Prolonged infective SARS-CoV-2 omicron variant shedding in a patient with diffuse large B cell lymphoma successfully cleared after three courses of remdesivir.

We report a case of prolonged shedding of the infective SARS-CoV-2 omicron variant BA.1.1.2 in a 79-year-old male patient with diffuse large B-cell lymphoma, after receiving chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). The patient was admitted to our hospital in late March 2022 for the sixth course of R-CHOP chemotherapy. Initially, the patient tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using an in-hospital loop-mediated amplification assay with a nasopharyngeal swab, both on the day of admission and three days later. However, the patient developed fever and was diagnosed with coronavirus disease (COVID-19) six days after admission and was suspected to have contracted the infection in the ward. Viral shedding continued for more than three months, with confirmed viral infectivity. As compared to the original Wuhan-Hu-1/2019 strain, amino acid substitutions including S36 N in non-structural protein (NSP)2, S148P, S1265del and L1266I in NSP3, G105D in NSP4, G496S, A831V, or V987F in spike protein, and I45T in open-reading frame (ORF)9b were randomly detected in isolated viruses. Although the patient had received two doses of the BNT162b2 vaccine approximately six months earlier and the third dose on day 127 after the infection, both serum anti-spike and anti-nuclear protein IgG and IgM tests were negative at day 92, 114, and 149 after the infection. The patient finally cleared the virus after the third course of remdesivir and did not have further recurrence.

A Rare Case of Persistent COVID-19 Infection With Aspergillosis in a 12-Year-Old Child.

At the end of 2019, coronavirus disease 2019 (COVID-19) was first detected in Wuhan. In March 2020, COVID-19 became a global pandemic. Saudi Arabia registered the first case of COVID-19 on March 2, 2020. COVID-19 can affect any organ in the body. It affects the respiratory system predominantly. Reverse transcriptase-polymerase chain reaction (RT-PCR) is used to diagnose COVID-19, and the preferred swab is the nasopharyngeal swab. The shedding of the virus continues for about 20 days after the onset of the symptoms. There may be prolonged shedding in a few cases without any symptoms. Viral cultures are used for the confirmation of the shedding. Although the preferred mode of diagnosis is RT-PCR, enzyme-linked immunosorbent assay helps in the diagnosis of antibodies. Here, we report a rare case of prolonged viral shedding for more than 14 weeks. The patient had a prolonged COVID-19 infection, which caused immunosuppression, following which the patient presented with an infection.

Prolonged Viral Shedding in Three Young Adult Cases of COVID-19

Severe acute respiratory syndrome coronavirus-2 infection is usually self-limited, with a short duration for viral shedding within several weeks. However, prolonged viral shedding has been observed in severe or immune-compromised coronavirus disease 2019 (COVID-19) cases. Here, we reported that three young adult cases of COVID-19 patients, who were either immunosuppressed nor severe, showed prolonged viral RNA shedding from the upper respiratory tract for 58, 81, and 137 days since initial diagnosis. To our knowledge, this is the longest duration of viral shedding reported to date in young adult patients. Further studies on factors relevant to prolonged viral positivity, as well as the correlation between viral positivity and transmission risk are needed for the optimal management of COVID-19 patients with prolonged nucleic acid positive. © Copyright 2022 The Chinese Medical Association, published by Wolters Kluwer Health, Inc.

Assessing the Efficacy of Early Therapies against SARS-CoV-2 in Hematological Patients: A Real-Life Study from a COVID-19 Referral Centre in Northern Italy.

Early therapies to prevent severe COVID-19 have an unclear impact on patients with hematological malignancies. The aim of this study was to assess their efficacy in this group of high-risk patients with COVID-19 in preventing hospitalizations and reducing the SARS-CoV-2 shedding. This was a single-center, retrospective, observational study conducted in the Fondazione IRCSS Policlinico San Matteo of Pavia, Northern Italy. We extracted the data of patients with hematologic malignancies and COVID-19 who received and did not receive early COVID-19 treatment between 23 December 2021, and May 2022. We used a Cox proportional hazard model to assess whether receiving any early treatment was associated with lower rates of hospitalization and reduced viral shedding. Data from 88 patients with hematologic malignancies were extracted. Among the patients, 55 (62%) received any early treatment, whereas 33 (38%) did not. Receiving any early therapy did not significantly reduce the hospitalization rate in patients with hematologic malignancies (HR 0.51; SE 0.63; p-value = 0.28), except in the vaccinated non-responders subgroup of patients with negative anti SARS-CoV-2 antibodies at the time of infection, who benefited from early therapies against SARS-CoV-2 (HR 0.07; SE 1.04; p-value = 0.001). Moreover, no difference on viral load decay was observed. In our cohort of patients with hematologic malignancies infected with SARS-CoV-2, early treatment were not effective in reducing the hospitalization rate due to COVID-19, neither in reducing its viral shedding.

Casirivimab/Imdevimab for Active COVID-19 Pneumonia Which Persisted for Nine Months in a Patient with Follicular Lymphoma during Anti-CD20 Therapy.

Immunocompromised patients are more likely to develop severe COVID-19, and exhibit high mortality. It is also hypothesized that chronic infection in these patients can be a risk factor for developing new variants. We describe a patient with prolonged active infection of COVID-19 who became infected during treatment with an anti-CD20 antibody (obinutuzumab) for follicular lymphoma. This patient had persistent RT-PCR positivity and live virus isolation for nine months despite treatment with remdesivir and other potential antiviral therapies. The computed tomography image of the chest showed that the viral pneumonia repeatedly appeared and disappeared in different lobes, as if a new infection had occurred continuously. The patient's SARS-CoV-2 antibody titer was negative throughout the illness, even after two doses of the BNT162b2 mRNA vaccine were administered in the seventh month of infection. A combination of monoclonal antibody therapy against COVID-19 (casirivimab and imdevimab) and antivirals resulted in negative RT-PCR results, and the virus was no longer isolated. The patient was clinically cured. During the 9-month active infection period, no fixed mutations in the spike (S) protein were detected, and the in vitro susceptibility to remdesivir was retained. Therapeutic administration of anti-SARS-CoV-2 monoclonal antibodies is essential in immunocompromised patients. Therefore, measures to prevent resistance against these key drugs are urgently needed.

Clinical Outcomes and Prolonged SARS-CoV-2 Viral Shedding in ICU Patients with Severe COVID-19 Infection and Nosocomial Bacterial Pneumonia: A Retrospective Cohort Study.

OBJECTIVES: This study explored the clinical outcomes and association of prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding in patients with severe coronavirus disease 2019 (COVID-19) infection who developed nosocomial pneumonia. METHODS: This was a retrospective study conducted in a medical center in Taiwan. From May to September 2021, patients from four intensive care units were enrolled after SARS-CoV-2 was confirmed through quantitative polymerase chain reaction and all cases were compatible with the definitions of severe COVID-19 infection. Baseline characteristics, disease severity, clinical outcomes, and times of viral shedding were recorded. RESULTS: A total of 72 patients were diagnosed as having severe COVID-19 infection and 30 developed nosocomial pneumonia, comprising hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). The patients with severe COVID-19 infection and concomitant HAP/VAP had longer intensive care unit (ICU) stays and fewer ventilator-free days at Day 28. An independent risk factor for nosocomial pneumonia was a greater SOFA score at admission. Furthermore, the patients with severe COVID-19 infection who developed HAP/VAP had a significantly longer duration of SARS-CoV-2 shedding (19.50 days vs. 15.00 days, p = 0.006). CONCLUSIONS: Patients with severe COVID-19 infection who developed nosocomial pneumonia had longer SARS-CoV-2 shedding days, more complications, and worse outcomes.

Anorexia nervosa and COVID-19 infection: Clinical case report.

The true risk of COVID-19 infection in anorexia nervosa (AN) including the duration of viral RNA shedding and infectivity is still unclear. We report on a case of a patient with severe AN with a mild course of COVID-19 and prolonged viral RNA shedding for at least 39 days after symptom onset. A careful evaluation of long-term infectivity must include viral load, live virus isolation, and viral genome sequencing.

Prolonged viral shedding prediction on non-hospitalized, uncomplicated SARS-CoV-2 patients using their transcriptome data.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is identified as a highly transmissible coronavirus which threatens the world with this deadly pandemic. WHO reported that it spreads through contact, droplet, airborne, formite, fecal-oral, bloodborne, mother-to-child and animal-to-human. Hence, viral shedding has a huge impact on this pandemic. This study uses transcriptome data of coronavirus disease 2019 (COVID-19) patients to predict the prolonged viral shedding of the corresponding patient. This prediction starts with the transcriptome features which gives the lowest root mean squared value of 16.3±3.3 using top 25 feature selected using forward feature selection algorithm and linear regression algorithm. Then to see the impact of few non-molecular features in this prediction, they were added to the model one by one along with the selected transcriptome features. However, this study shows that those features do not have any impact on prolonged viral shedding prediction. Further this study predicts the day since onset in the same way. Here also top 25 transcriptome features selected using forward feature selection algorithm gives a comparably good accuracy (accuracy value of 0.74±0.1). However, the best accuracy was obtained using the best 20 features from feature importance using SVM (0.78±0.1). Moreover, adding non-molecular features shows a great impact on mutual information selected features in this prediction.

Prolonged viral shedding identified from external splints and intranasal packings in immediately cured COVID-19 patients with nasal fractures: A retrospective study.

BACKGROUND: Our aim was to measure and compare prolonged viral shedding (PVS) identified from external splints (ES) and intranasal packings (IP) for isolated nasal fracture (INF) repair in immediately cured asymptomatic vs. mildly symptomatic COVID-19 patients (AS-COVID vs. MS-COVID). METHODS: We designed a retrospective cohort study and enroled a sample of post-AS-COVID and post-MS-COVID patients, whose INF were treated at a German level 1 trauma centre. The primary predictor variable was COVID severity presurgery (AS-COVD vs. MS-COVID). The main outcome variable was PVS detected in ES/IP. Other study variables were separated into demographic, clinical, and operative. Descriptive, bi- and multivariate statistics were computed, and statistical significance was set at P≤ 0.05. RESULTS: The study sample comprised 15 INF patients (53.3% females; 46.7% post-AS-COVID) with a mean age of 42.2 ± 22.7 years (range, 18-85). 13.3% ES and 53.3% IP were contaminated with SARS-CoV-2. However, only IP-contamination between the two cohorts reached statistical significance (P= 0.01; odds ratio, 0.02; 95% confidence interval, 0 to 0.47; Pearson's r= 0.73; post hoc power = 87.4%). Multiple linear regression models refuted the associations between PVS and the other parameters (i.e. age, gender, time to treatment, length of hospital stay, lengths of ES/IP placement). CONCLUSIONS: Despite a relative low sample size, our findings suggest PVS via endonasal materials removed from cured COVID-19 patients, especially those healed from MS-COVID. This PVS may trigger re-infection and surgical site infections and/or transmission to other humans, and thereby, requires further investigations.

Poor Respiratory Health Following Relapsing SARS-CoV-2 Infection in Children with Cystic Fibrosis.

Children with cystic fibrosis (CF) constitute a high-risk group for COVID-19 with underlying chronic lung disease. COVID-19 severity varying from mild infection to need of intensive care has been described in children with CF. Two children with significant underlying pulmonary morbidity are described here, who developed severe disease following SARS-CoV-2 infection. Case 1 (a 9-y-old boy) had pneumonia with respiratory failure requiring noninvasive ventilation support. He had delayed clearance of SARS-CoV-2, with recurrence of symptomatic disease with short asymptomatic period in between. He was also diagnosed with CF-related diabetes and allergic bronchopulmonary aspergillosis during the second episode. Case 2 (an 18-mo-old boy) had two episodes of SARS-CoV-2-related severe lower respiratory infection within a period of 2 mo, requiring high-flow nasal oxygen support. Both children had 3rd pulmonary exacerbation but SARS-CoV-2 was not detected in respiratory secretions. To conclude, children with CF with underlying pulmonary morbidity, can develop severe COVID-19 and prolonged SARS-CoV-2 shedding.

Viral Haplotypes in COVID-19 Patients Associated With Prolonged Viral Shedding.

Background: Recently, more patients who recovered from the novel coronavirus disease 2019 (COVID-19) may later test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) again using reverse transcription-polymerase chain reaction (RT-PCR) testing. Even though it is still controversial about the possible explanation for clinical cases of long-term viral shedding, it remains unclear whether the persistent viral shedding means re-infection or recurrence. Methods: Specimens were collected from three COVID-19-confirmed patients, and whole-genome sequencing was performed on these clinical specimens during their first hospital admission with a high viral load of SARS-CoV-2. Laboratory tests were examined and analyzed throughout the whole course of the disease. Phylogenetic analysis was carried out for SARS-CoV-2 haplotypes. Results: We found haplotypes of SARS-CoV-2 co-infection in two COVID-19 patients (YW01 and YW03) with a long period of hospitalization. However, only one haplotype was observed in the other patient with chronic lymphocytic leukemia (YW02), which was verified as one kind of viral haplotype. Patients YW01 and YW02 were admitted to the hospital after being infected with COVID-19 as members of a family cluster, but they had different haplotype characteristics in the early stage of infection; YW01 and YW03 were from different infection sources; however, similar haplotypes were found together. Conclusion: These findings show that haplotype diversity of SARS-CoV-2 may result in viral adaptation for persistent shedding in multiple recurrences of COVID-19 patients, who met the discharge requirement. However, the correlation between haplotype diversity of SARS-CoV-2 virus and immune status is not absolute. It showed important implications for the clinical management strategies for COVID-19 patients with long-term hospitalization or cases of recurrence.

Therapeutic Use of Convalescent Plasma in COVID-19 Infected Patients with Concomitant Hematological Disorders.

The use of convalescent plasma (CP) from individuals recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a promising therapeutic modality for the coronavirus disease 2019 (COVID-19). CP has been in use for at least a century to provide passive immunity against a number of diseases, and was recently proposed by the World Health Organization for human Ebola virus infection. Only a few small studies have so far been published on patients with COVID-19 and concomitant hematological malignancies (HM). The Italian Hematology Alliance on HM and COVID-19 has found that HM patients with COVID-19 clinically perform more poorly than those with either HM or COVID-19 alone. A COVID-19 infection in patients with B-cell lymphoma is associated with impaired generation of neutralizing antibody titers and lowered clearance of SARS-CoV-2. Treatment with CP was seen to increase antibody titers in all patients and to improve clinical response in 80% of patients examined. However, a recent study has reported impaired production of SARS-CoV-2-neutralizing antibodies in an immunosuppressed individual treated with CP, possibly supporting the notion of virus escape, particularly in immunocompromised individuals where prolonged viral replication occurs. This may limit the efficacy of CP treatment in at least some HM patients. More recently, it has been shown that CP may provide a neutralising effect against B.1.1.7 and other SARS-CoV-2 variants, thus expanding its application in clinical practice. More extensive studies are needed to further assess the use of CP in COVID-19-infected HM patients.

Risk factors for prolonged virus shedding of respiratory tract and fecal in adults with severe acute respiratory syndrome coronavirus-2 infection.

BACKGROUND: The dynamic alteration and comparative study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding pattern during treatment are limited. This study explores the potential risk factors influencing prolonged viral shedding in COVID-19. METHODS: A total of 126 COVID-19 patients were enrolled in this retrospective longitudinal study. A multivariate logistic regression analysis was carried out to estimate the potential risk factors. RESULTS: 38.1% (48/126) cases presented prolonged respiratory tract viral shedding, and 30 (23.8%) cases presented prolonged rectal swab viral shedding. Obesity (OR, 3.31; 95% CI, 1.08-10.09), positive rectal swab (OR, 3.43; 95% CI, 1.53-7.7), treatment by lopinavir/ritonavir with chloroquine phosphate (OR, 2.5; 95% CI, 1.04-6.03), the interval from onset to antiviral treatment more than 7 days (OR, 2.26; 95% CI, 1.04-4.93), lower CD4+ T cell (OR, 0.92; 95% CI, 0.86-0.99) and higher NK cells (OR, 1.11; 95% CI, 1.02-1.20) were significantly associated with prolonged respiratory tract viral shedding. CD3-CD56+ NK cells (OR, 0.87; 95% CI, 0.76-0.99) were related with prolonged fecal shedding. CONCLUSIONS: Obesity, delayed antiviral treatment, and positive SARS-CoV-2 for stool were independent risk factors for prolonged SARS-CoV-2 RNA shedding of the respiratory tract. A combination of LPV/r and abidol as the initial antiviral regimen was effective in shortening the duration of viral shedding compared with LPV/r combined with chloroquine phosphate. CD4+ T cell and NK cells were significantly associated with prolonged viral shedding, and further studies are to be warranted to determine the mechanism of immunomodulatory response in virus clearance.

Re-infection with a different SARS-CoV-2 clade and prolonged viral shedding in a hematopoietic stem cell transplantation patient.

Immunocompromised patients who have a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection pose many clinical and public health challenges. We describe the case of a hematopoietic stem cell transplantation patient with lymphoma who had a protracted illness requiring three consecutive hospital admissions. Whole genome sequencing confirmed two different SARS-CoV-2 clades. Clinical management issues and the unanswered questions arising from this case are discussed.

"Long COVID": A case report of persistent symptoms in a patient with prolonged SARS-CoV-2 shedding for over 110 days.

Coronavirus disease 2019 is a novel disease currently ravaging the world as a pandemic. More emphasis has been focused on the acute disease, with less attention on the detection and management of long-term sequelae which develop in some patients, variously termed "Long COVID," Post-coronavirus disease 2019 syndrome, or ongoing coronavirus disease. There are also various reports in the literature on the duration of viral shedding, with the longest known recorded being about 70 days, and whether this duration has an effect on prognosis or patients remaining infectious is still unknown. We report the case of a 22-year-old health care worker with prolonged multi-systemic features of coronavirus disease 2019 including cardiovascular, respiratory, central nervous system, and musculoskeletal symptoms lasting about 18 weeks from symptom onset, though never hospitalized, and persistent detection of severe acute respiratory syndrome coronavirus 2 attributed to viral shedding for over 110 days, which is the longest duration recorded to our knowledge.

Giant intracardiac thrombosis in an infant with leukaemia and prolonged COVID-19 viral RNA shedding: a case report.

BACKGROUND: COVID-19 can induce thrombotic disease both in the venous and arterial circulations, as a result of inflammation, platelet activation, endothelial dysfunction, and stasis. Although several studies have described the coagulation abnormalities and thrombosis in adult patients with COVID-19, there is limited data in children. Here, we present an 18-month-old boy with a prolonged SARS-CoV-2 RNA shedding and chronic right atrial and superior vena cava (SVC) thrombosis. CASE PRESENTATION: An 18-month-old boy with acute lymphoblastic leukemia (ALL) (pre-B cell ALL) and a history of chemotherapy was referred to our center due to intermittent fever with unknown origin. a positive nasopharyngeal PCR for COVID-19 was reported and stayed positive for eight consecutive weeks The high-resolution computed tomography (HRCT) showed no sign of pulmonary embolism. Initial echocardiography indicated a semilunar thrombotic mass extending from right SVC into the right atrium without coronary or myocardial involvement. Enoxaparin was administered with continuous monitoring of the level of anti-Xa activity. The serial echocardiographic studies found a slow but continuous reduction in the mass size. CONCLUSIONS: Our case shows that, as already described in adult patients, clinically relevant thrombosis can complicate the course of pediatric patients as well. In view of the specific and milder manifestations of COVID-19 in children, these complications may pose considerable diagnostic and therapeutic challenges.

Effects of oral care on prolonged viral shedding in coronavirus disease 2019 (COVID-19).

AIM: To assess the effects of oral care on prolonged viral shedding in coronavirus disease 2019 (COVID-19) patients. METHODS AND RESULTS: We evaluated the clinical course of eight COVID-19 patients, including their duration of viral shedding, by PCR testing of nasopharyngeal swabs. The average time from the onset of symptoms until the virus was no longer detectable was 31.6 ± 11.8 days (mean ± SD; range 17-53). Thus, it took 15.1 ± 14.7 (1-40) days from the time of clinical recovery for the virus to become undetectable. In two patients who had mental retardation and psychiatric disorders, the viral shedding period continued for 44 days or 53 days. These two patients did not voluntarily brush their teeth. When they were instructed on the importance of oral care, including tooth brushing and gargling, their tests for the coronavirus became negative. CONCLUSION: Most of the patients with COVID-19 had a viral shedding period of 30 days or less. In cases of prolonged viral shedding (≥44 days), noninfectious viral nucleic acid may have accumulated in uncleaned oral cavities and continued to be detected. We propose that tooth brushing and gargling remove such viral nucleic acid and improve the accuracy of PCR testing.