Negative Antibody Test Research Articles

PLEURAL FLUID IN A PNEUMOTHORAX: DON'T ANCHOR IN SHALLOW WATER

TOPIC: Chest Infections TYPE: Fellow Case Reports INTRODUCTION: During the 1980's Pneumocystis pneumonia (PCP) was the leading cause of HIV-AIDS related death. The diagnostic standard is by PCR. While pneumocystis is now an incorporated differential in HIV-AIDS patients with respiratory failure, sputum or bronchoalveolar lavage, samples can be difficult to obtain in non-intubated patients. We present a patient being presumptively treated for COVID in the midst of the pandemic, with spontaneous bilateral pneumothoraces and newly diagnosed HIV, for whom analysis of scant pleural fluid led to key diagnostic and treatment implications. CASE PRESENTATION: A 36-year-old, male with no medical history was admitted to an outside hospital for progressive hypoxemic respiratory failure requiring high-flow nasal cannula, secondary to presumptive COVID-19 pneumonia despite several negative PCR and antibody tests. He developed a secondary spontaneous pneumothorax on hospital day 10, for which a pigtail catheter was placed, and he subsequently was transferred to our institution for severe ARDS treatment. Prior to transfer, he received Tocilizumab, dexamethasone, and convalescent plasma per institutional COVID-19 guidelines. Due to persistently low WBC counts and failure to respond to therapy, an HIV test on hospital day 10 resulted positive, as well as a CD-4 count <50 cells/mm3. Due to the new diagnosis of HIV-AIDS, Pneumocystis pneumonia was suspected, and treatment was initiated despite pending diagnostic confirmation. On arrival, existing pigtail chest tube showed intermittent leak with enlarging pneumothorax thus a second tube was placed. After insertion, pleural fluid was sent for cell-count and microbiologic studies resulting in positive PCP. Treatment continued with Trimethoprim-Sulfamethoxazole. The patient ultimately developed bilateral pneumothoraces, required intubation, and subsequent ECMO. DISCUSSION: This case highlights two pertinent clinical points: the under-appreciated diagnostic utility of pleural-fluid sampling, and the importance of recognizing anchoring bias.While PCP is typically diagnosed from sputum or BAL samples, pleural fluid sampling has only been done anecdotally in the context of known PCP infections after prior treatment with Pentamidine. The positive PCP result on pleural fluid analysis confirmed the diagnosis despite the patient being unable to produce sputum and too unstable for BAL. While treatment was initiated empirically, the importance of diagnostic confirmation cannot be understated in a patient being subjected to immunosuppressive therapy and a worsening clinical course. Therefore, the under-appreciated and under-utilized analysis of the scant pleural fluid obtained after pneumothorax decompression, as well as the consequences of anchoring bias are exemplified in this case. CONCLUSIONS: Pneumothrax is a common complication of PCP, and minimal pleural fluid expelled after decompression is an important diagnostic source. REFERENCE #1: Thomas CF, Limper AH. Pneumocystis Pneumonia. N Engl J Med. 2004;350: 2487–2498. doi:10.1056/NEJMra032588 REFERENCE #2: Schaumberg TH, Schnapp LM, Taylor KG, Golden JA. Diagnosis of pneumocystis carinii infection in HIV-seropositive patients by identification of P carinii in pleural fluid. Chest. 1993;103: 1890–1891. REFERENCE #3: Horowitz ML, Schiff M, Samuels J, Russo R, Schnader J. Pneumocystis carinii Pleural Effusion: Pathogenesis and Pleural Fluid Analysis. Am Rev Respir Dis. 1993;148: 232–234. DISCLOSURES: No relevant relationships by Saad Ahmad, source=Web Response No relevant relationships by Alfredo Astua, source=Web Response No relevant relationships by Richard Durrance, source=Web Response No relevant relationships by Jonathan Vincent Reyes, source=Web Response

Analysis of the clinical characteristics of COVID-19 reinfection cases

Objective: To explore the epidemiological and clinical characteristics of COVID-19 reinfection cases. Methods: The published COVID-19 reinfection cases were reviewed and the relevant data were extracted, including the baseline characteristics of patients, the results of antibody tests, and the whole-genome sequencing results of the viral strains. Results: We reviewed 29 reinfection cases in 20 reports from 14 countries. The age of re-infected patients ranged from 21 to 90 years (median 53 years), and there was no significant difference in gender distribution. Among the 29 patients, 11 were health care workers, 6 received immunosuppressive drugs (including glucocorticoids), 17 presented more severe symptoms than their primary infections and 5 (all aged over 80 years) died. The interval of the two infections was usually less than 60 days when the patients were infected by the same viral strain,while the interval was much longer (median 78.5 days) when the patients were infected by different viral strains. Nine patients had negative antibody test results or low antibody titers when the reinfections were confirmed, and 5 of them had negative antibody test results even during the initial infection. Conclusions: Virus-specific antibodies had a protective effect against COVID-19 reinfection for the majority of the population, however, this effect may decrease over time. Occupational exposure, low levels of antibodies, or an inability to produce antibodies may be the main risk factors for reinfection. Advanced age was a major risk factor for a poor prognosis. Effective personal prevention and social distancing were still essential for the prevention of reinfection.

A clinicopathological description of COVID-19-induced chilblains (COVID-toes) correlated with a published literature review.

BackgroundThe abundance of publications of COVID‐19‐induced chilblains has resulted in a confusing situation.MethodsThis is a prospective single‐institution study from 15 March to 13 May 2020. Thirty‐two patients received PCR nasopharyngeal swabs. Of these, 28 patients had a thoracic CT‐scan, 31 patients had blood and urine examinations, 24 patients had skin biopsies including immunohistochemical and direct immunofluorescence studies, and four patients had electron microscopy.ResultsCOVID‐19‐induced chilblains are clinically and histopathologically identical to chilblains from other causes. Although intravascular thrombi are sometimes observed, no patient had a systemic coagulopathy or severe clinical course. The exhaustive clinical, radiological, and laboratory work‐up in this study ruled‐out other primary and secondary causes. Electron microscopy revealed rare, probable viral particles whose core and spikes measured from 120 to 133 nm within endothelium and eccrine glands in two cases.ConclusionThis study provides further clinicopathologic evidence of COVID‐19‐related chilblains. Negative PCR and antibody tests do not rule‐out infection. Chilblains represent a good prognosis, occurring later in the disease course. No systemic coagulopathy was identified in any patient. Patients presenting with acral lesions should be isolated, and chilblains should be distinguished from thrombotic lesions (livedo racemosa, retiform purpura, or ischemic acral necrosis).

Presence of SARS-CoV-2 Antibodies in Spent Peritoneal Dialysate.

Presence of SARS-CoV-2 Antibodies in Spent Peritoneal Dialysate.

Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey

BackgroundCoronaVac, an inactivated whole-virion SARS-CoV-2 vaccine, has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a good humoral response against SARS-CoV-2. We present the interim efficacy and safety results of a phase 3 clinical trial of CoronaVac in Turkey.MethodsThis was a double-blind, randomised, placebo-controlled phase 3 trial. Volunteers aged 18–59 years with no history of COVID-19 and with negative PCR and antibody test results for SARS-CoV-2 were enrolled at 24 centres in Turkey. Exclusion criteria included (but were not limited to) immunosuppressive therapy (including steroids) within the past 6 months, bleeding disorders, asplenia, and receipt of any blood products or immunoglobulins within the past 3 months. The K1 cohort consisted of health-care workers (randomised in a 1:1 ratio), and individuals other than health-care workers were also recruited into the K2 cohort (randomised in a 2:1 ratio) using an interactive web response system. The study vaccine was 3 μg inactivated SARS-CoV-2 virion adsorbed to aluminium hydroxide in a 0·5 mL aqueous suspension. Participants received either vaccine or placebo (consisting of all vaccine components except inactivated virus) intramuscularly on days 0 and 14. The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 at least 14 days after the second dose in the per protocol population. Safety analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04582344) and is active but no longer recruiting.FindingsAmong 11 303 volunteers screened between Sept 14, 2020, and Jan 5, 2021, 10 218 were randomly allocated. After exclusion of four participants from the vaccine group because of protocol deviations, the intention-to-treat group consisted of 10 214 participants (6646 [65·1%] in the vaccine group and 3568 [34·9%] in the placebo group) and the per protocol group consisted of 10 029 participants (6559 [65·4%] and 3470 [34·6%]) who received two doses of vaccine or placebo. During a median follow-up period of 43 days (IQR 36–48), nine cases of PCR-confirmed symptomatic COVID-19 were reported in the vaccine group (31·7 cases [14·6–59·3] per 1000 person-years) and 32 cases were reported in the placebo group (192·3 cases [135·7–261·1] per 1000 person-years) 14 days or more after the second dose, yielding a vaccine efficacy of 83·5% (95% CI 65·4–92·1; p<0·0001). The frequencies of any adverse events were 1259 (18·9%) in the vaccine group and 603 (16·9%) in the placebo group (p=0·0108) with no fatalities or grade 4 adverse events. The most common systemic adverse event was fatigue (546 [8·2%] participants in the vaccine group and 248 [7·0%] the placebo group, p=0·0228). Injection-site pain was the most frequent local adverse event (157 [2·4%] in the vaccine group and 40 [1·1%] in the placebo group, p<0·0001).InterpretationCoronaVac has high efficacy against PCR-confirmed symptomatic COVID-19 with a good safety and tolerability profile.FundingHealth Institutes of Turkey (TUSEB).

Persistence of Anti-SARS-CoV-2 Antibodies Six Months after Infection in an Outbreak with Five Hundred COVID-19 Cases in Borriana (Spain): A Prospective Cohort Study

In March 2020, several mass gathering events were related to the Falles festival in Borriana (Spain), resulting in a 536 laboratory-confirmed COVID-19 cases outbreak among participants. This article estimates anti-SARS-CoV-2 antibodies persistence six months after and factors associated with antibody response. A prospective population-based cohort study was carried out by the Public Health Centre of Castellon and the Emergency and Clinical Analysis and Microbiology Services of Hospital de la Plana in Vila-real. In October 2020, a seroepidemiologic study was used to estimate the persistence of anti-SARS-CoV-2 antibodies against nucleocapsid protein (N) by an electrochemiluminescence immunoassay (ECLIA) was implemented. We enrolled 484 (90.2%) of the 536 members of the initial outbreak cohort and detected persistent antibodies in 479 (99%) without reinfection episodes. Five participants had a negative antibody test. Factors associated with a negative result were a lower body mass index (BMI), and less contact with other COVID-19 cases. Among the 469 participants with two ECLIA tests, 96 (20.5%) had an increase of antibodies and 373 (79.5%) a decline. Increased antibodies were associated with older age, higher BMI, more severe illness, and low current smokers. Our results show that after a COVID-19 infection, a high proportion of cases maintain detectable anti-SARS-CoV-2 antibodies.

Factors for Negative Result in Serum Anti-Helicobacter pylori IgG Antibody Test in Adult Subjects With Nodular Gastritis: A Single-center Study.

Aim: Nodular gastritis has been demonstrated to be strongly associated with Helicobacter pylori infection. The present retrospective study was performed to elucidate factors related to a negative serum antibody test result in adults with nodular gastritis.Materials and methods: We investigated 116 H. pylori-positive subjects endoscopically diagnosed with nodular gastritis and subjected to a serum anti-H. pylori immunoglobulin G (IgG) antibody test. The degree of gastric mucosal atrophy and the presence of spotty redness in the gastric body and fornix were carefully determined by observations of endoscopic images.Results: Of the 116 investigated subjects, 108 were positive and 8 negative in serum anti-H. pylori IgG antibody test results. The degree of gastric mucosal atrophy was mild in seven among eight seronegative cases. The levels of pepsinogen II in serum in patients with negative antibody test findings were significantly lower as compared to those found positive, while the pepsinogen I/II ratio tended to be higher in subjects shown negative by the test. Only 1 of 69 with spotty redness was negative in serum anti-H. pylori IgG antibody testing, while 7 of 47 without spotty redness were negative. Multiple logistic regression analysis of subjects with a negative test result revealed that the absence of spotty redness shown by endoscopy was a significant risk factor.Conclusion: The absence of spotty redness, which may reflect the degree of gastric body inflammation, is a significant factor indicating increased risk for a negative serum anti-H. pylori IgG antibody test result in subjects with nodular gastritis.

Anti-neutrophil cytoplasmic antibody-associated vasculitis accompanied by type II heparin-induced thrombocytopenia resulting in asymptomatic cerebral infarction: a case report

BackgroundHeparin-induced thrombocytopenia (HIT) involves platelet activation and aggregation caused by heparin or HIT antibodies associated with poor survival outcomes. We report a case of HIT that occurred after hemodialysis was started for rapidly progressive glomerulonephritis (RPGN), which was caused by anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), and ultimately resulted in asymptomatic cerebral infarction.Case presentationA 76-year-old Japanese man was urgently admitted to our hospital for weight loss and acute kidney injury (serum creatinine: 12 mg/dL). Hemodialysis therapy was started using heparin for anticoagulation. Blood testing revealed elevated titers of myeloperoxidase anti-neutrophil cytoplasmic antibodies, and renal biopsy revealed crescentic glomerulonephritis with broad hyalinization of most of the glomeruli and a pauci-immune staining pattern. These findings fulfilled the diagnostic criteria for microscopic polyangiitis, and the patient was diagnosed with RPGN caused by AAV. Steroid pulse therapy, intermittent pulse intravenous cyclophosphamide, and oral steroid therapy failed to improve the patient’s renal function, and maintenance dialysis was started. However, on day 15, his platelet count had decreased to 47,000/µL, with clotting observed in the hemodialysis catheter. Magnetic resonance imaging of the head identified acute asymptomatic brain infarction in the left occipital lobe, and a positive HIT antibody test result supported a diagnosis of type II HIT. During hemodialysis, the anticoagulant treatment was changed from heparin to argatroban. Platelet counts subsequently normalized, and the patient was discharged. A negative HIT antibody test result was observed on day 622.ConclusionsThere have been several similar reports of AAV and HIT co-existence. However, this is a rare case report on cerebral infarction with AAV and HIT co-existence. Autoimmune diseases are considered risk factors for HIT, and AAV may overlap with other systemic autoimmune diseases. To confirm the relationship between these two diseases, it is necessary to accumulate more information from future cases with AAV and HIT co-existence. If acute thrombocytopenia and clotting events are observed when heparin is used as an anticoagulant, type II HIT should always be considered in any patient due to its potentially fatal thrombotic complications.

Atypical COVID-19 dynamics in a patient with mantle cell lymphoma exposed to rituximab

Patients with non-hodgkin lymphomas (NHL) represent a population of special interest during the current Coronavirus disease-19 (COVID-19) pandemics. NHLs are associated with disease- and treatment-related immunodeficiencies which may generate unusual COVID-19 dynamics and pose unique management challenges. We report the unusual clinical course of COVID-19 in a patient with mantle cell lymphoma (MCL) exposed to nine doses of Rituximab shortly before infection with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). He had a prolonged asymptomatic phase, with negative molecular and antibody testing for SARS-CoV-2, followed by a rapidly progressive evolution to severe COVID-19. Despite detection of viral RNA overlapped with first symptoms occurrence, anti-SARS-CoV-2 antibodies displayed an asynchronous pattern, with IgG first appearing 2 days after RNA positivity and IgM never being detected throughout the entire clinical course. While disease-associated immune derangements and/or previous treatments involving anti-CD20 antibodies might have contributed to COVID-19 dynamics in our patient, data suggests that antibody testings, without concurrent molecular assessment for SARS-CoV-2, may turn inadequate for monitoring of MCL patients, and in general NHL patients heavily exposed to anti-CD20 antibodies, during the current pandemics. We suggest that repeated molecular testing of nasopharyngeal swab should be implemented in these subjects despite a negative serology and absence of symptoms of SARS-CoV-2 infection. For the same reasons, a customized strategy needs to be developed for patients exposed to anti-CD20 antibodies, based on different features and mechanism of action of available SARS-CoV-2 vaccines and novel vaccinomics developments.

Prevalence and predictors of SARS-CoV-2 antibodies among solid organ transplant recipients with confirmed infection.

It remains uncertain whether immunocompromised patients including solid organ transplant (SOT) recipients will have a robust antibody response to SARS‐CoV‐2 infection. We enrolled all adult SOT recipients at our center with confirmed SARS‐CoV‐2 infection who underwent antibody testing with a single commercially available anti‐nucleocapsid antibody test at least 7 days after diagnosis in a retrospective cohort. Seventy SOT recipients were studied (56% kidney, 19% lung, 14% liver ± kidney, and 11% heart ± kidney recipients). Thirty‐six (51%) had positive anti‐nucleocapsid antibody testing, and 34 (49%) were negative. Recipients of a kidney allograft were less likely to have positive antibody testing compared to those who did not receive a kidney (p = .04). In the final multivariable model, the years from transplant to diagnosis (OR 1.26, p = .002) and baseline immunosuppression with more than two agents (OR 0.26, p = .03) were significantly associated with the antibody test result, controlling for kidney transplantation. In conclusion, among SOT recipients with confirmed infection, only 51% of patients had detectable anti‐nucleocapsid antibodies, and transplant‐related variables including the level and nature of immunosuppression were important predictors. These findings raise the concern that SOT recipients with COVID‐19 may be less likely to form SARS‐CoV‐2 antibodies.

Acceptability of blood-based HIV self-testing among adolescents aged 15-19 years at risk of HIV acquisition in Bangkok.

Young men who have sex with men (YMSM) and young transgender women (YTGW) in Thailand are at high HIV risk. HIV self-tests (HIVSTs) are rapidly administrable and prompt linkage to HIV treatment or prevention services. This study assesses the acceptability and feasibility of blood-based HIVST use in adolescents. A cross-sectional study was conducted among YMSM and YTGW aged 15-19years with HIV acquisition risk. Participants completed questionnaires on the HIVST and then administered INSTI® independently, an HIVST immunoassay detecting gp41 and gp36 antibodies from finger-stick blood. Confirmatory HIV antibody tests were performed. Between July and September 2020, 90 adolescents were enrolled. Mean (SD) age was 17.6 (1.1) years. Half (N = 45) were YMSM. Forty-six (51%) were first-time HIV testers, and 32 (36%) had "ever used" HIV pre-exposure prophylaxis (PrEP). Two (2.2%, 95% CI: 0.0-5.3) tested positive, 21 (23.4%) invalid, and 67 (74.4%) negative. Invalidity causes included 17 (81%) insufficient blood, 3 (14%) buffer spillage, and 1 (5%) procedural missteps; all had negative HIV antibody tests. HIV self-test acceptability was 87.8% (95% CI: 81.0-94.5). Most (79%) preferred HIVST performance in hospital rather than at home. HIVSTs are acceptable in HIV at-risk adolescents. Blood-based HIVSTs should be positioned as rapid point-of-care tests with real-time linkage to HIV services.

Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection

Understanding the effect of serum antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on susceptibility to infection is important for identifying at-risk populations and could have implications for vaccine deployment. The study purpose was to evaluate evidence of SARS-CoV-2 infection based on diagnostic nucleic acid amplification test (NAAT) among patients with positive vs negative test results for antibodies in an observational descriptive cohort study of clinical laboratory and linked claims data. The study created cohorts from a deidentified data set composed of commercial laboratory tests, medical and pharmacy claims, electronic health records, and hospital chargemaster data. Patients were categorized as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test in the database. Primary end points were post-index diagnostic NAAT results, with infection defined as a positive diagnostic test post-index, measured in 30-day intervals (0-30, 31-60, 61-90, >90 days). Additional measures included demographic, geographic, and clinical characteristics at the time of the index antibody test, including recorded signs and symptoms or prior evidence of coronavirus 2019 (COVID) diagnoses or positive NAAT results and recorded comorbidities. The cohort included 3 257 478 unique patients with an index antibody test; 56% were female with a median (SD) age of 48 (20) years. Of these, 2 876 773 (88.3%) had a negative index antibody result, and 378 606 (11.6%) had a positive index antibody result. Patients with a negative antibody test result were older than those with a positive result (mean age 48 vs 44 years). Of index-positive patients, 18.4% converted to seronegative over the follow-up period. During the follow-up periods, the ratio (95% CI) of positive NAAT results among individuals who had a positive antibody test at index vs those with a negative antibody test at index was 2.85 (95% CI, 2.73-2.97) at 0 to 30 days, 0.67 (95% CI, 0.6-0.74) at 31 to 60 days, 0.29 (95% CI, 0.24-0.35) at 61 to 90 days, and 0.10 (95% CI, 0.05-0.19) at more than 90 days. In this cohort study, patients with positive antibody test results were initially more likely to have positive NAAT results, consistent with prolonged RNA shedding, but became markedly less likely to have positive NAAT results over time, suggesting that seropositivity is associated with protection from infection. The duration of protection is unknown, and protection may wane over time.

Subclinical Hepatitis C Virus Infection in Patients with Chronic Obstructive Pulmonary Disease: Evidence from a Cross-Sectional Multicenter Observation Study

Background: Patients with hepatitis virus C (HCV) infection have declined levels of forced expiratory volume (FEV), which is a prognostic marker for chronic obstructive pulmonary disease (COPD). Objectives: The current study primarily aimed to investigate the incidence of subclinical HCV infection (clinical signs are absent but positive HCV RNA test performed by polymerase chain reaction) in patients with COPD of Zhejiang province, China, and its secondary aim was to investigate the clinical influence of HCV infection on COPD severity by body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) scoring index and pulmonary function tests (PFT). Methods: A total of 252 patients with COPD (confirmed by routine lab tests, BODE index, and PFT) were included in a cross-sectional multicenter study. An anti-HCV antibody test was used to diagnose HCV infection. Hepatitis virus C RNA was tested for patients with a HCV antibody-positive test. Results: Twelve patients had a positive anti-HCV antibody test. Of 12 anti-HCV antibody positive test patients, 10 were positive for the HCV RNA. The prevalence of anti-HCV antibody positivity and HCV RNA positivity was 12/ 252 and 10/ 252, respectively. The partial arterial pressure of oxygen was the same for patients with HCV RNA positive test compared to those with a negative anti-HCV antibody test (59.70 ± 5.50 mmHg vs. 63.84 ± 15.63 mmHg, P = 0.791). Patients with a positive HCV RNA test had a higher partial arterial pressure of carbon dioxide compared to those with a negative anti-HCV antibody test (43.70 ± 1.89 mmHg vs. 49.42 ± 7.33 mmHg, P = 0. 007). BODE index was higher for patients with HCV RNA positive test than those with anti-HCV antibody test negative (6 (3 - 7) vs. 4 (2 - 6), P &lt; 0.0001). Among the variables of BODE index scoring, the values of distance walked in 6 min (P &lt; 0.0001) and % predicted forced expiratory volume in 1 s (P &lt; 0.0001) were fewer for patients with HCV RNA positive test than those with a negative anti-HCV antibody test. Conclusion: This study demonstrated that subclinical HCV infection may be observed in COPD patients.

Seroprevalence of SARS‐CoV‐2 IgG antibodies in the current COVID‐19 pandemic amongst co‐workers at a UK renal transplant centre

INTRODUCTION: As lock-downs and social distancing measures around the world begin to ease after the global SARS-CoV-2 (COVID-19) pandemic, discussions surrounding immunity and antibody testing are on the rise. This single-centre observational study reports data from a UK renal transplant centre with regards to seroprevalence amongst staff members. Members of staff were tested for SARS-CoV-2 antibodies (IgG) with Abbott International assays. Electronic records were accessed for PCR RNA and antibody results, with data anonymised by hospital number. IgA antibodies were not tested due to test kit availability during this period. 200 members of staff (25% male, 75% female, mean age 45.3 ± 12.0 years) were tested for SARS-CoV-2 antibodies with 24/200 (12.0%) positive. Most interestingly, 2/30 (6.6%) co-workers had positive nose/throat RNA PCR but negative antibody tests. This study demonstrates that frontline healthcare workers have a relatively low seroprevalence rate of specific SARS-CoV-2 IgG antibodies. To further evaluate this, larger patient populations, multicentre studies and different antibody assays are needed to better understand whether detection of antibodies is suggestive of previous SARS-CoV-2 exposure.

SARS-CoV-2 serological cross-reactivity with autoantibodies.

In their report on the detection of IgM and IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with autoimmune diseases, Teng and colleagues1 found that the serological test that they assessed showed no cross-reactivity with autoantibodies present in patients with autoimmune disease. However, several potential confounding factors should be considered when assessing the study findings. Hypogammaglobulinaemia (reduced serum immunoglobulin concentrations) might result in false negative antibody test results; therefore, quantitative serum immunoglobulin measurements should be used to interpret SARS-CoV-2 serology results, along with knowledge of any patient history of immunodeficiencies.

COVID-19 Impact on Lymphoma Patients' Clinical Outcomes - an Observational Cohort Study

COVID-19 Impact on Lymphoma Patients' Clinical Outcomes - an Observational Cohort Study

O04 Large vessel vasculitis related to COVID-19 infection

Case report - IntroductionBy June 2020, 175,000 cases of COVID-19 had been identified in London alone. The most common symptoms include fever, headache, loss of smell, cough, myalgia, and sore throat. The major complication is acute respiratory distress syndrome (ARDS) but systemic complications such as cardiomyopathy, acute kidney injury, encephalopathy and coagulopathy are being identified. A delayed multi-system inflammatory syndrome in children has also been recognised and further complications are likely to be identified as our experience increases. Here, we report the case of a patient with large vessel vasculitis who initially presented with symptoms highly likely to be due to COVID-19 infection.Case report - Case descriptionA 36-year-old black African nurse presented in May 2020, with acute onset 7 days prior of high-grade fevers, rigors, nights sweats, generalised myalgia, sore throat, headache with photophobia, anosmia, dysgeusia and a widespread rash. She was a smoker with no other relevant medical, travel nor sexual history, and no drug use. A COVID-19 swab on day 2 had been negative and she had taken a course of Doxycycline.Examination revealed firm palpable subcutaneous nodules on lower limbs, upper back and forehead and cervical lymphadenopathy. She was photophobic with no meningism. The rest of her physical examination was normal. BP was 116/97 mmHg, heart rate 109 bpm and satO2 100%. Investigations demonstrated C-reactive protein 330mg/L, erythrocyte sedimentation rate 140, Ferritin 479, lymphopaenia 0.7x109, eGFR 54 with no haematoproteinuria, D-dimer 3.05 mg/L with INR 1.1, aPTT 1.3, fibrinogen 8.8 g/L. Hb, WCC, liver function, CK, serum ACE and triglycerides were normal. Infectious screen revealed negative blood cultures, HIV, Hepatitis B and C, EBV, CMV and Treponema pallidum serology. CT brain and CSF analysis were normal including bacterial culture and viral PCR. ANA, ENA, dsDNA, ANCA and aPL antibodies were negative with normal complement levels. Throat swab grew group A streptococcus and she was treated with broad spectrum antibiotics for 7 days maintaining fevers up to 39oC. Skin biopsy was non-specific with negative direct immunofluorescence but showed microvascular thrombi in the papillary dermis. COVID-19 PCR tests (three naso-pharyngeal swabs and one stool PCR) and IgG test (day 38) were negative. CT showed no pneumonitis but non-specific retroperitoneal stranding with medium/large vessel vasculitis involving both proximal renal arteries and a 6 cm segment of mid abdominal aorta on PET-CT. We started oral prednisolone 40mg with immediate resolution of her fevers, myalgia, and inflammatory markers, remaining well a month later.Case report - DiscussionTakayasu’s arteritis is the most common autoimmune large vessel vasculitis (LVV) affecting young females and involves inflammation of the arterial wall ultimately resulting in stenosis and obstruction of the vessel. However, it is rare in patients with African heritage and usually presents with a prolonged prodromal phase. Given the atypical presentation and symptoms consistent with COVID-19 infection we feel that this patients’ LVV may have been a complication of COVID-19 infection. The relationship between infections and vasculitis is complex. TB and syphilis cause aortitis and a relationship between infection and vasculitis has been proven in HBV associated PAN and HCV associated cryoglobulinemia.Experimental data supports a possible association between CMV and herpes virus and Takayasu arteritis. It could, therefore, be hypothesised that COVID-19 infection can trigger LVV. Our patient had a throat swab positive for Streptococcus pyogenes which is an uncommon cause of infective endocarditis and mycotic aneurism, but this patient had no evidence of either endocarditis or aneurism formation and so it was felt the throat swab finding was incidental. Our patient had repeated negative COVID-19 nasopharyngeal swabs and a negative antibody test at day 38.Although this argues against a diagnosis of COVID-19 related illness, the relative lack of information we currently have regarding sensitivities of the tests, at what point COVID-19 PCR becomes negative in the illness and when/if patients develop antibodies, means these negative tests in the presence of typical symptoms cannot exclude the diagnosis. We believe this case is extremely important to highlight a possible novel inflammatory complication of COVID-19 infection. We decided to treat this patient in line with guidance for the management of LVV, including the introduction of methotrexate, but it will be interesting to observe her long-term outcome. Case report - Key learning points Increasing numbers of COVID-19 related systemic inflammatory conditions are likely to be recognised over the coming months. We present the case of patient with large vessel vasculitis who initially presented atypically with symptoms consistent with COVID-19 infectionTo identify these complications, COVID-19 symptoms questioning should be part of any routine medical historyMore information is required regarding the sensitivity of COVID-19 PCR and antibody tests to aid the diagnosis of these conditionsThe long-term management of inflammatory conditions associated with COVID-19 infection is not clear and a discussion is warranted as to whether DMARDs should be initiated

HIV seronegativity in children, adolescents and young adults living with perinatally acquired HIV: A cross-sectional study in Thailand.

IntroductionEarly initiation of combination antiretroviral therapy (ART) with long‐term viral suppression may lead to seronegativity in grown‐up children with perinatally acquired HIV (PHIV). This study aimed to determine the frequency and associated factors of seronegativity in Thai children, adolescents and young adults with PHIV.MethodsA cross‐sectional HIV serological study was performed in children, adolescents and young adults two years or older who were receiving ART with undetectable HIV‐RNA for at least one year from August 2018 to August 2019. Medical records were extracted for multivariate analysis of independent factors for seronegativity.Results and discussionOf 110 patients, 50 male, median (range) age was 18.4 (4.8 to 26.6) years, 8 (7.3%) were seronegative, and 1 (0.9 %) was inconclusive. The seronegative group had a younger median (range) age at ART initiation: 3.0 (1.0 to 12.0) versus 40.0 (2.0 to 207.0) months, p = 0.045; and shorter median (range) duration from ART initiation to viral suppression: 16.8 (7.2 to 42.0) versus 55.2 (6.0 to 214.8) months, p = 0.036. Multivariate analysis identified younger age at ART initiation (aOR 0.69, 95% CI 0.49 to 0.98, p = 0.038) and shorter time to viral suppression after ART initiation (aOR 0.94, 95% CI 0.89 to 0.99, p = 0.019) as independent factors associated with HIV seronegativity. Of the infants who initiated ART < 3 and between three and six months of age, 50% and 26.7% became seronegative respectively.ConclusionsHIV seronegativity was observed in children and adolescents with PHIV who initiated ART early in infancy and had rapid and sustained virological response. Awareness of this phenomenon will help avoid inappropriate treatment interruption on the basis of negative antibody testing.

Tracheostomy for Coronavirus Disease 2019 Patients: Maintaining the Standard of Care.

Objectives:To respond to the new recommendations for delaying tracheostomy for coronavirus disease 2019 patients to day 21 post-intubation to ensure viral clearance.Design:Prospective observational cohort from April 1, 2020, to April 30, 2020, with 60 days follow-up.Setting:Academic medical center with nine adult ICUs dedicated to caring for coronavirus disease 2019 patients requiring mechanical ventilation.Patients:Mechanically ventilated patients with coronavirus disease 2019 pneumonia requiring tracheostomy for prolonged ventilatory support.Interventions:Adherence to the standard of care for timing of tracheostomy as deemed necessary by the intensivist without delay and utilizing the existing tracheostomy team in performing the needed procedures within 1 day of the request.Measurements and Main Results:One hundred eleven patients with coronavirus disease 2019 received tracheostomy in the month of April 2020. Median time to tracheostomy was 11 days. All procedures were performed percutaneously at bedside under bronchoscopic guidance. Sixty-three percent of patients who received tracheostomy either weaned or discharged alive within 60 days of the procedure. Performing tracheostomy on these patients without delay did not lead to coronavirus disease 2019 viral transmission to the tracheostomy team as evident by lack of symptoms and negative antibody testing.Conclusions:Adherence to standard of care in timing of tracheostomy is safe. Recommending delaying the procedure may lead to harmful consequences from prolonging mechanical ventilation and sedation without apparent benefit.

How to Manage Pediatric Orthopaedic Patients: Strategies to Provide Safer Care During the COVID-19 Outbreak in Wuhan, People's Republic of China.

How to Manage Pediatric Orthopaedic Patients: Strategies to Provide Safer Care During the COVID-19 Outbreak in Wuhan, People's Republic of China.