Patients with severe Coronavirus disease 19 (COVID-19) typically require supplemental oxygen as an essential treatment. We developed a machine learning algorithm, based on deep Reinforcement Learning (RL), for continuous management of oxygen flow rate for critically ill patients under intensive care, which can identify the optimal personalized oxygen flow rate with strong potentials to reduce mortality rate relative to the current clinical practice.We modeled the oxygen flow trajectory of COVID-19 patients and their health outcomes as a Markov decision process. Based on individual patient characteristics and health status, an optimal oxygen control policy is learned by using deep deterministic policy gradient (DDPG) and real-time recommends the oxygen flow rate to reduce the mortality rate. We assessed the performance of proposed methods through cross validation by using a retrospective cohort of 1,372 critically ill patients with COVID-19 from New York University Langone Health ambulatory care with electronic health records from April 2020 to January 2021.The mean mortality rate under the RL algorithm is lower than the standard of care by 2.57% (95% CI: 2.08–3.06) reduction (P<0.001) from 7.94% under the standard of care to 5.37 % under our proposed algorithm. The averaged recommended oxygen flow rate is 1.28 L/min (95% CI: 1.14–1.42) lower than the rate delivered to patients. Thus, the RL algorithm could potentially lead to better intensive care treatment that can reduce the mortality rate, while saving the oxygen scarce resources. It can reduce the oxygen shortage issue and improve public health during the COVID-19 pandemic.A personalized reinforcement learning oxygen flow control algorithm for COVID-19 patients under intensive care showed a substantial reduction in 7-day mortality rate as compared to the standard of care. In the overall cross validation cohort independent of the training data, mortality was lowest in patients for whom intensivists’ actual flow rate matched the RL decisions. Over the course of the past year, the rapid global spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has motivated multidisciplinary investigation efforts to identify effective medical management against coronavirus disease 2019 (COVID-19). Respiratory distress, including mild or moderate respiratory distress, acute respiratory distress syndrome (ARDS) and hypoxia, is a common complication of COVID-19 patients. The therapy of COVID-19 is guided by the knowledge and experience of moderate-to-severe ARDS treatment [A large collection of artificial intelligence (AI) and deep learning (DL) approaches have been proposed to accelerate the drug discovery and the process of diagnosis and treatment of COVID-19 disease , 4. ClinReinforcement learning has been successfully applied in the past to different healthcare problems such as multimorbidity management , HIV theFocusing on RL-based oxygen flow rate control (RL-oxygen), we studied its impact on mortality in COVID-19 patients with respiratory failure. The evolution of patients’ ICU histories, including treatments, vitals, and health outcomes, was modeled using a Markov decision process (MDP) , 16. At st 2020 to January 19th 2021. We excluded COVID-19 patients aged below 50 and not been hospitalized as the lacked consistent documentation of vital signs, treatments, and laboratory tests. This study was approved by the NYULH IRB and the data were de-identified to ensure anonymity.Our research team used a retrospective cohort of the New York University Langone Health (NYULH) EHR data on COVID-19 patients to derive and validate the RL algorithm. Eligible patients had positive COVID-19 PCR test and had oxygen therapy in hospital between March 1SaO2), oxygen saturation (SpO2), partial pressure of oxygen (PaO2) and bicarbonate (HCO3), is commonly used biomarkers measuring the severity of ARDS [For each patient, we had access to demographic data, including age, sex, race, ethnicity and smoking status, ICU admits and discharge information, in-hospital living status, comorbidities, treatments, and laboratory test data. The comorbidities, including hyperlipidemia, coronary artery disease, heart failure, hypertension, diabetes, asthma or chronic obstructive pulmonary, dementia and stroke, are defined based on the International Classification of Diseases (ICD)-10 diagnosis codes. To reduce the feature dimensionality, we selected 36 laboratory tests based on two criteria: (1) less than 28% missing values; and (2) COVID-19 related tests and vital signs. In specific, we explore the associations between laboratory tests and COVID-19 based on existing literature and clinical findings. For example, recent studies have shown that a reduced estimated glomerular filtration rate (eGFR), low platelet count, low serum calcium level, increased white blood cell count, Neutrophil-to-lymphocyte ratio (NLR), and red blood cell distribution width-coefficient of variation (RDW-CV) are related to high risk of severity and mortality in patients with COVID-19 –21. Addi of ARDS , 25.In this study, we employed leave-one-hospital-out validation to evaluate the model performance. The whole dataset was divided into 4 batches by the hospital and then we take one batch as validation set and the rest as training set in each simulation.t. The action refers to the oxygen flow rate. After a sequence of actions, the patient receives a reward if he/she survives in the next 7 days; otherwise, a penalty to death will be given. The cumulative return is defined as the discounted sum of all rewards of each patient received during the ICU stay. The intrinsic design of RL provides a powerful tool to handle sparse and time-delayed reward signals, which makes them well-suited to overcome the heterogeneity of patient responses to actions and the delayed indications of the efficacy of treatments [We model patient health trajectory and the clinical decisions during a course of intensive care over a period of ICU stay by a Markov decision process (MDP) with state, action, and reward. The state of a patient includes the observed patient demographics, vital signs, and laboratory tests at each time eatments . The detst: observed patient’s characteristics at each time t with information, including demographics, COVID-19 lab tests, and vital signs.State at: oxygen flow rate ranged from 0 L/min to 60 L/min.Action rt: the reward of an action at time t is measured by its associated ultimate health outcome given the patient’s health state. Similar to [Reward milar to , we usedγ: determines how much the RL agents balance rewards in the distant future relative to those in the immediate future. It can take values between 0 and 1 [Discount factor  0 and 1 . After ca, was chosen based on current health state, denoted by s, of the patient and then a new heath state s′ was observed at the next measurement time. We record the tuple  in the experience replay memory with the zero reward r = 0. At the end of the treatment, a positive reward was recorded  if patient survived; and a negative reward  was issued if the patient died. Then we applied deep deterministic policy gradient (DDPG), as shown at the top part of s, a, s′, r) from EHR data to concurrently learn a critic network (Q-function approximation) and an actor network (policy). The critic network, denoted by Qπ, is a nonlinear function that approximates the Q value functiona  given a patient’s health state s. The actor network representing a policy, denoted by πϕ(s), proposes an action for each given state through the mapping or equation a = πϕ(s). The critic loss, defined by the mean squared TD-error  using 4 metrics: similarity, accuracy, Chi-squared test, and concordance index. Overall, the cosine similarity between predicted and actual survival is greater than 99.9%, and the concordance index is 0.83. Both metrics indicate that the predictive model can effectively estimate unobserved health outcomes. Moreover, the paired Chi-squared test  shows no significant difference between true and predicted survival.Overall, 1,362 patients in NYULH EHR samples had a PCR-based COVID-19 diagnosis between March 2020 to January 2021. The demographic and clinic characteristics summary of the analysis cohort is shown in The performance of the RL-oxygen is summarized in The efficacy of the RL prescriptive algorithm was consistently observed across age, gender, BMI, and comorbidity subgroups . DemograWe further studied 7-days mortality when the actually administered oxygen flow rate differed from the oxygen flow rate suggested by the RL-oxygen in Last, we observed that the RL-oxygen and physicians recommended consistent flow rates in most times; see We used a RL approach to learn an optimal policy to continuously control the oxygen device for critically ill patients with COVID-19 who require oxygen therapy. As most people who become seriously unwell with COVID-19 have an acute respiratory illness , 30, ourOur analysis suggests the current practice remains some potential to be improved as actual oxygen flow rate administered by intensivists showed more than fifty percent discrepancy with RL-oxygen recommendations. Importantly, we observe that RL-oxygen tends to prescribe lower oxygen flow rate than physician’s prescribed rates but leads to better outcomes. This finding is especially important in the context of the ongoing and persistent medical oxygen shortages in some developing regions. As COVID-19 patient-care protocols have evolved, medical-grade oxygen is still considered as an essential resource to treatments for critically ill patients. In regions such as Africa, Middle East, and Asia, the surge in demand for medical oxygen to treat COVID-19 exacerbates preexisting gaps in medical-oxygen supplies, leading to substantial supply shortages.Our analysis also identified some clinical patterns that RL-oxygen particularly works well. For example, patients with high risk  observed higher efficacies than patients aged between 50 and 75 by using relatively lower averaged oxygen flow rate than actually administered. RL-oxygen also recommends a higher averaged oxygen flow rate may improve the health outcomes for patients aged from 50 to 65. Moreover, we also notice significant therapeutic discrepancies in patients with stroke and diabetes comorbidities. In both cases, RL-oxygen recommended higher averaged oxygen flow rate than doctors while showing a significant reduction in estimated mortality. In fact, these findings agree with recent studies which reported that “stroke survivors who underwent COVID-19 developed more acute respiratory distress syndrome and received more noninvasive mechanical ventilation”  and “diaAlthough our evaluation methodology controls for several confounding factors and shows high validation accuracy, sample scarcity and a large proportion of missing value may increase estimation uncertainty and affect the treatment recommendations. Larger training data are necessary to cover more of the state space and improve the policy optimization. Moreover, the COVID-19 cohort from NYULH may not be representative of the U.S. COVID-19 population or the oxygen clinical practices in other countries. To ultimately validate the efficacy of the RL algorithm, randomized clinical trials with patients randomly assigned to RL and clinician oxygen therapy would be needed.Through analyzing the EHR data from multiple ambulatory care centers, we demonstrated the feasibility of using reinforcement learning based oxygen therapy to improve the intensive care for COVID-19 patients. The RL-oxygen showed medium concordance (44%) with the current practice of critical care physicians. For all COVID-19 patients requiring oxygen therapy, RL recommendations significantly reduce the mortality rate compared to the current practice. The algorithm has the potential to be integrated into the clinical decision support system and assist physicians to provide timely personalized recommendations of oxygen flow rate for COVID-19 patients in ICU.1


Acute kidney injury (AKI) after lung transplantation (LuTx) is associated with increased long-term mortality. In this prospective observational study, commonly used AKI-definitions were examined regarding prediction of long-term mortality and compared to simple use of the serum creatinine value at day 7 for patients who did not receive hemodialysis, and serum creatinine value immediately before initiation of hemodialysis (d7/preHD-sCr).185 patients with LuTx were prospectively enrolled from 2013–2014 at our center. Kidney injury was assessed within 7 days by: (1) the Kidney Disease Improving Global Outcomes criteria (KDIGO-AKI), (2) the Acute Disease Quality Initiative 16 Workgroup classification (ADQI-AKI) and (3) d7/preHD-sCr. Prediction of all-cause mortality was examined by Cox regression analysis, and clinical as well as laboratory factors for impaired kidney function post-LuTx were analyzed.2 = 0.354, p < 0.001).AKI according to KDIGO and ADQI-AKI occurred in 115 patients (62.2%) within 7 days after LuTx. Persistent ADQI-AKI, KDIGO-AKI stage 3 and higher d7/preHD-sCr were associated with higher mortality in the univariable analysis. In the multivariable analysis, d7/preHD-sCr in combination with body weight and intra- and postoperative platelet transfusions predicted mortality after LuTx with similar performance as models using KDIGO-AKI and ADQI-AKI . Pre-transplant reduced renal function, diabetes, higher BMI, and intraoperative ECMO predicted higher d7/preHD-sCr (rOur results confirm the importance of AKI in lung transplant patients; however, a simple and pragmatic indicator of renal function, d7/preHD-sCr, predicts long-term mortality equally reliable as more complex AKI-definitions like KDIGO and ADQI. Acute kidney injury (AKI) is a common complication after lung transplantation (LuTx), with incidence rates of 39–69% –5 and isBased on these considerations and on the fact that categorization of a continuous parameter like serum creatinine may decrease its informational value , this stPatients were consecutively recruited for this study. In the period from June 2013 to December 2014, 193 adult patients received a LuTx, of which 185 patients consented to participate in the study (95.9%). Exclusion criteria were combined organ transplantations. The study was approved by the local ethics committee (no. 6895) and initiated in 2013 to examine the primary endpoint "AKI" in terms of clinical factors and biomarkers. The following results now refer to the secondary endpoint "long-term outcome". Clinical, laboratory and surgery-related factors were documented pre-, peri- and post-transplantation. Patients were followed up for 5 years post-transplant, with an annual routine consisting of clinical and laboratory parameters including renal function and immunosuppressive drug levels. The mean follow-up was 57 ± 20 months.Minimally invasive sternum-sparing anterolateral thoracotomy performed in the transplant procedure whenever possible. The majority of patients received bilateral LuTx ; only 3 patients had single LuTx. Initially, all patients received a triple maintenance immunosuppression with tacrolimus, mycophenolate mofetil and steroids. Within the first year after transplantation, tacrolimus target levels were 8–12 μg/liter. Induction therapy was not used. In all patients, primary graft function (PGD) was scored at different postoperative time points after transplantation according to the International Society for Heart and Lung Transplantation guidelines and PGD grade 3 was used for analysis , 15.Renal function was determined by calculating the estimated glomerular filtration rate (eGFR) with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)–formula . BaselinStatistical analyses were performed with IBM SPSS statistical software version 26.0 and the rms  package For the Cox regression analyses, linearity of continuous variables was verified by categorizing the variables and comparing the ß-coefficients from the univariate Cox regression. Variables with a p-value <0.05 in the univariate analysis and further variables that were deemed biologically relevant were included in the multivariable modeling, which was performed by stepwise backward selection . The bootstrapping procedures in R software were used to validate the models. The Harrell’s concordance index was used to report the performance of the models . Kaplan-Patient characteristics, pre- and postoperative factors of the entire study population and the subgroups with and without AKI stage I-III according to KDIGO are shown in Of the 185 patients, 115 (62.2%) developed KDIGO-AKI, mostly stage 1 (40.0%) and stage 2 (44.3%). Sixty patients with AKI (52.2%) did not recover renal function within 48 hours thus presenting with persistent ADQI-AKI . Fig 1 sIn the post-transplant follow-up period of 57 ±20 months, one patient was lost in the -to-follow-up and 36 (19.5%) patients died. Leading causes of death were infections , chronic lung allograft dysfunction  such as bronchiolitis obliterans syndrome and restrictive allograft syndrome, and malignancies in 4 patients. One patient each died from sudden cardiac death, acute graft failure, hemoptysis and ileus. Five of the 16 infectious deaths occurred in the early post-transplant course within the first 90 days. All infectious deaths except one were in patients with AKI. Overall, in the patients without AKI 9 deaths occurred, whereas the remaining 27 deaths were observed in patients with AKI, with the worst survival in KDIGO-AKI stage 3 . NotablyIn univariable Cox analyses , KDIGO-ABased on these univariable results , multivaThe calibration of the three models was comparable, with similar proportions of patients assigned to low, moderate and high mortality risk according to the model’s prognostic index . We alsoIn a post-hoc analysis of the long-term course after discharge from the hospital, renal function was examined in the patients assigned to low, moderate and high mortality risk. The four patients who required dialysis within the first 7 days were in the high-risk group. 2 = 0.354).To estimate the relationship between d7/preHD-sCr and several pre- and perioperative factors, univariable and multivariable linear regression analyses were performed . In the This study underlines the importance of kidney injury in patient outcomes after lung transplantation. Similar to previous studies we show that higher degree of AKI early after LuTx is associated with death , 5. In aUnlike previous studies which used more complex definitions of AKI in the prediction of mortality risk, this study suggests that simple use of d7/preHD-sCr is equally reliable. Regular laboratory monitoring after major surgery is essential and use of this information should be as simple as possible. This includes close monitoring of sCr to detect renal dysfunction and initiate further diagnostics and therapy. Mortality risk prediction based on KDIGO and ADQI criteria is established, but any reliable simplification is an improvement. There is good rationale to use the serum creatinine. First, categorization of variables that are continuous is rarely sensible because information is lost, particularly with broad categories . Second,Fairly accurate estimation of the mortality risk was shown with all parameters of kidney injury, d7/preHD-sCr, the KDIGO-AKI and the ADQI grading, together with a few additional clinical factors. The multivariable models all had similar concordance indices and differentiation of mortality risks as illustrated by the calibration studies. The model with d7/preHD-sCr included body weight and need of intra-operative and post-operative platelet infusions. These risk factors were also included in the other two models. Using the eGFR at day 7 instead of d7/preHD-sCr was not advantageous in the model, probably because of the inaccuracy of eGFR calculations in critically ill patients as reported in liver transplant patients , 24.The incidence of AKI is high early after LuTx, affecting one to two thirds of patients –5 and inApart from AKI, particularly factors that indicate a more complicated transplantation and post-transplantation course such as operation time, a greater need of substituting blood components, and post-surgical complications like re-operation showed associations with mortality. Platelet and plasma infusions were retained in the multivariable analyses, suggesting an independent effect on patient survival. Platelet transfusions were also a risk factor for mortality in patients with liver transplantation  and withMore complex surgical courses and postoperative complications in turn can precipitate AKI, which would be in this case a surrogate of a more severe transplant course. On the other hand, an independent effect of AKI on long-term survival is indicated by various studies. AKI was linked to the development of chronic kidney disease in several study populations , 35 In tGiven the clinical relevance of AKI, identifying patients at risk is important. Pre-existing diabetes mellitus, need of intraoperative ECMO, higher BMI and impaired renal function prior to LuTx allowed prediction of higher d7/preHD-sCr. These factors were risk factors for AKI in previous studies , 6. As tOur study has several limitations. First, this is a single-center study with a moderately-sized study population. Second, like in many other studies , 10, 11,This study demonstrates the importance of reduced renal function and AKI for the long-term survival after LuTx. Findings should help identify patients at risk for AKI and to adjust pre- and post-operative management accordingly. Together with few clinical factors, the continuous parameter d7/preHD-sCr predicts mortality equally well as the commonly used AKI definitions by KDIGO and ADQI and is easier to apply.S1 File(XLSX)Click here for additional data file.S1 Table(PDF)Click here for additional data file.


Since COVID-19 vaccine uptake was found to be especially low among young adults, the present study investigated COVID-19 risk perception as predictor of COVID-19 vaccination intention and actual COVID-19 vaccine uptake among this age group. More specifically, it was tested whether cognitive risk perception predicts vaccination uptake successively via affective risk perception and vaccination intention. In total, 680 students  between 17 and 28 years participated in this longitudinal online study. COVID-19 cognitive and affective risk perception, COVID-19 vaccination intention, and actual COVID-19 vaccine uptake were measured in t1: November/December 2020, t2: March 2021, and t3: June/July 2021, respectively. The mediation analysis revealed a significant indirect effect of perceived severity at t1 on vaccine uptake at t3 via worry at t1 and vaccination intention at t2. Stronger perceptions of perceived severity of COVID-19 were related to more worry about COVID-19, which led to a higher vaccination intention, which, in turn, increased the chance of COVID-19 vaccine uptake. To increase vaccine uptake among young adults it might be fruitful to emphasize the severity of COVID-19. However, one should take into account that tapping into fear works best when messages also include efficacy statements. Since the beginning of 2020, people worldwide have had to deal with the (consequences of the) outbreak of COVID-19, an illness caused by infection with the SARS-CoV-2 virus. The World Health Organization ,4,5. VacA specific group of interest regarding COVID-19 vaccine uptake is young adults. The spread of the coronavirus is most prevalent among this group ,15, whilRisk perception is a complex process, which is assumed to include both cognition as well as affect ,27. CognRegarding COVID-19, previous studies showed that both cognitive as well as affective risk perception stimulated adherence to the guidelines implemented to prevent the spread of COVID-19. That is, higher perceptions of chances to get infected with COVID-19 and higher perceived severity of COVID-19 were associated with a higher likelihood to implement protective behaviors ,30,31,32Previous studies also confirm the role of risk perception in COVID-19 vaccination intention ,24. One While previous research showed the importance of risk perception in COVID-19 vaccination intention, little is known about the role of both cognitive and affective risk perception in actual COVID-19 vaccine uptake. A recent systematic review , includiThe present longitudinal study examined COVID-19 risk perception as a predictor of COVID-19 vaccination intention and vaccine uptake among young adults in the Netherlands. Cognitive and affective risk perception were measured before any COVID-19 vaccine was fully developed . Vaccination intentions were measured when COVID-19 vaccines were released, but not yet available for young adults . Actual vaccine uptake was measured when young adults had access to different COVID-19 vaccines .Following the model proposed by Renner and Reuter  and prevThis study is part of a larger research project examining university students’ experiences during the COVID-19 outbreak. A longitudinal cohort study was performed during the academic year 2020/2021 with three points of measurement  among Dutch university students. Students were included when they studied at a university that switched from offline teaching to online or blended teaching because of COVID-19 measures. Students who studied at an open university, studied parttime, or were aged above 30 years were excluded. The study was approved by the Medical Ethics Review Committee of the Erasmus Medical Center (#2020-0815).Recruitment took place via student unions and student associations through email and social media posts, promoting a link to an online questionnaire in Qualtrics. After opening the link, students were informed about the purpose of the study and data handling. It was made explicit that participation was voluntary and anonymous, and that students could withdraw any time without any (negative) consequences. After providing informed consent, students could start filling in the questionnaire, which took them 20–30 min. Students who finished the questionnaire in less than 10 min were excluded from data analysis because this seemed unrealistic. Students received vouchers for participation  to stimulate participation and prevent drop-out.The online questionnaires measured several concepts regarding students’ experiences during COVID-19, such as life satisfaction, living circumstances, social interactions, study behavior, and learning outcomes. However, in this study, to test our hypothesized model, we only used a selection of variables. That is, we used background characteristics, risk perception measured at t1, vaccination intention measured at t2, and actual vaccine uptake measured at t3.Risk perception was measured by numerical-cognitive estimates of the perceived susceptibility and severity of COVID-19. Based on Renner and Reuter , studentVaccination intention was assessed with a single item adapted from Renner and Reuter . StudentVaccine uptake was measured with one question adapted from Renner and Reuter . StudentBackground variables were measured with one item each. At t1, participants indicated their age and their gender . Further, at all three measurement points, students indicated whether they had ever been infected with COVID-19 .Statistical analyses were performed with IBM SPSS Statistics Version 27 and Mplus version 8.5. Pearson correlations were calculated to investigate the bivariate associations between the study variables. As having been infected with COVID-19 was  significantly related to vaccination intention or vaccine uptake see , it was SD = 2.06). Only a small part of the students had a migration background . Most students lived in student housing or with friends (60.3%), followed by living with parents/family (26.2%), on their own (8.8%), with a partner (3.7%), or in another form (1.0%). The sample was representative for Dutch university students in terms of university affiliation, field of study, and study phase. However, males and students with migration background were underrepresented , indicating that for every one-unit increase in COVID-19 vaccination willingness at t2, the odds of being vaccinated against COVID-19 at t3 increased by 47%. Vaccination intention at t2 was significantly predicted by affective risk perception at t1, with more worry about COVID-19 leading to higher COVID-19 vaccination intention. Affective risk perception at t1 was significantly positively related to the cognitive risk perception dimension perceived severity at t1, with perceiving COVID-19 as more severe being associated with more worry about COVID-19.Additionally, a significant positive indirect effect of perceived severity at t1 on vaccine uptake at t3 through worry at t1 and vaccination willingness at t2 was found, β = 0.03, BC 95% CI . This indirect effect indicates that stronger perceptions that a COVID-19 infection is severe are related to more worry about COVID-19, which leads to a higher COVID-19 vaccination intention, which, in turn, increases the chance of COVID-19 vaccine uptake.This study examined the role of both cognitive and affective risk perception in vaccination intention and subsequently vaccine uptake among students in the Netherlands using a longitudinal design with three points of measurement.Our results showed that the intention to get vaccinated against COVID-19 is a significant predictor of actual COVID-19 vaccine uptake, confirming previous results from longitudinal studies regarding influenza vaccination ,41. FurtFor cognitive risk perception, significant positive associations of the dimension perceived severity of COVID-19 with worry about COVID-19 and to a lesser extent with COVID-19 vaccine uptake were found. This is largely in line with the assumption that cognitive risk perception informs affective risk perception ,27,29 anIn contrast, no significant effects were found for the cognitive risk perception dimension perceived susceptibility. That is, the perceived likelihood of getting infected with COVID-19 was neither related to worry about COVID-19 nor to COVID-19 vaccination intention and vaccine uptake. This is contrary to the expectations and previous research that found perceived susceptibility to be associated with more worry ,45 and tOur results showed that stronger perceptions of perceived severity of COVID-19 are related to more worry about COVID-19, which leads to a higher vaccination willingness, which, in turn, increases the chance of COVID-19 vaccine uptake. This finding indicates that emphasizing possible severe consequences of COVID-19 might be a reasonable approach to increase the vaccination rate among young adults. Another study found that highlighting the consequences for older vulnerable others might help young adults to adhere to the preventive guidelines . In a siWhile communicating about the risk of COVID-19 might be important to stimulate young adults to get vaccinated, it is also key to address efficacy aspects in risk messages . That isThis study provided unique insights into the role of risk perception in COVID-19 vaccine uptake. One key aspect was the longitudinal design used. This design allowed us to examine effects of risk perception and intention on actual vaccine uptake over time. Moreover, we operationalized cognitive risk perception differentiating between severity and susceptibility, enabling us to pinpoint the contribution of cognitive risk perception in COVID-19 vaccine uptake more precisely, showing that perceived severity is more relevant than perceived susceptibility in the case of COVID-19.However, some limitations of this study need to be considered. Firstly, while this study provides in-depth insight into the role of risk perception in vaccination, it did not include other possible determinants. Our model explained 9% of vaccine uptake, suggesting that while risk perception is a significant determinant of vaccine uptake, other perceptions might also play a role. For example, vaccine related perceptions such as necessity beliefs and concerns about side effects, may be other relevant determinants ,35. TherFuture research would benefit from including a diverse sample in terms of age and education level. In addition, a more complex model including multiple determinants might be tested in further studies.To stimulate young adults to get vaccinated against COVID-19, hereby increasing vaccine uptake and possibly stopping the spread of COVID-19, it might be fruitful to emphasize the severity of COVID-19 among this age group. Stronger perceptions of perceived severity of COVID-19 are related to more worry. Tapping into fear or worry, preferably combined with efficacy statements, may induce the intention to get vaccinated, which in turn may stimulate vaccine uptake.


Eighty-five KT recipients from DBD who received basiliximab were included as controls. From KT recipients who received thymoglobulin, 33.6/43.4% presented with an increase in AST/ALT at 72 h post-KT, respectively. Regarding donor type, the percentage of recipients who experienced 72 h post-KT hypertransaminasemia was higher in uDCD group . Within the control group, 9.4/12.9% of patients presented with AST/ALT elevation. One month after transplant, AST/ALT values returned to baseline in all groups. The multivariate analysis showed that uDCD recipients had 6- to 12-fold higher risk of developing early post-KT hypertransaminasemia. Early post-KT hypertransaminasemia is a frequent and transient event related to the kidney donor type, being more frequent in uDCD recipients.Early hypertransaminasemia after kidney transplantation (KT) is frequent. It has been associated with the crosstalk produced between the liver and the kidney in ischemia-reperfusion situations. However, the influence of the donor type has not been evaluated. We present a retrospective study analyzing the increase in serum aspartate aminotransferase/alanine aminotransferase (AST/ALT) during the first three months post-KT in 151 recipients who received thymoglobulin as induction therapy, either from brain-death donors (DBD,  Transaminases  and aspartate aminotransferase (AST)) are intracellular liver enzymes that act as markers of liver injury, as their elevation usually reflects hepatic cell damage. Other than in the hepatocytes, AST can be found in lower concentrations in the heart muscle, kidneys, and brain, amongst other organs . The norIn kidney transplant (KT) recipients, hypertransaminasemia is a frequent finding, affecting 7 to 24% of patients depending on the series ,4,5. TheHowever, these might not be the only reasons behind post-transplant hypertransaminasemia. Interconnection between organs is required for the proper functioning of the organism. The term organ crosstalk refers to the complex interactions maintaining the organism’s homeostasis. In case of organ dysfunction, this crosstalk may also facilitate the dysfunction of other organs through neuronal, endocrine, and paracrine pathways ,12,13. AIn KT, there is an initial injury to the kidney graft caused by ischemia-reperfusion damage, which results from an initial restriction of blood supply to the graft followed by its restoration and subsequent re-oxygenation. Paradoxically, the restoration of blood flow is often associated with an exacerbation of tissue damage and an inflammatory response activation that causes the so-called reperfusion damage . This inTherefore, the aim of our study was to evaluate the prevalence and evolution of hypertransaminasemia in the immediate post-KT period, if it has any relation with the donor type, and its possible association with post-KT outcomes as a prolonged delayed graft function (DGF).n = 163). Patients who received maintenance immunosuppression with mammalian target of rapamycin (mTOR) inhibitor instead of mycophenolic acid (n = 3), patients with immediate graft loss (n = 6), and those who died in the early post-transplant period (n = 3) were excluded from the analysis. A total 151 patients were analyzed, and of those: 43 recipients from uDCD who receive induction with thymoglobulin by protocol in our center; 33 KT recipients from controlled DCD (cDCD); and 75 KT from DBD -who receive thymoglobulin for high immunological risk-. Maintenance immunosuppression consisted of tacrolimus, mycophenolic acid, and prednisone. To be noted, tacrolimus had a delay-start among uDCD KT recipients, initiated between 3 and 5 days after transplant. Then, we added a control group of 85 DBD KT recipients (2016–2020) who received immunosuppression induction with basiliximab and maintenance with tacrolimus, mycophenolic acid, and prednisone. This is a retrospective patient cohort study including deceased-donor KT recipients who underwent KT between July 2004 and December 2020 at the Hospital del Mar, Barcelona, Spain. Initially, and to avoid potential confounders, only those recipients who received induction immunosuppression with thymoglobulin were selected , and quantitatively with the numerical value of AST and ALT (IU/L). Liver function was evaluated through bilirubin elevation above the upper limit of normality in our laboratory (1.20 mg/dL). Unfortunately, other data regarding liver failure as albumin levels and prothrombin time were not available during the early post-transplant period (first 72 h). Regarding types of donors: DBD refers to donors with diagnosis of death based on neurological criteria (severe and irreversible brain injury leading to death); DCD refers to organ donation after confirmation of cessation of circulation, and it can be controlled (cDCD), when cessation of circulation is expected, or uncontrolled (uDCD), when unexpected . DGF wasClinical data were collected from our local transplant database, including baseline demographic characteristics from donors and recipients, transplant characteristics and clinical follow-up variables periodically registered.To rule out a possible inadvertent basal liver disease in KT recipients, liver abnormalities identified by ultrasound or abdominal tomography performed during pre-transplant study were gathered. Additionally, other variables with a potential effect on transaminases were collected, such as cold ischemia time as a factor associated with the severity of ischemia-reperfusion damage; transfusion need and use of vasoactive drugs within the first 6 h after transplant (defined as post-KT low BP) as indicators of systemic hypoperfusion; and thymoglobulin total dose (mg/kg) and tacrolimus total dose (mg/kg) administered during the first week post-KT, as well as tacrolimus levels at 7 days post-KT as indicators of possible confounders, and hepatotoxic drugs. No other potential drugs able to induce liver injury were collected, as main drugs that recipients use during the first 72h after transplant are immunosuppressants.Kidney (serum creatinine) and liver function (transaminases and bilirubin) were evaluated at five time-points during the first 3 months after transplantation: baseline (pre-transplantation), at 72 h post-KT, 7, 30, and 90 days post-KT.Normality tests were performed in all quantitative variables: in case of meeting normality criteria, results are expressed as mean and standard deviation (SD); otherwise, as median and interquartile range (IQR). Categorical variables are described as counts and percentages. Comparisons between the four groups were conducted using ANOVA test for the variables with normal distribution and Kruskal-Wallis H test for the non-parametric ones. Mann-Whitney U test was used for comparisons between two groups in non-parametric variables. For categorical variables, Chi-Square and McNemar tests were used for the non-related and related groups, respectively.p-value < 0.1 in the univariate analysis were included. Results are expressed as Odds Ratio (OR) and 95% confidence interval (CI). A p-value < 0.05 was considered statistically significant. Statistical analysis was performed using SPSS V 20 .Two multivariable analyses were also performed using binary logistic regression. The first one to determine factors associated with early hypertransaminasemia after transplant. In the second analysis, our aim was to establish predictors of prolonged delayed graft function among uDCD KT recipients. For adjustment, only those variables with a Baseline characteristics of the four groups of patients are shown in Transplant characteristics are shown in Regarding renal function evolution, recipients from uDCD presented longer DGF (creatinine decline among uDCD-KT occurred by 16 days after transplantation vs. 2 days in the control group). One week after transplant, and considering those recipients with functioning graft, uDCD-KT presented with poorer kidney function, i.e., serum creatinine 6.2 mg/dl vs. 2.6mg/dl among DBD-KT. However, by three months after transplantation graft function was similar among groups, When analyzing the three main study groups , in terms of hypertransaminasemia and liver function, 36.6 and 43.4% of recipients presented with AST and ALT above normality limits at 72 h post-KT, We analyzed if donor type had any influence in early post-transplant hypertransaminasemia occurrence. The elevation of AST/ALT at 72 h post-KT was much more frequent among uDCD recipients , presentWe compared each group of KT recipients who received thymoglobulin with the control group. In the multivariable analysis of predictors for early hypertransaminasemia after transplant, uDCD KT recipients had the highest odds (OR 6.840 for AST elevation and 12.381 for ALT elevation). Cold ischemia time (OR 1.1 per hour) was also associated with AST elevation after transplant. We did not find that thymoglobulin use was independently associated with early hypertransaminasemia . On the The present study evaluates the prevalence of hypertransaminasemia in the immediate post-KT period, finding that 36.6 and 43.4% of KT recipients who receive thymoglobulin induction suffer AST and ALT elevation, respectively. This elevation occurs early, with a peak at 72 h post-KT, and is followed by an early decline and complete normalization. KT recipients from uDCD are 5 to 13 times more inclined to elevate transaminases than cDCD or DBD ones.Previous studies have shown that 7–23.3% of KT recipients may present post-transplant hepatic dysfunction but they usually referred to persistent or chronic liver damage (>6 months post-KT)  analyzedThe association between KT and hypertransaminasemia occurring in the immediate post-KT period might be explained by the liver-kidney crosstalk. During KT, ischemia-reperfusion damage occurs in the kidney graft. Evidence suggests that the inflammatory and oxidative stress associated to this damage may have detrimental effects on the liver . MultiplIf ischemia-reperfusion damage is linked to the liver-kidney crosstalk, its severity should correlate to liver damage. Krüger et al.  identifiFurthermore, to better assess the potential role of thymoglobulin in early hypertransminaemia, we included a control group of 85 recipients from DBD who received basiliximab. We did not find any difference among the control group and DBD-thymoglobulin KT recipients’ group, and thymoglobulin was not associated with early hypertransaminasemia in the multivariable analysis. This reinforces the hypothesis that despite thymoglobulin has been associated with liver toxicity ,10, otheFinally, as early hypertransaminasemia resolved quickly and it might reflect ischemia-reperfusion damage severity ,28, we aThe limitations of our study are those derived of its single-center and retrospective condition. The low number of uDCD recipients could have reduced the statistical power of the multivariable analysis. However, to our knowledge, this is the first study that explores early post-KT hypertransaminasemia and its relationship with donor type and it can be of interest to the transplant clinician: (1) hypertransaminasemia can be expected more frequently if the donor is uDCD; (2) it is going to be transient; and (3) it could correlate with the severity of I/R injury, although we were not able to demonstrate any association with prolonged DGF.We conclude that early post-KT hypertransaminasemia is a frequent and transient event related to donor type and being more frequent in recipients from uncontrolled circulatory death donors. More studies are needed to corroborate these results and possibly correlate this finding with the severity of ischemia-reperfusion damage.


With the rebound of coronavirus disease 2019 (COVID-19) epidemic in some countries with high vaccination rate, many concerns on vaccine efficacy have emerged. For example, are the current vaccines ineffective against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) variants? What’s the status of breakthrough infection? To what extent are non-pharmacological interventions (NPIs) lifted after high vaccination rate? To clarify these questions, we summarized important findings based on literature and Chinese experience.Vaccination is a crucial countermove against infectious diseases by two main mechanisms: 1) prevent infection; 2) reduce infectivity and severity and duration of symptoms of vaccinated patients. Since the outbreak of COVID-19, several vaccines have been developed and proved effective. For instance [ prevent  reduce iChinese government spares no efforts to promote vaccination. Owing to the high confidence for Chinese government and collectivism of Chinese people, the acceptance rate for COVID-19 vaccine was up to 96.2–100% in China . As of 1The breakthrough infection is another concern. In particular, several SARS-CoV-2 variants have continuously emerged, which may change transmission capacity and virulence. Though cross immunity exists, viral variants can become resistant to the immunity generated by existing vaccines, and the rate of breakthrough infection will inevitably increase . Given tEven if the vaccination rate reaches high level, the epidemic could not be controlled without NPIs. For instance, a border city in China, De Hong, had a 96.9% fully vaccination rate . Even soUp to date, vaccination against COVID-19 is effective under the existence of breakthrough infection and viral variants, and the combination of vaccination and NPIs could achieve successful control of COVID-19 in the future.


Enhancing tuberculosis (TB) prevention and care in a post-COVID-19-pandemic phase will be essential to ensure progress towards global TB elimination. In low-burden countries, asylum seekers constitute an important high-risk group. TB frequently arises post-immigration due to the reactivation of latent TB infection (LTBI). Upon-entry screening for LTBI and TB preventive treatment (TPT) are considered worthwhile if targeted to asylum seekers from high-incidence countries who usually present with higher rates of LTBI. However, there is insufficient knowledge about optimal incidence thresholds above which introduction could be cost-effective. We aimed to estimate, among asylum seekers in Germany, the health impact and costs of upon-entry LTBI screening/TPT introduced at different thresholds of country-of-origin TB incidence.We sampled hypothetical cohorts of 30–45 thousand asylum seekers aged 15 to 34 years expected to arrive in Germany in 2022 from cohorts of first-time applicants observed in 2017–2019. We modelled LTBI prevalence as a function of country-of-origin TB incidence fitted to data from observational studies. We then used a probabilistic decision-analytic model to estimate health-system costs and quality-adjusted life years (QALYs) under interferon gamma release assay (IGRA)-based screening for LTBI and rifampicin-based TPT . Incremental cost-effectiveness ratios (ICERs) were calculated for scenarios of introducing LTBI screening/TPT at different incidence thresholds.We estimated that among 15- to 34-year-old asylum seekers arriving in Germany in 2022, 17.5%  will be latently infected. Introducing LTBI screening/TPT above 250 per 100,000 country-of-origin TB incidence would gain 7.3 (2.7–14.8) QALYs at a cost of €51,000  per QALY. Lowering the threshold to ≥200 would cost an incremental €53,300  per additional QALY gained relative to the ≥250 threshold scenario; ICERs for the ≥150 and ≥ 100 thresholds were €55,900  and €62,000 , respectively, using the next higher threshold as a reference, and considerably higher at thresholds below 100.LTBI screening and TPT among 15- to 34-year-old asylum seekers arriving in Germany could produce health benefits at reasonable additional cost  if introduced at incidence thresholds ≥100. Empirical trials are needed to investigate the feasibility and effectiveness of this approach. Progress towards the global targets for eliminating tuberculosis (TB), an infectious disease that claimed an estimated 1.4 million lives in 2019, is seriously undermined by the concurrent COVID-19 pandemic and associated measures for its containment. Increases in the TB burden due to lockdowns and disruptions of healthcare service delivery have been predicted [In countries with a low TB burden, immigrants including asylum seekers carry a disproportionate burden of TB and therefore represent a key target group for prevention and care strategies . GuideliMycobacterium tuberculosis (M. tb) infection [M. tb infection among immigrants and providing TB preventive treatment (TPT) to those with LTBI may be cost-effective for TB control depending on local contexts [A considerable burden of incident TB among immigrants arises in the years following immigration –11, likenfection , 12. Thecontexts –15. Chilcontexts .Targeting LTBI screening and TPT towards individuals arriving from countries with higher TB incidence has been recommended as these are expected to have a higher prevalence of LTBI , 16. HowHere, we present a model-based cost-effectiveness analysis of upon-entry screening among asylum seekers arriving in Germany, the country with the highest number of asylum seekers in the European Union (EU) in recent years . Rates oWe aimed to estimate the health impact and costs of LTBI screening and TPT among asylum seekers of adolescent and young adult age (15 to 34 years) if implemented alongside the current mandatory CXR-based screening policy. A targeted approach was assumed, under which asylum seekers would be eligible for LTBI screening and TPT if they originated from a country with a high TB incidence. We aimed to explore the cost-effectiveness at different thresholds at which countries of origin would be considered ‘high incidence’ and asylum seekers would thus be eligible for LTBI screening and TPT.IfSG), regardless of country of origin, before being admitted to common housing/reception centers. Children, young adolescents aged < 15 years and pregnant women are primarily evaluated for M. tb infection either via tuberculin skin test (TST) or interferon gamma release assay (IGRA), whereas asylum seekers aged 15 years and older (who are not pregnant) are screened for TB disease via clinical and CXR examination. Evaluation for M. tb infection and TPT are recommended for the management of individuals exposed to infectious TB [Germany is the EU country with the largest population (83.2 million in 2020). In 2015/2016, approximately 1.16 million first-time asylum applicants were registered, accounting for 47% of applications in the European Union . This nuWe developed a probabilistic decision-analytic model using R statistical software (version 4.0.3). The model draws multiple random samples from the population of 15- to 34-year-old asylum applicants from 110 countries of origin who were registered in Germany between 2017 and 2019 [M. tb infection would be introduced among 15- to 34-year-old asylum seekers in addition to clinical and CXR examinations for TB disease that are currently mandatory for all asylum seekers aged 15 years and above. We investigated different scenarios under which IGRA-based screening would be restricted to asylum seekers arriving from countries of origin above a specific TB incidence threshold, based on 2019 World Health Organization (WHO) incidence estimates [We assumed that IGRA-based screening for stimates . FollowiM. tb infection (IGRA-positive), and in whom no diagnosis of active TB is established, would be considered latently infected and offered TPT. We assumed that TPT would consist of a short-course regimen of daily rifampicin (600 mg) for four months. The rationale for considering this regimen is that it is recommended and available for TPT in Germany [Individuals who screen positive for  Germany  and by t Germany . It is s(Box) Main assumptions for the study.A schematic of the decision-tree model is shown in Fig. Data about the prevalence of LTBI among asylum seekers arriving in Germany and other European countries are limited to date. We considered findings from an earlier literature review published in 2010  and, in M. tb infection among asylum seekers with probabilities similar to those estimated for individuals with active TB in the countries of origin. No preventive effect of TPT was assumed for individuals infected with rifampicin-resistant M. tb. Table IGRA results among asylum seekers with and without LTBI depend on test accuracy. We obtained estimates for IGRA sensitivity and specificity from two meta-analyses , 32. We We estimated total costs under the base-case scenario  and each incidence threshold scenario in 2020 Euro (€), adopting a German healthcare-system perspective. Cost estimates reflect resources for administering and processing IGRA-based tests, counselling and provision of TPT, and management of TPT-related adverse events in the German public healthcare system Table . We did We estimated the health impact of LTBI screening and TPT by calculating quality-adjusted life years (QALYs) that would be gained through the intervention . QALYs eWe estimated incremental cost-effectiveness ratios (ICERs) denoting the extra costs incurred per additional QALY gained for a particular incidence threshold, with respect to the next higher incidence threshold. ICERs are thus equivalent to the incremental cost per QALY gained for a specific stratum of country-of-origin TB incidence  compared to no LTBI screening at all. Germany does not specify a single threshold for the cost per QALY gained to be considered cost-effective . We estiWe conducted one-way sensitivity analyses to assess how sensitive our results were to the specified input parameter ranges. Sensitivity analysis refers to the incremental cost-effectiveness of introducing LTBI screening and TPT at an incidence threshold of ≥150 per 100,000 country-of-origin TB incidence.While the primary analysis does not take transmission into account, we conducted secondary analysis for which we considered additional health benefits to accrue from the prevention of onward transmission from asylum seekers with LTBI reactivation. We assumed a simple scenario in which secondary TB would arise in contacts of equal age compared with the index case (average age at LTBI reactivation: 31 years), an average serial interval of 8–10 years, and similar reductions in quality of life due to TB, and case fatality, compared with those estimated for the index case  individuals. Of these, 346 (159–592) will develop incident TB due to the reactivation of LTBI post-immigration.We estimate that among 15- to 34-year-old asylum seekers arriving in Germany in 2022, 17.5%  will be latently infected with An overview of estimated health-system costs, TB cases prevented, and QALYs gained under different incidence thresholds at which asylum seekers would become eligible for LTBI screening and TPT is shown in Table The highest incremental health benefit was estimated for the ≥150 incidence threshold. Here, 11.8 (4.4–23.7) additional QALYs would be gained at marginally higher incremental cost per QALY, relative to the ≥200 incidence threshold. The same threshold would allow to detect an estimated 44% (35–52%) of all LTBIs and prevent 16% (10–23%) of incident TB cases expected among all 15- to 34-year-old asylum seekers in the absence of LTBI screening/TPT.If healthcare services were willing to pay an extra €81,100 per additional QALY gained (~twice the 2020 GDP per capita for Germany), an incidence threshold ≥250 would have a probability of 87% of being cost-effective, relative to no LTBI screening / no TPT  suggesting that LTBI screening and TPT are unlikely to be cost-effective unless targeted to asylum seekers from countries with higher TB incidence, consistent with findings from a similar analysis in the United Kingdom . The higM. tb, for example to child and adult household contacts. Secondary analyses in which we recalculated incremental cost-effectiveness ratios for varying average numbers of secondary TB cases showed that these indirect benefits could be relevant for determining cost-effectiveness of LTBI screening and TPT among asylum seekers. In an earlier study conducted in Berlin [Our estimates of health benefits and costs represent conservative estimates that do not take into account additional health benefits and savings due to reductions in onward transmission of n Berlin , we founWe assumed that LTBI screening and TPT would be offered in addition to clinical and CXR-based examinations that are currently mandatory for all asylum seekers aged 15 years and older upon-entry to Germany. Whether the current status quo of screening for TB disease is cost-effective for TB, and whether LTBI screening and TPT should therefore complement or replace the disease-based screening approach is currently not known. A recent modelling study of CXR-based screening in one of the German federal states  suggesteLow rates of initiating and completing preventive treatment are important concerns ahead of introducing LTBI screening among asylum seekers  as not eOur study constitutes a first step towards a better understanding of the benefits and costs of LTBI screening and TPT among asylum seekers in Germany, a country that traditionally relies on CXR-based screening for TB disease. We note the following limitations.Our model is based on numbers of asylum seekers registered in Germany in recent years, their distribution by country-of-origin TB incidence, and recent TB-related cost estimates specific for Germany. There is currently a lack of country-specific data about the prevalence of LTBI, the rate of LTBI reactivation, losses in quality of life due to TB and case fatality among asylum seekers. Given the sparsity of studies and data in the German context, we relied, where necessary, on estimates from studies conducted elsewhere in Europe. There is considerable uncertainty around parameter estimates. We accounted for this uncertainty by specifying wide uncertainty ranges at probabilistic analysis. We note that our model could be easily updated to consider estimates from future research necessary to improve the validity and precision of the parameter estimates.Total numbers of asylum seekers considered for this study reflect declining trends observed in the years prior to the COVID-19 pandemic. Lockdowns, travel restrictions and suspensions of asylum-related activities during the COVID-19 pandemic have resulted in substantial additional decreases in asylum applications in Germany and other European countries  with conWe modelled variation in LTBI prevalence by country of origin, taking several European studies into account. We note considerable heterogeneity in LTBI prevalence estimates within and between these studies, suggesting that factors other than country of origin have contributed to the observed prevalence of LTBI among asylum seekers. WHO estimates of country-level TB incidence may not accurately reflect the risk of LTBI among asylum seekers; infection may also happen after leaving the country of origin . While uM. tb infection via IGRA or TST is already recommended as part of their screening for TB disease in Germany [Finally, we focused our analysis on asylum seekers aged 15 to 34 years. We did not include children and young adolescents aged < 15 years since their evaluation for  Germany . Also, t Germany  showed tOur findings suggest that introducing LTBI screening and TPT among 15- to 34-year-old asylum seekers upon entry to Germany could produce health benefits and reasonable costs if targeted to individuals from countries with a high TB incidence. An incidence threshold of 150 per 100,000 population would allow for the detection of a reasonable fraction of LTBI and produce considerable health benefits at low incremental costs compared to higher thresholds. Additional empirical research is needed to improve our estimates and provide further guidance for policy making. This includes studies of LTBI prevalence among asylum seekers upon entry, stratified by country-of-origin TB incidence, and the rate of TB in the years post-entry. Our results support the conduct of pragmatic trials to assess the feasibility, effectiveness and cost-effectiveness of LTBI screening and TPT among asylum seekers. Alternative short-term preventive treatment regimens, such as rifapentine/isoniazid daily for 1 month  or weeklIf well implemented, LTBI screening and TPT among asylum seekers could complement current efforts to address and reduce the risk of TB among immigrants  and othe


Companion animals are susceptible to SARS-CoV-2 infection and sporadic cases of pet infections have occurred in the United Kingdom. Here we present the first large-scale serological survey of SARS-CoV-2 neutralising antibodies in dogs and cats in the UK. Results are reported for 688 sera  collected by a large veterinary diagnostic laboratory for routine haematology during three time periods; pre-COVID-19 (January 2020), during the first wave of UK human infections (April-May 2020) and during the second wave of UK human infections (September 2020-February 2021). Both pre-COVID-19 sera and those from the first wave tested negative. However, in sera collected during the second wave, 1.4% (n=4) of dogs and 2.2% (n=2) cats tested positive for neutralising antibodies. The low numbers of animals testing positive suggests pet animals are unlikely to be a major reservoir for human infection in the UK. However, continued surveillance of in-contact susceptible animals should be performed as part of ongoing population health surveillance initiatives. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in Wuhan, China at the end of 2019 [Although initially there were only sporadic cases of infection in cats and dogs –5, thereCanine and feline sera used in this study were obtained from the UK Virtual Biobank, which uses health data from commercial diagnostic laboratories participating in the Small Animal Veterinary Surveillance Network (SAVSNET) to target left over diagnostic samples in the same laboratories for enhanced phenotypic and genomic analyses . All sam2, fixed with 10% formalin and stained with 0.05% crystal violet solution. PRNT80 was determined by the highest dilution with 80% reduction in plaques compared to the control. Samples with detectable neutralising antibody titre were repeated as technical replicates for confirmation. Where titres differed between technical replicates, the lowest dilution was reported.Serum samples were screened for SARS-CoV-2 neutralising antibodies using the plaque reduction neutralisation test (PRNT) as previously described , with thst January 2020 [A total of 732 samples were received from the diagnostic laboratory and tested for SARS-CoV-2 neutralising antibodies. Linking of data to the samples found that 22 samples were duplicates (duplicate samples gave the same result in each replicate and are therefore reported as one sample). Seven samples were from animals with non-UK postcodes, two samples did not have species data, two samples were received as dogs but were actually from cats and were collected outside the two time periods of cat sample collection and eleven samples were missing postcodes; these samples were excluded. Results are therefore reported for 688 sera  of which 558  were collected during the SARS-CoV-2 pandemic and 130  were collected from animals before the first confirmed human case in the UK (21ary 2020 ) - pre-CSARS-CoV-2 emerged in humans in China late in 2019, rapidly spreading across the world. tudies of companion animals from several countries have shown that they too can be infected with the virus. In the UK, there are sporadic reports of infection in cats and dogs , 29, howSera from two time points during the pandemic were analysed. Sera collected early in the pandemic, during March and April 2020, from both cats and dogs were negative for neutralising antibodies. Previous studies using European samples have shown a low level of infection, highest in Italy, where 3.3% 15/451) of dog sera and 5.8% (11/191) cat sera collected between March and May 2020 had measurable neutralising antibody titres /451 of d, and witIn sera collected later in the pandemic, 4/287 (1.4%) dogs and 2/90 (2.2%) cats tested positive. Positive dog samples were collected in November 2020 and January and February of 2021. Positive cats were collected in January 2021. This is again broadly in line with a recent German survey conducted from September 2020 to February 2021, showing a seroprevalence of 1.36%, that the authors concluded corresponded with the rise of reported cases in the human population, and was suggestive of ongoing transmission from owners to their cats .st January 2020 [Cats and dogs can be infected with other coronaviruses, leading to the possibility that SARS-CoV-2 neutralising antibodies in cats and dogs may result from previous infection with a different virus. We and others have previously demonstrated a lack of cross-reactivity between SARS-CoV-2 and samples containing antibodies to feline coronavirus (FCoV), canine enteric coronavirus (CeCoV) and canine respiratory coronavirus (CRCoV) , 15, 16;ary 2020 ). All prary 2020 , suggestHere we made use of samples collected from a commercial diagnostic laboratory contributing data to a voluntary national surveillance scheme (SAVSNET) to efficiently test for evidence of prior SARS-CoV-2 infection in UK cats and dogs. The major limitations of such a system are the relatively sparse data available for each sample such that individual animals, that are not identifiable, may have been sampled twice or have come from the same household. In addition, such samples lack detailed information on the health of the animals and whether they were from a COVID-19-positive household. However, acquiring such samples from the UK Virtual Biobank, offers a responsive resource for studying national patterns of disease in UK pets .We report here the detection of SARS-CoV-2 neutralising antibodies during the second wave of human infections in the UK. Other groups have previously reported that cats and dogs can become infected, likely through their interactions with humans. Although animal-to-animal transmission has been reported, for example on mink farms and in experimental infections , 22, 34,


With the continuation of the COVID-19 pandemic, shifting active COVID-19 care from short-term acute care hospitals (STACHs) to long-term acute care hospitals (LTACHs) could decrease STACH census during critical stages of the pandemic and maximize limited resources.This study aimed to describe the characteristics, clinical management, and patient outcomes during and after the acute COVID-19 phase in an LTACH in the Northeastern United States.This was a single-center group comparative retrospective analysis of the electronic medical records of patients treated for COVID-19–related impairments from March 19, 2020, through August 14, 2020, and a reference population of medically complex patients discharged between December 1, 2019, and February 29, 2020. This study was conducted to evaluate patient outcomes in response to the holistic treatment approach of the facility.P=.04). There were similar proportions of males and females between cohorts (P=.38); however, the proportion of non-White/non-Caucasian patients was higher in the COVID-19 cohort than in the reference cohort . The mean length of stay in the COVID-19 cohort was similar to that in the reference cohort . Interestingly, a positive correlation between patient age and length of stay was observed in the COVID-19 cohort , but not in the reference cohort. Ambulation assistance scores improved in both the reference and COVID-19 cohorts from admission to discharge (P<.001). However, the mean assistance score was greater in the COVID-19 cohort than in the reference cohort at discharge . Similarly, the mean change in gait distance was greater in the COVID-19 cohort than in the reference cohort . Of the 16 patients mechanically ventilated at admission, 94% (15/16) were weaned before discharge (mean 11.3 days). Of the 75 patients admitted with a restricted diet, 75% (56/75) were discharged on a regular diet.Of the 127 total COVID-19 admissions, 118 patients were discharged by the data cutoff. At admission, 29.9% (38/127) of patients tested positive for SARS-CoV-2 infection. The mean age of the COVID-19 cohort was lower than that of the reference cohort (63.3, 95% CI 61.1-65.4 vs 65.5, 95% CI 63.2-67.8 years; The majority of patients treated at the LTACH for severe COVID-19 and related complications benefited from coordinated care and rehabilitation. In comparison to the reference cohort, patients treated for COVID-19 were discharged with greater improvements in ambulation distance and assistance needs during a similar length of stay. These findings indicate that other patients with COVID-19 would benefit from care in an LTACH. Patients hospitalized with severe COVID-19 caused by SARS-CoV-2 infection may face a long hospital length of stay (LOS), making it unreasonable to expect a direct discharge to home [Long-term acute care hospitals (LTACHs) can provide these postacute care and rehabilitation services in the post-COVID phase. They can also provide an alternative to conventional short-term acute care hospitals (STACHs) for active COVID-19 treatment, thereby reducing the burden on the STACH system when resources are already limited ,4.LTACHs are certified acute care hospitals equipped to provide long-term (average LOS of 25-28 days) acute level care to medically complex patients. LTACHs are able to treat patients who require a higher level of care than what other rehabilitation facilities may be able to provide. Medically complex patients are often transferred to the LTACH setting as soon as they are found to be hemodynamically stable. Once at the LTACH, an interdisciplinary care plan, including continued treatment for underlying conditions and targeted holistic rehabilitation, is started. While it is the hope that each patient is able to be discharged to home, patients may also be transferred to other facilities such as skilled nursing facilities to continue their recovery if necessary.It has been proposed that patients with severe COVID-19 may benefit from the inpatient respiratory, functional, and neurological rehabilitation provided at LTACHs . Early rHere, we report on patient characteristics, clinical management strategies, and patient outcomes from an LTACH caring for patients with severe COVID-19, as well as make comparisons with the typical medical population cared for at the LTACH.This retrospective study was conducted at Gaylord Specialty Healthcare, a rehabilitation-focused LTACH in the Northeastern United States. COVID-19–related data were collected from March 19, 2020, through August 14, 2020. The study data are for 117 individuals who were treated in regional STACHs for acute COVID-19 and then discharged to the LTACH for post–COVID-19 care and rehabilitation. Due to STACH readmissions for acute decompensation, 8 of the 117 individuals accounted for 10 additional admissions, for a total of 127 admissions. Of the 127 total admissions/readmissions, there were 118 total discharges by the data cutoff of August 14, 2020, with 9 admissions remaining as active patients.Data from a historical reference cohort (control population) consisting of 157 individuals discharged from December 1, 2019, through February 29, 2020, were also collected. Similar to the COVID-19 cohort, some individuals required temporary readmission to a STACH before being readmitted to the LTACH setting. Ten of the 157 individuals accounted for 13 additional readmissions in the reference cohort, for a total of 170 admissions and discharges. Although this led to uneven population sizes, the 2-month time frame for the historical control was selected to normalize potential seasonal variances and minimize the effect of annual regulatory and insurance changes.When describing patient demographics, we compared the 117 individual patients admitted for COVID-19–related rehabilitation and the 157 individuals admitted during the reference time frame. When comparing LOS, we used the LOS for the 118 total COVID-19 discharges and the LOS for the 170 total reference cohort discharges. For all other comparisons, we used data from the total admissions or subpopulations.Similar to arrangements made by other LTACH facilities with regional hospitals, patients who required postacute care for COVID-19–related issues and those who were still SARS-CoV-2 positive were accepted from STACHs to help unburden those facilities . AdditioPatients with active or prior SARS-CoV-2 infection were housed on separate floors of the hospital, similar to the practical arrangements of other postacute care facilities . PatientPersonal protective equipment protocols for the COVID-19 cohort included the use of face shields, N95 particulate respirator masks or duck bill surgical masks, scrub caps, and boot covers, as well as uniform laundering at an outside facility. Powered air-purifying respirators were available if needed. Due to a facility shortage of N95 respirator masks , these masks were sterilized for reuse by an outside facility.To decrease personnel exposure to patients with suspected or confirmed SARS-CoV-2 infection and conserve personal protective equipment, we developed multidisciplinary “COVID-19 teams” responsible for patient isolation, testing, implementation of droplet precautions, and cluster care. Further, a dedicated respiratory therapist and intubation box were used to treat patients with active SARS-CoV-2 infection requiring mechanical ventilation or having a tracheostomy.Using standardized measures and functional assessments, interdisciplinary clinical teams evaluated patients to determine functional impairments at admission. When applicable, a speech-language pathologist assessed patients for voicing, swallowing, and cognitive-communication impairments. Patients were mobilized throughout the day, including chair positioning of the bed, transfer to a bedside chair, and other exercises/ambulation as appropriate.Within 24 hours of admission, patients with a tracheostomy were assessed for in-line speaking valve use. As patients progressed with the speaking valve, they were transitioned to tracheostomy capping and placed on the decannulation protocol . When apSARS-CoV-2–positive patients completed self-directed exercises in their rooms, were seen for individual or co-treatment sessions in their rooms, and, once SARS-CoV-2 negative, participated in group pulmonary exercise therapy and education classes.Patients who were desaturating or acutely decompensating were placed in the prone position by a multidisciplinary team . Prior to placing patients in the prone position, staff participated in training sessions on how to safely prone and reposition patients, manage leads and lines, and perform cardiopulmonary resuscitation while in the prone position. Patients who were functionally capable or were previously placed in the prone position during acute care, were educated on how to safely put themselves in the prone position and encouraged to do so when appropriate.Many patients in the COVID-19 cohort presented with cognitive-communication deficits, potentially as a result of COVID-19–induced hypoxia, prolonged intubation, or sedation . When apFor the purpose of this study, the functional communication measure scores were used to assign an overall cognitive-communication status, including the following: unable to assess, profound impairment, severe impairment, moderate-severe impairment, moderate impairment, mild-moderate impairment, mild impairment, within functional limits, or baseline. To facilitate statistical analysis, these statuses were then given a numerical value ranging from 1 (unable to assess) to 9 (baseline cognition). Due to the retrospective nature of the study, similar values were not readily available for the reference cohort and were not included.Due to the correlation between prolonged intubation and dysphagia, speech-language pathology interventions also targeted swallowing dysfunction . DysphagAt admission, physical therapists evaluated patient ambulatory status by assessing functional ability and gait distance. Patients received standard individualized physical therapy, and their gait quality and distance were challenged for progression as tolerated. Hypotension or tachycardia was present in some patients in the COVID-19 cohort. For these individuals, therapy was aimed at improving tolerance and progression. Functional Independence Measure (FIM) assistance level scores and gait distance were used to describe the functional ability of patients throughout recovery. With a mean interrater reliability ranging from 0.89 to 1.00, the FIM is a 2-domain  18-item assessment. This measure uses a 7-point ordinal scale to measures the amount of assistance provided by the therapist during treatment -20. HereData were analyzed using GraphPad Prism version 9.0.0 (GraphPad Software). Prior to analysis, data were tested for normality using the Shapiro-Wilk test. Each data set was found to have one or more nonnormally distributed groups, and nonparametric tests were used accordingly. For hypothesis testing between 2 unpaired groups, the Mann-Whitney rank comparison test was conducted. For paired 2-group testing, the Wilcoxon matched-pairs signed-rank test was conducted. For hypothesis testing between 3 groups, the Kruskal-Wallis analysis of variance (ANOVA) test with the Dunn multiple comparison posthoc test was conducted.To compare the proportions of racial demographics of the reference and COVID-19 cohorts, we subdivided the individuals into either self-reported White/Caucasian or non-White/non-Caucasian  racial demographics. The rationale behind this was 2-fold. First, since the start of the pandemic, there has been a reported disparity in the number of White and non-White individuals being infected with SARS-CoV-2. By comparing these proportions, we wished to determine if this was also reflected in our population. Second, due to their lower representation in our population, individuals who self-reported as bi/multiracial in the COVID-19 cohort did not meet the criteria to conduct reliable chi-square testing across more than 2 groups. We were left with the option to either exclude these individuals or combine them. While combining Asian and bi/multiracial individuals into 1 category would have worked, we opted to combine and compare all non-White/non-Caucasian  individuals to White/Caucasian individuals. Doing this also allowed us to conduct the Fisher exact test, which is preferred to the approximation calculated with chi-square testing. Additionally, the odds ratios (ORs) for the proportions and the respective 95% CIs (Baptiste Pike testing) were calculated. Moreover, the Fisher exact test, ORs, and Baptiste Pike test were used to compare the proportions of male and female individuals between the cohorts.Nonlinear regression analysis was conducted to determine the correlation between 2 conditions using least-squares regression; 95% CIs are reported. An extra sum-of-squares F test was performed to evaluate the calculated slope of each regression against a hypothetical slope of 0.U tests.When data from multiple time points and two or more groups were present, a 2-way mixed effects model ANOVA was used. This was to evaluate for the presence or absence of time effects independent of the cohort, cohort effects independent of time, and the effects of time and cohort combined. The Šídák multiple comparisons test was then used to calculate all in-group and between-group comparisons. Included in this analysis were the admission and discharge values for ambulation assistance  and gait distance travelled. Changes in FIM scores and gait distance were compared using Mann-Whitney This study was written in compliance with our institutional privacy policy, the Health Insurance Portability and Accountability Act, and the standards set by the Declaration of Helsinki. Prior to beginning, this retrospective study was reviewed and given an exempt status by the Gaylord Specialty Healthcare Institutional Review Board.2=0.03, P=.09; P=.84; During the study period, 117 individuals, accounting for 127 total admissions, were admitted for COVID-19 or post–COVID-19 care as described above . COVID-1P=.38), was younger , the COVID-19 cohort  had a similar ratio of males to females .At discharge, the most common discharge destinations of the reference cohort included home with health services , skilled nursing facility , emergent transfer to a STACH , and home without health services . The COVID-19 cohort discharge destinations were similar in nature and included home with health services , skilled nursing facility , home without health services , and emergent transfer to a STACH  . Using c2=0.05; P=.02; 2=0.07; P=.02; 2=0.001; P=.55; Using LOS as a read out for disease severity , regression analyses were performed to determine if patient sex, age, or BMI affected LOS, all of which have been noted to increase the risk of severe or prolonged COVID-19 illness ,24. Exam2=0.001; P=.73; BMI was greater in the COVID-19 cohort than in the reference cohort . Using rP=.23). Given the small number of patients being mechanically ventilated in the reference cohort (n=7), we also compared the COVID-19 cohort wean time to that of all patients for fiscal year 2019  in the LTACH  and found no difference between the 2 groups  required mechanical ventilation and 62.8% (27/43) did not; 93.8% (15/16) of mechanically ventilated patients in the COVID-19 cohort were weaned by the data cutoff. Compared to the reference cohort, the mean ventilator wean time in the COVID-19 cohort tended to be shorter  of admissions were recommended for speech-language pathology evaluation. Of those, 81% (61/75) were admitted with a modified diet or instructions for nothing by mouth or nil per os (NPO). Following a dysphagia evaluation, most patients were upgraded from NPO to a regular consistency diet. At discharge, 75% (56/75) of patients were consuming a regular consistency diet. Further, 49% (37/75) of patients evaluated by a speech-language pathologist were admitted with a tracheostomy, with or without mechanical ventilation, and 73% (27/37) were found to have some form of voicing disorder, including aphonia (13/37), dysphonia (13/37), or dysarthria (1/37). At discharge, only 35% (13/37) of patients had voicing limitations.P<.001; Speech-language pathologists also evaluated patients for cognitive-communication deficits using the modified NOMS scale shown in Due to wheelchair dependence prior to STACH admission, emergent readmission to a STACH, continuing care at the time of data cutoff, and incomplete data collection, complete  gait and functional status data (FIM scores and gait distance) were only available for 99 of 127 total COVID-19 admissions and 90 of 170 reference cohort admissions. At admission, 44% (40/90) of patients in the reference cohort and 53% (52/99) of patients in the COVID-19 cohort were unable to ambulate or required maximum assistance . The majF1,187=335.7; P<.001) on FIM scores, with overall discharge scores (mean=4.498) being greater than admission scores (mean=2.584). Although we also observed a significant interaction effect between time and cohort designation , we did not observe a significant main effect of cohort designation  on FIM scores alone. The pooled mean FIM score of the reference cohort (mean=3.406) was marginally lesser than that of the COVID-19 cohort (mean=3.677).For ambulation FIM scores, the mean ambulation assistance scores increased in both the reference  and COVID-19  cohorts . Two-wayP<.001), further highlighting the main time effect noted in the 2-way mixed effects ANOVA (P=.39) (P=.001)  . This in(P=.001) . TogetheP<.001; We then compared the mean FIM assistance score change from admission to discharge in the 2 groups. The score change was greater in the COVID-19 cohort than in the reference cohort  on gait distance, with the pooled discharge distance (mean=219.3 feet) being greater than the pooled admission distance (mean=35.5 feet). Although a significant interaction effect was observed between time and cohort designation , a significant main effect related to cohort designation  on gait distance was not observed, with the pooled gait distance being marginally lesser in the reference cohort (mean=116.7 feet) than in the COVID-19 cohort (mean=138.1 feet).The same analysis was conducted for gait distance (feet). The mean gait distance increased in both the reference  and COVID-19  cohorts . Two-wayP<.001), further highlighting the main time effect noted in the 2-way mixed effects ANOVA (P=.82) (P=.08).Using the Šídák multiple comparisons test, we again tested to see what in-group and between-group comparisons were significantly different. In-group comparisons for both cohorts showed a significant increase in gait distance between admission and discharge (ts ANOVA . Between (P=.82) . This inP<.001; Further, we compared the mean change in gait distance from admission to discharge in the 2 groups. The gait change was greater in the COVID-19 cohort than in the reference cohort  requiring consultation; 30% were located on the face, usually on both cheeks, with one more severe than the other and having thick eschar development. Conservative treatment without sharp debridement resolved most cases of facial pressure injuries. New injuries were prevented by implementing adhesive foam cushioning to facial pressure areas. Patients were also likely more hemodynamically stable during LTACH care and therefore somewhat less likely to develop pressure injuries.Unilateral and bilateral wrist and foot drop were also observed in some patients, potentially due to prolonged prone positioning in the STACH causing peripheral nerve compression. Patients with wrist drop showed some improvement, though some required orthoses or occupational therapy after discharge. Some COVID-19 patients presented conditions atypical for respiratory diseases, such as neurological findings, peripheral nerve injuries, paresthesia, and cognitive impairment. Neurological symptoms may have resulted from the use of paralytics or prolonged prone positioning during STACH treatment ,25.The emergence of the novel coronavirus SARS-CoV-2 has resulted in a worldwide pandemic with 281 million infections and 5.4 million deaths as of this writing . For othDuring the study period, 93% of patients admitted on mechanical ventilation were weaned, and 96% of patients admitted with a tracheostomy without mechanical ventilation were decannulated. Though many patients had functional limitations and were nonambulatory at admission, the COVID-19 cohort showed significant functional improvement by discharge, including a 149% greater change in gait distance travelled compared to the reference cohort. While both cohorts had similar FIM assistance scores at admission and both improved over time, the FIM assistance scores of the COVID-19 cohort were significantly greater than those of the reference cohort at discharge. Patients receiving speech-language therapy also showed improvements during their LTACH treatment, with 40.5% fewer patients having voicing limitations at discharge and only 28% having residual cognitive-communication deficits. Together, these observations indicate the potential benefits of individualized, focused, and holistic rehabilitation in a population severely affected by COVID-19 .Though not significant, the COVID-19 cohort ventilator wean time (10.4 days) was shorter than historical facility wean times  . Based oIn regard to patient susceptibility and risk for severe COVID-19 illness, we observed a positive correlation between patient age and patient LOS. In contrast to what has been reported, we did not observe a correlation between patient BMI and disease severity/LOS ,24. ThesThe quick progression in cognitive-communication skills during LTACH stay was also likely multifactorial, involving discontinuation of sedatives, improved metabolic status, awareness of deficits, and an ability for patients to carry over compensatory strategies learned in therapy. However, ongoing cognitive-communication impairment is possible in patients who have had COVID-19, and these individuals may benefit from continued therapy services after discharge .. To protect from aerosols when assessing patients with unknown or suspected positive SARS-CoV-2 status, speech-language pathologists should consider the continued use of clear face masks, face shields, and other eye protection during therapy sessions.Many of our patients were admitted on a modified diet or NPO because of their inability to participate in swallowing assessments at acute care, the severity of their medical condition, or limited access to instrumental assessments during speech-language pathology evaluations due to droplet precautions. The prompt advancement of diet in the LTACH setting was mostly the result of clinical swallowing evaluations showing minimal residual weakness within the oropharyngeal swallowing mechanism. Therefore, it is possible to largely rely on clinical swallowing evaluations for patients with COVID-19, thus minimizing the risk of viral exposure by limiting aerosol-generating instrumental assessments . To protPatients also likely received emotional benefit from the formation of inpatient COVID-19 support groups. These groups, facilitated by a physical therapist and a social worker, were a collaborative effort to provide patients who were recovering from COVID-19 with the opportunity to speak with other patients experiencing similar concerns during their hospital course. With guidance from the group facilitators, patients were encouraged to ask questions and share their experiences in an open discussion format, which ultimately generated insightful feedback for the staff on patient care during the pandemic. Conversation topics focused on processing the initial illness onset and acute hospital stay; acknowledging and learning to cope with their physical, respiratory, emotional, and social changes; and preparing for their future after LTACH discharge. Participation was capped at 6 patients per meeting, and multiple meetings were convened as necessary to accommodate all interested patients.a priori power analysis and sample size estimation were not conducted. Further, as this was a single-center study, the findings may or may not fully reflect the expected findings of other LTACHs or similarly structured institutions. Additionally, in an effort to create a reference for comparison of this unique population, a retrospective historical control was used. As such, all outcome measures could not be compared . This also resulted in the population sizes being uneven despite the COVID-19 data being collected over 5 months versus 3 months for the reference.When evaluating these findings, several limitations need to be considered. First, as this was a retrospective study, There is also a possibility that the COVID-19 cohort received treatment at a slightly less intensity due to initial droplet precautions and isolation to the room. However, due to similarities in the baseline status , we are confident the populations were generally comparable as department standards for treatment and therapy doses for medically complex patients were followed in both cohorts.It needs to be considered that the best treatment practices were actively being developed and implemented during the study period. Thus, the first COVID-19 patients admitted and treated may not have benefited from the knowledge gained over time. For example, as testing guidelines, isolation procedures, and intubation and ventilation recommendations changed, so did the treatment practices.This study is strengthened by the breadth of quantitative outcomes and the detailed descriptions of potential presentations and complications that can be expected for patients with COVID-19 being treated in a LTACH setting. The goal of this study was to discuss typical symptom presentation and recovery patterns for the COVID-19 population in the LTACH setting so as to guide treatment planning choices at other similar facilities.Patients cared for at LTACHs typically have complex medical conditions and are at increased risk for infection and fever; thus, there was a pressing need to isolate any potential source of SARS-CoV-2. Despite what symptoms have been described as “typical” COVID-19 symptoms, patients presented with a spectrum of respiratory symptoms, ranging from asymptomatic to respiratory distress. Consequently, all febrile patients were required to undergo SARS-CoV-2 testing and were isolated with droplet precautions until ruled out. With only 1 exception, all non–COVID-19 patients tested negative for SARS-CoV-2 during this time, indicating that our protocols effectively isolated the 37 patients who were admitted with active SARS-CoV-2 infections. Our observation supports preemptive testing in LTACHs and other health care facilities to lower the incidence of SARS-CoV-2 transmission . Given tOne limiting aspect of care during this period of the pandemic was the length of time it took to obtain SARS-CoV-2 test results for patients who were admitted with an active infection, so they could come off droplet precautions, which was over 2 months in many cases . On May It was also evident early on that regular, clear, and transparent communication was, and still is, vital for staff acceptance of the constantly changing situation, guidelines, and personal protective equipment protocols. To support this, department directors and managers devoted time each day to discussing COVID-19–related patient issues. These directors then met weekly with key staff members to further discuss the issues and disseminate information. Further, emails were frequently sent to all employees detailing COVID-19–related changes, statistics, and other topics of interest. In-person communication was also helpful in correcting rumors and serving as a forum for establishing best practices in the ever-changing situation.To alleviate crowded and overwhelmed STACH facilities, we envision the strategic use of LTACHs earlier in a patient’s hospital course to treat and rehabilitate those with severe COVID-19. With a greater understanding of rehabilitation progression, clinical care can be adapted to maximize the recovery of this population.