Abstract
Background
Protection afforded from prior disease among patients with coronavirus disease 2019 (COVID-19) infection is unknown. If infection provides substantial long-lasting immunity, it ...may be appropriate to reconsider vaccination distribution.
Methods
This retrospective cohort study of 1 health system included 150 325 patients tested for COVID-19 infection via polymerase chain reaction from 12 March 2020 to 30 August 2020. Testing performed up to 24 February 2021 in these patients was included. The main outcome was reinfection, defined as infection ≥90 days after initial testing. Secondary outcomes were symptomatic infection and protection of prior infection against reinfection.
Results
Of 150 325 patients, 8845 (5.9%) tested positive and 141 480 (94.1%) tested negative before 30 August. A total of 1278 (14.4%) positive patients were retested after 90 days, and 62 had possible reinfection. Of those, 31 (50%) were symptomatic. Of those with initial negative testing, 5449 (3.9%) were subsequently positive and 3191 of those (58.5%) were symptomatic. Protection offered from prior infection was 81.8% (95% confidence interval CI, 76.6–85.8) and against symptomatic infection was 84.5% (95% CI, 77.9–89.1). This protection increased over time.
Conclusions
Prior infection in patients with COVID-19 was highly protective against reinfection and symptomatic disease. This protection increased over time, suggesting that viral shedding or ongoing immune response may persist beyond 90 days and may not represent true reinfection. As vaccine supply is limited, patients with known history of COVID-19 could delay early vaccination to allow for the most vulnerable to access the vaccine and slow transmission.
Patients with a confirmed history of infection with severe acute respiratory syndrome coronavirus 2 are less likely to be retested or reinfected more than 90 days after their initial infection. Protectiveness of prior infection against subsequent infection is high.
To determine the association of catecholamine dose, lactate concentration, and timing from shock onset at vasopressin initiation with in-hospital mortality.
Retrospective, observational study using ...segmented and multivariable logistic regression to evaluate the associations of catecholamine dose, lactate concentration, and timing from shock onset at vasopressin initiation with in-hospital mortality.
Multiple hospitals within the Cleveland Clinic Health System.
Adult patients who met criteria for septic shock based on the U.S. Centers for Disease Control and Prevention Adult Sepsis Event definition.
All patients received continuous infusion vasopressin as an adjunct to catecholamine vasopressors.
In total, 1,610 patients were included with a mean Acute Physiology and Chronic Health Evaluation III 109.0 ± 35.1 and Sequential Organ Failure Assessment 14.0 ± 3.5; 41% of patients survived the hospital admission. At the time of vasopressin initiation, patients had median (interquartile range) lactate concentration 3.9 mmol/L (2.3-7.2 mmol/L), norepinephrine-equivalent dose 25 µg/min (18-40 µg/min), and 5.3 hours (2.1-12.2 hr) elapsed since shock onset. The odds of in-hospital mortality increased 20.7% for every 10 µg/min increase in norepinephrine-equivalent dose up to 60 µg/min at the time of vasopressin initiation (adjusted odds ratio, 1.21 95% CI, 1.09-1.34), but no association was detected when the norepinephrine-equivalent dose exceeded 60 µg/min (adjusted odds ratio, 0.96 95% CI, 0.84-1.10). There was a significant interaction between timing of vasopressin initiation and lactate concentration (p = 0.02) for the association with in-hospital mortality. A linear association between increasing in-hospital mortality was detected for increasing lactate concentration at the time of vasopressin initiation, but no association was detected for time elapsed from shock onset.
Higher norepinephrine-equivalent dose at vasopressin initiation and higher lactate concentration at vasopressin initiation were each associated higher in-hospital mortality in patients with septic shock who received vasopressin.
In response to skeletal muscle contraction during exercise, paracrine factors coordinate tissue remodeling, which underlies this healthy adaptation. Here we describe a pH-sensing metabolite signal ...that initiates muscle remodeling upon exercise. In mice and humans, exercising skeletal muscle releases the mitochondrial metabolite succinate into the local interstitium and circulation. Selective secretion of succinate is facilitated by its transient protonation, which occurs upon muscle cell acidification. In the protonated monocarboxylic form, succinate is rendered a transport substrate for monocarboxylate transporter 1, which facilitates pH-gated release. Upon secretion, succinate signals via its cognate receptor SUCNR1 in non-myofibrillar cells in muscle tissue to control muscle-remodeling transcriptional programs. This succinate-SUCNR1 signaling is required for paracrine regulation of muscle innervation, muscle matrix remodeling, and muscle strength in response to exercise training. In sum, we define a bioenergetic sensor in muscle that utilizes intracellular pH and succinate to coordinate tissue adaptation to exercise.
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•Mouse and human muscle selectively release succinate during exercise•Muscle cells release succinate by pH-gated secretion via MCT1•Extracellular succinate regulates paracrine responses to exercise through SUCNR1•SUCNR1 signaling mediates muscle remodeling responses to exercise training
Reddy et al. identify a bioenergetic sensor that uses pH and succinate to regulate muscle tissue adaptation to exercise.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Initial fluid resuscitation volume for sepsis is controversial, particularly in patients at high baseline risk for complications. This study was designed to assess the association between 30 mL/kg ...crystalloids and intubation in patients with sepsis or septic shock and heart failure, end-stage renal disease, or cirrhosis.
This propensity score-matched retrospective cohort study included patients with sepsis or septic shock admitted to a large medical ICU. Primary exposure was IV fluid volume in the first 6 h following sepsis diagnosis, divided into two cohorts: ≥ 30 mL/kg (standard group) and < 30 mL/kg (restricted group). The primary outcome was need for mechanical ventilation within 72 h following initiation of fluid resuscitation. Secondary outcomes were length of stay, ventilator days, and time to intubation.
A total of 208 patients were included, with 104 (50%) in the restricted group (< 30 mL/kg) and 104 in the standard group (≥ 30 mL/kg). No difference in intubation incidence was detected between the two groups, with 36 patients (35%) in the restricted group and 33 (32%) in the standard group (adjusted OR, 0.75; 95% CI, 0.41-1.36; P = .34) intubated. There was no difference between standard and restricted groups in alive ICU-free days (17 ± 11 days vs 17 ± 10 days; P = .64), duration of mechanical ventilation (10 ± 12 days vs 11 ± 16 days; P = .96), or hours to intubation (16 ± 19 h vs 14 ± 15; P = .55).
No differences were detected in the incidence of intubation in patients with sepsis and cirrhosis, end-stage renal disease, or heart failure who received guideline-recommended fluid resuscitation with 30 mL/kg compared with patients initially resuscitated with a lower fluid volume.
Historically, norepinephrine has been administered through a central venous catheter (CVC) because of concerns about the risk of ischemic tissue injury if extravasation from a peripheral IV catheter ...(PIVC) occurs. Recently, several reports have suggested that peripheral administration of norepinephrine may be safe.
Can a protocol for peripheral norepinephrine administration safely reduce the number of days a CVC is in use and frequency of CVC placement?
This was a prospective observational cohort study conducted in the medical ICU at a quaternary care academic medical center. A protocol for peripheral norepinephrine administration was developed and implemented in the medical ICU at the study site. The protocol was recommended for use in patients who met prespecified criteria, but was used at the treating clinician's discretion. All adult patients admitted to the medical ICU receiving norepinephrine through a PIVC from February 2019 through June 2021 were included.
The primary outcome was the number of days of CVC use that were avoided per patient, and the secondary safety outcomes included the incidence of extravasation events. Six hundred thirty-five patients received peripherally administered norepinephrine. The median number of CVC days avoided per patient was 1 (interquartile range, 0-2 days per patient). Of the 603 patients who received norepinephrine peripherally as the first norepinephrine exposure, 311 patients (51.6%) never required CVC insertion. Extravasation of norepinephrine occurred in 35 patients (75.8 events/1,000 d of PIVC infusion 95% CI, 52.8-105.4 events/1,000 d of PIVC infusion). Most extravasations caused no or minimal tissue injury. No patient required surgical intervention.
This study suggests that implementing a protocol for peripheral administration of norepinephrine safely can avoid 1 CVC day in the average patient, with 51.6% of patients not requiring CVC insertion. No patient experienced significant ischemic tissue injury with the protocol used. These data support performance of a randomized, prospective, multicenter study to characterize the net benefits of peripheral norepinephrine administration compared with norepinephrine administration through a CVC.
Nrf2 is essential to antioxidant response element (ARE)-mediated host defense. Sulforaphane (SFN) is a phytochemical antioxidant known to affect multiple cellular targets including Nrf2-ARE pathway ...in chemoprevention. However, the role of SFN in non-malignant airway disorders remain unclear. To test if pre-activation of Nrf2-ARE signaling protects lungs from oxidant-induced acute injury, wild-type (Nrf2+/+) and Nrf2-deficient (Nrf2−/−) mice were given SFN orally or as standardized broccoli sprout extract diet (SBE) before hyperoxia or air exposure. Hyperoxia-induced pulmonary injury and oxidation indices were significantly reduced by SFN or SBE in Nrf2+/+ mice but not in Nrf2−/− mice. SFN upregulated a large cluster of basal lung genes that are involved in mitochondrial oxidative phosphorylation, energy metabolism, and cardiovascular protection only in Nrf2+/+ mice. Bioinformatic analysis elucidated ARE-like motifs on these genes. Transcript abundance of the mitochondrial machinery genes remained significantly higher after hyperoxia exposure in SFN-treated Nrf2+/+ mice than in SFN-treated Nrf2−/− mice. Nuclear factor-κB was suggested to be a central molecule in transcriptome networks affected by SFN. Minor improvement of hyperoxia-caused lung histopathology and neutrophilia by SFN in Nrf2−/− mice implies Nrf2-independent or alternate effector mechanisms. In conclusion, SFN is suggested to be as a preventive intervention in a preclinical model of acute lung injury by linking mitochondria and Nrf2. Administration of SFN alleviated acute lung injury-like pathogenesis in a Nrf2-dependent manner. Potential AREs in the SFN-inducible transcriptome for mitochondria bioenergetics provided a new insight into the downstream mechanisms of Nrf2-mediated pulmonary protection.
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•Sulforaphane prevented murine acute lung injury in an Nrf2-dependent manner.•Pulmonary sulforaphane activity was featured by linking mitochondria and Nrf2.•Potential ARE motifs were enriched in sulforaphane-induced energy metabolism genes.•Enhanced mitochondrial biogenesis conveyed airway defense against oxidant disorders.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: Vasopressin decreases vasopressor requirements in patients with septic shock. However, the optimal norepinephrine dose for initiation or cessation of vasopressin is unclear. Objective: ...Analyze monthly intensive care unit (ICU) mortality rates 1 year preimplementation and postimplementation of a guideline suggesting a norepinephrine dose of 50 µg/min or more for initiation of vasopressin and early cessation of vasopressin. Methods: This retrospective quasi-experimental study included adult patients with septic shock admitted to the medical ICU of a tertiary care medical center over 2 years. Time periods were evaluated with interrupted time series analysis. Results: A total of 1148 patients were included: 573 patients preguideline and 575 patients postguideline. Group characteristics were well balanced at baseline, except patients postguideline had higher sequential organ failure assessment scores. Postguideline, fewer patients were initiated on vasopressin (305 53.2% vs 217 37.7%, absolute difference −15.5% 95% CI −21.2% to −9.8%), and the norepinephrine dose at vasopressin initiation was higher (median 25 interquartile range 18, 40 µg/min vs 40 22, 52 µg/min; median difference 15 95% CI 11 to 19 µg/min; P < 0.01). After guideline implementation, there was no evidence for a difference in ICU mortality rate slope (slope change 0.07% 95% CI −0.8% to 1.0% per month; P 0.87), but the vasoactive cost level decreased by US$183 (95% CI −US$327 to −US$39) per patient immediately after implementation. Conclusion and Relevance: Implementation of a guideline suggesting a high norepinephrine dose threshold for vasopressin initiation and early vasopressin cessation in patients with septic shock appears to be safe and may decrease vasoactive costs.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
To describe the use of a medical intensive care unit (MICU) delirium order set pilot and its associated impact on utilization of nonpharmacologic and pharmacologic interventions, pharmacologic ...continuation at transitions of care, and resolution of ICU delirium.
This was a retrospective cohort analysis of MICU patients who received delirium management using an order set pilot compared to standard care. Patients 18 years of age or older admitted to the MICU between May 2019 and January 2020 who received an antipsychotic or valproic acid for the treatment of delirium were included.
Pharmacologic treatment continuation past ICU discharge occurred in 30% of patients in the pilot cohort (n = 50) compared to 54% of patients receiving standard care (n = 50; P = 0.027). On treatment days 1 through 7, utilization of deliriogenic medications was significantly lower in the pilot cohort (78% vs 96%, P = 0.007). No differences were observed between the groups in delirium resolution, delirium recurrence, hospital and ICU length of stay, or mortality.
A MICU order set prioritizing nonpharmacologic management and limiting the duration of pharmacologic agents for delirium may aid providers in the management of ICU delirium and reduce exposure to pharmacologic interventions.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
IV pushes of phenylephrine may be used for patients with septic shock with the intent of rapidly achieving mean arterial pressure (MAP) goals. However, the clinical effectiveness and safety of this ...approach are unclear.
In patients with septic shock, is administration of a phenylephrine push before norepinephrine initiation associated with a higher incidence of hemodynamic stability?
This retrospective, multicenter cohort study included adult patients with septic shock initiated on norepinephrine. Propensity scores for initial phenylephrine push receipt were generated, and patients receiving an initial phenylephrine push were propensity score-matched 1:2 to those not receiving an initial phenylephrine push. The primary outcome was achievement of hemodynamic stability (defined as maintaining MAP of ≥ 65 mm Hg for at least 6 h without an increase in continuous infusion vasoactive agent dosage) within 3 and 12 h of norepinephrine initiation.
Of 1,317 included patients, 181 received an initial phenylephrine push; 141 phenylephrine push patients were matched to 282 patients not receiving a phenylephrine push. More patients who received a phenylephrine push achieved hemodynamic stability at hour 3 than those who did not receive a phenylephrine push (28.4% vs 18.8%; risk difference, 10%; 95% CI, 0.9%-18%). Phenylephrine push receipt was associated independently with hemodynamic stability within 3 h (adjusted OR, 1.8; 95% CI, 1.09-2.97), but not at 12 h (adjusted OR, 1.42; 95% CI, 0.93-2.16). Phenylephrine push receipt was associated independently with higher ICU mortality (adjusted OR, 1.88; 95% CI, 1.1-3.21).
Phenylephrine pushes were associated with a higher incidence of early, but not sustained, hemodynamic stability and were associated independently with higher ICU mortality. Caution is warranted when clinicians are considering the use of phenylephrine pushes in patients with septic shock.
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