Detection of SARS-CoV-2 in Cancellous Bone of Patients with COVID-19 Disease Undergoing Orthopedic Surgery: Laboratory Findings and Clinical Applications.

An emerging issue for orthopedic surgeons is how to manage patients with active or previous COVID-19 disease, avoiding any major risks for the surgeons and the O.R. personnel. This monocentric prospective observational study aims to assess the prevalence of SARS-CoV-2 viral RT-PCR RNA in cancellous bone samples in patients with active or previous COVID-19 disease. We collected data about 30 consecutive patients from our institution from January 2021 to March 2021 with active or previous COVID-19 disease. The presence of SARS-CoV-2 in the samples was determined using two different PCR-based assays. Eighteen of the thirty patients included in the study had a positive nasopharyngeal swab at the time of surgery. Twelve patients had a negative nasopharyngeal swab with a mean days since negativization of 138 ± 104 days, ranging from 23 to 331 days. Mean days of positivity to the nasal swab were 17 ± 17. Twenty-nine out of thirty (96.7%) samples were negative for the presence of SARS-CoV-2 RNA. In one sample, low SARS-CoV-2 load (Cycle threshold (Ct) 36.6.) was detected but not confirmed using an additional confirmatory assay. The conducted study demonstrates the absence of the viral genome within the analyzed cancellous bone. We think that the use of personal protection equipment (PPE) to only protect from aerosol produced during surgery, both in active and recovered patients, is not strictly necessary. We think that the use of PPE should not be employed by surgeons and the O.R. personnel to protect themselves from aerosols produced from the respiratory tract. Moreover, we think that our results could represent a valid basis for further studies related to the possibility of bone donation in patients that suffered and recovered from COVID-19.

Patients with Musculoskeletal Disorders Presenting to the Emergency Department: The COVID-19 Lesson.

BACKGROUND: Musculoskeletal disorders (MSKDs) are the most common class of complaints among patients presenting for care in the Emergency Department (ED). There is a non-urgent patient population with musculoskeletal complaints attending ED services that creates a burgeoning waiting list and contributes to overcrowding in Emergency Departments (EDs), which is a major concern worldwide. The recent (Coronavirus disease-19) COVID-19 pandemic is an unprecedented challenge that is revealing the structural and situational strengths and weaknesses of healthcare systems. METHODS: This study retrospectively and prospectively assessed patients presenting to the Emergency Department before and after the COVID-19 outbreak (from 21 February 2019 to 3 May 2019 and from 21 February 2020 to 3 May 2020) with non-traumatic or low-severity musculoskeletal conditions to test the hypothesis that these patients should have access to care outside the ED and that the COVID-19 outbreak has changed patients' care and health perception. RESULTS: A total of 613 patients were identified, and 542 of them (87.56%) participated in a personalized survey. From this number, 81.73% of the total accesses took place in 2019, and only 18.27% of the accesses took place during the first outbreak and lockdown. More than 90% of patients admitted to the ED accessed care during the day shift in both periods. A total of 87.30% of patients presenting to the ED with a MSKD followed their general practitioner's (GP) advice/referral in 2019, and 73.87% did so in 2020. The differences in the means of transport to the ED was statistically significant (p-value 0.002). CONCLUSIONS: The outbreak and lockdown period confirmed that there is an inappropriate use of the ED related to patients with MSKD. However, the ED appears to be the only available solution for these patients. New services and pathways are therefore needed to enhance MSKD management and reduce ED crowding. Additional observational studies shall be developed to confirm and compare our findings with those of various EDs. The main limit of the inferential part of the study is probably due to the small sample of patients in 2020.

The epidemiology of proximal femur fractures during COVID-19 emergency in Italy: a multicentric study.

BACKGROUND AND AIM: After the first Italian case of Covid-19, the Government imposed the complete closure of all areas involved by the spread of the virus to contain transmissions. There was a massive reorganization of Hospitals, a stop of all elective activities and a convertion of many hospitals in "Covid Centers''. AITOG (Associazione Italiana Traumatologia e Ortopedia Geriatrica) conducted a retrospective study on all proximal femur fractures surgeries that occurred in this period, to find out whether the pandemic and the correlated lockdown somehow changed the incidence of these events.  Methods: 10 Italian orthopedic centers were involved in the study. Considering the geographic location, three groups were created (North, Centre and South). The considered period is the Italian "Phase 1" (February 23rd - May 3rd 2020). RESULTS: the cohort is composed of 412 patients, 116 male and 296 female (mean age 81.1 ± 9.1 years). The same period of 2019 has been used as control group, with 558 patients, 156 male and 402 female (mean age 84.2 ± 8.0 years). In 2020 we counted 323 (78.4%) fractures occurred at home, 61 (14.8%) in retirement houses and 28 (6.8%) in different locations. We mainly treated fractures with intramedullary nails (n.237 57.5%). Among all patients we had 46 (11.1%) Covid-19 positive. The mortality rate within 30 days was of 51 patients (12.4%); 23 of these died because of complications related to Covid-19 while 31 of  these were in treatment with anticoagulant/antiaggregant. CONCLUSIONS: AITOG analysis demonstrates a decrease in surgical interventions for proximal femur fractures from 2019 to 2020, a reduction in patients mean age and an increase in trauma occurred in domestic environment. We also registered a consistent difference between the North, Center and South of the Country.

Do standards of care and early outcomes of periprosthetic fractures change during the COVID-19 pandemic? A multicentre study.

BACKGROUND: Periprosthetic fractures (PPFs) are a growing matter for orthopaedic surgeons, and patients with PPFs may represent a frail target in the case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The purpose of this study is to investigate whether hospital reorganisations during the most severe phase of the SARS-CoV-2 pandemic affected standards of care and early outcomes of patients treated for PPFs in Northern Italy. MATERIALS AND METHODS: Data were retrieved from a multicentre retrospective orthopaedics and traumatology database, including 14 hospitals. The following parameters were studied: demographics, results of nasopharyngeal swabs, prevalence of coronavirus disease 2019 (COVID-19), comorbidities, general health status (EQ-5D-5L Score), frailty (Clinical Frailty Scale, CFS), pain (visual analogue scale, VAS), anaesthesiologic risk (American Society of Anaesthesiology Score, ASA Score), classification (unified classification system, UCS), type of operation and anaesthesia, in-hospital and early complications (Clavien-Dindo Classification, CDC), and length of stay (LOS). Data were analysed by means of descriptive statistics. Out of 1390 patients treated for any reason, 38 PPFs were included. RESULTS: Median age was 81 years (range 70-96 years). Twenty-three patients (60.5%) were swabbed on admission, and two of them (5.3%) tested positive; in three patients (7.9%), the diagnosis of COVID-19 was established on a clinical and radiological basis. Two more patients tested positive post-operatively, and one of them died due to COVID-19. Thirty-three patients (86.8%) presented a proximal femoral PPF. Median ASA Score was 3 (range, 1-4), median VAS score on admission was 3 (range, 0-6), median CFS was 4 (range, 1-8), median EQ-5D-5L Score was 3 in each one of the categories (range, 1-5). Twenty-three patients (60.5%) developed post-operative complications, and median CDC grade was 3 (range, 1-5). The median LOS was 12.8 days (range 2-36 days), and 21 patients (55.3%) were discharged home. CONCLUSIONS: The incidence of PPFs did not seem to change during the lockdown. Patients were mainly elderly with comorbidities, and complications were frequently recorded post-operatively. Despite the difficult period for the healthcare system, hospitals were able to provide effective conventional surgical treatments for PPFs, which were not negatively influenced by the reorganisation. Continued efforts are required to optimise the treatment of these frail patients in the period of the pandemic, minimising the risk of contamination, and to limit the incidence of PPFs in the future. LEVEL OF EVIDENCE: IV.

Early mortality in hip fracture patients admitted during first wave of the COVID-19 pandemic in Northern Italy: a multicentre study.

BACKGROUND: Treatment of hip fractures during the coronavirus disease 2019 (COVID-19) pandemic has posed unique challenges for the management of COVID-19-infected patients and the maintenance of standards of care. The primary endpoint of this study is to compare the mortality rate at 1 month after surgery in symptomatic COVID-positive patients with that of asymptomatic patients. A secondary endpoint of the study is to evaluate, in the two groups of patients, mortality at 1 month on the basis of type of fracture and type of surgical treatment. MATERIALS AND METHODS: For this retrospective multicentre study, we reviewed the medical records of patients hospitalised for proximal femur fracture at 14 hospitals in Northern Italy. Two groups were formed: COVID-19-positive patients (C+ group) presented symptoms, had a positive swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and received treatment for COVID-19; COVID-19-negative patients (C- group) were asymptomatic and tested negative for SARS-CoV-2. The two groups were compared for differences in time to surgery, survival rate and complications rate. The follow-up period was 1 month. RESULTS: Of the 1390 patients admitted for acute care for any reason, 477 had a proximal femur fracture; 53 were C+ but only 12/53 were diagnosed as such at admission. The mean age was > 80 years, and the mean American Society of Anesthesiologists (ASA) score was 3 in both groups. There was no substantial difference in time to surgery (on average, 2.3 days for the C+ group and 2.8 for the C- group). As expected, a higher mortality rate was recorded for the C+ group but not associated with the type of hip fracture or treatment. No correlation was found between early treatment (< 48 h to surgery) and better outcome in the C+ group. CONCLUSIONS: Hip fracture in COVID-19-positive patients accounted for 11% of the total. On average, the time to surgery was > 48 h, which reflects the difficulty of maintaining normal workflow during a medical emergency such as the present pandemic and notwithstanding the suspension of non-urgent procedures. Hip fracture was associated with a higher 30-day mortality rate in COVID-19-positive patients than in COVID-19-negative patients. This fact should be considered when communicating with patients and/or their family. Our data suggest no substantial difference in hip fracture management between patients with or without COVID-19 infection. In this sample, the COVID-19-positive patients were generally asymptomatic at admission; therefore, routine screening is recommended. LEVEL OF EVIDENCE: Therapeutic study, level 4.

The orthopaedic and traumatology scenario during Covid-19 outbreak in Italy: chronicles of a silent war.

BACKGROUND: From February 21, the day of hospitalisation in ICU of the first diagnosed case of Covid-19, the social situation and the hospitals' organisation throughout Italy dramatically changed. METHODS: The CIO (Club Italiano dell'Osteosintesi) is an Italian society devoted to the study of traumatology that counts members spread in public and private hospitals throughout the country. Fifteen members of the CIO, Chairmen of 15 Orthopaedic and Trauma Units of level 1 or 2 trauma centres in Italy, have been involved in the study. They were asked to record data about surgical, outpatients clinics and ER activity from the 23rd of February to the 4th of April 2020. The data collected were compared with the data of the same timeframe of the previous year (2019). RESULTS: Comparing with last year, overall outpatient activity reduced up to 75%, overall Emergency Room (ER) trauma consultations up to 71%, elective surgical activity reduced up to 100% within two weeks and trauma surgery excluding femoral neck fractures up to 50%. The surgical treatment of femoral neck fractures showed a stable reduction from 15 to 20% without a significant variation during the timeframe. CONCLUSIONS: Covid-19 outbreak showed a tremendous impact on all orthopaedic trauma activities throughout the country except for the surgical treatment of femoral neck fractures, which, although reduced, did not change in percentage within the analysed timeframe.

Fractures in Patients With COVID-19 Infection: Early Prognosis and Management. A Case Series of 20 Patients in a Single Institution in Lombardy, Northern Italy.

Fifty-eight percent of the total infections in Italy of COVID-19 were found in northern Italy, in particular, Lombardy. From February 21, 2020, to March 23, 2020, 20 patients with a fracture and a diagnosis of COVID-19 were hospitalized. Demographic data, COVID-19 symptoms, laboratory and radiographic examinations, and treatment methods were recorded. At 1-month follow-up, patients were assessed with the SF-36 score. This case series includes 20 patients (16 women and 4 men), with an average age of 82.35 years (range 59-95). Eleven patients (55%) had a femur fracture. Fourteen patients (70%) had 3 or more comorbidities or previous pathologies. Three patients with severe comorbidities died during the hospitalization. Thirteen patients (65%) had fever, 18 patients (90%) asthenia, and 17 patients (85%) dyspnea. All patients (100%) were given antibiotic therapy, whereas 16 patients (80%) underwent hydroxychloroquine therapy and 8 (40%) were treated with corticosteroids. Eighteen patients (90%) underwent antithromboembolic prophylaxis. Eighteen patients (90%) had lymphopenia. All 20 patients (100%) required noninvasive mechanical ventilation. High D-dimer and polymerase chain reaction values were found in all patients (100%), whereas lactate dehydrogenase was increased in 18 patients (90%). Patients with fractures, especially in the lower limbs, frequently require hospitalization, making these patients more subjected to the risk of COVID-19 infection. COVID-19 infection therefore does not seem to influence the fracture pattern in the elderly population but can lead to health deterioration with increased mortality. The typical symptoms of COVID-19 disease have not changed when associated with a fracture or trauma. Laboratory data are in line with what is reported in recent studies, whereas a more invasive assisted ventilation is associated with a poor prognosis. Finally, analyzing the data obtained from the SF-36 score, significantly lower values emerged when compared with those reported in the literature. LEVEL OF EVIDENCE:: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Unique immunological profile in patients with COVID-19.

The relationship between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and host immunity is poorly understood. We performed an extensive analysis of immune responses in 32 patients with severe COVID-19, some of whom succumbed. A control population of healthy subjects was included. Patients with COVID-19 had an altered distribution of peripheral blood lymphocytes, with an increased proportion of mature natural killer (NK) cells and low T-cell numbers. NK cells and CD8+ T cells overexpressed T-cell immunoglobulin and mucin domain-3 (TIM-3) and CD69. NK cell exhaustion was attested by increased frequencies of programmed cell death protein 1 (PD-1) positive cells and reduced frequencies of natural killer group 2 member D (NKG2D)-, DNAX accessory molecule-1 (DNAM-1)- and sialic acid-binding Ig-like lectin 7 (Siglec-7)-expressing NK cells, associated with a reduced ability to secrete interferon (IFN)γ. Patients with poor outcome showed a contraction of immature CD56bright and an expansion of mature CD57+ FcεRIγneg adaptive NK cells compared to survivors. Increased serum levels of IL-6 were also more frequently identified in deceased patients compared to survivors. Of note, monocytes secreted abundant quantities of IL-6, IL-8, and IL-1ß which persisted at lower levels several weeks after recovery with concomitant normalization of CD69, PD-1 and TIM-3 expression and restoration of CD8+ T cell numbers. A hyperactivated/exhausted immune response dominate in severe SARS-CoV-2 infection, probably driven by an uncontrolled secretion of inflammatory cytokines by monocytes. These findings unveil a unique immunological profile in COVID-19 patients that will help to design effective stage-specific treatments for this potentially deadly disease.