ABSTRACT
Background: Unselected data of nationwide studies of hospitalized patients with COVID-19 is still sparse, but these data are of outstanding interest not to exceed hospital capacities and to avoid overloading of national health-care systems. Purpose(s): Thus, we sought to analyze seasonal/regional trends, predictors of in-hospital case-fatality and mechanical ventilation (MV) in patients with COVID-19 in Germany. Method(s): We used the German nationwide inpatient sample to analyze all hospitalized patients with confirmed COVID-19 diagnosis in Germany between January 1st and December 31st in 2020 (source: RDC of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2020, own calculations). Covid-19-inpatients with MV vs. without MV and survivors vs. non-survivors were compared. Logistic regression models were calculated to investigate associations between patients' characteristics as well as adverse events and i) necessity of MV and ii) in-hospital death. Result(s): We analyzed data of 176,137 hospitalizations of patients with confirmed COVID-19-infection. Among those, 31,607 (17.9%) died, whereby in-hospital case-fatality grew exponentially with age. Cardiovascular comorbidities were common in hospitalized patients with confirmed COVID-19-infections: Overall, almost half of the patients (46.8%;n=82,480) had arterial hypertension and 25,574 (14.4%) had a diagnosis of coronary artery disease. In 60.7% (n=106,913) of the hospitalizations, pneumonia was reported, 8.6% (n=15,061) had an acute infection of the upper or lower airways other than pneumonia, and 6.6% (n=11,594) suffered from an acute respiratory distress syndrome (ARDS) during hospitalization Age >=70 years (OR 5.91, 95% CI 5.70-6.13, P<0.001), pneumonia (OR 4.58, 95% CI 4.42-4.74, P<0.001) and acute respiratory distress syndrome (OR 8.51, 95% CI 8.12-8.92, P<0.001) were strong predictors of in-hospital death. Most COVID-19-patients were treated in hospitals in urban areas (n=92,971) associated with lowest case-fatality (17.5%) as compared to hospitals in suburban (18.3%) or rural areas (18.8%). MV demand was highest in November/December 2020 (32.3%, 20.3%) in patients between 6th and 8th age-decade. In the first age-decade, 78 of 1861 children (4.2%) with COVID-19-infection were treated with MV and five of them died (0.3%). Conclusion(s): The results of our study indicate seasonal and regional variations concerning number of COVID-19-patients, necessity of MV and casefatality in Germany. These findings may help to ensure flexible allocation of intensive care (human) resources, which is essential for managing enormous societal challenges worldwide to avoid overloaded regional healthcare systems.
ABSTRACT
Background: Although a high prevalence of pulmonary embolism (PE) has been reported as a complication during severe COVID-19 infections in critical ill patients, nationwide data of hospitalized patients with COVID-19 with PE is still limited. Thus, we sought to analyze seasonal trends and predictors of in-hospital case-fatality in patients with COVID-19 and PE in Germany. Method(s): We used the German nationwide inpatient sample to analyze all data on hospitalizations for COVID-19 patients with and without PE in Germany during the year 2020 and to compare changes of PE prevalence to 2019. Result(s):We analyzed data of 176,137 hospitalizations because of COVID- 19 in 2020. Among those, PE was recorded in 1.9% (n=3,362) of discharge or death certificates. Almost one third of patients with COVID-19 and PE died during the in-hospital course (28.7%). The case-fatality rate increased with patients' age peaking in the 9th life-decade. Regardless of COVID-19, 196,203 inpatients were diagnosed with PE in Germany between 2019 and 2020. The number of PE hospitalizations were widely equally distributed between both years (98,485 vs. 97,718), while the case-fatality rate of all patients with PE was slightly lower in 2019 compared to 2020 (12.7% vs. 13.1%, P<0.001). In contrast, considerable differences in prevalence and case-fatality were demonstrated in 2020 regarding PE patients with and without COVID-19 infection (28.7% vs. 13.1%, P<0.001) (Figure 1). A COVID-19-infection was associated with a 2.8-fold increased risk of casefatality in patients with PE (OR 2.81, 95% CI 1.66-2.12, P<0.001). Conclusion(s): In Germany, the prevalence of PE events complicating hospitalizations was similar in 2019 and 2020. However, the fatality rate among patients with COVID-19-associated PE was substantially higher than that in those without either COVID-19 or PE, indicating an additive prognostic effect of these two conditions.
ABSTRACT
Background: The COVID-19 pandemic caused a large number of excess deaths. COVID-19 emerged as a prothrombotic disease often complicated by pulmonary embolism (PE). In light of this, we hypothesized that PErelated mortality rates (stable before the pandemic) would be characterized by an increasing trend following the COVID-19 outbreak. Purpose(s): To investigate the mortality rates associated with PE among deaths with or without COVID-19 during the 2020 pandemic in the United States (US). Method(s): For this retrospective epidemiological study, we analyzed public medically certified vital registration data (death certificates encompassing underlying and multiple causes of death) from the Mortality Multiple Cause-of-Death database provided by the Division of Vital Statistics of the US Centers for Disease Control and Prevention (CDC;US, 2018-20). We investigated the time trends in monthly PE-related crude mortality rates for 2018-2019 and for 2020 (the latter associated vs. not associated with COVID-19), utilizing annual national population totals from the US Census Bureau. Second, we calculated the PE-related proportionate mortality among COVID-19 deaths (overall and limited to autopsy-based diagnosis). We performed subgroup analyses based on age groups, sex and race. Result(s): During 2020, 49,423 deaths in association with PE were reported, vs. 39,450 in 2019 and 38,215 in 2018. The crude PE-related mortality rate without COVID-19 was 13.3 per 100,000 population in 2020 compared to 11.7 in 2018 and 12.0 in 2019 (Figure 1A). The PE-related mortality rate with COVID-19 was 1.6 per 100,000 population in 2020. Among non- COVID-19-related deaths, the crude PE-related mortality rate was higher in women;among COVID-19-related deaths, it was higher in men. PE-related mortality rates were approximately two-fold higher among black (vs. white) general population irrespective of COVID-19 status (Figures 1B and 1C). Among COVID-19 deaths, PE-related deaths corresponded to 1.4% of total;the value rose to 6.0% when an autopsy was performed. This figure was higher in men and its time evolution is depicted in Figure 2A. The proportionate mortality of PE in COVID-19 deaths was higher for younger age groups (15-44 years) compared to non-COVID-19-related deaths (Figure 2B). Conclusion(s): In 2020, an overall 20%-increase in PE-related mortality was reported, not being limited to patients with COVID-19. Our findings could be interpreted in the context of undiagnosed COVID-19 cases, uncounted late sequelae, and possibly sedentary lifestyle and avoidance of healthcare facilities during the pandemic that may have prevented timely diagnosis and treatment of other diseases. Whether vaccination programs had an impact on PE-associated mortality in the year 2021, remains to be determined.
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Recent research has shown the mental health consequence of social distancing during the COVID-19 pandemic, but longitudinal data are relatively scarce. It is unclear whether the pattern of isolation and elevated stress seen at the beginning of the pandemic persists over time. This study evaluates change in social interaction over six months and its mental health impact among older adults. We drew data from a panel study with six repeated assessments of social interaction and mental health conducted monthly May through October 2020. The sample included a total of 380 White, Black and Hispanic participants aged 50 and over, of whom 33% had low income, who residing in fourteen U.S. states with active stay-at-home orders in May 2020. The analysis examined how change in living arrangement, in-person interaction outside the household, quality of relationship with family and friends, and perceived social support affected trajectories of isolation stress, COVID worry and sadness. While their living arrangements and relationship quality remained stable, older adults experienced fluctuations in perceived social support and increases in in-person conversations outside the household. Living with a spouse/partner stabilized isolation stress and COVID worry over time. Individuals with better relationship quality with friends became happier over time. Changes in social support were associated with greater fluctuations in isolation stress and COVID worry. During the pandemic, social interactions are protective and lack of stability in feeling supported makes older adults vulnerable to stress. Efforts should focus on (re)building and maintaining companionship and support to mitigate the pandemic's negative impact.
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Introduction: Deficits in nephrin and other podocyte components are known to result in congenital nephrotic and familial FSGS syndromes. Weins et. al. recently described acquired anti-nephrin antibody localizing in glomerular podocytes of patients with minimal change disease. Case Description: A 16 year old male referred for new onset nephrotic syndrome progressive over 2 weeks was found to have serum albumin 1.2 gm/dL, UPCR 3.1, and elevated lipids with BP 160/100 mm Hg. Hepatitis B/C, HIV, SLE screens were negative. Renal biopsy demonstrated focal collapsing lesions with diffuse podocyte effacement. Immunofluorescence showed punctate IgG, kappa and lambda light chain staining in podocytes, but no albumin. Anti-human IgG colocalized with nephrin in the granular staining. ParvoB19 and COVID-19 titers were negative. Creatinine rose from 0.65 to 1.65 and UPCR to 10.3 but improved rapidly with high dose prednisone and ACEi. Serology for circulating anti-nephrin 2 weeks into treatment was negative, consistent with previous finding that circulating antibody levels quickly drop to low or undetectable with partial clinical remission. Discussion: This case strengthens evidence that anti-nephrin antibodies cause disruption of the slit pore diaphragm which appears to be readily responsive to immune therapy. Anti-nephrin mediated podocytopathy may present with a spectrum of glomerular histopathology, which on the background of other susceptibility factors, can lead to more severe presentations such as collapsing FSGS.
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Background: Vaccine-triggered complications, including autoimmune diseases and minimal change disease (MCD), were reported during recent COVID-19 vaccine rollout. Anti-nephrin autoantibodies were described in nephrotic syndrome (NS) with kidney biopsy (Kbx)-proven MCD. Therefore, we examined patients with COVID-19 vaccineassociated NS for anti-nephrin autoantibodies. Methods: 5 patients presenting with nephrotic-range proteinuria 1-3 weeks after COVID-19 vaccine and a KBx were identified (3 Pfizer/BioNTech, 2 Moderna). Past medical history and lab tests including serum creatinine (sCr), urine protein-to-creatinine ratio (UPCR), and serological workup were recorded. KBx were routinely evaluated by light microscopy (LM), immunofluorescence microscopy (IF), and electron microscopy (EM), followed by confocal examination of relative IgG and nephrin localization in all patients;serological studies for anti-nephrin antibodies using human glomerular extract and recombinant nephrin extracellular domain were performed using plasma available on 2 patients. Results: In all patients, sCr was 0.5-1.2 mg/dl and UPCR 4.5-7.6 g/g. 1 patient had MCD in remission diagnosed 6 months prior;others had no relevant PMH. All workup was negative, except low positive ANA in 2 patients. On KBx, diagnosis of MCD was made in 4 and stage I membranous nephropathy (MN) in 1 patient(s) (serum albumin 2.0-2.4g/dl in MCD and 3.6g/dl in MN patient(s));all had mild chronic changes. All 4 MCD patients had fine granular punctate podocyte staining for polyclonal IgG colocalizing with nephrin by IF and diffuse FPE by EM;in 1 patient plasma was saved during NS and was serologically positive for anti-nephrin. The MN patient had 3+ fine granular IF staining for polyclonal IgG and PLA2r along GBMs with sparse superficial subepithelial electron-dense deposits on EM, and was serologically negative for antinephrin. All MCD patients were successfully treated with oral glucocorticoids, while the MN patient was monitored closely under RAAS blockage. Conclusions: COVID-19 mRNA vaccines can trigger de-novo or relapsing anti-nephrin-and PLA2r-mediated NS, thus adding both autoimmune-mediated podocytopathies to vaccine-induced complications. Temporal association is essential for diagnosis;prompt accurate diagnosis benefits treatment and response.
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Objective: To report neuropathological findings and quantify SARS-CoV-2 viral burden for 18 consecutive coronavirus disease 2019 (COVID-19) autopsies. Background: COVID-19 is a respiratory disease caused by SARS-CoV-2, a virus known to infect lung epithelial cells, yet data about SARS-CoV-2 neuropathology in human brain autopsies is limited. Design/Methods: Brain tissue specimens were sampled from 18 subjects (10 standard areas), fixed in formalin, and stained with hematoxylin and eosin for histopathological analysis. SARSCoV-2 immunohistochemistry and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were performed on 10 brain sections from 2 subjects and 2 sections (medulla and frontal lobe with olfactory nerve) from the remaining 16 subjects. Results: Median age was 62 years (interquartile range, 53 to 75), and 14 patients (78%) were men. Presenting neurologic symptoms were myalgia (n=3), headache (n=2), and decreased taste (n=1);11 received mechanical ventilation. Acute hypoxic injury was detected in cerebrum, hippocampus, and cerebellum in all patients;rare foci of perivascular lymphocytes (n=2) or focal leptomeningeal inflammation (n=1) were also detected. RT-qPCR showed limited evidence of viral RNA. In 10 unique specimens from two subjects, results were equivocal (viral load <5.0 copies/mm3) in 4 and 5 sections, respectively. In the remaining 16 patients, 3 medulla sections and 3 frontal lobe and olfactory sections were positive (5.0 to 59.4 copies/mm3) while the rest were equivocal or negative. SARS-CoV-2 viral load did not correlate with the interval between the onset of symptoms and death or histopathological findings. Immunohistochemical staining for SARS-CoV-2 nucleocapsid protein was negative in neurons, glia, endothelium, and immune cells. Conclusions: Histopathology of brain specimens revealed hypoxia with limited evidence of direct viral damage, including no viral protein. Concordantly, although SARS-CoV-2 was detected by RT-qPCR in some sections, viral load was low and did not correlate with other pathological features.
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Objective: To determine the odds of critical illness by day 28 and duration of mechanical ventilation (MV) over 45-day observation period in patients with history of cerebrovascular disease and COVID-19. Background: COVID-19-associated morbidity is correlated with multiple factors including age, comorbidities, and host response to the virus. Our understanding of the risk of critical illness due to prior neurological conditions remains limited. Here, we hypothesized that prior cerebrovascular disease is a risk factor for severe outcomes in COVID-19, including increased duration of MV. Design/Methods: A cross-sectional study of 1128 consecutive adult patients admitted to a tertiary care center in Boston, Massachusetts, and diagnosed with laboratory-confirmed COVID-19. The association between history of cerebrovascular disease and critical illness defined as MV or death was examined using logistic regression with inverse probability weighting of the propensity score. Cumulative incidence of successful extubation without death over 45 days was examined using competing risk analysis. Results: Of the 1128 adults admitted with COVID-19, 350 (36%) were critically ill by day 28. The median age was 59 years (standard deviation: 18 years), 640 (57%) were men, and 401 (36%) were Latinx ethnicity. As of June 2nd, 2020, 127 (11%) patients died. A total of 257 (23%) of patients had a prior neurological diagnosis;most common was cerebrovascular disease (16%). Prior cerebrovascular disease was significantly associated with critical illness (OR 1.54 [95% CI: 1.14 - 2.07]), lower rate of successful extubation (cause-specific HR 0.57 [95% CI: 0.33-0.98]), and increased duration of intubation (restricted mean time difference 4.02 days [95% CI: 0.34- 10.92]) compared to patients without cerebrovascular disease. Conclusions: History of cerebrovascular disease adversely affects COVID-19 outcomes including increased risk of critical illness and prolonged intubation. Further studies are needed to define measures that reduce risk of poor outcomes in this subpopulation.