key: cord-1027641-if1wy45r
authors: Kovoor, Joshua G.; Tivey, David R.; Williamson, Penny; Tan, Lorwai; Kopunic, Helena S.; Babidge, Wendy J.; Collinson, Trevor G.; Hewett, Peter J.; Hugh, Thomas J.; Padbury, Robert T. A.; Frydenberg, Mark; Douglas, Richard G.; Kok, Jen; Maddern, Guy J.
title: Screening and Testing for COVID‐19 Before Surgery
date: 2020-08-07
journal: ANZ J Surg
DOI: 10.1111/ans.16260
sha: 95881109189d87adc2993f3e317e16dc1c2383d7
doc_id: 1027641
cord_uid: if1wy45r

BACKGROUND: Preoperative screening for coronavirus disease 2019 (COVID‐19) aims to preserve surgical safety for both patients and surgical teams. This rapid review provides an evaluation of current evidence with input from clinical experts to produce guidance for screening for active COVID‐19 in a low prevalence setting. METHODS: An initial search of PubMed (until 6 May 2020) was combined with targeted searches of both PubMed and Google Scholar until 1 July 2020. Findings were streamlined for clinical relevance through the advice of an expert working group that included seven senior surgeons and a senior medical virologist. RESULTS: Patient history should be examined for potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Hyposmia and hypogeusia may present as early symptoms of COVID‐19, and can potentially discriminate from other influenza‐like illnesses. Reverse transcription‐polymerase chain reaction (RT‐PCR) is the gold standard diagnostic test to confirm SARS‐CoV‐2 infection, and although sensitivity can be improved with repeated testing, the decision to retest should incorporate clinical history and the local supply of diagnostic resources. At present, routine serological testing has little utility for diagnosing acute infection. To appropriately conduct preoperative testing, the temporal dynamics of SARS‐CoV‐2 must be considered. Relative to other thoracic imaging modalities, computed tomography has the greatest utility for characterising pulmonary involvement in COVID‐19 patients who have been diagnosed by RT‐PCR. CONCLUSION: Through a rapid review of the literature and advice from a clinical expert working group, evidence‐based recommendations have been produced for the preoperative screening of surgical patients with suspected COVID‐19.

Coronavirus disease 2019 (COVID-19) has disrupted surgical care worldwide. Infection with the causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with considerable postoperative mortality and morbidity for surgical patients. [1] [2] [3] The global backlog of operations resulting from the temporary suspension of elective surgery could take close to a year to resolve. 4 Although both Australia and New Zealand have experienced a relatively low COVID-19 caseload on an international scale, 5 surgical systems within both countries have still been affected. During the initial phase of COVID-19, evidence-based guidance was required [reference GM editorial] from organisations such as the Royal Australasian College of Surgeons (RACS) and other specialty surgical societies and associations for safe intraoperative practice, 6, 7 appropriate personal protective equipment (PPE), management of surgical departments 8, 9 , and effective surgical triage 10, 11 in order to preserve the safety of surgical patients and staff. With the recommencement of elective surgery, clarity is required regarding the most appropriate methods of screening for active SARS-CoV-2 infection before surgery. 12 We aimed to evaluate the literature and produce evidence-based guidance regarding screening methods for active SARS-CoV-2 infection before surgery in a setting of low COVID-19 prevalence.

A rapid review of the literature was combined with the advice of a working group comprising clinical experts across Australia and New Zealand, including seven senior surgeons (five general surgeons, one urologist and one otorhinolaryngologist) and a senior medical virologist. Input was also provided by five representatives from other areas of medicine, surgery and healthcare management.

A rapid review methodology 13 with the World Health Organization"s identification of the novel coronavirus. 14 This was supplemented with targeted searches of the peer-reviewed literature until 1 July 2020, using both the PubMed and Google Scholar databases, which were informed by the working group.

Study selection was performed by JGK and DRT, and was expedited using the web application, Rayyan. 15 Data extraction from each study was performed by a single reviewer (JGK, PW, LT, HSK) using a standard template, and a sample of the extractions were checked by JGK and DRT. Inclusion was not limited by language as any relevant non-English articles were translated using Artificial Intelligence translation tools where necessary.

Case series with a sample size under 40 were excluded, apart from articles deemed important by the reviewers. 16, 17 Median values and interquartile ranges of the datapoints on the demographics and symptoms associated with COVID-19 were calculated from the retrieved studies.

The literature search yielded an initial pool of 5,762 citations, from which 1,395 human studies were identified (Appendix A). After screening of title and abstract, this pool was refined to 255 relevant articles, for which full-text versions were retrieved. Information deemed pertinent from this pool of 255 articles were synthesised along with findings from the targeted searches.

Given the considerable postoperative morbidity and mortality associated with operating on COVID-19 patients, 1-3 it is imperative that all surgical patients with suspected SARS-CoV-2 infection undergo appropriate screening prior to surgery. However, this must be balanced with the urgency of surgery to ensure optimal outcomes for the patient, and surgery should not be delayed unnecessarily. Non-elective surgery should not be delayed for confirmation of COVID-19 diagnosis in suspected patients, 11 rather it should proceed with surgical staff wearing full PPE 9 and undertaking appropriate intraoperative precautions, especially during aerosol-generating procedures. 6 If turnaround times of reverse transcription-polymerase chain reaction (RT-PCR) testing are within 24 hours, results of patients with suspected COVID-19 Accepted Article should be awaited prior to surgery provided that the delays do not adversely affect patient outcomes.

Patients that receive a positive result in preoperative RT-PCR testing should be managed on a case-by-case basis by the treating clinical team. 11 Surgical decision-making should incorporate the urgency of the patient"s condition, local supply of hospital resources, and potential postoperative outcomes if the operation is postponed for repeat testing or symptom resolution.

Evidence-based recommendations have been produced (Table 1 ) along with a proposed schema for the preoperative screening of surgical patients suspected of having COVID-19 (Table 2) . A printable questionnaire has also been developed for verbally screening patients for both symptoms of COVID-19 and a history of potential SARS-CoV-2 exposure, either during face-to-face or telemedicine consultations at any point in the preoperative setting (Appendix B). The proportion of patients responding positively to the questionnaire (Appendix B) or requiring diagnostic workup ( Table 2 ) will vary significantly depending on the local prevalence of COVID-19. The use of existing preoperative screening checklists should also be considered, 18 particularly if recommended by local institutions.

Due to the high level of SARS-CoV-2 shedding in the upper respiratory tract which is estimated to begin two to three days prior to the onset of symptoms, 19, 20 asymptomatic or presymptomatic persons with COVID-19 are capable of transmitting the virus to others during this period 21 and at other times during the disease course. 22, 23 It has been estimated that up to 17.9% of COVID-19 cases could be asymptomatic, 24 and that approximately 44% of secondary cases in a given cohort could have been infected during the presymptomatic stage of index cases. 20

As SARS-CoV-2 can spread rapidly even when clinically undetectable, patient history must be screened for potential sources of exposure to the virus (Table 1) . Surgical patients from population groups at high risk of contracting COVID-19 20, 25 should be treated with appropriate perioperative precautions, 6, 9, 11 and if it is unlikely to worsen postoperative outcomes, surgery should be delayed for preoperative RT-PCR testing ( Table 2 ). Patients from "essential" professions that are at high risk of exposure to COVID-19 (e.g. workers in Accepted Article healthcare, allied health facilities, supermarkets, schools, delivery, factory and farming, and transport) 26 should be treated with caution and undergo RT-PCR testing if symptomatic.

An assessment of patient symptoms is insufficient as a sole method of diagnosing COVID-19 (Table 1) From 31 selected studies investigating a total of 53,538 patients with laboratory-confirmed SARS-CoV-2 infection, the symptoms most frequently reported in association with COVID-19 included fever, cough, sore throat, dyspnoea (including shortness of breath or tachypnoea), diarrhoea, nausea or vomiting, and myalgia or arthralgia (Table 3) 

Immunological dysfunction due to COVID-19 can potentially result in the derangement of haematological, hepatic and renal laboratory markers. 17 75 However, although useful for gauging disease severity, 45 no individual laboratory marker within a multisystem workup provides specific utility for diagnosing active SARS-CoV-2 infection. 76 Thus, non-diagnostic laboratory investigations have little utility within the preoperative screening for COVID-19 (Table 1) .

At the time of this publication, the RT-PCR test is considered the gold standard diagnostic test for SARS-CoV-2 infection. 77 Given the poor outcomes reported after surgery in COVID-19 patients, 1-3 RT-PCR testing is imperative for all elective surgery patients suspected of SARS-CoV-2 infection. However, diagnostic accuracy remains challenging, 78 with the test"s false negative rate estimated to be 2-29%. 79 Accordingly, due to the test"s high specificity but relatively moderate sensitivity, a positive result on RT-PCR should be treated with more weight in surgical decision-making than a negative result. 80 Test outcome may be influenced by site of sample collection, 81 variation in specimen collection protocol and handling, 82 and time since exposure to SARS-CoV-2. 83 Corresponding to temporal fluctuations in viral load, 20, 84, 85 the probability of recording a false negative result has been reported as being highest in the four days prior to the onset of symptoms, with the lowest probability occurring on the day of symptom onset. 83 Thus, if a patient displays any symptoms associated with COVID-19, RT-PCR testing should be conducted even if the patient has previously tested negative for SARS-CoV-2 (Table 1) . Further, as RT-PCR is less sensitive for SARS-CoV-2 early in its incubation period, a 14-day quarantine prior to surgery should be considered in asymptomatic patients with a history of potential exposure to the virus (Appendix B), so as to allow time for resolution or presentation of the symptomatic phase. 86 Although repeat testing may overcome the limitations in RT-PCR sensitivity 78 RT-PCR tests detecting SARS-CoV-2 should demonstrate high sensitivity and specificity in addition to minimal cross-reactivity with other coronaviruses, and a cycle threshold value below 40 is generally accepted as the criterion for positivity. 88 Although the SARS-CoV-2 genes selected for amplification vary depending on the manufacturer, 89-91 within Australia and New Zealand there is good concordance in the analytical performance between in-house developed and commercial RT-PCR tests. 92, 93 Surgical staff are encouraged to seek clarification from their local pathology service regarding the local availability of validated tests 94, 95 (including other methods for nucleic acid amplification 96 ) and their turnaround times.

Serological detection of antibodies produced in the host immune response to SARS-CoV-2 infection can be utilised as a method of diagnosing COVID-19. 77, 97 Seroconversion or a fourfold or greater rise in antibody levels between acute and convalescent samples is considered definitive laboratory evidence of SARS-CoV-2 infection. 98 Large-scale analyses of seropositivity for immunoglobulin (Ig) M and G produced in response to SARS-CoV-2 infection have revealed the propensity for variation between populations depending on demographic differences and the population"s overall duration of exposure to the virus. [99] [100] [101] IgG and IgA are the antibodies most reliably detected in blood samples following SARS-CoV-2 infection, however global seroprevalence rates following the first wave of the pandemic ranged from 0.1%-47%, with considerable geographic variation. 102 Serological testing alone has little utility within preoperative screening for COVID-19 as it can neither confirm nor exclude a diagnosis of acute SARS-CoV-2 infection, nor provide information on potential infectivity (Table 1 ). Positivity for IgG or IgM may not be an assurance of protective immunity, 103 and there is uncertainty as to the period of immunity conferred. 104 The type of assay to use has been debated, with enzyme-linked immunosorbent assay (ELISA) possibly more reliable than blotting assays, 105 and questions have been raised regarding which antigen (derived from SARS-CoV-2) should be targeted 106 

To appropriately integrate testing for SARS-CoV-2 infection into preoperative surgical triage, 11 the temporal dynamics of the virus must be considered. The incubation period of SARS-CoV-2 has been estimated to be approximately four to five days 29, 110, 111 and viral load decreases after symptom onset, 20, 84, 85 although SARS-CoV-2 RNA may be detected up to 37 days later. 61 The virus is infectious both before 21 and after the onset of symptoms, 20 however infectivity is likely to decline after the first week of symptoms, when live virus may not be isolated in cell culture despite high viral loads in respiratory tract samples. 19 In an evidence-based timeline of the various diagnostic markers of SARS-CoV-2 infection, 77 Sethuraman et al. estimated that RT-PCR detection (which merely confirms the presence of viral RNA, not viable virus 19, 112 ) is likely to produce a positive result in the first three weeks after symptom onset. 113 Antibodies are most likely to be detected in serological tests after Accepted Article approximately two weeks of symptoms, 114 with IgG levels generally greater than IgM levels from about four weeks after symptom onset. 115 It is important to note that RT-PCR positivity has not been shown to correlate with clinical severity, 113 and has been found in cases when symptoms have completely resolved. 116

Thoracic imaging serves the purpose of characterising the extent of pulmonary involvement from COVID-19, rather than providing a method of definitively diagnosing SARS-CoV-2 infection. Chest computed tomography (CT), radiography and ultrasonography have all been discussed within the literature as imaging modalities that can potentially provide evaluative utility alongside RT-PCR assays. However, due to the considerable overlap between findings associated with pulmonary involvement in COVID-19 and those of other respiratory illnesses, no single thoracic imaging modality should be used as a sole method of diagnosing SARS-CoV-2 infection.

Outside its known utility within the initial evaluation of suspected community-acquired pneumonia, 117 there is little evidence that chest radiography provides added diagnostic specificity for cases of suspected COVID-19. 118, 119 Similarly, although ultrasonography can potentially provide a low-cost, easily-disinfected, radiation-free alternative to CT in settings of high COVID-19 prevalence or low medical resources, [120] [121] [122] in settings of low COVID-19 prevalence and adequate resources its lack of specificity limits diagnostic utility. Groundglass opacities, consolidation, pleural thickening, interlobular septal thickening and air bronchograms have been reported in the literature as the chest CT findings most commonly associated with COVID-19, with lesions more likely to be found in the lower lobes. 123 However, there is variation in reported CT features based on time within the COVID-19 disease course. 124, 125 Chest CT could potentially have even greater sensitivity for detecting respiratory involvement of SARS-CoV-2 infection than RT-PCR, 126, 127 however multiple meta-analyses within the literature have estimated the specificity of the modality to be below 40% for COVID-19. 128, 129 Thus while the sole use of chest CT to screen for SARS-CoV-2 infection cannot be recommended, 130 it can be useful for characterising the pulmonary involvement within COVID-19 patients that have been confirmed by RT-PCR (Table 1) .

This article is protected by copyright. All rights reserved.

On the basis of a rapid review of the literature, evidence-based recommendations have been produced along with a proposed schema for the preoperative screening of surgical patients with suspected SARS-CoV-2 infection in a low prevalence setting. RT-PCR testing remains the gold standard diagnostic test for SARS-CoV-2 infection. However, relevant patient history suggesting potential exposure to the virus and clinical presentation, particularly the presence of hyposmia or hypogeusia, must also be considered within preoperative screening for COVID-19. Surgical decision-making should incorporate the urgency of the individual patient"s condition, the temporal dynamics of SARS-CoV-2, and local supply of medical resources. A printable questionnaire has also been developed for verbally screening patients for COVID-19 during face-to-face or telemedicine consultations. 

This article is protected by copyright. All rights reserved. The use of chest CT scanning alone to diagnose COVID-19 is not recommended due to nonspecific findings that may overlap with other respiratory illnesses.

This article is protected by copyright. All rights reserved. Accepted Article

This article is protected by copyright. All rights reserved.

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This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Any risk of potential SARS-CoV-2 exposure, including:  Close contact with a confirmed case of COVID-19 in the past two weeks  Close contact with someone who displays symptoms of hyposmia (loss of smell), hypogeusia (loss of taste), cough, sore throat, or dyspnoea in the past two weeks (including in the three days prior to onset of symptoms)  Overseas or interstate (if state of journey"s origin contains active cases of COVID-19) travel in the past two weeks, either by plane or cruise ship, or close contact with someone who has  Presence within an aged care facility in the past two weeks, either as a resident, worker, or visitor  Presence within a detention facility in the past two weeks, either as a resident, worker, or visitor  Presence within a group residential setting in the past two weeks, either as a resident, worker or visitor  Presence within other facilities that have relatively high risk of COVID-19 transmission  Profession that includes regular interaction with COVID-19 cases (e.g. workers in healthcare, allied health facilities, supermarkets, schools, delivery, factories, farming, and transport)

Any of the following symptoms in the past two weeks:

 Cough  Sore throat  Dyspnoea RT-PCR assay AND CT scan of chest

No preoperative investigation for SARS-CoV-2 infection † † Proceed to surgery with surgical staff wearing full PPE and taking appropriate intraoperative precautions, especially for potential aerosol-generating procedures. 6, 9, 11 Isolate patient postoperatively and test for SARS-CoV-2 infection when possible. OR assessment* OR use*)))) OR ((Bedside AND (Computing OR Technology)))) OR (("in field detection" OR POC OR POCT)))))) OR (((((((((((("Serologic Tests"[Mesh]) OR "Molecular Diagnostic Techniques"[Mesh]) OR (("IgM" OR "IgG" OR "Ag"))) OR ((Immunoglobulin OR "antiviral immunoglobulin-G"))) OR ((Serologic* AND (test OR testing OR tests OR conversion* OR assay* OR analysis OR diagnostic OR diagnostics OR diagnosi* OR diagnose* OR screen*)))) OR ((Serology or seroconversion OR seroepidemiology OR serodiagnos* or seroprevalence*))) OR (((Antibod* AND (test OR tests OR testing OR serum OR detection* OR response*))))) OR ((Antigen OR antigeni* OR antigens*))) OR Immunoassa*) OR ((Molecular AND (diagnostic OR diagnostics OR diagnosi* OR diagnose*)))) OR Dynamic* profile)))) 4,672,773 ))) OR ((detect* OR laboratory OR evaluat* OR validat* OR clinical OR perform* OR sensitivity OR specificity OR area under the curve OR positive predictive value OR PPV OR negative predictive value OR NPV OR predictive value OR feasibility OR accuracy OR likelihood ratio OR false negative OR false positive OR Positive rate OR validation OR diagnostic odds ratio OR DOR OR valid*))) OR ((Diagnostic AND (value OR panel OR tool*)))) OR ((diagnosa* OR diagnosi* OR diagnose* OR diagnoss* OR diagnostic OR diagnostics))) OR (((Test OR tests OR testing) AND (infection OR virus OR disease OR diseases OR disease, OR antibod* OR blood OR nucleic acid or diagnostic OR diagnostics OR diagnosi* OR diagnose* OR diagnose*)))))) 17,661,043 ) OR ((CT X*Ray* OR CT))) OR (((CT OR CAT OR chest OR lung or lungs or thoracic* OR thorax*) AND (Scan or screen* or imaging or film or radiograph* or radiogram or radiolog*)))) OR Compute* tomograph*) OR ((Cine-CT or "Cine CT"))) OR (((Thoracic* OR thorax* OR lung OR lungs OR Chest) AND CT))) OR (("Chest CT" AND (scan or imaging )))) OR ((X*ray* computed or x-ray compute*))) OR ((Compute* assist* tomograph* OR compute* axial tomograph*))) OR ((chest radiological imaging OR Roentgenolog* or roentgen ray*or roentgen OR Grenz Ray* or X*Radiation*)) 664,529 6 X-ray Imaging (((((("Radiography, Thoracic"[Mesh]) OR "Mass Chest X-Ray"[Mesh]) OR "X-Rays"[Mesh]) OR (((CXR OR CR OR x*ray* OR radiograph*)))) OR (((chest AND (film* OR radiograph*))))) OR ((((chest OR lung OR lungs OR thoracic* OR thorax*) AND (x*ray* OR radiograph* or radiogram* or radiolog*))))) OR (((Chest X-ray radiography OR chest radiological imaging OR thoracic radiology OR Roentgenolog* or roentgen ray*or roentgen OR Grenz Ray* or X*Radiation*))) 1,438,818 

(transcriptase OR transcription)) AND (PCR OR PCRs OR polymerase chain reaction)))))) OR ((Multiplex AND (PCR OR PCRs OR polymerase chain reaction)))) OR ((nucleic acid OR nucleic acid detection OR RNA))) OR (("Hologic Panther Fusion" OR "Hologic" OR "Hologic Panther" OR "DiaSorin Simplexa" OR "DiaSorin" OR "Roche Cobas 6800" OR "DiaSorin Simplexa COVID*19 Direct" OR "Cepheid Xpert Xpress SARS*CoV*2" OR "Cepheid Xpert Xpress" OR "QIAstat-Dx Respiratory SARS*CoV*2 Panel" OR "QIAstat-SARS" OR "QIAstat"))) OR (((lateral flow immunoassay) OR "LFIA"))) OR "LAMP assay" ) OR ((((Point*of*care OR bedside OR rapid OR real*time OR near*patient OR fast OR prompt OR early))) AND ((Ultrasound OR ultrasonography OR ultrasonic OR sonography OR sonographic)))) OR ((((Chest OR thoraci* OR thorax* OR lung or lungs))) AND ((Ultrasound OR ultrasonography OR ultrasonic OR sonography OR sonographic)))) OR ((((Chest OR thoraci* OR thorax* OR lung or lungs))) AND US)) OR ((((Point*of*care OR bedside OR rapid OR real*time OR near*patient OR fast OR prompt OR early))) AND ((Image OR imaging OR images)))) OR ((((Chest OR thoraci* OR thorax* OR lung or lungs))) AND ((Image OR imaging OR images)))) OR ((((Ultrasound OR ultrasonography OR ultrasonic OR sonography OR sonographic))) AND ((diagnosa* OR diagnosi* OR diagnose* OR diagnoss* OR diagnostic OR diagnostics))) 2,361,046 Accepted Article This article is protected by copyright. All rights reserved.Appendix B. Printable questionnaire for screening patients for symptoms of COVID-19 or history of potential SARS-CoV-2 exposure 12

Over the past two weeks, have you been in close contact with someone who has been suspected of, or diagnosed with COVID-19? Over the past two weeks, have you been unwell or experienced any of the following symptoms: Loss of smell  Loss of taste  Fever  Cough  Sore throat  Shortness of breath or difficulty breathing  Diarrhoea  Nausea or vomiting  Muscle aches Over the past two weeks, have you been in close contact with someone who has been unwell or displayed any of the above symptoms (including in the three days prior to the onset of their symptoms)? Have you travelled overseas in the past two weeks, either by plane or cruise ship, or been in contact with someone who has? Have you travelled interstate in the past two weeks?* Have you been within an aged care facility, either as a resident, worker, or visitor, in the past two weeks? Have you been within a detention facility, either as a resident, worker, or visitor, in the past two weeks? Do you live in a group residential setting, or have you visited one in the past two weeks? Do you regularly interact with people with COVID-19 as part of your job? *Applicable only if active cases within state of journey"s origin Accepted Article