key: cord-0778904-z0jq0zl2
authors: Hamilton, Thomas W.; Ingelsrud, Lina Holm; Gutman, Michael; Shearman, Alexander; Gromov, Kirill; Alvand, Abtin; Troelsen, Anders; Parvizi, Javad; Price, Andrew
title: Pre-operative SARS-CoV-2 PCR test at between 48 and 72hours pre-operatively is safe for patients undergoing primary and revision hip and knee arthroplasty – a multicentre international study.
date: 2022-03-17
journal: J Arthroplasty
DOI: 10.1016/j.arth.2022.03.049
sha: cb326f7c12620ecd58f80717131858cf0018f4a6
doc_id: 778904
cord_uid: z0jq0zl2

Introduction Patients undergoing lower limb arthroplasty who are SARS-CoV-2 positive at the time of surgery have a high-risk of mortality. The National Institute for Health and Clinical Care Excellence and the British Orthopaedic Association advise self-isolation for 14-days pre-operatively in patients at high-risk of adverse outcomes due to COVID-19. The aim of the study is to assess whether pre-operative PCR for SARS-CoV-2 could be performed at between 48 and-72 hours pre-operatively with specific advice about minimising the risk of SARS-CoV-2 restricted to between PCR and admission. Methods A multi-centre, international, observational cohort study of 1000 lower limb arthroplasty cases was performed. The dual primary outcomes were thirty-day conversion to SARS-CoV-2 positive and thirty-day SARS-CoV-2 mortality. Secondary outcomes included thirty-day SARS-CoV-2 morbidity. Results Of the 1000 cases, 935 (94%) had a PCR between 48 and 72-hours pre-operatively. All cases were admitted to, and had surgery through a COVID-free pathway. Primary knee arthroplasty was performed in 41% of cases, primary hip arthroplasty in 40%, revision knee arthroplasty in 11% and revision hip arthroplasty in 9%. Six-percent of operations were emergency operations. No cases of SARS-CoV-2 were identified within the first thirty-days. Conclusion Pre-operative SARS-CoV-2 PCR test between 48 and 72-hours pre-operatively with advice about minimising the risk of SARS-CoV-2 restricted to between PCR and admission in conjunction with a COVID-free pathway is safe for patients undergoing primary and revision hip and knee arthroplasty. Pre-operative SARS-CoV-2 PCR test alone may be safe but further, adequately powered studies are required. This information is important for shared decision making with patients during the current pandemic.

Whilst the incidence of coronavirus disease 2019 continues to fluctuate in many nations 29 attention must now be turned to how to maintain the safe provision of non-emergency, routine 30 healthcare, including elective joint arthroplasty [1, 2] . Over the last year the number of patients 31 waiting for joint arthroplasty has grown substantially and waiting lists have lengthened significantly 32 [3] . Delaying arthroplasty is known to be associated with worse outcomes and the number of patients 33 waiting for joint arthroplasty with quality of life scores worse than death has nearly doubled during 34 the current pandemic [4] . 35

For patients and medical staff, the hospital presents a risk of nosocomial infection with, during the 36 first wave (February to July 2020), across the UK between 20 to 25% of all infections estimated to be 37 nosocomial in nature [5, 6] . Improved knowledge about severe acute respiratory syndrome 38 coronavirus 2 (SARS-CoV-2), as well as improved hospital protocols, public health measures and 39 vaccination should all reduce this risk and outcomes of patients with COVID-19 continue to improve. 40

Despite this, for the foreseeable future, SARS-CoV-2 will be present within healthcare systems and we 41 will have to manage the risk that it, and future variants, present. 42 In April 2020 in the UK over three quarters of patients listed for joint arthroplasty did not want to 43 proceed with surgery, and whilst that number has decreased, SARS-CoV-2 still presents a significant 44 risk to this patient population [7] . It is now well established that surgery in patients who test positive 45 for SARS-CoV-2, or who contract SARS-CoV-2 within 30-days, whether this is symptomatic or 46 asymptomatic, is associated with a high risk of adverse outcomes including mortality [8, 9] . In lower 47 limb arthroplasty, prior to the introduction of vaccination, a mortality of between 20 to 40% was 48 reported with the risk of mortality normalising when surgery was performed seven weeks following 49 SARS-CoV-2 diagnosis, provided any symptoms have resolved [8] [9] [10] [11] [12] . To reduce the risk that SARS-50 CoV-2 presents to patients undergoing lower limb joint arthroplasty it is prudent to we ensure that 51 patients having surgery are not infected SARS-CoV-2 at the time of surgery and that they do get 52 infected with SARS-CoV-2 during their recovery. 53

The National Institute for Health and Clinical Care Excellence (NICE) recommends that patients at high 54 risk of adverse outcomes due to COVID-19, and those at high risk of developing the disease, may wish 55 to self-isolate for 14-days with a SARS-CoV-2 polymerase chain reaction (PCR) test taken 48 to 72-56 hours pre-operatively [13] . This is mirrored by the British Orthopaedic Association who advises the 57 use of COVID-free pathways with pre-and post-operative 14-day self-isolation or shielding and PCR 58 for SARS-CoV-2 72-hours pre-operatively [1, 2] . Using a 14-day pre-operative isolation, pre-operative 59 SARS-CoV-2 PCR and a COVID-free pathway previous studies have reported that the rate of nosocomial 60 SARS-CoV-2 infection in patients undergoing elective arthroplasty can be kept under 1% [7, [14] [15] [16] [17] . 61

However independent analysis has found that over 80% of patients cite a 14 day pre-operative 62 isolation period being a barrier to proceeding with surgery [7] . The aim of the study was to assess 63 whether, in patients undergoing primary and revision hip and knee arthroplasty, pre-operative PCR 64 for SARS-CoV-2 could be performed at between 48 and 72-hours pre-operatively with specific advice 65 about minimising the risk of SARS-CoV-2, including the duration of behavioural modification, reduced 66 to between PCR and admission (<72-hours). 67 68

Between 27 April and 10 November 2020 a consecutive series of 1000 patients who were undergoing 70 primary or revision hip or knee arthroplasty on COVID-free pathways following negative PCR for SARS-71

CoV-2 were included. The study was conducted at three tertiary referral centres (Nuffield Orthopaedic 72 Centre, Oxford; Rothman Orthopaedic Institute, Philadelphia; Copenhagen University Hospital 73

Hvidovre, Copenhagen).. Nasopharangeal swabs were taken at two centres (Nuffield Orthopaedic 74

Centre and Rothman Orthopaedic Institute) and oropharangeal at one centre (Copenhagen University 75 Hospital Hvidovre). Patients were excluded from the study if they were identified as SARS-CoV-2 76 positive at the time of surgery. Both planned and emergency cases were included. Planned cases had 77 a PCR performed between 48 and 72-hours prior to admission and following PCR were advised to 78 modify their behaviour to reduce the risk of SARS-CoV-2 infection. Emergency cases required a 79 negative PCR for SARS-CoV-2 prior to admission to the orthopaedic unit but, due to the nature of their 80 presentation did not complete a period of behavioural modification. The study start date varied 81 between institutions due to the fact that it required the implementation of COVID-free pathways 82 involving short duration behavioural modification at each centre. At the Nuffield Orthopaedic Centre 83 and Rothman Orthopaedic Institute following their PCR for SARS-CoV-2 patients were advised to 84 isolate, or shield within their household until their admission, whereas at Copenhagen University 85 Hospital Hvidovre, there was no request for patients to isolate but they were advised to follow the 86 general restrictions (social distancing, washing of hands, ventilation of rooms) set by the Danish Health 87

Authority. The study continued for a consecutive series of 1000 patients equally split across the three 88 study sites. Both elective and emergency cases, who may not have not have a period of behavioural 89 modification pre-operatively, were included provided they have a negative SARS-CoV-2 result before 90 surgery. Emergency arthroplasty cases were included as is all centres these cases were managed by 91 the same surgical teams on the same pathways, as primary cases and as such presented a risk of secondary infection. Other non-trauma, non-lower limb arthroplasty, orthopaedic patients were 93 managed on the same unit on a COVID-free pathway but due to differences in surgical teams, 94 presenting diagnosis and patient demographics they were not included in the analysis. 95

The dual primary outcomes were thirty-day conversion to SARS-CoV-2 positive and thirty-day SARS-96

CoV-2 related mortality. Secondary outcomes included thirty-day SARS-CoV-2 related morbidity 97 including: pneumonia, acute respiratory distress syndrome (ARDS), or unexpected postoperative 98 ventilation. Where patients were diagnosed as COVID-19 positive within the 30-days of surgery we 99 extended the period of follow-up to establish their final outcome. Post-operatively patients were 100 routinely tested by PCR for SARS-CoV-2 if they developed any symptoms of COVID-19 (high 101 temperature, continuous cough and from May 2020 loss of taste or smell), if they were a contact of 102 another patient or staff member who tested positive, on discharge to another hospital or care home. 103

Data was retrieved from Electronic Medical Records (EMR) through review of laboratory data as well 104 as general health assessment performed at follow up clinic four to eight weeks post-operatively. The 105 study was approved by the ethics and audit committee at each site with signed data sharing 106 agreements in place prior to the commencement of the study. 107 108 109

A total of 1000 patients were studied across the three sites. At all centres for planned cases patients 111

were seen prior to their procedure and the risks of COVID-19 and surgery were discussed as part of 112 the informed consent process with a SARS-CoV-2 swab taken 48 to 72-hours prior to admission. Swabs 113 were taken a minimum of 48-hours before admission to ensure that the swab could be processed prior 114

to admission as at times the laboratories were under extreme pressure processing emergency 115 samples. For planned cases admission (935 patients) was on the day of, or in isolated cases day prior 116 to, surgery via a COVID-free pathway with symptomatic screening for COVID-19 on admission. At one 117 site, Oxford, admission was to stand alone, COVID-free, hospital. At the two other sites admission was 118 to a COVID-free, dedicated orthopaedic units within the general hospital which was also treating 119 patients with COVID-19. In addition to planned elective cases in all centres, emergency arthroplasty 120 (65 patients) cases were operated on during the study period and were also included. Fifteen of the 121 65 emergency cases had PCR between 24 and 72-hours prior to admission (typically when transferred 122 from another hospital), when this had not been performed PCR was performed on admission. In 123 addition on admission all emergency cases were screened for symptoms with a negative result of clinical and laboratory assessment required for admission to the orthopaedic unit. A flow chart of 125 study participants is outlined in Figure 1 . The disease burden of SARS-CoV-2 in each country during 126 the study period is outlined in Figure 2 . 127 Patient demographics are recorded in Table 1 Across the three centres no patients swabbed positive for SARS-CoV-2. Across the whole cohort two 141 patients died within 30 days postoperatively, both after undergoing primary elective hip arthroplasty. 142

One patient died as an inpatient on the third post-operative day due to a cardiac arrest. They did not 143 have any clinical symptoms of signs of COVID-19 and did not have a post operative PCR SARS-CoV-2 144 test. One further patient died on the twenty-eighth post-operative day due to pneumonia. They had 145 had three negative oropharyngeal SARS-CoV-2 PCR tests and negative bronchoalveolar sampling and 146 their death was not attributed to COVID-19. Overall 24% of patients received a post operative SARS-147

CoV-2 test within 30 days of surgery (Oxford 22%, Philadelphia 11%, Copenhagen 40%). 148

This study has confirmed that pre-operative SARS-CoV-2 PCR test between 48 and 72-hours pre-150 operatively with specific advice about minimising the risk of SARS-CoV-2 restricted to between PCR 151 and admission (<72-hours) in conjunction with a COVID-free pathway is safe for patients undergoing 152 primary and revision hip and knee arthroplasty. There were no symptomatic or PCR-confirmed cases 153 of SARS-CoV-2 cases within 30-days across the cohort of 1000 patients with 239 patients having post-154 operative PCR for a range of indications. These results are consistent with the results seen previously 155 with a 14-day pre-operative isolation period which demonstrate that elective lower limb arthroplasty 156 can be safely delivered during the COVID-19 pandemic [14] [15] [16] [17] . 157

The key to the COVID free, pathway is to ensure that patients who are infected with SARS-CoV-2 are 158 not admitted to ring fenced wards, do not undergo surgery and in addition it is important that patients 159 undergoing arthroplasty do not contract COVID-19 during their recovery period. Previous reports have 160 demonstrated that up to 18% of orthopaedic trauma patients may be infected with SARS-CoV-2 at 161 initial presentation, particularly those from institutional living accommodation [19] [20] [21] [22] . Early in the 162 COVID-19 pandemic there was reliance on symptomatic assessment to determine SARS-CoV-2 status 163 however it has since been established that substantial proportion of patients may be asymptomatic 164 and as such testing for COVID-19 prior to arthroplasty is now recommended by all major societies [1, 165 2, 13, 23] . Mathematical modelling of the performance of COVID-19 testing to assess for SARS-CoV-2 166 status prior to surgery has suggested a 1 in 1,400 risk of a false negative pre-operative swab result 167 assuming a PCR sensitivity of 71%, specificity of 95%, and disease prevalence of 0.24%. The modelling 168 results match those of our study which identified no cases of SARS-CoV-2 out of 1000 patients 169 admitted following a negative PCR result [24] . 170

Another key component to ensuring the success of a COVID-free pathway is making sure that patients 171 do not acquire COVID-19 as an inpatient. The use of COVID-free sites have been reported to be 172 associated with a lower risk of nosocomial SARS-CoV-2 infection. In our study one site was COVID-free, 173 with the two other sites using dedicated wards to minimise the risk. Both methodologies were 174 associated with a very low risk of COVID-19 transmission and the results of this study suggest either 175 method would be appropriate to reduce nosocomial transmission. Whilst we did not evaluate the 176 influence of length of stay on risk of nosocomial infection previous work has identified that length of 177 stay, particularly greater than 3-days, is a key modifiable risk factor, and it must be noted that all 178 centres in this study minimise length of stay through evidence based protocols covering anaesthetic, 179 surgical and rehabilitation [25] . 180

The natural extension to this work is to question whether there firstly there is any requirement for 181 isolation prior to elective lower limb arthroplasty, and secondly whether PCR for SARS-CoV-2 could 182 instead be performed on admission. The benefit of a short, <72-hour, period of absolute isolation 183 remains uncertain. At Copenhagen University Hospital Hvidovre, where none of the elective patients 184 isolated, but instead followed general restrictions (social distancing, washing of hands, ventilation of 185 rooms), no positive SARS-CoV-2 cases were recorded in elective patients. Likewise, in the 65 186 emergency cases, that had a negative PCR swab, but who had not undergone pre-operative isolation 187 there were no positive SARS-CoV-2 cases. This indicates that pre-operative SARS-CoV-2 PCR test alone may be safe but further, adequately powered studies are required to guide practice as it may be that 189 isolation is not required, or is only required in high risk patient groups such as those in institutional 190 living, or at time of high community prevalence. Until definitive evidence is available about whether 191 patients should isolate or not, it would be prudent to follow a cautious approach that takes into 192 account not only the safety of the patient, but also that of the medical staff and other inpatients who 193 would be potentially be put at risk of nosocomial transmission. 194

Admission PCR is another option to reduce hospital contacts, and the burden on patients. At present 195 the turnaround time for PCR is variable and institution specific and therefore the logistics of 196 performing PCR on admission for all patients may limit its application. The original rationale for PCR 197 at between 48 and 72-hours prior to admission was to permit adequate time for processing of samples, 198 but performing PCR early has several other potential advantages. Firstly, whilst the majority of 199 patients with infection will be identified through pre-operative PCR, some may not. One group is those 200 that are very early in their disease course, where PCR may have a false negative result, which may 201 become positive on serial testing due to a temporally increasing viral load. In this group serial 202 assessment at both between 48 and 72-hours prior, and then again on admission, provides a further 203 opportunity to assess for signs and symptoms of disease. Whilst, in our center, prior to the start of 204 this study, we piloted PCR on admission (in addition to between 48 and 72-hours prior) we found that 205 the results of the admission PCR were not available in time to change the clinical pathway and 206 therefore we moved to assess all patients on admission to the orthopaedic unit by way of clinical 207 screening questions. Another advantage of performing PCR early is that patients positive for SARS-208

CoV-2, and who can't go ahead with their planned surgical procedure, are identified early which is 209 helpful in ensuring that a replacement surgical case can be identified and screened for SARS-CoV-2 in 210 adequate time. An alternative approach to PCR, is to use point of care tests devices such as lateral 211 flow tests which produce results much quicker that laboratory assessment, typically within 30 minutes. 212

Lateral flow tests however have a lower sensitivity and as such, at low prevalence of disease between 213 one half and three quarters of positive results would be false positives, which would lead to a high 214 level of potentially unnecessary cancellations and unnecessary anxiety for all concerned [26] . The 215 outcomes of day of surgery testing have not been reported in elective orthopaedics however the 216 IMPACT-Scot 2 report found the false-negative rate of admission nasopharyngeal PCR swab to be 0% 217 in asymptomatic hip fracture patients, as compared to 2.9% in symptomatic patients indicating that 218 admission testing may be a valid approach [22] . Whilst further work is required to confirm these 219 findings there should be caution about extrapolating these results into current practice, as external 220 factors, such as the behavioural change invoked by scheduled pre-operative testing may also influence 221 J o u r n a l P r e -p r o o f the risk of infection with SARS-CoV-2 in this population and in addition admission testing may not 222 detect SARS-CoV-2 detected in the days immediately preceding admission. 223

The limitations of this study include that the cohort of patients presented represents the experience 224 of three tertiary referral centres operating between the first and second peaks of the COVID-19 225 pandemic. Whilst a lot had been learnt during the first peak, our policies and procedures have 226 continued to evolve to reflect global and local knowledge about the disease. At the time of this report, 227 outside of clinical trials, no patients were vaccinated against COVID-19, but equally the prevalence of 228 new, potentially more infectious variants was low. During the study period the mean national weekly 229 confirmed new COVID-19 cases was 50/100,000, but this ranged from 1/100,000 to 254/100,000 230

weekly new cases varying between study sites (Figure 2) , and the prevalence of disease within the 231 population of patients waiting for lower limb arthroplasty was uncertain [27] . Finally, not all patients 232 underwent screening for SARS-CoV-2 post-operatively, some patients may have been asymptomatic 233 and some patients infection not captured by our EMR or follow up general health assessment and as 234 such the prevalence of infection may be higher than we identified. Whilst asymptomatic infection 235

does not likely present a risk to the individual patient, the risk of spread is uncertain. 236

Overall this study offers important information to patients, surgeons and healthcare providers about 237 the potential level of risk associated with orthopaedic surgery in patients undergoing lower limb joint 238 arthroplasty. Based on the data presented we believe that pre-operative SARS-CoV-2 PCR test 239 between 48 and 72-hours pre-operatively with specific advice about minimising the risk of SARS-CoV-240 2 restricted to between PCR and admission (<72-hours) in conjunction with a COVID-free pathway 241 minimises the risk to patients and that elective lower limb joint arthroplasty can be safely conducted 242 at the present time. As the number of patients, and their relatives, vaccinated against COVID-19 243 increases we expect the risk presented by this disease to decrease, none the less we must be mindful 244 of the local situation with regards to prevalence of disease and the presence of new variants, from 245 which current vaccination may offer less protection. 246

In summary, pre-operative SARS-CoV-2 PCR test between 48 and 72-hours pre-operatively with 248 specific advice about minimising the risk of SARS-CoV-2 restricted to between PCR and admission 249 (<72hours) in conjunction with a COVID-free pathway is safe for patients undergoing primary and 250 revision hip and knee arthroplasty. Pre-operative SARS-CoV-2 PCR test alone may be safe but further, 251 adequately powered studies are required. 8% (84) 61% (690) 29% (294) 1% (13) 17% (55) 55% (184) 26% (88) 2% (7) 1% (2) 64% (212) 34% (114) 2% (5) 8% (27) J o u r n a l P r e -p r o o f

British Orthopaedic Association: Statement regarding NICE COVID-19 rapid guideline on 295 arranging planned care

Growing backlog of planned surgery due to covid-19

The number of patients "worse than death" while waiting for a hip or 299 knee arthroplasty has nearly doubled during the COVID-19 pandemic

Nosocomial infections among patients with COVID-19, SARS and MERS: a rapid 302 review and meta-analysis

The rate of patient deferral and barriers to going forward with elective 305 orthopaedic surgery during the COVID-19 pandemic

Mortality and pulmonary complications in patients undergoing surgery 307 with perioperative SARS-CoV-2 infection: an international cohort study

30-day outcome after orthopaedic surgery in patients assessed as negative for 309 COVID-19 at the time of surgery during the peak of the pandemic

Reinstating elective orthopaedic surgery in the age of COVID-19

Clinical characteristics and outcomes of patients undergoing surgeries during the 314 incubation period of COVID-19 infection

Timing of surgery following SARS-CoV-316 2 infection: an international prospective cohort study

Elective orthopaedic surgery with a designated COVID-19-free pathway 319 results in low perioperative viral transmission rates

The rate of COVID-19 and associated mortality after elective hip and knee 321 arthroplasty prior to cessation of elective services in UK

Safety evaluation of a strategy to restart elective orthopaedic surgery during 324 the de-escalation phase of the COVID-19 pandemic

Elective Orthopaedic Surgery During COVID-19: A Safe Way to Get Back on 326 Track

Clinical Guide to Surgical Prioritisation during the Coronavirus 328 Pandemic

COVID-19 pandemic and hip fractures: impact and lessons learned

Mortality Rates of Patients with Proximal Femoral Fracture in a 332 Worldwide Pandemic: Preliminary Results of the Spanish HIP-COVID Observational Study

The impact of COVID-19 on trauma and orthopaedic patients requiring 335 surgery during the peak of the pandemic: a retrospective cohort study

IMPACT-Scot report on COVID-19 and hip fractures

Resuming Elective Orthopaedic Surgery During the COVID-19 Pandemic: 340 Guidelines Developed by the International Consensus Group (ICM)

The theoretical mortality risk of an asymptomatic patient with a negative 343 SARS-CoV-2 test developing COVID-19 following elective orthopaedic surgery

IMPACT-Restart: the influence of COVID-19 on postoperative mortality 346 and risk factors associated with SARS-CoV-2 infection after orthopaedic and trauma surgery

Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-349

CoV-2 infection