Cholangitis in three critically ill patients after a severe CoVID-19 infection.

Coronavirus disease 2019 (CoVID-19) is a viral disease. Although the predominant presentation is respiratory disease, other manifestations such as gastrointestinal manifestations are commonly reported. Nevertheless, it has not been associated with chronic cholangitis or hepatic injury. In this study, we report three cases of severe CoVID-19 infection that required ICU admission, intubation, and sedation with ketamine. All three patients had abnormal liver function despite recovery and were diagnosed with cholangitis in the context of CoVID-19.

Emergence of E484K Mutation Following Bamlanivimab Monotherapy among High-Risk Patients Infected with the Alpha Variant of SARS-CoV-2.

An Emergency Use Authorization was issued in the United States and in Europe for a monoclonal antibody monotherapy to prevent severe COVID-19 in high-risk patients. This study aimed to assess the risk of emergence of mutations following treatment with a single monoclonal antibody. Bamlanivimab was administered at a single dose of 700 mg in a one-hour IV injection in a referral center for the management of COVID-19 in France. Patients were closely monitored clinically and virologically with nasopharyngeal RT-PCR and viral whole genome sequencing. Six patients were treated for a nosocomial SARS-CoV-2 infection, all males, with a median age of 65 years and multiple comorbidities. All patients were infected with a B.1.1.7 variant, which was the most frequent variant in France at the time, and no patients had E484 mutations at baseline. Bamlanivimab was infused in the six patients within 4 days of the COVID-19 diagnosis. Four patients had a favorable outcome, one died of complications unrelated to COVID-19 or bamlanivimab, and one kidney transplant patient treated with belatacept died from severe COVID-19 more than 40 days after bamlanivimab administration. Virologically, four patients cleared nasopharyngeal viral shedding within one month after infusion, while two presented prolonged viral excretion for more than 40 days. The emergence of E484K mutants was observed in five out of six patients, and the last patient presented a Q496R mutation potentially associated with resistance. CONCLUSIONS: These results show a high risk of emergence of resistance mutants in COVID-19 patients treated with monoclonal antibody monotherapy.

Long-Term Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infectiousness Among Three Immunocompromised Patients: From Prolonged Viral Shedding to SARS-CoV-2 Superinfection.

BACKGROUND: Guidelines for stopping coronavirus disease 2019 patient isolation are mainly symptom-based, with isolation for 10 to 20 days depending on their condition. METHODS: In this study, we describe 3 deeply immunocompromised patients, each with different clinical evolutions. We observed (1) the patients' epidemiological, clinical, and serological data, (2) infectiousness using viral culture, and (3) viral mutations accumulated over time. RESULTS: Asymptomatic carriage, symptom resolution, or superinfection with a second severe acute respiratory syndrome coronavirus 2 strain were observed, all leading to prolonged infectious viral shedding for several months. CONCLUSIONS: Understanding underlying mechanisms and frequency of prolonged infectiousness is crucial to adapt current guidelines and strengthen the use of systematic polymerase chain reaction testing before stopping isolation in immunocompromised populations.

Observer agreement and clinical significance of chest CT reporting in patients suspected of COVID-19.

OBJECTIVES: To assess interobserver agreement and clinical significance of chest CT reporting in patients suspected of COVID-19. METHODS: From 16 to 24 March 2020, 241 consecutive patients addressed to hospital for COVID-19 suspicion had both chest CT and SARS-CoV-2 RT-PCR. Eight observers (2 thoracic and 2 general senior radiologists, 2 junior radiologists, and 2 emergency physicians) retrospectively categorized each CT into one out of 4 categories (evocative, compatible for COVID-19 pneumonia, not evocative, and normal). Observer agreement for categorization between all readers and pairs of readers with similar experience was evaluated with the Kappa coefficient. The results of a consensus categorization were correlated to RT-PCR. RESULTS: Observer agreement across the 4 categories was good between all readers (κ value 0.61 95% CI 0.60-0.63) and moderate to good between pairs of readers (0.54-0.75). It was very good (κ 0.81 95% CI 0.79-0.83), fair (κ 0.32 95% CI 0.29-0.34), moderate (κ 0.56 95% CI 0.54-0.58), and moderate (0.58 95% CI 0.56-0.61) for the categories evocative, compatible, not evocative, and normal, respectively. RT-PCR was positive in 97%, 50%, 31%, and 11% of cases in the respective categories. Observer agreement was lower (p < 0.001) and RT-PCR positive cases less frequently categorized evocative in the presence of an underlying pulmonary disease (p < 0.001). CONCLUSION: Interobserver agreement for chest CT reporting using categorization of findings is good in patients suspected of COVID-19. Among patients considered for hospitalization in an epidemic context, CT categorized evocative is highly predictive of COVID-19, whereas the predictive value of CT decreases between the categories compatible and not evocative. KEY POINTS: • In patients suspected of COVID-19, interobserver agreement for chest CT reporting into categories is good, and very good to categorize CT "evocative." • Chest CT can participate in estimating the likelihood of COVID-19 in patients presenting to hospital during the outbreak, CT categorized "evocative" being highly predictive of the disease whereas almost a third of patients with CT "not evocative" had a positive RT-PCR in our study. • Observer agreement is lower and CTs of positive RT-PCR cases less frequently "evocative" in presence of an underlying pulmonary disease.

SARS-COV2 infection in 30 HIV-infected patients followed-up in a French University Hospital.

INTRODUCTION: An acute respiratory disease caused by a novel coronavirus (SARSCOV2) is spreading from China since January 2020. Surprisingly, few cases of Covid-19 have been reported in people living with HIV (PLWHIV). METHODS: Here we present a series of 30 PLWHIV diagnosed for SARS-COV2 infection. The principal outcome was to describe clinical characteristics of this population. RESULTS: Eighteen (60%) patients were men, 10/30 (33,3%) women and 2/30 (6,7%) transgender women. Median age was 53,7 years (range 30-80 years) and 23/30 patients (76,7%) were born in a foreign country (out of France). The most common comorbidities were cardiovascular disease (11/30, 36,7%), hypertension (11/30, 36,7%), diabetes (9/30,30%) obesity (7/30, 23%) and chronic renal disease (5/30, 16,7%). Twenty (66,7%) patients presented overweight. Five patients (16,7%) had a Charlson comorbidity (Quan et al., 2011) score ≥3. Twenty-seven (90%) patients were virologically suppressed.CD4 count was >500cell/mm 3 in 23/30 (76,6%) patients. An antiviral treatment for SARS-COV2 was administered, in addition to HIV treatment, in 5/30 patients (16,3%). Twenty-four patients (80%) recovered from covid-19, 3/30 (10%) required invasive mechanical ventilation, 2/30 (6,7%) patients died and 4/30 (13,3%) patients were still hospitalized. CONCLUSIONS: Most of the patients were virologically suppressed with CD4>500 mm3. Risk factors were the same as those described in other SARS-COV2 series, suggesting that HIV infection is probably not an independent risk factor for covid-19.

Case report study of the first five COVID-19 patients treated with remdesivir in France.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the virus responsible for the coronavirus disease 2019 (COVID-19) outbreak worldwide. Data on treatment are scare and parallels have been made between SARS-CoV-2 and other coronaviruses. Remdesivir is a broad-spectrum antiviral with efficient in vitro activity against SARS-CoV-2. Evidence of clinical improvement in patients with severe COVID-19 treated with remdesivir is controversial. The aim of this study was to describe the clinical outcomes and virological monitoring of the first five COVID-19 patients admitted to the intensive care unit of Bichat-Claude Bernard University Hospital, Paris, France, for severe pneumonia related to SARS-CoV-2 and treated with remdesivir. Quantitative reverse transcription PCR was used to monitor SARS-CoV-2 in blood plasma and the lower and upper respiratory tract. Among the five patients treated, two needed mechanical ventilation and one needed high-flow cannula oxygen. A significant decrease in SARS-CoV-2 viral load in the upper respiratory tract was observed in most cases, but two patients died with active SARS-CoV-2 replication in the lower respiratory tract. Plasma samples were positive for SARS-CoV-2 in only one patient. Remdesivir was interrupted before the initialy planned duration in four patients, two because of alanine aminotransferase elevations (3 to 5 normal range) and two because of renal failure requiring renal replacement. This case series of five COVID-19 patients requiring intensive care unit treatment for respiratory distress and treated with remdesivir, highlights the complexity of remdesivir use in such critically ill patients.