Cognitive concerns are a risk factor for mortality in people with HIV and coronavirus disease 2019.

BACKGROUND: Data supporting dementia as a risk factor for coronavirus disease 2019 (COVID-19) mortality relied on ICD-10 codes, yet nearly 40% of individuals with probable dementia lack a formal diagnosis. Dementia coding is not well established for people with HIV (PWH), and its reliance may affect risk assessment. METHODS: This retrospective cohort analysis of PWH with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR positivity includes comparisons to people without HIV (PWoH), matched by age, sex, race, and zipcode. Primary exposures were dementia diagnosis, by International Classification of Diseases (ICD)-10 codes, and cognitive concerns, defined as possible cognitive impairment up to 12 months before COVID-19 diagnosis after clinical review of notes from the electronic health record. Logistic regression models assessed the effect of dementia and cognitive concerns on odds of death [odds ratio (OR); 95% CI (95% confidence interval)]; models adjusted for VACS Index 2.0. RESULTS: Sixty-four PWH were identified out of 14 129 patients with SARS-CoV-2 infection and matched to 463 PWoH. Compared with PWoH, PWH had a higher prevalence of dementia (15.6% vs. 6%, P  = 0.01) and cognitive concerns (21.9% vs. 15.8%, P  = 0.04). Death was more frequent in PWH ( P  < 0.01). Adjusted for VACS Index 2.0, dementia [2.4 (1.0-5.8), P  = 0.05] and cognitive concerns [2.4 (1.1-5.3), P  = 0.03] were associated with increased odds of death. In PWH, the association between cognitive concern and death trended towards statistical significance [3.92 (0.81-20.19), P  = 0.09]; there was no association with dementia. CONCLUSION: Cognitive status assessments are important for care in COVID-19, especially among PWH. Larger studies should validate findings and determine long-term COVID-19 consequences in PWH with preexisting cognitive deficits.

Distinguishing SARS-CoV-2 persistence and reinfection: A retrospective cohort study.

BACKGROUND: SARS-CoV-2 reinfection is poorly understood, partly because few studies have systematically applied genomic analysis to distinguish reinfection from persistent RNA detection related to initial infection. We aimed to evaluate the characteristics of SARS-CoV-2 reinfection and persistent RNA detection using independent genomic, clinical, and laboratory assessments. METHODS: All individuals at a large academic medical center who underwent a SARS-CoV-2 nucleic acid amplification test (NAAT) ≥ 45 days after an initial positive test, with both tests between March 14th and December 30th, 2020, were analyzed for potential reinfection. Inclusion criteria required having ≥2 positive NAATs collected ≥45 days apart with a cycle threshold (Ct) value <35 at repeat testing. For each included subject, likelihood of reinfection was assessed by viral genomic analysis of all available specimens with a Ct value <35, structured Ct trajectory criteria, and case-by-case review by infectious diseases physicians. RESULTS: Among 1,569 individuals with repeat SARS-CoV-2 testing ≥45 days after an initial positive NAAT, 65 (4%) met cohort inclusion criteria. Viral genomic analysis characterized mutations present, and was successful for 14/65 (22%) subjects. Six subjects had genomically-supported reinfection and eight subjects had genomically-supported persistent RNA detection. Compared to viral genomic analysis, clinical and laboratory assessments correctly distinguished reinfection from persistent RNA detection in 12/14 (86%) subjects but missed 2/6 (33%) genomically-supported reinfections. CONCLUSION: Despite good overall concordance with viral genomic analysis, clinical and Ct value-based assessments failed to identify 33% of genomically-supported reinfections. Scaling-up genomic analysis for clinical use would improve detection of SARS-CoV-2 reinfections.

Discharge to post-acute care and other predictors of prolonged length of stay during the initial COVID-19 surge: a single site analysis.

BACKGROUND: During the initial surge of coronavirus disease 2019 (COVID-19), health-care utilization fluctuated dramatically, straining acute hospital capacity across the USA and potentially contributing to excess mortality. METHODS: This was an observational retrospective study of patients with COVID-19 admitted to a large US urban academic medical center during a 12-week COVID-19 surge in the Spring of 2020. We describe patterns in length of stay (LOS) over time. Our outcome of interest was prolonged LOS (PLOS), which we defined as 7 or more days. We performed univariate analyses of patient characteristics, clinical outcomes and discharge disposition to evaluate the association of each variable with PLOS and developed a final multivariate model via backward elimination, wherein all variables with a P-value above 0.05 were eliminated in a stepwise fashion. RESULTS: The cohort included 1366 patients, of whom 13% died and 29% were readmitted within 30 days. The LOS (mean: 12.6) fell over time (P < 0.0001). Predictors of PLOS included discharge to a post-acute care (PAC) facility (odds ratio [OR]: 11.9, 95% confidence interval [CI] 2.6-54.0), uninsured status (OR 3.2, CI 1.1-9.1) and requiring intensive care and intubation (OR 18.4, CI 11.5-29.6). Patients had a higher readmission rate if discharged to PAC facilities (40%) or home with home health agency (HHA) services (38%) as compared to patients discharged home without HHA services (26%) (P < 0.0001). CONCLUSION: Patients hospitalized with COVID-19 during a US COVID-19 surge had a PLOS and high readmission rate. Lack of insurance, an intensive care unit stay and a decision to discharge to a PAC facility were associated with a PLOS. Efforts to decrease LOS and optimize hospital capacity during COVID-19 surges may benefit from focusing on increasing PAC and HHA capacity and resources.

Fecal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) RNA Is Associated With Decreased Coronavirus Disease 2019 (COVID-19) Survival.

The clinical significance of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) RNA in stool remains uncertain. We found that extrapulmonary dissemination of infection to the gastrointestinal tract, assessed by the presence of SARS-CoV-2 RNA in stool, is associated with decreased coronavirus disease 2019 (COVID-19) survival. Measurement of SARS-CoV-2 RNA in stool may have utility for clinical risk assessment.

Effect modification by age of the association between obstructive lung diseases, smoking, and COVID-19 severity.

INTRODUCTION: Obstructive lung diseases (asthma and chronic obstructive pulmonary disease (COPD)) and smoking are associated with greater risk of respiratory infections and hospitalisations, but conflicting data exist regarding their association with severity of COVID-19, and few studies have evaluated whether these associations differ by age. OBJECTIVES: To examine the associations between asthma, COPD and smoking on the severity of COVID-19 among a cohort of hospitalised patients, and to test for effect modification by age. METHODS: We performed a retrospective analysis of electronic health record data of patients admitted to Massachusetts General Hospital, assigning the maximal WHO Clinical Progression Scale score for each patient during the first 28 days following hospital admission. Using ordered logistic regression, we measured the association between maximal severity score and asthma, COPD and smoking and their interaction with age. MEASUREMENTS AND MAIN RESULTS: Among 1391 patients hospitalised with COVID-19, we found an increased risk of severe disease among patients with COPD and prior smoking, independent of age. We also found evidence of effect modification by age with asthma and current smoking; in particular, asthma was associated with decreased COVID-19 severity among older adults, and current smoking was associated with decreased severity among younger patients. CONCLUSIONS: This cohort study identifies age as a modifying factor for the association between asthma and smoking on severity of COVID-19. Our findings highlight the complexities of determining risk factors for COVID-19 severity, and suggest that the effect of risk factors may vary across the age spectrum.

Understanding the Link Between Obesity and Severe COVID-19 Outcomes: Causal Mediation by Systemic Inflammatory Response.

BACKGROUND: Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood. OBJECTIVE: To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes. METHODS: This hospital-based, observational study included 3828 SARS-CoV-2-infected patients who were hospitalized February to May 2020 at Massachusetts General Hospital (MGH) or Columbia University Irving Medical Center/New York Presbyterian Hospital (CUIMC/NYP). We use mediation analysis to evaluate whether peak inflammatory biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], D-dimer, ferritin, white blood cell count and interleukin-6) are in the causal pathway between obesity (BMI ≥ 30) and mechanical ventilation or death within 28 days of presentation to care. RESULTS: In the MGH cohort (n = 1202), obesity was associated with greater likelihood of ventilation or death (OR = 1.73; 95% CI = [1.25, 2.41]; P = 0.001) and higher peak CRP (P < 0.001) compared with nonobese patients. The estimated proportion of the association between obesity and ventilation or death mediated by CRP was 0.49 (P < 0.001). Evidence of mediation was more pronounced in patients < 65 years (proportion mediated = 0.52 [P < 0.001] vs 0.44 [P = 0.180]). Findings were more moderate but consistent for peak ESR. Mediation by other inflammatory markers was not supported. Results were replicated in CUIMC/NYP cohort (n = 2626). CONCLUSION: Findings support systemic inflammatory pathways in obesity-associated severe COVID-19 disease, particularly in patients < 65 years, captured by CRP and ESR. Contextualized in clinical trial findings, these results reveal therapeutic opportunity to target systemic inflammatory pathways and monitor interventions in high-risk subgroups and particularly obese patients.

Prolonged Intubation in Patients With Prior Cerebrovascular Disease and COVID-19.

Objectives: Patients with comorbidities are at increased risk for poor outcomes in COVID-19, yet data on patients with prior neurological disease remains limited. Our objective was to determine the odds of critical illness and duration of mechanical ventilation in patients with prior cerebrovascular disease and COVID-19. Methods: A observational study of 1,128 consecutive adult patients admitted to an academic center in Boston, Massachusetts, and diagnosed with laboratory-confirmed COVID-19. We tested the association between prior cerebrovascular disease and critical illness, defined as mechanical ventilation (MV) or death by day 28, using logistic regression with inverse probability weighting of the propensity score. Among intubated patients, we estimated the cumulative incidence of successful extubation without death over 45 days using competing risk analysis. Results: Of the 1,128 adults with COVID-19, 350 (36%) were critically ill by day 28. The median age of patients was 59 years (SD: 18 years) and 640 (57%) were men. As of June 2nd, 2020, 127 (11%) patients had died. A total of 177 patients (16%) had a prior cerebrovascular disease. 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. Interpretation: Prior cerebrovascular disease adversely affects COVID-19 outcomes in hospitalized patients. Further study is required to determine if this subpopulation requires closer monitoring for disease progression during COVID-19.

Massachusetts general hospital Covid-19 registry reveals two distinct populations of hospitalized patients by race and ethnicity.

OBJECTIVE: To evaluate differences by race/ethnicity in clinical characteristics and outcomes among hospitalized patients with Covid-19 at Massachusetts General Hospital (MGH). METHODS: The MGH Covid-19 Registry includes confirmed SARS-CoV-2-infected patients hospitalized at MGH and is based on manual chart reviews and data extraction from electronic health records (EHRs). We evaluated differences between White/Non-Hispanic and Hispanic patients in demographics, complications and 14-day outcomes among the N = 866 patients hospitalized with Covid-19 from March 11, 2020-May 4, 2020. RESULTS: Overall, 43% of patients hospitalized with Covid-19 were women, median age was 60.4 [IQR = (48.2, 75)], 11.3% were Black/non-Hispanic and 35.2% were Hispanic. Hispanic patients, representing 35.2% of patients, were younger than White/non-Hispanic patients [median age 51y; IQR = (40.6, 61.6) versus 72y; (58.0, 81.7) (p<0.001)]. Hispanic patients were symptomatic longer before presenting to care (median 5 vs 3d, p = 0.039) but were more likely to be sent home with self-quarantine than be admitted to hospital (29% vs 16%, p<0.001). Hispanic patients had fewer comorbidities yet comparable rates of ICU or death (34% vs 36%). Nonetheless, a greater proportion of Hispanic patients recovered by 14 days after presentation (62% vs 45%, p<0.001; OR = 1.99, p = 0.011 in multivariable adjusted model) and fewer died (2% versus 18%, p<0.001). CONCLUSIONS: Hospitalized Hispanic patients were younger and had fewer comorbidities compared to White/non-Hispanic patients; despite comparable rates of ICU care or death, a greater proportion recovered. These results have implications for public health policy and the design and conduct of clinical trials.

Disproportionate burden of coronavirus disease 2019 among racial minorities and those in congregate settings among a large cohort of people with HIV.

BACKGROUND: Many people living with HIV (PLWH) have comorbidities which are risk factors for severe coronavirus disease 2019 (COVID-19) or have exposures that may lead to acquisition of severe acute respiratory distress syndrome coronavirus 2. There are few studies, however, on the demographics, comorbidities, clinical presentation, or outcomes of COVID-19 in people with HIV. OBJECTIVE: To evaluate risk factors, clinical manifestations, and outcomes in a large cohort of PLWH with COVID-19. METHODS: We systematically identified all PLWH who were diagnosed with COVID-19 at a large hospital from 3 March to 26 April 2020 during an outbreak in Massachusetts. We analyzed each of the cases to extract information including demographics, medical comorbidities, clinical presentation, and illness course after COVID-19 diagnosis. RESULTS: We describe a cohort of 36 PLWH with confirmed COVID-19 and another 11 patients with probable COVID-19. Almost 85% of PLWH with confirmed COVID-19 had a comorbidity associated with severe disease, including obesity, cardiovascular disease, or hypertension. Approximately 77% of PLWH with COVID-19 were non-Hispanic Black or Latinx whereas only 40% of the PLWH in our clinic were Black or Latinx. Nearly half of PLWH with COVID-19 had exposure to congregate settings. In addition to people with confirmed COVID-19, we identified another 11 individuals with probable COVID-19, almost all of whom had negative PCR testing. CONCLUSION: In the largest cohort to date of PLWH and confirmed COVID-19, almost all had a comorbidity associated with severe disease, highlighting the importance of non-HIV risk factors in this population. The racial disparities and frequent link to congregate settings in PLWH and COVID-19 need to be explored urgently.

Diabetes as a Risk Factor for Poor Early Outcomes in Patients Hospitalized With COVID-19.

OBJECTIVE: Diabetes and obesity are highly prevalent among hospitalized patients with coronavirus disease 2019 (COVID-19), but little is known about their contributions to early COVID-19 outcomes. We tested the hypothesis that diabetes is a risk factor for poor early outcomes, after adjustment for obesity, among a cohort of patients hospitalized with COVID-19. RESEARCH DESIGN AND METHODS: We used data from the Massachusetts General Hospital (MGH) COVID-19 Data Registry of patients hospitalized with COVID-19 between 11 March 2020 and 30 April 2020. Primary outcomes were admission to the intensive care unit (ICU), need for mechanical ventilation, and death within 14 days of presentation to care. Logistic regression models were adjusted for demographic characteristics, obesity, and relevant comorbidities. RESULTS: Among 450 patients, 178 (39.6%) had diabetes-mostly type 2 diabetes. Among patients with diabetes versus patients without diabetes, a higher proportion was admitted to the ICU (42.1% vs. 29.8%, respectively, P = 0.007), required mechanical ventilation (37.1% vs. 23.2%, P = 0.001), and died (15.9% vs. 7.9%, P = 0.009). In multivariable logistic regression models, diabetes was associated with greater odds of ICU admission (odds ratio 1.59 [95% CI 1.01-2.52]), mechanical ventilation (1.97 [1.21-3.20]), and death (2.02 [1.01-4.03]) at 14 days. Obesity was associated with greater odds of ICU admission (2.16 [1.20-3.88]) and mechanical ventilation (2.13 [1.14-4.00]) but not with death. CONCLUSIONS: Among hospitalized patients with COVID-19, diabetes was associated with poor early outcomes, after adjustment for obesity. These findings can help inform patient-centered care decision making for people with diabetes at risk for COVID-19.