Coinfection with Strongyloides and SARS-CoV-2: A Systematic Review.

BACKGROUND: Treatments for COVID-19, including steroids, might exacerbate Strongyloides disease in patients with coinfection. We aimed to systematically review clinical and laboratory features of SARS-CoV-2 and Strongyloides coinfection, investigate possible interventions, assess outcomes, and identify research gaps requiring further attention. METHODS: We searched two electronic databases, LitCOVID and WHO, up to August 2022, including SARS-CoV-2 and Strongyloides coinfection studies. We adapted the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system for standardized case causality assessment to evaluate if using corticosteroids or other immunosuppressive drugs in COVID-19 patients determined acute manifestations of strongyloidiasis. RESULTS: We included 16 studies reporting 25 cases of Strongyloides and SARS-CoV-2 coinfection: 4 with hyperinfection syndrome; 2 with disseminated strongyloidiasis; 3 with cutaneous reactivation of strongyloidiasis; 3 with isolated digestive symptoms; and 2 with solely eosinophilia, without clinical manifestations. Eleven patients were asymptomatic regarding strongyloidiasis. Eosinopenia or normal eosinophil count was reported in 58.3% of patients with Strongyloides reactivation. Steroids were given to 18/21 (85.7%) cases. A total of 4 patients (19.1%) received tocilizumab and/or Anakirna in addition to steroids. Moreover, 2 patients (9.5%) did not receive any COVID-19 treatment. The causal relationship between Strongyloides reactivation and COVID-19 treatments was considered certain (4% of cases), probable (20% of patients), and possible (20% of patients). For 8% of cases, it was considered unlikely that COVID-19 treatment was associated with strongyloidiasis reactivations; the relationship between the Strongyloides infection and administration of COVID-19 treatment was unassessable/unclassifiable in 48% of cases. Of 13 assessable cases, 11 (84.6%) were considered to be causally associated with Strongyloides, ranging from certain to possible. CONCLUSIONS: Further research is needed to assess the frequency and risk of Strongyloides reactivation in SARS-CoV-2 infection. Our limited data using causality assessment supports recommendations that clinicians should screen and treat for Strongyloides infection in patients with coinfection who receive immunosuppressive COVID-19 therapies. In addition, the male gender and older age (over 50 years) may be predisposing factors for Strongyloides reactivation. Standardized guidelines should be developed for reporting future research.

Respiratory virus coinfections with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) continue to be rare one year into the coronavirus disease 2019 (COVID-19) pandemic in Alberta, Canada (June 2020-May 2021).

To assess the burden of respiratory virus coinfections with severe acute respiratory coronavirus virus 2 (SARS-CoV-2), this study reviewed 4,818 specimens positive for SARS-CoV-2 and tested using respiratory virus multiplex testing. Coinfections with SARS-CoV-2 were uncommon (2.8%), with enterovirus or rhinovirus as the most prevalent target (88.1%). Respiratory virus coinfection with SARS-CoV-2 remains low 1 year into the coronavirus disease 2019 (COVID-19) pandemic.

Patient and ward related risk factors in a multi-ward nosocomial outbreak of COVID-19: Outbreak investigation and matched case-control study.

BACKGROUND: Risk factors for nosocomial COVID-19 outbreaks continue to evolve. The aim of this study was to investigate a multi-ward nosocomial outbreak of COVID-19 between 1st September and 15th November 2020, occurring in a setting without vaccination for any healthcare workers or patients. METHODS: Outbreak report and retrospective, matched case-control study using incidence density sampling in three cardiac wards in an 1100-bed tertiary teaching hospital in Calgary, Alberta, Canada. Patients were confirmed/probable COVID-19 cases and contemporaneous control patients without COVID-19. COVID-19 outbreak definitions were based on Public Health guidelines. Clinical and environmental specimens were tested by RT-PCR and as applicable quantitative viral cultures and whole genome sequencing were conducted. Controls were inpatients on the cardiac wards during the study period confirmed to be without COVID-19, matched to outbreak cases by time of symptom onset dates, age within ± 15 years and were admitted in hospital for at least 2 days. Demographics, Braden Score, baseline medications, laboratory measures, co-morbidities, and hospitalization characteristics were collected on cases and controls. Univariate and multivariate conditional logistical regression was used to identify independent risk factors for nosocomial COVID-19. RESULTS: The outbreak involved 42 healthcare workers and 39 patients. The strongest independent risk factor for nosocomial COVID-19 (IRR 3.21, 95% CI 1.47-7.02) was exposure in a multi-bedded room. Of 45 strains successfully sequenced, 44 (97.8%) were B.1.128 and differed from the most common circulating community lineages. SARS-CoV-2 positive cultures were detected in 56.7% (34/60) of clinical and environmental specimens. The multidisciplinary outbreak team observed eleven contributing events to transmission during the outbreak. CONCLUSIONS: Transmission routes of SARS-CoV-2 in hospital outbreaks are complex; however multi-bedded rooms play a significant role in the transmission of SARS-CoV-2.

Barriers and Facilitators to the Use of Personal Protective Equipment in Long-Term Care: A Scoping Review.

OBJECTIVE: To review existing literature evaluating barriers and facilitators to the use of personal protective equipment (PPE) by health care workers in long-term care (LTC). DESIGN: Scoping review. SETTING AND PARTICIPANTS: Health care workers in LTC settings. METHODS: Several online databases were searched and a gray literature search was conducted. Study inclusion criteria were (1) conducted in nursing homes or LTC settings, (2) focused on LTC health care workers as the study population, and (3) identified barriers and/or facilitators to PPE use. The Theoretical Domains Framework (TDF), which assesses barriers to implementation across 14 behavioral change domains, was used to extract and organize data about barriers and facilitators to appropriate use of PPE from the included studies. RESULTS: A total of 5216 references were screened for eligibility and 10 studies were included in this review. Eight of the 10 studies were conducted during the COVID-19 pandemic. Several barriers and facilitators to PPE use were identified. The most common TDF domain identified was environmental context and resources, which was observed in 9 of the 10 studies. Common barriers to PPE use included supply issues (n = 7 studies), the cost of acquisition (n = 3 studies), unclear guidelines on appropriate use of PPE (n = 2 studies), difficulty providing care (n = 2 studies), and anxiety about frightening patients (n = 2 studies). Having PPE readily available facilitated the use of PPE (n = 2 studies). CONCLUSIONS AND IMPLICATIONS: Further research is necessary to identify barriers and facilitators more extensively across behavior change domains to develop effective strategies to improve PPE use and prevent infection transmission within LTC.

Viral Cultures, Cycle Threshold Values and Viral Load Estimation for Assessing SARS-CoV-2 Infectiousness in Haematopoietic Stem Cell and Solid Organ Transplant Patients: A Systematic Review.

BACKGROUND: Solid organ and haematopoietic stem cell transplant recipients are at increased vulnerability to SARS-CoV-2 due to immunosuppression and may pose a continued transmission risk especially within hospital settings. Detailed case reports including symptoms, viral load and infectiousness, defined by the presence of replication-competent viruses in culture, provide an opportunity to examine the relationship between clinical course, burden and contagiousness, and provide guidance on release from isolation. OBJECTIVES: We performed a systematic review to investigate the relationship in transplant recipients between serial SARS-CoV-2 RT-PCR cycle threshold (Ct) value or cycle of quantification value (Cq), or other measures of viral burden and the likelihood and duration of the presence of infectious virus based on viral culture including the influence of age, sex, underlying pathologies, degree of immunosuppression, and/or vaccination on this relationship. METHODS: We searched LitCovid, medRxiv, Google Scholar and WHO Covid-19 databases, from 1 November 2019 until 26 October 2022. We included studies reporting relevant data for transplantees with SARS-CoV-2 infection: results from serial RT-PCR testing and viral culture data from the same respiratory samples. We assessed methodological quality using five criteria, and synthesised the data narratively and graphically. RESULTS: We included 13 case reports and case series reporting on 41 transplantees including 22 renal, 5 cardiac, 1 bone marrow, 2 liver, 1 bilateral lung, and 10 blood stem cell transplants. We observed a relationship between proxies of viral burden and likelihood of shedding replication-competent SARS-CoV-2. Three individuals shed replication-competent viruses for over 100 days after infection onset. Lack of standardisation of testing and reporting platforms precludes establishing a definitive viral burden cut-off. However, the majority of transplantees stopped shedding replication-competent viruses when the RT-PCR cycle threshold was above 30 despite differences across platforms. CONCLUSIONS: Viral burden is a reasonable proxy for infectivity when considered within the context of the clinical status of each patient. Standardised study design and reporting are essential to standardise guidance based on an increasing evidence base.

Physical interventions to interrupt or reduce the spread of respiratory viruses.

BACKGROUND: Viral epidemics or pandemics of acute respiratory infections (ARIs) pose a global threat. Examples are influenza (H1N1) caused by the H1N1pdm09 virus in 2009, severe acute respiratory syndrome (SARS) in 2003, and coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 in 2019. Antiviral drugs and vaccines may be insufficient to prevent their spread. This is an update of a Cochrane Review last published in 2020. We include results from studies from the current COVID-19 pandemic. OBJECTIVES: To assess the effectiveness of physical interventions to interrupt or reduce the spread of acute respiratory viruses. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, CINAHL, and two trials registers in October 2022, with backwards and forwards citation analysis on the new studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster-RCTs investigating physical interventions (screening at entry ports, isolation, quarantine, physical distancing, personal protection, hand hygiene, face masks, glasses, and gargling) to prevent respiratory virus transmission.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. MAIN RESULTS: We included 11 new RCTs and cluster-RCTs (610,872 participants) in this update, bringing the total number of RCTs to 78. Six of the new trials were conducted during the COVID-19 pandemic; two from Mexico, and one each from Denmark, Bangladesh, England, and Norway. We identified four ongoing studies, of which one is completed, but unreported, evaluating masks concurrent with the COVID-19 pandemic. Many studies were conducted during non-epidemic influenza periods. Several were conducted during the 2009 H1N1 influenza pandemic, and others in epidemic influenza seasons up to 2016. Therefore, many studies were conducted in the context of lower respiratory viral circulation and transmission compared to COVID-19. The included studies were conducted in heterogeneous settings, ranging from suburban schools to hospital wards in high-income countries; crowded inner city settings in low-income countries; and an immigrant neighbourhood in a high-income country. Adherence with interventions was low in many studies. The risk of bias for the RCTs and cluster-RCTs was mostly high or unclear. Medical/surgical masks compared to no masks We included 12 trials (10 cluster-RCTs) comparing medical/surgical masks versus no masks to prevent the spread of viral respiratory illness (two trials with healthcare workers and 10 in the community). Wearing masks in the community probably makes little or no difference to the outcome of influenza-like illness (ILI)/COVID-19 like illness compared to not wearing masks (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.84 to 1.09; 9 trials, 276,917 participants; moderate-certainty evidence. Wearing masks in the community probably makes little or no difference to the outcome of laboratory-confirmed influenza/SARS-CoV-2 compared to not wearing masks (RR 1.01, 95% CI 0.72 to 1.42; 6 trials, 13,919 participants; moderate-certainty evidence). Harms were rarely measured and poorly reported (very low-certainty evidence). N95/P2 respirators compared to medical/surgical masks We pooled trials comparing N95/P2 respirators with medical/surgical masks (four in healthcare settings and one in a household setting). We are very uncertain on the effects of N95/P2 respirators compared with medical/surgical masks on the outcome of clinical respiratory illness (RR 0.70, 95% CI 0.45 to 1.10; 3 trials, 7779 participants; very low-certainty evidence). N95/P2 respirators compared with medical/surgical masks may be effective for ILI (RR 0.82, 95% CI 0.66 to 1.03; 5 trials, 8407 participants; low-certainty evidence). Evidence is limited by imprecision and heterogeneity for these subjective outcomes. The use of a N95/P2 respirators compared to medical/surgical masks probably makes little or no difference for the objective and more precise outcome of laboratory-confirmed influenza infection (RR 1.10, 95% CI 0.90 to 1.34; 5 trials, 8407 participants; moderate-certainty evidence). Restricting pooling to healthcare workers made no difference to the overall findings. Harms were poorly measured and reported, but discomfort wearing medical/surgical masks or N95/P2 respirators was mentioned in several studies (very low-certainty evidence).  One previously reported ongoing RCT has now been published and observed that medical/surgical masks were non-inferior to N95 respirators in a large study of 1009 healthcare workers in four countries providing direct care to COVID-19 patients.  Hand hygiene compared to control Nineteen trials compared hand hygiene interventions with controls with sufficient data to include in meta-analyses. Settings included schools, childcare centres and homes. Comparing hand hygiene interventions with controls (i.e. no intervention), there was a 14% relative reduction in the number of people with ARIs in the hand hygiene group (RR 0.86, 95% CI 0.81 to 0.90; 9 trials, 52,105 participants; moderate-certainty evidence), suggesting a probable benefit. In absolute terms this benefit would result in a reduction from 380 events per 1000 people to 327 per 1000 people (95% CI 308 to 342). When considering the more strictly defined outcomes of ILI and laboratory-confirmed influenza, the estimates of effect for ILI (RR 0.94, 95% CI 0.81 to 1.09; 11 trials, 34,503 participants; low-certainty evidence), and laboratory-confirmed influenza (RR 0.91, 95% CI 0.63 to 1.30; 8 trials, 8332 participants; low-certainty evidence), suggest the intervention made little or no difference. We pooled 19 trials (71, 210 participants) for the composite outcome of ARI or ILI or influenza, with each study only contributing once and the most comprehensive outcome reported. Pooled data showed that hand hygiene may be beneficial with an 11% relative reduction of respiratory illness (RR 0.89, 95% CI 0.83 to 0.94; low-certainty evidence), but with high heterogeneity. In absolute terms this benefit would result in a reduction from 200 events per 1000 people to 178 per 1000 people (95% CI 166 to 188). Few trials measured and reported harms (very low-certainty evidence). We found no RCTs on gowns and gloves, face shields, or screening at entry ports. AUTHORS' CONCLUSIONS: The high risk of bias in the trials, variation in outcome measurement, and relatively low adherence with the interventions during the studies hampers drawing firm conclusions. There were additional RCTs during the pandemic related to physical interventions but a relative paucity given the importance of the question of masking and its relative effectiveness and the concomitant measures of mask adherence which would be highly relevant to the measurement of effectiveness, especially in the elderly and in young children. There is uncertainty about the effects of face masks. The low to moderate certainty of evidence means our confidence in the effect estimate is limited, and that the true effect may be different from the observed estimate of the effect. The pooled results of RCTs did not show a clear reduction in respiratory viral infection with the use of medical/surgical masks. There were no clear differences between the use of medical/surgical masks compared with N95/P2 respirators in healthcare workers when used in routine care to reduce respiratory viral infection. Hand hygiene is likely to modestly reduce the burden of respiratory illness, and although this effect was also present when ILI and laboratory-confirmed influenza were analysed separately, it was not found to be a significant difference for the latter two outcomes. Harms associated with physical interventions were under-investigated. There is a need for large, well-designed RCTs addressing the effectiveness of many of these interventions in multiple settings and populations, as well as the impact of adherence on effectiveness, especially in those most at risk of ARIs.

Transmission of SARS-CoV-2 Associated with Cruise Ship Travel: A Systematic Review.

BACKGROUND: Maritime and river travel may be associated with respiratory viral spread via infected passengers and/or crew and potentially through other transmission routes. The transmission models of SARS-CoV-2 associated with cruise ship travel are based on transmission dynamics of other respiratory viruses. We aimed to provide a summary and evaluation of relevant data on SARS-CoV-2 transmission aboard cruise ships, report policy implications, and highlight research gaps. METHODS: We searched four electronic databases (up to 26 May 2022) and included studies on SARS-CoV-2 transmission aboard cruise ships. The quality of the studies was assessed based on five criteria, and relevant findings were reported. RESULTS: We included 23 papers on onboard SARS-CoV-2 transmission (with 15 reports on different aspects of the outbreak on Diamond Princess and nine reports on other international cruises), 2 environmental studies, and 1 systematic review. Three articles presented data on both international cruises and the Diamond Princess. The quality of evidence from most studies was low to very low. Index case definitions were heterogeneous. The proportion of traced contacts ranged from 0.19 to 100%. Studies that followed up >80% of passengers and crew reported attack rates (AR) up to 59%. The presence of a distinct dose-response relationship was demonstrated by findings of increased ARs in multi-person cabins. Two studies performed viral cultures with eight positive results. Genomic sequencing and phylogenetic analyses were performed in individuals from three cruises. Two environmental studies reported PCR-positive samples (cycle threshold range 26.21-39.00). In one study, no infectious virus was isolated from any of the 76 environmental samples. CONCLUSION: Our review suggests that crowding and multiple persons per cabin were associated with an increased risk of transmission on cruise ships. Variations in design, methodology, and case ascertainment limit comparisons across studies and quantification of transmission risk. Standardized guidelines for conducting and reporting studies on cruise ships of acute respiratory infection transmission should be developed.

Asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in adults is uncommon using rigorous symptom characterization and follow-up in an acute-care adult hospital outbreak.

Asymptomatic coronavirus disease 2019 (COVID-19) has been reported as a significant driver of COVID-19 outbreaks. Our hospital ward outbreak analysis suggests that comprehensive symptoms and signs assessment, in combination with adequate follow-up, allows a more precise determination of COVID-19 symptoms. Asymptomatic infection was quite uncommon among adults in this setting.

Longitudinal SARS-CoV-2 RNA wastewater monitoring across a range of scales correlates with total and regional COVID-19 burden in a well-defined urban population.

Wastewater-based epidemiology (WBE) is an emerging surveillance tool that has been used to monitor the ongoing COVID-19 pandemic by tracking SARS-CoV-2 RNA shed into wastewater. WBE was performed to monitor the occurrence and spread of SARS-CoV-2 from three wastewater treatment plants (WWTP) and six neighborhoods in the city of Calgary, Canada (population 1.44 million). A total of 222 WWTP and 192 neighborhood samples were collected from June 2020 to May 2021, encompassing the end of the first-wave (June 2020), the second-wave (November end to December 2020) and the third-wave of the COVID-19 pandemic (mid-April to May 2021). Flow-weighted 24-hour composite samples were processed to extract RNA that was then analyzed for two SARS-CoV-2-specific regions of the nucleocapsid gene, N1 and N2, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Using this approach SARS-CoV-2 RNA was detected in 98.06% (406/414) of wastewater samples. SARS-CoV-2 RNA abundance was compared to clinically diagnosed COVID-19 cases organized by the three-digit postal code of affected individuals' primary residences, enabling correlation analysis at neighborhood, WWTP and city-wide scales. Strong correlations were observed between N1 & N2 gene signals in wastewater and new daily cases for WWTPs and neighborhoods. Similarly, when flow rates at Calgary's three WWTPs were used to normalize observed concentrations of SARS-CoV-2 RNA and combine them into a city-wide signal, this was strongly correlated with regionally diagnosed COVID-19 cases and clinical test percent positivity rate. Linked census data demonstrated disproportionate SARS-CoV-2 in wastewater from areas of the city with lower socioeconomic status and more racialized communities. WBE across a range of urban scales was demonstrated to be an effective mechanism of COVID-19 surveillance.

Detection and quantification of infectious severe acute respiratory coronavirus-2 in diverse clinical and environmental samples.

To explore the potential modes of Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) transmission, we collected 535 diverse clinical and environmental samples from 75 infected hospitalized and community patients. Infectious SARS-CoV-2 with quantitative burdens varying from 5 plaque-forming units/mL (PFU/mL) up to 1.0 × 106 PFU/mL was detected in 151/459 (33%) of the specimens assayed and up to 1.3 × 106 PFU/mL on fomites with confirmation by plaque morphology, PCR, immunohistochemistry, and/or sequencing. Infectious virus in clinical and associated environmental samples correlated with time since symptom onset with no detection after 7-8 days in immunocompetent hosts and with N-gene based Ct values ≤ 25 significantly predictive of yielding plaques in culture. SARS-CoV-2 isolated from patient respiratory tract samples caused illness in a hamster model with a minimum infectious dose of ≤ 14 PFU. Together, our findings offer compelling evidence that large respiratory droplet and contact (direct and indirect i.e., fomites) are important modes of SARS-CoV-2 transmission.

Antimicrobial resistance (AMR) in COVID-19 patients: a systematic review and meta-analysis (November 2019-June 2021).

BACKGROUND: Pneumonia from SARS-CoV-2 is difficult to distinguish from other viral and bacterial etiologies. Broad-spectrum antimicrobials are frequently prescribed to patients hospitalized with COVID-19 which potentially acts as a catalyst for the development of antimicrobial resistance (AMR). OBJECTIVES: We conducted a systematic review and meta-analysis during the first 18 months of the pandemic to quantify the prevalence and types of resistant co-infecting organisms in patients with COVID-19 and explore differences across hospital and geographic settings. METHODS: We searched MEDLINE, Embase, Web of Science (BioSIS), and Scopus from November 1, 2019 to May 28, 2021 to identify relevant articles pertaining to resistant co-infections in patients with laboratory confirmed SARS-CoV-2. Patient- and study-level analyses were conducted. We calculated pooled prevalence estimates of co-infection with resistant bacterial or fungal organisms using random effects models. Stratified meta-analysis by hospital and geographic setting was also performed to elucidate any differences. RESULTS: Of 1331 articles identified, 38 met inclusion criteria. A total of 1959 unique isolates were identified with 29% (569) resistant organisms identified. Co-infection with resistant bacterial or fungal organisms ranged from 0.2 to 100% among included studies. Pooled prevalence of co-infection with resistant bacterial and fungal organisms was 24% (95% CI 8-40%; n = 25 studies: I2 = 99%) and 0.3% (95% CI 0.1-0.6%; n = 8 studies: I2 = 78%), respectively. Among multi-drug resistant organisms, methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and multi-drug resistant Candida auris were most commonly reported. Stratified analyses found higher proportions of AMR outside of Europe and in ICU settings, though these results were not statistically significant. Patient-level analysis demonstrated > 50% (n = 58) mortality, whereby all but 6 patients were infected with a resistant organism. CONCLUSIONS: During the first 18 months of the pandemic, AMR prevalence was high in COVID-19 patients and varied by hospital and geography although there was substantial heterogeneity. Given the variation in patient populations within these studies, clinical settings, practice patterns, and definitions of AMR, further research is warranted to quantify AMR in COVID-19 patients to improve surveillance programs, infection prevention and control practices and antimicrobial stewardship programs globally.

Viral load of SARS-CoV-2 in droplets and bioaerosols directly captured during breathing, speaking and coughing.

Determining the viral load and infectivity of SARS-CoV-2 in macroscopic respiratory droplets, bioaerosols, and other bodily fluids and secretions is important for identifying transmission modes, assessing risks and informing public health guidelines. Here we show that viral load of SARS-CoV-2 Ribonucleic Acid (RNA) in participants' naso-pharyngeal (NP) swabs positively correlated with RNA viral load they emitted in both droplets >10 [Formula: see text] and bioaerosols <10 [Formula: see text] directly captured during the combined expiratory activities of breathing, speaking and coughing using a standardized protocol, although the NP swabs had [Formula: see text] 10[Formula: see text] more RNA on average. By identifying highly-infectious individuals (maximum of 18,000 PFU/mL in NP), we retrieved higher numbers of SARS-CoV-2 RNA gene copies in bioaerosol samples (maximum of 4.8[Formula: see text] gene copies/mL and minimum cycle threshold of 26.2) relative to other studies. However, all attempts to identify infectious virus in size-segregated droplets and bioaerosols were negative by plaque assay (0 of 58). This outcome is partly attributed to the insufficient amount of viral material in each sample (as indicated by SARS-CoV-2 gene copies) or may indicate no infectious virus was present in such samples, although other possible factors are identified.

Prolonged SARS-CoV-2 infection following rituximab treatment: clinical course and response to therapeutic interventions correlated with quantitative viral cultures and cycle threshold values.

BACKGROUND: Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is completed through reverse transcriptase-PCR (RT-PCR) from either oropharyngeal or nasopharyngeal swabs, critically important for diagnostics but also from an infection control lens. Recent studies have suggested that COVID-19 patients can demonstrate prolonged viral shedding with immunosuppression as a key risk factor. CASE PRESENTATION: We present a case of an immunocompromised patient with SARS-CoV-2 infection demonstrating prolonged infectious viral shedding for 189 days with virus cultivability and clinical relapse with an identical strain based on whole genome sequencing, requiring a multi-modal therapeutic approach. We correlated clinical parameters, PCR cycle thresholds and viral culture until eventual resolution. CONCLUSIONS: We successfully demonstrate resolution of viral shedding, administration of COVID-19 vaccination and maintenance of viral clearance. This case highlights implications in the immunosuppressed patient towards infection prevention and control that should consider those with prolonged viral shedding and may require ancillary testing to fully elucidate viral activity. Furthermore, this case raises several stimulating questions around complex COVID-19 patients around the role of steroids, effect of antiviral therapies in absence of B-cells, role for vaccination and the requirement of a multi-modal approach to eventually have successful clearance of the virus.

Transmission of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) from pre and asymptomatic infected individuals: a systematic review.

BACKGROUND: The role of SARS-Cov-2-infected persons who develop symptoms after testing (presymptomatics) or not at all (asymptomatics) in the pandemic spread is unknown. OBJECTIVES: To determine infectiousness and probable contribution of asymptomatic persons (at the time of testing) to pandemic SARS-CoV-2 spread. DATA SOURCES: LitCovid, medRxiv, Google Scholar, and WHO Covid-19 databases (to 31 March 2021) and references in included studies. STUDY ELIGIBILITY CRITERIA: Studies with a proven or hypothesized transmission chain based either on serial PCR cycle threshold readings and/or viral culture and/or gene sequencing, with adequate follow-up. PARTICIPANTS: People exposed to SARS-CoV-2 within 2-14 days to index asymptomatic (at time of observation) infected individuals. INTERVENTIONS: Reliability of symptom and signs was assessed within contemporary knowledge; transmission likelihood was assessed using adapted causality criteria. METHODS: Systematic review. We contacted all included studies' corresponding authors requesting further details. RESULTS: We included 18 studies from a diverse setting with substantial methodological variation (this field lacks standardized methodology). At initial testing, prevalence of asymptomatic cases was 12.5-100%. Of these, 6-100% were later determined to be presymptomatic, this proportion varying according to setting, methods of case ascertainment and population. Nursing/care home facilities reported high rates of presymptomatic: 50-100% (n = 3 studies). Fourteen studies were classified as high risk of, and four studies as at moderate risk of symptom ascertainment bias. High-risk studies may be less likely to distinguish between presymptomatic and asymptomatic cases. Six asymptomatic studies and four presymptomatic studies reported culturing infectious virus; data were too sparse to determine infectiousness duration. Three studies provided evidence of possible and three of probable/likely asymptomatic transmission; five studies provided possible and two probable/likely presymptomatic SARS-CoV-2 transmission. CONCLUSION: High-quality studies provide probable evidence of SARS-CoV-2 transmission from presymptomatic and asymptomatic individuals, with highly variable estimated transmission rates.

Transmission of SARS-CoV-2 associated with aircraft travel: a systematic review.

RATIONALE FOR THE REVIEW: Air travel may be associated with viruses spread via infected passengers and potentially through in-flight transmission. Given the novelty of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, transmission associated with air travel is based on transmission dynamics of other respiratory viruses. Our objective was to provide a rapid summary and evaluation of relevant data on SARS-CoV-2 transmission aboard aircraft, report policy implications and to highlight research gaps requiring urgent attention. METHODS: We searched four electronic databases (1 February 2020-27 January 2021) and included studies on SARS-CoV-2 transmission aboard aircraft. We assessed study quality based on five criteria and reported important findings. KEY FINDINGS: We included 18 studies on in-flight SARS-CoV-2 transmission (130 unique flights) and 2 studies on wastewater from aircraft. The quality of evidence from most published studies was low. Two wastewater studies reported PCR-positive samples with high cycle threshold values (33-39). Index case definition was heterogeneous across studies. The proportion of contacts traced ranged from 0.68 to 100%. Authors traced 2800/19 729 passengers, 140/180 crew members and 8/8 medical staff. Altogether, 273 index cases were reported, with 64 secondary cases. Three studies, each investigating one flight, reported no secondary cases. Secondary attack rate among studies following up >80% of passengers and crew (including data on 10 flights) varied between 0 and 8.2%. The studies reported on the possibility of SARS-CoV-2 transmission from asymptomatic, pre-symptomatic and symptomatic individuals. Two studies performed viral cultures with 10 positive results. Genomic sequencing and phylogenetic analysis were performed in individuals from four flights. CONCLUSION: Current evidence suggests SARS-CoV-2 can be transmitted during aircraft travel, but published data do not permit any conclusive assessment of likelihood and extent. The variation in design and methodology restricts the comparison of findings across studies. Standardized guidelines for conducting and reporting future studies of transmission on aircraft should be developed.