Comparison of clinical characteristics between patients with coronavirus disease 2019 (COVID-19) who retested RT-PCR positive versus negative: a retrospective study of data from Nanjing

BackgroundThe epidemiological and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) have been reported. However, the prevalence of retesting positive by RT-PCR for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated patient characteristics, remain unclear.MethodsWe included 90 confirmed cases of COVID-19 treated in the Nanjing Public Health Center from January 20, 2020 to February 16, 2020 in this retrospective study. All patients completed treatment for COVID-19 and were retested by RT-PCR for SARS-CoV-2 4–20 days after completion of therapy. The clinical characteristics between patients with who retested positive versus negative by RT-PCR were compared, and the factors predictive of positive retesting were analyzed. Positive retesting was modeled with the area under the receiver operating characteristic curve (AUC).ResultsThe age range of the study population was 0.8–97 years, and all patients were cured or showed improvement. A total of 10 (11%) patients retested positive by RT-PCR 4–20 days after completion of therapy. As compared with patients who retested negative, those who retested positive had a lower percentage of pre-admission fever, a higher percentage of post-admission fever, a lower percentage of bilateral lung infection, higher white blood cell (WBC) count and creatine phosphokinase, and lower hypersensitive c-reactive protein (hs-CRP), interleukin-6 and erythrocyte sedimentation rates (all P<0.05). Logistic regression analysis of the above eight key variables showed that lower hs-CRP and higher WBC were independently associated with positive retesting by RT-PCR. A combination of hs-CRP and WBC were predictive of positive retesting, with an AUC of 0.859.ConclusionsPatients with COVID-19 who retested positive by RT-PCR for SARS-CoV-2 had mild symptoms and better blood testing results. A combination of hs-CRP and WBC may predict positive retesting by RT-PCR; however, the sensitivity and specificity should be studied further.     

Myelin oligodendrocyte glycoprotein antibody-associated optic neuritis in a COVID-19 patient: A case report

Rationale:Coronavirus disease 2019 (COVID-19) has spread worldwide. It involves multiple organs of infected individuals and encompasses diverse clinical manifestations. We report a case of acute optic neuritis (ON) associated with myelin oligodendrocyte glycoprotein (MOG) antibody possibly induced by COVID-19.Patient concerns:A 47-year-old man presented to our clinic with left eye pain and vision loss. Magnetic resonance imaging of the orbit revealed the bilateral high intensity of the optic nerve sheaths. He tested positive for COVID-19 by polymerase chain reaction (PCR) testing on the day of admission but he had no signs of respiratory illness. Laboratory testing revealed that MOG immunoglobulin G (MOG IgG) was positive, but other antibodies including aquaporin-4 were negative.Diagnosis:The patient was diagnosed with MOG antibody-positive acute ON possibly induced by COVID-19.Interventions:Steroid pulse therapy consisting of methylprednisolone 1 g/day for a total of 3 days, followed by an oral prednisolone taper was performed.Outcomes:His left eye pain was immediately relieved, and his decimal vision improved from 0.03 to 0.1 on the day of discharge. Outpatient follow-up 2 weeks later revealed left a decimal vision of 1.2, and a complete resolution of the left eye pain.Lessons:Our case indicated that COVID-19 might trigger an autoimmune response that leads to MOG antibody-associated ON, similar to other pathogens that were reported in the past. The treatment response to steroid pulse therapy was preferable following a typical course of MOG antibody-positive ON.     

Prolonged viral positivity induced recurrent coronavirus disease 2019 (COVID-19) pneumonia in patients receiving anti-CD20 monoclonal antibody treatment: Case reports

Introduction:The outbreak of novel coronavirus (severe acute respiratory syndrome coronavirus 2), which causes the coronavirus disease 2019 (COVID-19), is the most important current health problem. The number of patients is increasing worldwide. Pneumonia is the most life-threatening complication of the disease. Prolonged viral shedding in hematological patients with COVID-19 has been demonstrated; however, data on COVID-19 patients receiving anti-CD20 monoclonal antibody therapy are limited. Accordingly, focusing on humoral immunity, herein, we present 4 COVID-19 patients who were on anti-CD20 monoclonal antibody treatment and had prolonged pneumonia.Patient concerns:Two of 4 patients were on rituximab and the other 2 were on obinutuzumab therapy.Diagnosis:The polymerase chain reaction test results for severe acute respiratory syndrome coronavirus 2 were positive for all 4 patients and their COVID pneumonia lasted for >50 days.Interventions:Although all patients were treated with an adequate amount of convalescent plasma, prolonged polymerase chain reaction positivity and prolonged pneumonia were possibly due to the lack of ability of the immune system to initiate its antibody response.Outcomes:Despite the administration of standard therapies, recurrent pneumonia observed in the present case series of non-neutropenic patients, in whom primary malignancies were under control.Conclusions:It is suggested that further investigations should be performed to understand the underlying pathophysiology.     

Systematic Review of COVID-19 Related Myocarditis: Insights on Management and Outcome

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also referred to as COVID-19, was declared a pandemic by the World Health Organization in March 2020. The manifestations of COVID-19 are widely variable and range from asymptomatic infection to multi-organ failure and death. Like other viral illnesses, acute myocarditis has been reported to be associated with COVID-19 infection. However, guidelines for the diagnosis of COVID-19 myocarditis have not been established.MethodsUsing a combination of search terms in the PubMed/Medline, Ovid Medline and the Cochrane Library databases and manual searches on Google Scholar and the bibliographies of articles identified, we reviewed all cases reported in the English language citing myocarditis associated with COVID-19 infection.ResultsFourteen records comprising a total of fourteen cases that report myocarditis/myopericarditis secondary to COVID-19 infection were identified. There was a male predominance (58%), with the median age of the cases described being 50.4 years. The majority of patients did not have a previously identified comorbid condition (50%), but of those with a past medical history, hypertension was most prevalent (33%). Electrocardiogram findings were variable, and troponin was elevated in 91% of cases. Echocardiography was performed in 83% of cases reduced function was identified in 60%. Endotracheal intubation was performed in the majority of cases. Glucocorticoids were most commonly used in treatment of myocarditis (58%). Majority of patients survived to discharge (81%) and 85% of those that received steroids survived to discharge.ConclusionGuidelines for diagnosis and management of COVID-19 myocarditis have not been established and our knowledge on management is rapidly changing. The use of glucocorticoids and other agents including IL-6 inhibitors, IVIG and colchicine in COVID-19 myocarditis is debatable. In our review, there appears to be favorable outcomes related to myocarditis treated with steroid therapy. However, until larger scale studies are conducted, treatment approaches have to be made on an individualized case-by-case basis.     

COVID-19: A year later: COVID-19 outbreak in a personal service setting in Kingston,Ontario, 2020

BackgroundDuring the coronavirus disease 2019 (COVID-19) pandemic, Ontario created a three-phase reopening framework for the economy. Outbreaks were expected at each phase. One week after Phase Two of reopening in the provincial public health administration region of Kingston, Frontenac, Lennox and Addington (KFL&A), a positive case was reported after three weeks of zero new COVID-19 cases. The objective of this report is to describe this COVID-19 outbreak, linked to a personal service setting (PSS), and the public health response to contain the outbreak.MethodsThe outbreak investigation included all COVID-19 cases in KFL&A between June 20, 2020 and July 3, 2020. Public health inspectors and nurses were rapidly deployed to inspect the PSS. A multimodal approach to high-volume testing involved fixed assessment centres, drive-through testing capacity and targeted testing at the outbreak site. Testing was conducted through a real-time polymerase chain reaction assay at the local Public Health Ontario laboratory.ResultsThirty-seven cases were associated with the outbreak: 38% through direct PSS exposure; 32% through household contact; and 30% through social and workplace contact. A superspreading event contributed to 38% of total cases. The majority of cases were in the low to mid-quintiles when analyzed for material deprivation. Testing rates increased four-fold compared to the prior baseline weeks in response to media attention and public health messaging, resulting in a low percent positivity.ConclusionThe interplay of aggressive accessible testing, quick lab turnaround time, contact tracing within 24 hours of positive laboratory results as per provincial standards, frequent public communication, rapid inspections, mandatory self-isolation and face coverings were measures successful in halting the outbreak. Inspections or self-audits should be required at all PSSs prior to reopening and outbreak management must work with PSSs to reduce the possibility of superspreading events.     

Clinical usefulness of tomographic standards for COVID-19 pneumonia diagnosis: Experience from a Brazilian reference center

BackgroundCOVID-19 is a new disease and the most common complication is pneumonia. The Radiological Society of North America (RSNA) proposed an expert consensus for imaging classification for COVID-19 pneumonia.ObjectiveTo evaluate sensitivity, specificity, accuracy, and reproducibility of chest CT standards in the beginning of the Brazilian COVID-19 outbreak.MethodsCross-sectional study performed from March 1st to April 14th, 2020. Patients with suspected COVID-19 pneumonia submitted to RT-PCR test and chest computed tomography (CT) were included. Two thoracic radiologists blinded for RT-PCR and clinical and laboratory results classified every patient scan according to the RSNA expert consensus. A third thoracic radiologist also evaluated in case of discordance, and consensus was reached among the three radiologists. A typical appearance was considered a positive chest CT for COVID-19 pneumonia. Sensitivity, specificity, positive and negative predictive values were calculated. Cohen’s kappa coefficient was used to evaluate intra- and inter-rater agreements.ResultsA total of 159 patients were included (mean age 57.9 ± 18.0 years; 88 [55.3%] males): 86 (54.1%) COVID-19 and 73 (45.9%) non-COVID-19 patients. Eighty (50.3%) patients had a positive CT for COVID-19 pneumonia. Sensitivity and specificity of typical appearance were 88.3% (95%CI, 79.9–93.5) and 94.5% (95%CI, 86.7–97.8), respectively. Intra- and inter-rater agreement were assessed (Cohen’s kappa = 0.924, P = 0.06; Cohen’s kappa=0.772, P = 0.05, respectively).ConclusionChest CT categorical classification of COVID-19 findings is reproducible and demonstrates high level of agreement with clinical and RT-PCR diagnosis of COVID-19. In RT-PCR scarcity scenarios or in equivocal cases, it may be useful for attending physicians in the evaluation of suspected COVID-19 pneumonia patients attended at the emergency unit.     

The Proportion of Long-term Response to Anti-N IgG Antibody after 12 Months for COVID-19 Subclinical Infections and a Longitudinal Survey for COVID-19 Subclinical Infections in 2021

Objective To examine the continuation of antibody prevalence status after 12 months and background factors in antibody-positive subjects following asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We initially determined the SARS-CoV-2 anti-nucleocapsid protein immunoglobulin G (anti-N IgG) antibody prevalence in 1,603 patients, doctors, and nurses at 65 medical institutions in Kanagawa Prefecture, Japan. We then obtained consent from 33 of the 39 subjects who tested positive and performed follow-up for 12 months. Results Follow-up for up to 12 months showed that a long-term response of the anti-N IgG antibody could be detected in 6 of the 33 participants (18.2%). The proportions with hypertension, using an angiotensin-receptor blocker, and without a drinking habit were higher among the participants with a long-term anti-N IgG antibody response for up to 12 months than among those without a long-term antibody response. Conclusions The proportion of individuals with subclinical COVID-19 who continuously had a positive result for the anti-N IgG antibody at 12 months was low.     

Performance of an alternative RT-PCR procedure using residual sample from the Panbio™ Ag COVID-19 test

IntroductionIn the current standard of care (SoC) RT-PCR method for COVID-19, the patient's swab was extracted in viral transport media (VTM). For the Panbio™ COVID-19 Ag Rapid Test, the patient swab is flushed out in extraction buffer, of which a small fraction is used for testing, leaving more than half the sample unused. This study was designed to show that RT-PCR results from the residual sample of the Panbio™ COVID-19 Ag Rapid Test (called Novel RT-PCR) are not worse than the SoC RT-PCR result.MethodsThe study was performed using (1) dilution series of five patient samples, and (2) 413 patient samples comparing SOC versus Novel RT-PCR results.ResultsFor the dilution series samples, all tested positive by both methods. The bias between Ct values of Novel RT-PCR and SoC RT-PCR did not exceed 3.00 Ct using primers N1 and N2. A total of 413 COVID symptomatic patients seeking COVID testing were tested, of which 89 patients tested positive and 324 tested negative with SoC RT-PCR. In 324 patients who tested negative with SoC RT-PCR, 323 tested negative with Novel RT-PCR, and one (1) tested positive. Out of 89 who tested positive with SoC RT-PCR, 80 tested positive with the Novel RT-PCR, and nine patients showed a negative test result. The Overall Percent Agreement for the 413 valid patient sample pairs was 97.5 [95% CI 97 to 98].ConclusionThe study demonstrated that the performance of the Novel RT-PCR method is acceptable compared to the SoC RT-PCR method and can be a useful tool to perform RT-PCR without the need for new swab collections.     

Optimal symptom combinations to aid COVID-19 case identification: Analysis from a community-based,prospective, observational cohort

ObjectivesDiagnostic work-up following any COVID-19 associated symptom will lead to extensive testing, potentially overwhelming laboratory capacity whilst primarily yielding negative results. We aimed to identify optimal symptom combinations to capture most cases using fewer tests with implications for COVID-19 vaccine developers across different resource settings and public health.MethodsUK and US users of the COVID-19 Symptom Study app who reported new-onset symptoms and an RT-PCR test within seven days of symptom onset were included. Sensitivity, specificity, and number of RT-PCR tests needed to identify one case (test per case [TPC]) were calculated for different symptom combinations. A multi-objective evolutionary algorithm was applied to generate combinations with optimal trade-offs between sensitivity and specificity.FindingsUK and US cohorts included 122,305 (1,202 positives) and 3,162 (79 positive) individuals. Within three days of symptom onset, the COVID-19 specific symptom combination (cough, dyspnoea, fever, anosmia/ageusia) identified 69% of cases requiring 47 TPC. The combination with highest sensitivity (fatigue, anosmia/ageusia, cough, diarrhoea, headache, sore throat) identified 96% cases requiring 96 TPC.InterpretationWe confirmed the significance of COVID-19 specific symptoms for triggering RT-PCR and identified additional symptom combinations with optimal trade-offs between sensitivity and specificity that maximize case capture given different resource settings.     

Prevalence and risk factors associated with repeat positive SARS-CoV-2 nucleic acid test results among discharged COVID-19 patients: A protocol for systematic review and meta-analysis

Background:The COVID-19 (coronavirus disease 2019) pandemic continues to have an immense impact on the world at large. COVID-19 patients who meet the discharge criteria, may subsequently exhibit positive viral RNA test results upon subsequent evaluation. This phenomenon has been a major source of research and public health interest, and poses a major challenge to COVID-19 prevention, treatment, and standardized patient management.Methods:We will search the PubMed, MEDLINE, Embase, Cochrane Clinical Trials Database, China National Knowledge Infrastructure, Wanfang Database, Chinese Science Journal Database, and China Biology Medicine databases for all studies published as of November 2021. Data will be extracted independently by two researchers according to the eligibility criteria. Finally, RevMan 5.3.0 will be implemented for statistical analyses.Results:The results of this study will show the prevalence and risk factors associated with repeat positive SARS-CoV-2 nucleic acid test results among discharged COVID-19 patients.Conclusions:This study will provide a reliable evidence-based for the prevalence and risk factors associated with repeat positive SARS-CoV-2 nucleic acid test results among discharged COVID-19 patients.Trial registration number:CRD42021272447.     

Systemic lupus erythematosus after coronavirus disease-2019 (COVID-19) infection: Case-based review

BackgroundCoronavirus disease-2019 (COVID-19) is a novel infectious disease, which presents with various clinical manifestations. There is growing evidence of an association between COVID-19 infection and autoimmune diseases. The aim of this case report was to demonstrate the association of COVID-19 infection and the development of systemic lupus erythematosus (SLE).Case presentationA 38 year old Iranian woman presented with progressive icterus, pleuritic chest pain, palpitation, dyspnea, photosensitivity and arthralgia 18-days after COVID-19 symptoms proved by a positive polymerized chain reaction (PCR). The chest and abdomen computerized tomography (CT) scan showed pericardial and pleural effusion and enlarged liver and abdominal lymph nodes. Antinuclear antibody (ANA), anti-double stranded deoxyribonucleic acid (anti-ds DNA) antibody and perinuclear anti-neutrophil cytoplasmic antibody (P-ANCA) were positive. She was diagnosed as SLE and was successfully treated with prednisolone 30 mg daily, hydroxychloroquine 200 mg daily and azathioprine 150 mg daily and she remarkably improved. Repeated anti-ds DNA antibody was positive. Due to nausea and abdominal discomfort, azathioprine was discontinued and replaced with mycophenolate mofetil 1500 mg daily. In the article, similar cases were presented; the mean interval between COVID symptoms and SLE presentations was 24.86 days. Pulmonary and renal involvements were the most common presentations of SLE triggered by COVID-19. The most frequently reported autoantibody was ANAConclusionIt is necessary to be aware of the development of lupus disease in COVID-19 infected patients, because prompt diagnosis and treatment is very important to improve their outcome.