The coronavirus disease 2019 (COVID-19) pandemic had an unprecedented impact in the world [1]. Numerous changes were implemented across the healthcare system to mitigate the risk of viral spread to healthcare workers while providing care to those who were infected. Surgical care was deeply affected as it was not exempt to the evolving adjustments produced by the pandemic, including the early deployment of surgeons to non-surgical responsibilities where much help was needed [2,3,4]. In addition, millions of elective surgeries were canceled to both safeguard the needed resources for the incoming influx of infected patients, as well to protect the healthcare providers from a potential infection. [2]

Based on extrapolated data from other viruses, there was a fear that surgeons could be exposed to infective levels of virus while performing surgery [5, 6]. Some societies published recommendations cautioning against the use of laparoscopy in COVID-positive patients as this was considered to be a potential aerosolizing procedure [5, 6]. The hypothesis was that if the virus were present in the abdominal tissues, it could be aerosolized and travel along with the insufflation gas or surgical plume during laparoscopic port insertion and removal, port venting, during instrument exchanges or specimen extraction, and hence transmitted to the operating room staff. However, as previously mentioned, for a potential transmission, the virus would need to be present in the abdominal cavity. As such, several groups investigated the presence of the COVID-19 virus in the abdominal cavity, as well as in other abdominal tissues to which surgeons are exposed. [7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]

Nevertheless, the results were conflicting, in addition to being based just on case reports and case series [7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43]. Early during the pandemic, a systematic review attempted to clarify the issue by pooling the available data [44]. However, they could not support the hypothesis that the COVID-19 virus could be aerosolized in the operating room, and the majority of publications analyzed for inclusion were case reports. Since then, more studies have been published in this matter. As the world recovers from the COVID-19 pandemic we must be prepare for the ongoing emergence of new variants and future pandemics. Thus, the objective of the present study was to study the presence of the COVID-19 virus in the abdominal tissues and fluids.

Methods

Study design

A systematic literature search to identify relevant studies regarding the presence of severe acute respiratory disease syndrome coronavirus (SARS-CoV-2), the virus responsible for COVID-19, in abdominal tissues or fluids. The query was performed using the following databases: PubMed, Web of Science, EMBASE and Cochrane Central Library. It was restricted to articles in English and Spanish languages and was not time limited. References from previous reviews, as well as references from relevant primary studies were manually searched to identify any additional studies. The search was completed on March 1st, 2023. The systematic review was conducted in conformity with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and was registered in the prospective international register of systematic reviews (PROSPERO: CRD42023408176). [45]

Search strategy

Medical subject heading (MeSH) terms to search was broad to encompass articles related to the identification of SARS-CoV-2 RNA in samples of abdominal tissues or fluids in patients with SARS-CoV-2 infection. Therefore, the terms were as follow: “SARS-COV-2”, “abdominal tissue*”, “abdominal fluid*”, “peritoneal fluid*”, “biologic* fluid*”, “swab test”, “bile”, “biliary”, and “surgery”. All identified abstracts were assessed for inclusion or exclusion by 2 independent evaluators (G.R-V. and G.P-B). There was no disagreement between evaluators that required the participation of a third investigator. Studies meeting the inclusion criteria were retrieved and the full texts reviewed.

Study selection

Observational studies (retrospective or prospective cohorts, case series, and case reports) that included patients with SARS-CoV-2 infection who underwent any abdominal procedure and in which samples of abdominal tissues or fluids were taken for qualitative detection of SARS-CoV-2 RNA were included in this systematic review.

Data extraction

Information extracted from eligible studies included basic study data (last name of the first author, country, design, sample size), demographic data (gender, age), SARS-CoV-2 infection status and symptoms (diagnostic test status, respiratory symptoms, radiologic signs of pneumonia, severity, length of disease), abdominal procedure parameters (type of procedure – surgery, paracentesis, dialysis, endoscopic procedures), and sample analysis (type, performed test for detection of SARS-CoV-2, positive status and timing with the surgery). Severe COVID-19 infection was defined as the patient requiring invasive respiratory support, intensive care unit admission or death [46]. Data were extracted and verified by three independent investigators (G.R-V, G.P-B, and M.A.Z.).

Analysis

Data within individual studies was extracted to fields within an Excel (Microsoft, Redmond, WA, USA) database. Data manipulation and analysis was performed using SAS v9.4 (SAS, Cary, NC, USA). The positivity between patients with severe and non-severe disease was analyzed with Chi-square, and statistical significance was defined as p < 0.05.

Results

Search results and study characteristics

A total of 335 studies (G.P-B. and G.R-V.) were identified from the previously described search strategy. After duplicates were removed, the titles and full abstracts of 259 studies were evaluated, from which only 45 were assessed for eligibility. The full text of these 45 articles were reviewed, and 36 were identified for inclusion (Fig. 1). From the included studies, 18 were case series (Table 1), and 18 were case reports (Table 2).

Fig. 1
figure 1

PRISMA flowchart

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Table 1 Case series included in the review
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Table 2 Case reports included in the review
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Descriptive analysis

A total of 295 patients were included, of whom 76% were female (n = 224). Age range was between 12 and 95 years. At least 141 (47.8%) patients were positive for SARS-CoV-2 at the moment of sample collection, in whom respiratory symptoms were registered in 109 (36.9%), and radiologic findings were described in 46 (15.6%). Severe COVID-19 infection, as previously defined was registered in 32 patients (10.8%).

Abdominal sample characteristics

Reverse transcriptase-polymerase chain reaction (RT-PCR) was the test used in all of the cases. Collection time of the abdominal sample from the presence of symptoms ranged between 0 and 63 days. Samples for detection of SARS-CoV-2 were obtained from direct swab of the peritoneum or peritoneal fluid during surgery or paracentesis in 259 individuals, from peritoneal dialysis in 43, from smoke during surgery in 25, from bile or other gastrointestinal fluid in 13, and 17 from other tissues (including omentum, subcutaneous tissue, and hollow organs). Out of 357 total samples, 21 were reported to be positive (5.9%).

From all positive samples, 12 were in patients with severe COVID-19 infection (57.1%). Patients with severe COVID-19 infection were more likely to have positive samples compared to patients without severe infection (37.5% vs 3.8%, p < 0.001). Description of SARS-CoV-2 positive samples from abdominal sources is shown in Table 3 There were no healthcare provider infections reported across the included studies.

Table 3 Description of positive abdominal samples
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Discussion

As the world emerges from the COVID-19 pandemic there is opportunity to re-examine and collate the data collected during the pandemic to draw more concrete conclusions and prepare for potential future pandemics. As we are likely to experience new variants and future pandemics, surgeons need to be prepared and understand the potential risks for viral exposure and infection in the operating room. A key component to comprehend the potential for COVID-19 transmission during abdominal operations is to delimit the presence of the virus in the abdominal cavity. As there are conflicting results coming from case reports and small case series, the purpose of this study was to assess all the available data. We found that although a rare occurrence, SARS-CoV-2 can be isolated from abdominal tissues and fluids. While this study includes a small number of asymptomatic patients, it is noted that positive intra-peritoneal samples were noted among patients without disease symptoms.

Our study has some strengths and fills in a gap in the literature which are worth noting. First, more studies have been published since the previous systematic review in this topic was published, which allows to expand on the prior conclusions [44]. In addition, compared to the recently published guidelines by the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) for the use of laparoscopy in the era of COVID-19, our search strategy included the presence of SARS-CoV-2 in different specimens rather than just surgical plume. [5]

Our results support the recommendation by SAGES in which protective measures should be employed when operating on patients with COVID-19 for all cases regardless of the approach [5]. Nevertheless, it should be pointed out that even though SARS-CoV-2 has been found in the abdominal cavity by RT-PCR, the potential of these particles to infect has never been demonstrated [47]. In fact, none of the studies included in our review reported health care associated infections to the operating room staff. It is important to highlight that the type and extent of personal protective equipment or other isolation measures employed in the included studies are not known. Infections among healthcare workers may also be difficult to attribute to a specific exposure, as any worker in that environment presumably could have multiple potential opportunities for viral exposure throughout their routine course of work. Thus, a definitive statement regarding transmissibility of the detected viral loads is not possible and future studies should focus on the potential infectivity of viral particles found in the abdominal cavity.

Furthermore, the source of SARS-CoV-2 found in the peritoneum has also been investigated. Some reports have considered positive samples to be due to contamination by feces, bile or blood, which are well known to convey viral particles [36, 38, 44, 48,49,50]. Although some of the included cases in our review could be explained by contamination, the virus was also found in the dialysate effluent of peritoneal dialysis which likely is not prone to this contamination. This suggests that peritoneal viral translocation could occur in the absence of inflammation, but also be potentiated in the setting of inflammation [49]. Another important consideration in this regard is the correlation we found between severe COVID-19 disease and positive samples. Fabbri et al. have previously suggested the possibility that severe disease would translate to higher viral load and hence the increased possibility of translocation to the abdominal cavity [32]. Regardless of the mechanism responsible for the presence of the virus in the abdominal cavity, the data suggest that surgeons could be exposed to viral particles when operating.

There are important limitations of the current study. First and most important, although we have evaluated multiple studies, the data comes from case series and case reports which are prone to selection bias. Also, there was significant heterogeneity of RT-PCR used, including varying promoter sequences and pooling or non-pooling techniques, the sampling site, and timing between COVID-19 diagnosis and specimen collection. In addition, these studies were completed during varying phases of the pandemic and likely include multiple SARS-COV2 variants and subvariants and whether a specific subvariant is more likely to be found in intra-abdominal tissues is not known. All of these factors in addition to the fact that RT-PCR may not have been validated for viral RNA detection from samples obtained from the abdominal cavity has been previously acknowledged by Fabbri et al. [49] Specifically, there may be a high false positive rate of RT-PCR, and nucleic acid amplification tests such as RT-PCR may remain positive for weeks to months after infection. Moreover, some tests designed and approved for screening and others for confirmatory diagnostic testing, which necessarily have different performance characteristics and expected positivity rates.

This study supports the assertion that SARS-CoV-2 can be identified from abdominal tissues and fluids that would be normally encountered during surgery. It seems that the presence of the virus in the abdominal tissues and fluids is more likely in patients with severe disease. Protective measures are needed in the operating room to protect the staff when operating patients with COVID-19.