In-hospital mortality prediction using frailty scale and severity score in elderly patients with severe COVID-19

Bajema K.L., Dahl R.M., Evener S.L., Prill M.M., Rodriguez-Barradas M.C., Marconi V.C., Beenhouwer D.O., Holodniy M., Lucero-Obusan C., Brown S.T., Tremarelli M., Epperson M., Mills L., Park S.H., Rivera-Dominguez G., et. al.

The mRNA COVID-19 vaccines (Moderna and Pfizer-BioNTech) provide strong protection against severe COVID-19, including hospitalization, for at least several months after receipt of the second dose (1,2).However, studies examining immune responses and differences in protection against COVID-19-associated hospitalization in real-world settings, including by vaccine product, are limited.To understand how vaccine effectiveness (VE) might change with time, CDC and collaborators assessed the comparative effectiveness of Moderna and Pfizer-BioNTech vaccines in preventing COVID-19-associated hospitalization at two periods (14-119 days and ≥120 days) after receipt of the second vaccine dose among 1,896 U.S. veterans at five Veterans Affairs medical centers (VAMCs) during February 1-September 30, 2021.Among 234 U.S. veterans fully vaccinated with an mRNA COVID-19 vaccine and without evidence of current or prior SARS-CoV-2 infection, serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2 were also compared.Adjusted VE 14-119 days following second Moderna vaccine dose was 89.6% (95% CI = 80.1%-94.5%)and after the second Pfizer-BioNTech dose was 86.0% (95% CI = 77.6%-91.3%);at ≥120 days VE was 86.1% (95% CI = 77.7%-91.3%)for Moderna and 75.1% (95% CI = 64.6%-82.4%)for Pfizer-BioNTech.Antibody levels were significantly higher among Moderna recipients than Pfizer-BioNTech recipients across all age groups and periods since vaccination; however, antibody levels among recipients of both products declined between 14-119 days and ≥120 days.These findings from a cohort of older, hospitalized veterans with high prevalences of underlying conditions suggest the importance of booster doses to help maintain long-term protection against severe COVID-19.†

Dessie Z.G., Zewotir T.

Mortality rates of coronavirus disease-2019 (COVID-19) continue to rise across the world. The impact of several risk factors on coronavirus mortality has been previously reported in several meta‐analyses limited by small sample sizes. In this systematic review, we aimed to summarize available findings on the association between comorbidities, complications, smoking status, obesity, gender, age and D-dimer, and risk of mortality from COVID-19 using a large dataset from a number of studies. Electronic databases including Google Scholar, Cochrane Library, Web of Sciences (WOS), EMBASE, Medline/PubMed, COVID-19 Research Database, and Scopus, were systematically searched till 31 August 2020. We included all human studies regardless of language, publication date or region. Forty-two studies with a total of 423,117 patients met the inclusion criteria. To pool the estimate, a mixed-effect model was used. Moreover, publication bias and sensitivity analysis were evaluated. The findings of the included studies were consistent in stating the contribution of comorbidities, gender, age, smoking status, obesity, acute kidney injury, and D-dimer as a risk factor to increase the requirement for advanced medical care. The analysis results showed that the pooled prevalence of mortality among hospitalized patients with COVID-19 was 17.62% (95% CI 14.26–21.57%, 42 studies and 423,117 patients). Older age has shown increased risk of mortality due to coronavirus and the pooled odds ratio (pOR) and hazard ratio (pHR) were 2.61 (95% CI 1.75–3.47) and 1.31 (95% CI 1.11–1.51), respectively. A significant association were found between COVID-19 mortality and male (pOR = 1.45; 95% CI 1.41–1.51; pHR = 1.24; 95% CI 1.07–1.41), and current smoker (pOR = 1.42; 95% CI 1.01–1.83). Furthermore, risk of mortality among hospitalized COVID-19 patients is highly influenced by patients with Chronic Obstructive Pulmonary Disease (COPD), Cardiovascular Disease (CVD), diabetes, hypertension, obese, cancer, acute kidney injury and increase D-dimer. Chronic comorbidities, complications, and demographic variables including acute kidney injury, COPD, diabetes, hypertension, CVD, cancer, increased D-dimer, male gender, older age, current smoker, and obesity are clinical risk factors for a fatal outcome associated with coronavirus. The findings could be used for disease’s future research, control and prevention.

Herrmann M.L., Hahn J., Walter-Frank B., Bollinger D.M., Schmauder K., Schnauder G., Bitzer M., Malek N.P., Eschweiler G.W., Göpel S.

Background Cohorts of hospitalized COVID-19 patients have been studied in several countries since the beginning of the pandemic. So far, there is no complete survey of older patients in a German district that includes both outpatients and inpatients. In this retrospective observational cohort study, we aimed to investigate risk factors, mortality, and functional outcomes of all patients with COVID-19 aged 70 and older living in the district of Tübingen in the southwest of Germany. Methods We retrospectively analysed all 256 patients who tested positive for SARS-CoV-2 in one of the earliest affected German districts during the first wave of the disease from February to April 2020. To ensure inclusion of all infected patients, we analysed reported data from the public health department as well as the results of a comprehensive screening intervention in all nursing homes of the district (n = 1169). Furthermore, we examined clinical data of all hospitalized patients with COVID-19 (n = 109). Results The all-cause mortality was 18%. Screening in nursing homes showed a point-prevalence of 4.6%. 39% of residents showed no COVID-specific symptoms according to the official definition at that time. The most important predictors of mortality were the need for inpatient treatment (odds ratio (OR): 3.95 [95%-confidence interval (CI): 2.00–7.86], p<0.001) and care needs before infection (non-hospitalized patients: OR: 3.79 [95%-CI: 1.01–14.27], p = 0.037, hospitalized patients: OR: 2.89 [95%-CI 1.21–6.92], p = 0.015). Newly emerged care needs were a relevant complication of COVID-19: 27% of previously self-sufficient patients who survived the disease were not able to return to their home environment after discharge from the hospital. Conclusion Our findings demonstrate the importance of a differentiated view of risk groups and long-term effects within the older population. These findings should be included in the political and social debate during the ongoing pandemic to evaluate the true effect of COVID-19 on healthcare systems and individual functional status.

Singhal S., Kumar P., Singh S., Saha S., Dey A.B.

Few studies have focused on exploring the clinical characteristics and outcomes of COVID-19 in older patients. We conducted this systematic review and meta-analysis to have a better understanding of the clinical characteristics of older COVID-19 patients. A systematic search of PubMed and Scopus was performed from December 2019 to May 3rd, 2020. Observational studies including older adults (age ≥ 60 years) with COVID-19 infection and reporting clinical characteristics or outcome were included. Primary outcome was assessing weighted pooled prevalence (WPP) of severity and outcomes. Secondary outcomes were clinical features including comorbidities and need of respiratory support. Forty-six studies with 13,624 older patients were included. Severe infection was seen in 51% (95% CI– 36-65%, I2–95%) patients while 22% (95% CI– 16-28%, I2–88%) were critically ill. Overall, 11% (95% CI– 5-21%, I2–98%) patients died. The common comorbidities were hypertension (48, 95% CI– 36-60% I2–92%), diabetes mellitus (22, 95% CI– 13-32%, I2–86%) and cardiovascular disease (19, 95% CI – 11-28%, I2–85%). Common symptoms were fever (83, 95% CI– 66-97%, I2–91%), cough (60, 95% CI– 50-70%, I2–71%) and dyspnoea (42, 95% CI– 19-67%, I2–94%). Overall, 84% (95% CI– 60-100%, I2–81%) required oxygen support and 21% (95% CI– 0-49%, I2–91%) required mechanical ventilation. Majority of studies had medium to high risk of bias and overall quality of evidence was low for all outcomes. Approximately half of older patients with COVID-19 have severe infection, one in five are critically ill and one in ten die. More high-quality evidence is needed to study outcomes in this vulnerable patient population and factors affecting these outcomes.

Aliberti M.J., Szlejf C., Avelino‐Silva V.I., Suemoto C.K., Apolinario D., Dias M.B., Garcez F.B., Trindade C.B., Amaral J.R., Melo L.R., Aguiar R.C., Coelho P.H., Hojaij N.H., Saraiva M.D., Silva N.O., et. al.

Background Frailty screening using the Clinical Frailty Scale (CFS) has been proposed to guide resource allocation in acute care settings during the pandemic. However, the association between frailty and coronavirus disease 2019 (COVID-19) prognosis remains unclear. Objectives To investigate the association between frailty and mortality over 6 months in middle-aged and older patients hospitalized with COVID-19 and the association between acute morbidity severity and mortality across frailty strata. Design Observational cohort study. Setting Large academic medical center in Brazil. Participants A total of 1830 patients aged ≥50 years hospitalized with COVID-19 (March–July 2020). Measurements We screened baseline frailty using the CFS (1–9) and classified patients as fit to managing well (1–3), vulnerable (4), mildly (5), moderately (6), or severely frail to terminally ill (7–9). We also computed a frailty index (0–1; frail >0.25), a well-known frailty measure. We used Cox proportional hazards models to estimate the association between frailty and time to death within 30 days and 6 months of admission. We also examined whether frailty identified different mortality risk levels within strata of similar age and acute morbidity as measured by the Sequential Organ Failure Assessment (SOFA) score. Results Median age was 66 years, 58% were male, and 27% were frail to some degree. Compared with fit-to-managing-well patients, the adjusted hazard ratios (95% confidence interval [CI]) for 30-day and 6-month mortality were, respectively, 1.4 (1.1–1.7) and 1.4 (1.1–1.7) for vulnerable patients; 1.5 (1.1–1.9) and 1.5 (1.1–1.8) for mild frailty; 1.8 (1.4–2.3) and 1.9 (1.5–2.4) for moderate frailty; and 2.1 (1.6–2.7) and 2.3 (1.8–2.9) for severe frailty to terminally ill. The CFS achieved outstanding accuracy to identify frailty compared with the Frailty Index (area under the curve = 0.94; 95% CI = 0.93–0.95) and predicted different mortality risks within age and acute morbidity groups. Conclusions Our results encourage the use of frailty, alongside measures of acute morbidity, to guide clinicians in prognostication and resource allocation in hospitalized patients with COVID-19.

Zhang L., Hou J., Ma F., Li J., Xue S., Xu Z.

Coronavirus disease 2019 (COVID-19), defined by the World Health Organization (WHO), has affected more than 50 million patients worldwide and caused a global public health emergency. Therefore, there is a recognized need to identify risk factors for COVID-19 severity and mortality. A systematic search of electronic databases (PubMed, Embase and Cochrane Library) for studies published before September 29, 2020, was performed. Studies that investigated risk factors for progression and mortality in COVID-19 patients were included. A total 344,431 participants from 34 studies were included in this meta-analysis. Regarding comorbidities, cerebrovascular disease (CVD), chronic kidney disease (CKD), coronary heart disease (CHD), and malignancy were associated with an increased risk of progression and mortality in COVID-19 patients. Regarding clinical manifestations, sputum production was associated with a dramatically increased risk of progression and mortality. Hemoptysis was a risk factor for death in COVID-19 patients. In laboratory examinations, increased neutrophil count, decreased lymphocyte count, decreased platelet count, increased C-reactive protein (CRP), coinfection with bacteria or fungi, increased alanine aminotransferase (ALT) and creatine kinase (CK), increased N-terminal pronatriuretic peptide (NT-proBNP), and bilateral pneumonia in CT/X-ray were significantly more frequent in the severe group compared with the non-severe group. Moreover, the proportion of patients with increased CRP and total bilirubin (TBIL) was also significantly higher in the deceased group than in the survival group. CVD, CKD, sputum production, increased neutrophil count, decreased lymphocyte count, decreased platelet count, increased CRP, coinfection with bacteria or fungi, increased ALT and CK, increased NT-proBNP, and bilateral pneumonia in CT/X-ray were associated with an increased risk of progression in COVID-19 patients. Moreover, the proportion of patients with increased sputum production, hemoptysis, CRP and TBIL was also significantly higher in the deceased group.

Booth A., Reed A.B., Ponzo S., Yassaee A., Aral M., Plans D., Labrique A., Mohan D.

Aim COVID-19 clinical presentation is heterogeneous, ranging from asymptomatic to severe cases. While there are a number of early publications relating to risk factors for COVID-19 infection, low sample size and heterogeneity in study design impacted consolidation of early findings. There is a pressing need to identify the factors which predispose patients to severe cases of COVID-19. For rapid and widespread risk stratification, these factors should be easily obtainable, inexpensive, and avoid invasive clinical procedures. The aim of our study is to fill this knowledge gap by systematically mapping all the available evidence on the association of various clinical, demographic, and lifestyle variables with the risk of specific adverse outcomes in patients with COVID-19. Methods The systematic review was conducted using standardized methodology, searching two electronic databases (PubMed and SCOPUS) for relevant literature published between 1st January 2020 and 9th July 2020. Included studies reported characteristics of patients with COVID-19 while reporting outcomes relating to disease severity. In the case of sufficient comparable data, meta-analyses were conducted to estimate risk of each variable. Results Seventy-six studies were identified, with a total of 17,860,001 patients across 14 countries. The studies were highly heterogeneous in terms of the sample under study, outcomes, and risk measures reported. A large number of risk factors were presented for COVID-19. Commonly reported variables for adverse outcome from COVID-19 comprised patient characteristics, including age >75 (OR: 2.65, 95% CI: 1.81–3.90), male sex (OR: 2.05, 95% CI: 1.39–3.04) and severe obesity (OR: 2.57, 95% CI: 1.31–5.05). Active cancer (OR: 1.46, 95% CI: 1.04–2.04) was associated with increased risk of severe outcome. A number of common symptoms and vital measures (respiratory rate and SpO2) also suggested elevated risk profiles. Conclusions Based on the findings of this study, a range of easily assessed parameters are valuable to predict elevated risk of severe illness and mortality as a result of COVID-19, including patient characteristics and detailed comorbidities, alongside the novel inclusion of real-time symptoms and vital measurements.

Jung C., Flaatten H., Fjølner J., Bruno R.R., Wernly B., Artigas A., Pinto B.B., Schefold J.C., Wolff G., Kelm M., Beil M., Sigal S., Heerden P.V., Szczeklik W., Czuczwar M., et. al.

Abstract BackgroundThe COVID-19 pandemic has led highly developed healthcare systems to the brink of collapse due to the large numbers of patients being admitted into hospitals. One of the potential prognostic indicators in patients with COVID-19 is frailty. The degree of frailty could be used to assist both the triage into intensive care, and decisions regarding treatment limitations. Our study sought to determine the interaction of frailty and age in elderly COVID-19 ICU patients.MethodsA prospective multi-centre study of COVID-19 patients ≥ 70 years admitted to intensive care in 138 ICUs from 28 countries was conducted. The primary endpoint was 30-day mortality. Frailty was assessed using the Clinical Frailty Scale (CFS). Additionally, comorbidities, management strategies and treatment limitations were recorded.ResultsThe study included 1346 patients (28% female) with a median age of 75 years (IQR 72-78, range 70-96), 16.3% were older than 80 years and 21% of the patients were frail. The overall survival at 30 days was 59% (95%CI 56-62), with 66% (63-69) in fit, 53% (47-61) in vulnerable and 41% (35-47) in frail patients (p<0.001). In frail patients, there was no difference in 30 day survival between different age categories. Frailty was linked to an increased use of treatment limitations and less use of mechanical ventilation. In a model controlling for age, disease severity, sex, treatment limitations and comorbidities, frailty was independently associated with lower survival.ConclusionFrailty provides relevant prognostic information in elderly COVID-19 patients in addition to age and comorbidities.

Pranata R., Henrina J., Lim M.A., Lawrensia S., Yonas E., Vania R., Huang I., Lukito A.A., Suastika K., Kuswardhani R.A., Setiati S.

National Institute for Health and Care Excellence (NICE) endorsed clinical frailty scale (CFS) to help with decision-making. However, this recommendation lacks an evidence basis and is controversial. This meta-analysis aims to quantify the dose-response relationship between CFS and mortality in COVID-19 patients, with a goal of supplementing the evidence of its use.We performed a systematic literature search from several electronic databases up until 8 September 2020. We searched for studies investigating COVID-19 patients and reported both (1) CFS and its distribution (2) CFS and its association with mortality. The outcome of interest was mortality, defined as clinically validated death or non-survivor. The odds ratio (ORs) will be reported per 1% increase in CFS. The potential for a non-linear relationship based on ORs of each quantitative CFS was examined using restricted cubic splines with a three-knots model.There were a total of 3817 patients from seven studies. Mean age was 80.3 (SD 8.2), and 53% (48-58%) were males. The pooled prevalence for CFS 1-3 was 34% (32-36%), CFS 4-6 was 42% (40-45%), and CFS 7-9 was 23% (21-25%). Each 1-point increase in CFS was associated with 12% increase in mortality (OR 1.12 (1.04, 1.20), p = 0.003; I2: 77.3%). The dose-response relationship was linear (Pnon-linearity=0.116). The funnel-plot analysis was asymmetrical; Trim-and-fill analysis by the imputation of two studies on the left side resulted in OR of 1.10 [1.03, 1.19].This meta-analysis showed that increase in CFS was associated with increase in mortality in a linear fashion.

Berenguer J., Borobia A.M., Ryan P., Rodríguez-Baño J., Bellón J.M., Jarrín I., Carratalà J., Pachón J., Carcas A.J., Yllescas M., Arribas J.R.

ObjectiveTo develop and validate a prediction model of mortality in patients with COVID-19 attending hospital emergency rooms.DesignMultivariable prognostic prediction model.Setting127 Spanish hospitals.ParticipantsDerivation (DC) and external validation (VC) cohorts were obtained from multicentre and single-centre databases, including 4035 and 2126 patients with confirmed COVID-19, respectively.InterventionsPrognostic variables were identified using multivariable logistic regression.Main outcome measures30-day mortality.ResultsPatients’ characteristics in the DC and VC were median age 70 and 61 years, male sex 61.0% and 47.9%, median time from onset of symptoms to admission 5 and 8 days, and 30-day mortality 26.6% and 15.5%, respectively. Age, low age-adjusted saturation of oxygen, neutrophil-to-lymphocyte ratio, estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, dyspnoea and sex were the strongest predictors of mortality. Calibration and discrimination were satisfactory with an area under the receiver operating characteristic curve with a 95% CI for prediction of 30-day mortality of 0.822 (0.806–0.837) in the DC and 0.845 (0.819–0.870) in the VC. A simplified score system ranging from 0 to 30 to predict 30-day mortality was also developed. The risk was considered to be low with 0–2 points (0%–2.1%), moderate with 3–5 (4.7%–6.3%), high with 6–8 (10.6%–19.5%) and very high with 9–30 (27.7%–100%).ConclusionsA simple prediction score, based on readily available clinical and laboratory data, provides a useful tool to predict 30-day mortality probability with a high degree of accuracy among hospitalised patients with COVID-19.

Alves V., Casemiro F., Araujo B., Lima M., Oliveira R., Fernandes F., Gomes A.V., Gregori D.

Keywords: SARS-CoV-2; COVID-19 ; Non Communicable diseases (NCDs). Clinical features; Institucionalized or hospitalized elderly; meta-analisys.

Pepe M., Maroun-Eid C., Romero R., Arroyo-Espliguero R., Fernàndez-Rozas I., Aparisi A., Becerra-Muñoz V.M., Garcìa Aguado M., Brindicci G., Huang J., Alfonso-Rodríguez E., Castro-Mejía A.F., Favretto S., Cerrato E., Albiol P., et. al.

There is limited information on the presenting characteristics, prognosis, and therapeutic approaches of young patients hospitalized for coronavirus disease 2019 (COVID-19). We sought to investigate the baseline characteristics, in-hospital treatment, and outcomes of a wide cohort < 65 years admitted for COVID-19. Using the international multicenter HOPE-COVID-19 registry, we evaluated the baseline characteristics, clinical presentation, therapeutic approach, and prognosis of patients < 65 years discharged (deceased or alive) after hospital admission for COVID-19, also compared with the elderly counterpart. Of the included 5746 patients, 2676 were < 65 and 3070 ≥ 65 years. All risk factors and several parameters suggestive of worse clinical presentation augmented through increasing age classes. In-hospital mortality rates were 6.8% and 32.1% in the younger and older cohort, respectively (p < 0.001). Among young patients, mortality, access to ICU and treatment with IMVwere positively correlated with age. Contrariwise, over 65 years of age this trend was broken so that only the association between age and mortality was persistent, while the rates of access to ICU and IMV started to decline. Younger patients also recognized specific predictors of case fatality, such as obesity and gender. Age negatively impacts on mortality, access to ICU and treatment with IMV in patients < 65 years. In elderly patients only case fatality rate keeps augmenting in a stepwise manner through increasing age categories, while therapeutic approaches become more conservative. Besides age, obesity, gender, history of cancer, and severe dyspnea, tachypnea, chest X-ray bilateral abnormalities, abnormal level of creatinine and leucocyte among admission parameters seem to play a central role in the outcome of patients younger than 65 years.

Joynt G.M., Leung A.K., Ho C., So D., Shum H., Chow F., Yeung A.W., Lee K., Tang G.K., Yan W.

Baden L.R., El Sahly H.M., Essink B., Kotloff K., Frey S., Novak R., Diemert D., Spector S.A., Rouphael N., Creech C.B., McGettigan J., Khetan S., Segall N., Solis J., Brosz A., et. al.

Abstract Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P

Polack F.P., Thomas S.J., Kitchin N., Absalon J., Gurtman A., Lockhart S., Perez J.L., Pérez Marc G., Moreira E.D., Zerbini C., Bailey R., Swanson K.A., Roychoudhury S., Koury K., Li P., et. al.

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

Sundarsingh V., Manoj Kumar R., Kulkarni M., Pradhan D., Rodrigues P.R., Baliga N., Prasad M., Yadav P., Thomas M., Pinto T.E.

Chuansangeam M., Srithan B., Pattharanitima P., Phadungsaksawasdi P.

Background: Early detection of elderly patients with COVID-19 who are at high risk of mortality is vital for appropriate clinical decisions. We aimed to evaluate the risk factors associated with all-cause in-hospital mortality among elderly patients with COVID-19. Methods: In this retrospective study, the medical records of elderly patients aged over 60 who were hospitalized with COVID-19 at Thammasat University Hospital from 1 July to 30 September 2021 were reviewed. Multivariate logistic regression was used to identify independent predictors of mortality. The sum of weighted integers was used as a total risk score for each patient. Results: In total, 138 medical records of patients were reviewed. Four identified variables based on the odds ratio (age, respiratory rate, glomerular filtration rate and history of stroke) were assigned a weighted integer and were developed to predict mortality risk in hospitalized elderly patients. The AUROC of the scoring system were 0.9415 (95% confidence interval, 0.9033–0.9716). The optimized scoring system was developed and a risk score over 213 was considered a cut-off point for high mortality risk. Conclusions: A simple predictive risk score provides an initial assessment of mortality risk at the time of admission with a high degree of accuracy among hospitalized elderly patients with COVID-19.

Santiago González N., García-Hernández M.D., Cruz-Bello P., Chaparro-Díaz L., Rico-González M.D., Hernández-Ortega Y.

The objective was to evaluate the Modified Early Warning Score in patients hospitalized for COVID-19 plus chronic disease. Methods: Retrospective observational study, 430 hospitalized patients with COVID-19 and chronic disease. Instrument, Modified Early Warning Score (MEWS). Data analysis, with Cox and logistic regression, to predict survival and risk. Results: Of 430 patients, 58.6% survived, and 41.4% did not. The risk was: low 53.5%, medium 23.7%, and high 22.8%. The MEWS score was similar between survivors 3.02, p 0.373 (95% CI: −0.225–0.597) and non-survivors 3.20 (95% CI: −0.224–0.597). There is a linear relationship between MEWS and mortality risk R 0.920, ANOVA 0.000, constant 4.713, and coefficient 4.406. The Cox Regression p 0.011, with a risk of deterioration of 0.325, with a positive coefficient, the higher the risk, the higher the mortality, while the invasive mechanical ventilation coefficient was negative −0.757. By providing oxygen and ventilation, mortality is lower. Conclusions: The predictive value of the modified early warning score in patients hospitalized for COVID-19 and chronic disease is not predictive with the MEWS scale. Additional assessment is required to prevent complications, especially when patients are assessed as low-risk.

Corona-Nakamura A.L., Arias-Merino M.J., Morfín-Otero R., Rodriguez-Zavala G., León-Gil A., Camarillo-Escalera J.R., Reyes-Cortés I.B., Valdovinos-Ortega M.G., Nava-Escobar E.R., Villaseñor-Corona A.M., Mireles-Ramírez M.A., Cisneros-Aréchiga A.G., Torre O.P., Pérez-Gómez H.R., Rodríguez-Noriega E.

The aim of this study was to analyze the risk factors and predictors of mortality in a retrospective cohort of patients with coronavirus disease (COVID-19) who presented central nervous system (CNS) manifestations and complications when admitted to hospital. Patients hospitalized from 2020 to 2022 were selected. Demographic variables; history of neurological, cardiological and pulmonary manifestations; comorbidities; prognostic severity scales; and laboratory tests were included. Univariate and adjusted analyses were performed to determine risk factors and predictors of mortality. A forest plot diagram was used to show the strength of the associated risk factors. The cohort included 991 patients; at admission, 463 patients presented CNS damage and of these, 96 hospitalized patients presented de novo CNS manifestations and complications. We estimate a general mortality of 43.7% (433/991) and 77.1% (74/96), for hospitalized patients with de novo CNS manifestations and complications, respectively. The following were identified as risks for the development of hospital CNS manifestations and complications when in hospital: an age of ≥64 years, a history of neurological disease, de novo deep vein thrombosis, D-dimer ≥ 1000 ng/dL, a SOFA ≥ 5, and a CORADS 6. In a multivariable analysis, the mortality predictors were an age of ≥64 years, a SOFA ≥ 5, D-dimer ≥ 1000 ng/mL and hospital CNS manifestations and complications when admitted to hospital. Old age, being hospitalized in critical condition, and having CNS manifestations and complications in hospital are predictors of mortality in hospitalized patients with COVID-19.

van Son J.E., Kahn E.C., van der Bol J.M., Barten D.G., Blomaard L.C., van Dam C., Ellerbroek J., Jansen S.W., Lekx A., van der Linden C.M., Looman R., Maas H.A., Mattace-Raso F.U., Mooijaart S.P., van Munster B.C., et. al.

To study the association between atypical presentation of COVID-19, frailty and adverse outcomes, as well as the incidence of atypical presentation. In this study, an atypical presentation of COVID-19 was significantly associated with frailty. However, patients with an atypical presentation of COVID-19 did not have worse disease outcomes. Physicians need to remain alert for COVID-19 in frail older patients, as they may present without typical complaints. Older patients with COVID-19 can present with atypical complaints, such as falls or delirium. In other diseases, such an atypical presentation is associated with worse clinical outcomes. However, it is not known whether this extends to COVID-19. We aimed to study the association between atypical presentation of COVID-19, frailty and adverse outcomes, as well as the incidence of atypical presentation. We conducted a retrospective observational multi-center cohort study in eight hospitals in the Netherlands. We included patients aged ≥ 70 years hospitalized with COVID-19 between February 2020 until May 2020. Atypical presentation of COVID-19 was defined as presentation without fever, cough and/or dyspnea. We collected data concerning symptoms on admission, demographics and frailty parameters [e.g., Charlson Comorbidity Index (CCI) and Clinical Frailty Scale (CFS)]. Outcome data included Intensive Care Unit (ICU) admission, discharge destination and 30-day mortality. We included 780 patients, 9.5% (n = 74) of those patients had an atypical presentation. Patients with an atypical presentation were older (80 years, IQR 76–86 years; versus 79 years, IQR 74–84, p = 0.044) and were more often classified as severely frail (CFS 6–9) compared to patients with a typical presentation (47.6% vs 28.7%, p = 0.004). Overall, there was no significant difference in 30-day mortality between the two groups in univariate analysis (32.4% vs 41.5%; p = 0.173) or in multivariate analysis [OR 0.59 (95% CI 0.34–1.0); p = 0.058]. In this study, patients with an atypical presentation of COVID-19 were more frail compared to patients with a typical presentation. Contrary to our expectations, an atypical presentation was not associated with worse outcomes.

Barie P.S., Brindle M.E., Khadaroo R.G., Klassen T.L., Huston J.M.

Background: Active and recent coronavirus disease 2019 (COVID-19) infections are associated with morbidity and mortality after surgery in adults. Current recommendations suggest delaying elective surgery in survivors for four to 12 weeks, depending on initial illness severity. Recently, the predominant causes of COVID-19 are the highly transmissible/less virulent Omicron variant/subvariants. Moreover, increased survivability of primary infections has engendered the long-COVID syndrome, with protean manifestations that may persist for months. Considering the more than 600,000,000 COVID-19 survivors, surgeons will likely be consulted by recovered patients seeking elective operations. Knowledge gaps of the aftermath of Omicron infections raise questions whether extant guidance for timing of surgery still applies to adults or should apply to the pediatric population. Methods: Scoping review of relevant English-language literature. Results: Most supporting data derive from early in the pandemic when the Alpha variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) predominated. The Omicron variant/subvariants generally cause milder infections with less organ dysfunction; many infections are asymptomatic, especially in children. Data are scant with respect to adult surgical outcomes after Omicron infection, and especially so for pediatric surgical outcomes at any stage of the pandemic. Conclusions: Numerous knowledge gaps persist with respect to the disease, the recovered pre-operative patient, the nature of the proposed procedure, and supporting data. For example, should the waiting period for all but urgent elective surgery be extended beyond 12 weeks, e.g., after serious/critical illness, or for patients with long-COVID and organ dysfunction? Conversely, can the waiting periods for asymptomatic patients or vaccinated patients be shortened? How shall children be risk-stratified, considering the distinctiveness of pediatric COVID-19 and the paucity of data? Forthcoming guidelines will hopefully answer these questions but may require ongoing modifications based on additional new data and the epidemiology of emerging strains.

Buyukaydin B., Karaaslan T., Uysal O.