronavirus disease 2019 (COVID-19) hospitalizations and deaths. However, little is known about the benefits experienced by different population groups and/or using distinct vaccines. METHODS: The Spanish public registry was analyzed to examine associations between weekly vaccination scale-up and the incidence of COVID-19 hospitalizations by age, sex, and vaccine modality. The study period extended from January 2020 to June 2021. RESULTS: A total of 363 960 COVID-19 hospitalizations were recorded in Spain during the study period, with three peaks in March 2020, November 2020, and January 2021. The incidence of COVID-19 hospitalizations per 100 000 population increased exponentially with age, on average 71.5% for each decade older. Overall, individuals older than 60 years of age accounted for 65% of all COVID-19 hospitalizations. The speedy vaccination rollout since the end of 2020, with prioritization of the elderly groups, resulted in a rapid fall in COVID-19 hospitalizations starting in February 2021. The benefit was already noticed 3-4 weeks after the first dose, regardless of the vaccine modality. CONCLUSIONS: COVID-19 hospitalizations increased exponentially with age in all three peaks of SARS-CoV-2 infection in Spain. Early mass vaccination of people over 60 years of age prevented a fourth wave of COVID-19 hospitalizations during the spring of 2021.

Oral antivirals for the prevention and treatment of SARS-CoV-2 infection.

Vaccines and antivirals are the classical weapons deployed to contain, prevent, and treat life-threatening viral illnesses. Specifically, for SARS-CoV-2 infection, vaccines protect against severe COVID-19 disease manifestations and complications. However, waning immunity and emergence of vaccine escape mutants remains a growing threat. This is highlighted by the current surge of the omicron COVID-19 variant. Thus, there is a race to find treatment alternatives. We contend that oral small molecule antivirals that halt SARSCoV- 2 infection are essential. Compared to currently available monoclonal antibodies and remdesivir, where parenteral administration is required, oral antivirals offer treatments in an outpatient setting with dissemination available on a larger scale. In response to this need at 2021's end, regulatory agencies provided emergency use authorization for both molnupiravir and nirmatrelvir. These medicines act on the viral polymerase and protease, respectively. Each is given for 5 days and can reduce disease progression by 30% and 89%, respectively. The advent of additional oral antivirals, the assessment of combination therapies, the formulation of extended-release medications, and their benefit for both early treatment and prophylaxis will likely transform the landscape of the COVID-19 pandemic.

Short Communication: Impact of COVID-19 on Case Reporting for HTLV and HIV-2 in Spain.

The medical demand imposed by COVID-19 has distracted proper care of other illnesses. Herein, we report the impact on new diagnoses of HTLV-1, HTLV-2, and HIV-2 in Spain, where these infections are mostly driven by immigration flows from endemic regions. As expected, case reporting declined for all three retroviral infections with respect to prior years. Furthermore, late presentations were more common. The two major reasons for these observations were significant declines in the arrival of foreigners from endemic regions and a shift in medical resources to prioritize COVID-19.

Bacterial infections in patients hospitalized with COVID-19.

Bacterial infections may complicate the course of COVID-19 patients. The rate and predictors of bacterial infections were examined in patients consecutively admitted with COVID-19 at one tertiary hospital in Madrid between March 1st and April 30th, 2020. Among 1594 hospitalized patients with COVID-19, 135 (8.5%) experienced bacterial infectious events, distributed as follows: urinary tract infections (32.6%), bacteremia (31.9%), pneumonia (31.8%), intra-abdominal infections (6.7%) and skin and soft tissue infections (6.7%). Independent predictors of bacterial infections were older age, neurological disease, prior immunosuppression and ICU admission (p < 0.05). Patients with bacterial infections who more frequently received steroids and tocilizumab, progressed to lower Sap02/FiO2 ratios, and experienced more severe ARDS (p < 0.001). The mortality rate was significantly higher in patients with bacterial infections as compared to the rest (25% vs 6.7%, respectively; p < 0.001). In multivariate analyses, older age, prior neurological or kidney disease, immunosuppression and ARDS severity were associated with an increased mortality (p < 0.05) while bacterial infections were not. Conversely, the use of steroids or steroids plus tocilizumab did not confer a higher risk of bacterial infections and improved survival rates. Bacterial infections occurred in 8.5% of patients hospitalized with COVID-19 during the first wave of the pandemic. They were not independently associated with increased mortality rates. Baseline COVID-19 severity rather than the incidence of bacterial infections seems to contribute to mortality. When indicated, the use of steroids or steroids plus tocilizumab might improve survival in this population.

Severe Lymphopenia as a Predictor of COVID-19 Mortality in Immunosuppressed Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has a high mortality in certain group of patients. We analysed the impact of baseline immunosuppression in COVID-19 mortality and the role of severe lymphopenia in immunocompromised subjects. METHODS: We analysed all patients admitted with COVID-19 in a tertiary hospital in Madrid between March 1st and April 30th 2020. Epidemiological and clinical data, including severe lymphopenia (<500 lymphocytes/mm3) during admission, were analysed and compared based on their baseline immunosuppression condition. RESULTS: A total of 1594 patients with COVID-19 pneumonia were hospitalised during the study period. 166 (10.4%) were immunosuppressed. Immunocompromised patients were younger (64 vs. 67 years, p = 0.02) but presented higher rates of hypertension, diabetes, heart, neurological, lung, kidney and liver disease (p < 0.05). They showed more severe lymphopenia (53% vs 24.1%, p < 0.001), lower SapO2/FiO2 ratios (251 vs 276, p = 0.02) during admission and higher mortality rates (27.1% vs 13.5%, p < 0.001). After adjustment, immunosuppression remained as an independent factor related to mortality (Odds Ratio (OR): 2.24, p < 0.001). In the immunosuppressed group, age (OR = 1.06, p = 0.01), acute respiratory distress syndrome (ARDS) (OR = 12.27, p = 0.017) and severe lymphopenia (OR = 3.48, p = 0.04) were the factors related to high mortality rate. CONCLUSION: Immunosuppression is an independent mortality risk factor in COVID-19. Severe lymphopenia should be promptly identified in these patients.

Third wave of COVID-19 in Madrid, Spain.

A third wave of COVID-19 occurred after Christmas 2020 in Madrid, one of the European pandemic epicenters. We noticed 6 major differential features to previous waves. First, household contacts were a large proportion of cases. Second, access to rapid antigen tests allowed prompt diagnosis and isolation. Third, clinically severe cases and mortality rates were lower. Fourth, the more transmissible B.1.1.7 strain was increasingly found. Fifth, vaccination benefits were seen in healthcare workers and nursing homes. Lastly, reinfections were more common. By Easter 2021, approximately 25% of the population in Madrid had been infected with SARS-CoV-2. Therefore, massive and accelerated vaccination campaigns are warranted to prevent new COVID-19 waves.

Major determinants of death in patients hospitalized with COVID-19 during the first epidemic wave in Madrid, Spain.

ABSTRACT: Spain is one of the European countries most largely affected by COVID-19, being Madrid the epicenter. A good knowledge of the main features of hospitalized patients during the complete lockdown should improve the management of new COVID-19 surges.All patients hospitalized at one large tertiary hospital in Madrid for suspected COVID-19 pneumonia from March 1 to May 31 were retrospectively identified.A total of 1752 patients were admitted with suspected pneumonia due to SARS-CoV-2 infection during the 3-month study period. The peak of daily admissions (n = 84) was reached on March 24, whereas the maximal cumulative number of hospitalized patients (n = 626) occurred on March 30. Overall, 85.3% had a positive PCR test for SARS-CoV-2 at least once during admission. Their median age was 65 (54-77) and 59.9% were male. The median length of hospitalization was of 7 (4-13) days. Roughly 6.5% were admitted at the intensive care unit.Death occurred in 242 (13.8%). Overall, 75% of deaths occurred in patients older than 75 years-old. It was 38.2% in patients hospitalized older than 80 years-old versus 2.2% in patients younger than 60 years-old (p < 0.001). Up to 94 (38.8%) of deceased patients had been transferred from nursing homes. The median Charlson co-morbidity score was 6 in deceased patients.The in-hospital mortality rate during the first wave of COVID-19 in Madrid was 14%. It was largely driven by older age, the presence of underlying chronic conditions (≥2) and living at nursing homes.

Main differences between the first and second waves of COVID-19 in Madrid, Spain.

BACKGROUND: The emergence and rapid global spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) represents a major challenge to health services, and has disrupted social and economic activities worldwide. In Spain, the first pandemic wave started in mid-March 2020 and lasted for 3 months, requiring home confinement and strict lockdown. Following relaxation of the measures during the summer, a second wave commenced in mid-September 2020 and extended until Christmas 2020. METHODS: The two pandemic waves were compared using information collected from rapid diagnostic tests and polymerase chain reaction assays at one university clinic in Madrid, the epicentre of the pandemic in Spain. RESULTS: In total, 1569 individuals (968 during the first wave and 601 during the second wave) were tested for SARS-CoV-2-specific antibodies using fingerprick capillary blood. In addition, during the second wave, 346 individuals were tested for SARS-CoV-2-specific antigen using either oral swabs or saliva. The overall seroprevalence of first-time-tested individuals was 12.6% during the first wave and 7.7% during the second wave (P < 0.01). Seroconversions and seroreversions within 6 months occurred at low rates, both below 5%. During the second wave, 3.5% of tested individuals were SARS-CoV-2 antigen positive, with two cases considered as re-infections. Severe clinical symptoms occurred in a greater proportion of cases during the first wave compared with the second wave (27.8% vs 10.6%, respectively; P = 0.03). CONCLUSION: The cumulative seroprevalence of SARS-CoV-2 antibodies in Madrid at the end of 2020 was approximately 20%. Seroreversions within 6 months occurred in 4% of cases. Seroconversions and re-infections were clinically less severe during the second wave than during the first wave. Hypothetically, a lower viral inoculum as a result of social distancing, increased use of face masks, promotion of outdoor activities and restrictions on gatherings may have contributed to this lower pathogenicity.

Inflammatory-Related Clinical and Metabolic Outcomes in COVID-19 Patients.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) infection elicits inflammatory manifestations that relate with a "cytokine storm." OBJECTIVE: The aim of this research was to assess the role of circulating interleukin 6 (IL-6) levels and other inflammatory markers in patients with coronavirus disease 2019 (COVID-19) on metabolic functions and accompanying clinical complications. Patients and Methods. A total of 165 patients diagnosed with COVID-19 pneumonia were examined for medical features and inflammatory markers such as blood IL-6, CRP, ferritin, LDH, neutrophil/lymphocyte index (NLI), D-Dimer, and Red Cell Distribution Width (RDW). Regression analyses concerning electronically collected medical data were adjusted by appropriate factors and confounding variables. Results. Plasma IL-6 determinations evidenced a consistent association with hospital stay days, Intensive Care Unit (ICU) admission, and mortality rates. Similar trends were found for other proinflammatory variables, where ferritin and NLI showed a remarkable value as surrogates. Hyperglycaemia and the Charlson Comorbidity Index Score were positively associated with the inflammatory response induced by the SARS-COV-2 infection. An unhealthy lifestyle such as smoking and alcoholic drinks consumption as well as excessive body adiposity influenced inflammatory-related outcomes in the screened patients. CONCLUSION: IL-6 together with other inflammatory biomarkers accompanied poor clinical and metabolic outcomes in COVID-19-infected patients. IL-6 may result in a suitable proxy to individually categorise patients in order to manage this infectious pandemic.