Outcomes associated with SARS-CoV-2 reinfection in individuals with natural and hybrid immunity.

BACKGROUND: Studies comparing SARS-CoV-2 reinfection outcomes among individuals with previous infection (natural immunity) and previous infection plus vaccination (hybrid immunity) are limited. METHODS: Retrospective cohort study comparing SARS-CoV-2 reinfection among patients with hybrid immunity (cases) and natural immunity (controls) from March 2020 to February 2022. Reinfection was defined as positive PCR> 90 days after initial laboratory-confirmed SARS-CoV-2 infection. Outcomes included time to reinfection, symptom severity, COVID-19-related hospitalization, critical COVID-19 illness (need for intensive care unit, invasive mechanical ventilation, or death), length of stay (LOS). RESULTS: A total of 773 (42%) vaccinated and 1073 (58%) unvaccinated patients with reinfection were included. Most patients (62.7%) were asymptomatic. Median time to reinfection was longer with hybrid immunity (391 [311-440] vs 294 [229-406] days, p < 0.001). Cases were less likely to be symptomatic (34.1% vs 39.6%, p = 0.001) or develop critical COVID-19 (2.3% vs 4.3%, p = 0.023). However, there was no significant difference in rates of COVID-19-related hospitalization (2.6% vs 3.8%, p = 0.142) or LOS (5 [2-9] vs 5 [3-10] days, p = 0.446). Boosted patients had longer time to reinfection (439 [IQR 372-467] vs 324 [IQR 256-414] days, p < 0.001) and were less likely to be symptomatic (26.8% vs 38%, p = 0.002) compared to unboosted patients. Rates of hospitalization, progression to critical illness and LOS were not significantly different between the two groups. CONCLUSIONS: Natural and hybrid immunity provided protection against SARS-CoV-2 reinfection and hospitalization. However, hybrid immunity conferred stronger protection against symptomatic disease and progression to critical illness and was associated with longer time to reinfection. The stronger protection conferred by hybrid immunity against severe outcomes due to COVID-19 should be emphasized with the public to further the vaccination effort, especially in high-risk individuals.

Real-world Experience of Sotrovimab in High-risk, Immunocompromised COVID-19 Patients.

We completed a real-world analysis of 498 consecutive high-risk nonimmunocompromised and immunocompromised patients who received sotrovimab during the B.1.1.529 surge. Emergency department visits/hospitalizations and 30-day all-cause mortality between the 2 groups were similar. When administered early, sotrovimab is effective at preventing coronavirus disease 2019 progression in immunocompromised and nonimmunocompromised patients.

Outcomes of COVID-19 in a Large Cohort of Lung Transplant Recipients: A Retrospective Study

Background: Early reports of COVID-19 in lung transplant recipients (LTRs) showed high hospitalization and mortality rates. However, the outcomes of COVID-19 in LTRs since the advent of newer therapies and vaccines have been poorly defined. Methods: We evaluated the risks for SARS-CoV-2-related hospitalization and mortality in a cohort of LTRs at the Henry Ford Lung Transplant Program in Detroit, Michigan during the study period March 2020–March 2022. Univariate logistic regression, followed by multivariable modeling were performed to estimate the odds ratio (OR) with 95% confident intervals (CI). Results: Sixty-four laboratory-confirmed SARS-CoV-2 infections were identified in 59 patients. For the primary analysis of the hospitalization and mortality risks, we included these 59 patients with symptomatic COVID-19. SARS-CoV-2 infections were confirmed with real-time polymerase chain reaction (RT-PCR) from a nasopharynx swab. The mean age (±STD) was 61 (±12), 63% were males, 27% were African Americans, and the time from lung transplant to COVID-19 was 5.5 (±4.8) years. Thirty-four (57.6%) patients were hospitalized, and the inpatient mortality rate was 24% (8/34). A multivariable analysis showed that patients with a higher baseline forced expiratory volume (FEV1) were less likely to be hospitalized (OR = 0.91 and 95% CI 0.87–0.98, p = 0.02). Seventy-five percent (75%;6/8) of patients on invasive mechanical ventilation died, compared with only 8% mortality rate in those without mechanical ventilation (OR = 36.0 and 95% CI 4.2–310.4, p < 0.01). Although a trend toward a higher risk of death was observed in those infected during the Alpha (p = 0.17) and Delta (p = 0.22) waves, no significant risk was detected after adjusting for other covariates. Five LTRs were diagnosed with COVID-19 twice. Thirty of the sixty-four COVID-19 cases (46.8%) occurred in LTRs that had received at least two doses of any of the available mRNA vaccines at a median of 123 days (IQR 98–164 days) after vaccination. Twelve of the thirty (40%) were hospitalized, and four patients (33%) died during their hospitalizations. Conclusions: In our LTR population, the hospitalization and mortality rates associated with COVID-19 were high despite the increased use of new therapies. Vaccine-breakthrough infections were common and were associated with poor outcomes. Studies are needed to determine optimal prevention and therapeutic strategies to improve COVID-19 outcomes in LTRs.

Progression to Critical Illness and Death in Patients With Breakthrough Hospitalizations.

Background: Characterization of disease progression and outcomes after coronavirus disease 2019 (COVID-19)-related hospitalization in vaccinated compared with unvaccinated individuals is limited. Methods: This was a retrospective case-control study of symptomatic vaccinated (cases) and unvaccinated (controls) participants hospitalized for COVID-19 between December 30, 2020, and September 30, 2021, in Southeast Michigan. Hospitalized adult patients with lab-confirmed COVID-19 were identified through daily census report. Breakthrough infection was defined as detection of severe acute respiratory syndrome coronavirus 2 ≥14 days after completion of the primary vaccination series. The association between prior vaccination and critical COVID-19 illness (composite of intensive care unit [ICU] admission, invasive mechanical ventilation [IMV], 28-day mortality) was examined. Results: Two hundred ten (39%) fully vaccinated and 325 (61%) unvaccinated patients were evaluated. Compared with controls, cases were older, had more comorbidities (4 [3-7] vs 2 [1-4]; P < .001), and were more likely to be immunocompromised. Cases had less severe symptoms compared with controls (2 [1-2] vs 2 [2-3]; P < .001) and were less likely to progress to critical COVID-19 illness (33.3% vs 45.5%; P < .001); 28-day mortality was significantly lower in cases (11.0% vs 24.9%; P < .001). Symptom severity (odds ratio [OR], 2.59; 95% CI, 1.61-4.16; P < .001) and modified Sequential Organ Failure Assessment score on presentation (OR, 1.74; 95% CI, 1.48-2.06; P < .001) were independently associated with development of critical COVID-19 illness. Prior vaccination (OR, 0.528; 95% CI, 0.307-0.910; P = .020) was protective. Conclusions: COVID-19-vaccinated patients were less likely to develop critical COVID-19 illness and more likely to survive. Disease severity at presentation was a predictor of adverse outcomes regardless of vaccination status.

Real-World Experience of Sotrovimab in High-Risk, Immunocompromised COVID-19 Patients

We completed a real-world analysis of 498 consecutive high-risk non-immunocompromised and immunocompromised patients who received sotrovimab during B.1.1.529 surge. Emergency department visits/hospitalizations and 30-day all-cause mortality between the two groups were similar. Sotrovimab is an effective therapy when administered early in preventing COVID-19 disease progression in immunocompromised and non-immunocompromised patients.

SARS-CoV-2 neutralizing antibodies for COVID-19: Outcomes for bamlanivimab versus bamlanivimab-etesevimab combination in a racially diverse cohort of patients with significant comorbidities.

WHAT IS KNOWN AND OBJECTIVE: Anti-spike monoclonal antibodies (MAB) including bamlanivimab (BAM) and bamlanivimab/etesevimab (BAM/E) have shown reduced hospitalization rates for non-severe coronavirus disease 2019 (COVID-19) in clinical trials. Recent data have provided real-world hospitalization rates for high-risk patients treated with BAM, however, data on a similar cohort treated with BAM/E are lacking. METHODS: This retrospective cohort study evaluated outpatients ≥18 years with laboratory-confirmed mild/moderate COVID-19 who received MAB from 1 December 2020 to 19 April 2021. Use of BAM monotherapy changed to BAM/E combination on 27 March 2021. Primary outcome was overall rate of COVID-19 related-hospitalization, including comparison of hospitalization rates between MAB-formulation groups. Secondary outcomes were 30-day mortality and length of stay (LOS). RESULTS AND DISCUSSION: The population included 643 patients (BAM and BAM/E); median age was 58 years, 43% were male, median BMI was 33 kg/m2 , and 24% self-identified as Black. Patients in the BAM/E combination group were significantly younger with higher median BMI and a longer time from symptom onset to infusion. The incidence of 30-day COVID-19 related hospitalization was similar between patients receiving either BAM or BAM/E combination (7.8% and 7.2%, respectively). WHAT IS NEW AND CONCLUSION: This study represents the first such publication of real-world BAM/E hospitalization outcomes. Hospitalization rates utilizing BAM/E were comparable to BAM in our real-world study.

Risk Factors Associated With Hospitalization and Death in COVID-19 Breakthrough Infections.

Background: Characterizations of coronavirus disease 2019 (COVID-19) vaccine breakthrough infections are limited. We aim to characterize breakthrough infections and identify risk factors associated with outcomes. Methods: This was a retrospective case series of consecutive fully vaccinated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a multicenter academic center in Southeast Michigan, between December 30, 2020, and September 15, 2021. Results: A total of 982 patients were identified; the mean age was 57.9 years, 565 (59%) were female, 774 (79%) were White, and 255 (26%) were health care workers (HCWs). The median number of comorbidities was 2; 225 (23%) were immunocompromised. BNT162b2 was administered to 737 (75%) individuals. The mean time to SARS-CoV-2 detection was 135 days. The majority were asymptomatic or exhibited mild to moderate disease, 154 (16%) required hospitalization, 127 (13%) had severe-critical illness, and 19 (2%) died. Age (odds ratio [OR], 1.14; 95% CI, 1.04-1.07; P < .001), cardiovascular disease (OR, 3.02; 95% CI, 1.55-5.89; P = .001), and immunocompromised status (OR, 2.57; 95% CI, 1.70-3.90; P < .001) were independent risk factors for hospitalization. Additionally, age (OR, 1.06; 95% CI, 1.02-1.11; P = .006) was significantly associated with mortality. HCWs (OR, 0.15; 95% CI, 0.05-0.50; P = .002) were less likely to be hospitalized, and prior receipt of BNT162b2 was associated with lower odds of hospitalization (OR, 0.436; 95% CI, 0.303-0.626; P < .001) and/or death (OR, 0.360; 95% CI, 0.145-0.898; P = .029). Conclusions: COVID-19 vaccines remain effective at attenuating disease severity. However, patients with breakthrough infections necessitating hospitalization may benefit from early treatment modalities and COVID-19-mitigating strategies, especially in areas with substantial or high transmission rates.

A center experience with lung transplantation for COVID-19 ARDS.

COVID-19 can cause irreversible lung damage from acute respiratory distress syndrome (ARDS), chronic respiratory failure associated with post COVID-19 de novo fibrosis or worsening of an underlying fibrotic lung disease. Pregnant women are at increased risk for invasive mechanical ventilation, extracorporeal membrane oxygenation, and death. The Centers for Disease Control and Prevention reported more than 22,000 hospitalizations and 161 deaths for COVID-19 in pregnant women. Between August 2020 and September 2021, five patients underwent bilateral lung transplant (LT) for COVID-19 ARDS at the Henry Ford Hospital in Detroit, Michigan. De-identified demographics data, clinical characteristics, perioperative challenges, explanted lung pathology, and post-transplant outcomes are described. In post-hospitalization follow-up (median survival 273 days), we see improving endurance and excellent lung function. One patient did not survive to hospital discharge and succumbed to complications 5 months after LT. We report the first cases of bilateral LT in two postpartum women.

Low- Versus High-Dose Methylprednisolone in Adult Patients With Coronavirus Disease 2019: Less Is More.

BACKGROUND: Corticosteroids use in severe coronavirus disease 2019 (COVID-19) improves survival; however, the optimal dose is not established. We aim to evaluate clinical outcomes in patients with severe COVID-19 receiving high-dose corticosteroids (HDC) versus low-dose corticosteroids (LDC). METHODS: This was a quasi-experimental study conducted at a large, quaternary care center in Michigan. A corticosteroid dose change was implemented in the standardized institutional treatment protocol on November 17, 2020. All patients admitted with severe COVID-19 that received corticosteroids were included. Consecutive patients in the HDC group (September 1 to November 15, 2020) were compared to the LDC group (November 30, 2020 to January 20, 2021). High-dose corticosteroids was defined as 80 mg of methylprednisolone daily in 2 divided doses, and LDC was defined as 32-40 mg of methylprednisolone daily in 2 divided doses. The primary outcome was all-cause 28-day mortality. Secondary outcomes included progression to mechanical ventilation, hospital length of stay (LOS), discharge on supplemental oxygen, and corticosteroid-associated adverse events. RESULTS: Four-hundred seventy patients were included: 218 (46%) and 252 (54%) in the HDC and LDC groups, respectively. No difference was observed in 28-day mortality (14.5% vs 13.5%, P = .712). This finding remained intact when controlling for additional variables (odds ratio, 0.947; confidence interval, 0.515-1.742; P = .861). Median hospital LOS was 6 and 5 days in the HDC and LDC groups, respectively (P < .001). No differences were noted in any of the other secondary outcomes. CONCLUSIONS: Low-dose methylprednisolone had comparable outcomes including mortality to high-dose methylprednisolone for the treatment of severe COVID-19.

Low versus High Dose Methylprednisolone in Adult Patients with COVID-19: Less is More

Background Corticosteroids use in severe COVID-19 improves survival;however, the optimal dose is not established. We aim to evaluate clinical outcomes in patients with severe COVID-19 receiving high-dose corticosteroids (HDC) versus low-dose corticosteroids (LDC). Methods This was a quasi-experimental study conducted at a large, quaternary care center in Michigan. A corticosteroid dose change was implemented in the standardized institutional treatment protocol on 17 November 2020. All patients admitted with severe COVID-19 that received corticosteroids were included. Consecutive patients in the HDC group (1 September to 15 November 2020) were compared to the LDC group (30 November 2020 to 20 January 2021). HDC was defined as methylprednisolone 80 mg daily in two divided doses and LDC was defined as methylprednisolone 32-40 mg daily in two divided doses. The primary outcome was all-cause 28-day mortality. Secondary outcomes included progression to mechanical ventilation, hospital length of stay (LOS), discharge on supplemental oxygen, and corticosteroid-associated adverse events. Results Four-hundred and seventy patients were included;218 (46%) and 252 (54%) in the HDC and LDC groups, respectively. No difference was observed in 28-day mortality (14.5% vs 13.5%, p=0.712). This finding remained intact when controlling for additional variables (OR 0.947, [CI 0.515-1.742], p=0.861). Median hospital LOS was 6 and 5 days in the HDC and LDC groups, respectively (p<0.001). No differences were noted in any of the other secondary outcomes. Conclusions Low-dose methylprednisolone had comparable outcomes including mortality to high-dose methylprednisolone for the treatment of severe COVID-19.

Association Between Implementation of a Universal Face Mask Policy for Healthcare Workers in a Health Care System and SARS-CoV-2 Positivity Testing Rate in Healthcare Workers.

OBJECTIVE: Examine the effect of a universal facemask policy for healthcare workers (HCW) and incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity. METHODS: Daily number of symptomatic HCW tested, SARS-CoV-2 positivity rates, and HCW job-descriptions were collected pre and post Universal HCW facemask policy (March 26, 2020). Multiple change point regression was used to model positive-test-rate data. SARS-CoV-2 testing and positivity rates were compared for pre-intervention, transition, post-intervention, and follow-up periods. RESULTS: Between March 12 and August 10, 2020, 19.2% of HCW were symptomatic for COVID-19 and underwent SARS-CoV-2 testing. A single change point was identified ∼March 28-30 (95% probability). Before the change point, the odds of a tested HCW having a positive result doubled every 4.5 to 7.5 days. Post-change-point, the odds of a tested HCW having a positive result halved every 10.5 to 13.5 days. CONCLUSIONS: Universal facemasks were associated with reducing HCW's risk of acquiring COVID-19.

The Impact of Sociodemographic Factors, Comorbidities, and Physiologic Responses on 30-Day Mortality in Coronavirus Disease 2019 (COVID-19) Patients in Metropolitan Detroit.

BACKGROUND: The relationship of health disparities and comorbidities in coronavirus disease 2019 (COVID-19)-related outcomes are an ongoing area of interest. This report assesses risk factors associated with mortality in patients presenting with COVID-19 infection and healthcare disparities. METHODS: We conducted a retrospective cohort study of consecutive patients presenting to emergency departments within an integrated health system who tested positive for COVID-19 between 7 March and 30 April 2020 in metropolitan Detroit. The primary outcomes were hospitalization and 30-day mortality. RESULTS: A total of 3633 patients with a mean age of 58 years were included. The majority were female and Black non-Hispanic. Hospitalization was required for 64% of patients, 56% of whom were Black. Hospitalized patients were older, more likely to reside in a low-income area, and had a higher burden of comorbidities. By 30 days, 433 (18.7%) hospitalized patients died. In adjusted analyses, the presence of comorbidities, an age >60 years, and more severe physiological disturbance were associated with 30-day mortality. Residence in low-income areas (odds ratio [OR], 1.02; 95% confidence interval [CI], .76-1.36) and public insurance (OR, 1.24; 95% CI, .76-2.01) were not independently associated with a higher risk of mortality. Black female patients had a lower adjusted risk of mortality (OR, 0.46; 95% CI, .27-.78). CONCLUSIONS: In this large cohort of COVID-19 patients, those with comorbidities, advanced age, and physiological abnormalities on presentation had higher odds of death. Disparities in income or source of health insurance were not associated with outcomes. Black women had a lower risk of dying.

Rapid Reorganization of an Academic Infectious Diseases Program During the Coronavirus Disease 2019 Pandemic in Detroit: A Novel Unit-based Group Rounding Model.

The surge of coronavirus disease 2019 (COVID-19) hospitalizations at our 877-bed quaternary care hospital in Detroit led to an emergent demand for Infectious Diseases (ID) consultations. The traditional 1-on-1 consultation model was untenable. Therefore, we rapidly restructured our ID division to provide effective consultative services. We implemented a novel unit-based group rounds model that focused on delivering key updates to teams and providing unit-wide consultations simultaneously to all team members. Effectiveness of the program was studied using Likert-scale survey data. The survey captured data from the first month of the Detroit COVID-19 pandemic. During this period there were approximately 950 patients hospitalized for treatment of COVID-19. The survey of trainees and faculty reported an overall 95% positive response to delivery of information, new knowledge acquisition, and provider confidence in the care of COVID-19 patients. This showed that the unit-based consult model is a sustainable effort to provide care during epidemics.

COVID-19: disease pathways and gene expression changes predict methylprednisolone can improve outcome in severe cases.

MOTIVATION: COVID-19 has several distinct clinical phases: a viral replication phase, an inflammatory phase, and in some patients, a hyper-inflammatory phase. High mortality is associated with patients developing cytokine storm syndrome. Treatment of hyper-inflammation in these patients using existing, approved therapies with proven safety profiles could address the immediate need to reduce mortality. RESULTS: We analyzed the changes in the gene expression, pathways and putative mechanisms induced by SARS-CoV2 in NHBE, and A549 cells, as well as COVID-19 lung vs. their respective controls. We used these changes to identify FDA approved drugs that could be repurposed to help COVID-19 patients with severe symptoms related to hyper-inflammation. We identified methylprednisolone (MP) as a potential leading therapy. The results were then confirmed in five independent validation data sets including Vero E6 cells, lung and intestinal organoids, as well as additional patient lung sample vs. their respective controls. Finally, the efficacy of MP was validated in an independent clinical study. Thirty-day all-cause mortality occurred at a significantly lower rate in the MP-treated group compared to control group (29.6% vs. 16.6%, p = 0.027). Clinical results confirmed the in silico prediction that MP could improve outcomes in severe cases of COVID-19. A low number needed to treat (NNT = 5) suggests MP may be more efficacious than dexamethasone or hydrocortisone. AVAILABILITY: iPathwayGuide is available at https://ipathwayguide.advaitabio.com/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Clinical characteristics and outcomes of COVID-19 in solid organ transplant recipients: A cohort study.

Solid organ transplant recipients (SOTr) with coronavirus disease 2019 (COVID-19) are expected to have poorer outcomes compared to nontransplant patients because of immunosuppression and comorbidities. The clinical characteristics of 47 SOTr (38 kidneys and 9 nonkidney organs) were compared to 100 consecutive hospitalized nontransplant controls. Twelve of 47 SOTr managed as outpatients were subsequently excluded from the outcome analyses to avoid potential selection bias. Chronic kidney disease (89% vs 57% P = .0007), diabetes (66% vs 33% P = .0007), and hypertension (94% vs 72% P = .006) were more common in the 35 hospitalized SOTr compared to controls. Diarrhea (54% vs 17%, P < .0001) was more frequent in SOTr. Primary composite outcome (escalation to intensive care unit, mechanical ventilation, or in-hospital all-cause mortality) was comparable between SOTr and controls (40% vs 48%, odds ratio [OR] 0.72 confidence interval [CI] [0.33-1.58] P = .42), despite more comorbidities in SOTr. Acute kidney injury requiring renal replacement therapy occurred in 20% of SOTr compared to 4% of controls (OR 6 CI [1.64-22] P = .007). Multivariate analysis demonstrated that increasing age and clinical severity were associated with mortality. Transplant status itself was not associated with mortality.