Safety of systemic anti-cancer treatment in oncology patients with non-severe COVID-19: a cohort study.

BACKGROUND: The viral pandemic coronavirus disease 2019 (COVID-19) has disrupted cancer patient management around the world. Most reported data relate to incidence, risk factors, and outcome of severe COVID-19. The safety of systemic anti-cancer therapy in oncology patients with non-severe COVID-19 is an important matter in daily practice. METHODS: ONCOSARS-1 was a single-center, academic observational study. Adult patients with solid tumors treated in the oncology day unit with systemic anti-cancer therapy during the initial phase of the COVID-19 pandemic in Belgium were prospectively included. All patients (n = 363) underwent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) serological testing after the first peak of the pandemic in Belgium. Additionally, 141 of these patients also had a SARS-CoV-2 RT-PCR test during the pandemic. The main objective was to retrospectively determine the safety of systemic cancer treatment, measured by the rate of adverse events according to the Common Terminology Criteria for Adverse Events, in SARS-CoV-2-positive patients compared with SARS-CoV-2-negative patients. RESULTS: Twenty-two (6%) of the 363 eligible patients were positive for SARS-CoV-2 by RT-PCR and/or serology. Of these, three required transient oxygen supplementation, but none required admission to the intensive care unit. Hematotoxicity was the only adverse event more frequently observed in SARS-CoV-2 -positive patients than in SARS-CoV-2-negative patients: 73% vs 35% (P < 0.001). This association remained significant (odds ratio (OR) 4.1, P = 0.009) even after adjusting for performance status and type of systemic treatment. Hematological adverse events led to more treatment delays for the SARS-CoV-2-positive group: 55% vs 20% (P < 0.001). Median duration of treatment interruption was similar between the two groups: 14 and 11 days, respectively. Febrile neutropenia, infections unrelated to COVID-19, and bleeding events occurred at a low rate in the SARS-CoV-2-positive patients. CONCLUSION: Systemic anti-cancer therapy appeared safe in ambulatory oncology patients treated during the COVID-19 pandemic. There were, however, more treatment delays in the SARS-CoV-2-positive population, mainly due to a higher rate of hematological adverse events.

Expert Consensus Statements on the Use of Corticosteroids in Non-severe COVID-19.

INTRODUCTION: There is strong evidence for the use of corticosteroid in the management of severe coronavirus disease-2019 (COVID-19). However, there is still uncertainty about the timing of corticosteroids. We undertook a modified Delphi study to develop expert consensus statements on the early identification of a subset of patients from non-severe COVID-19 who may benefit from using corticosteroids. METHODS: A modified Delphi was conducted with two anonymous surveys between April 30, 2021, and May 3, 2021. An expert panel of 35 experts was selected and invited to participate through e-mail. The consensus was defined as >70% votes in multiple-choice questions (MCQ) on Likert-scale type statements, while strong consensus as >90% votes in MCQ or >50% votes for "very important" on Likert-scale questions in the final round. RESULTS: Twenty experts completed two rounds of the survey. There was strong consensus for the increased work of breathing (95%), a positive six-minute walk test (90%), thorax computed tomography severity score of >14/25 (85%), new-onset organ dysfunction (using clinical or biochemical criteria) (80%), and C-reactive protein >5 times the upper limit of normal (70%) as the criteria for patients' selection. The experts recommended using oral or intravenous (IV) low-dose corticosteroids (the equivalent of 6 mg/day dexamethasone) for 5-10 days and monitoring of oxygen saturation, body temperature, clinical scoring system, blood sugar, and inflammatory markers for any "red-flag" signs. CONCLUSION: The experts recommended against indiscriminate use of corticosteroids in mild to moderate COVID-19 without the signs of clinical worsening. Oral or IV low-dose corticosteroids (the equivalent of 6 mg/day dexamethasone) for 5-10 days are recommended for patients with features of disease progression based on clinical, biochemical, or radiological criteria after 5 days from symptom onset under close monitoring. HOW TO CITE THIS ARTICLE: How to cite this article: Nasa P, Chaudhry D, Govil D, Daga MK, Jain R, Chhallani AA, et al. Expert Consensus Statements on the Use of Corticosteroids in Non-severe COVID-19. Indian J Crit Care Med 2021;25(11):1280-1285.

Continuous thrombocytopenia after SARS-CoV-2 nucleic acid negative in a non-severe COVID-19 patient for several months.

BACKGROUND: Thrombocytopenia was common in the coronavirus disease (Covid-19) patients during the infection, especially in severe COVID-19 patients, but was less in the non-severe Covid-19 patients. However, the platelet count would be restored after antivirus treatment. In this paper, we report continuous thrombocytopenia in a non-severe Covid-19 case after a negative nucleic acid test for Covid-19. CASE PRESENTATION: A non-severe COVID-19 patient had the platelet continuous decrease for several months after the SARS-CoV-2 nucleic acid turning negative, and without well response to the glucocorticoid. The dynamic change of platelet count followed that of the lymphocyte count. After excluding the medicines possibility, immune system disorders, other specific virus infection and specific antibody of platelet, the thrombocytopenia continuously lasted for several months. The upward trend did not begin until June 2020 and she took the tapering dose of prednisone under the instruction of the hematologist. CONCLUSION: Excluding other potentialities inducing thrombocytopenia, we highly hypothesized the SARS-CoV-2 may cause thrombocytopenia by disturbing the immune system to induce the thrombocytopenia in our report,, which needs longer time to restore the immune system and platelet count via the glucocorticoid. We firstly reported this case in order to contribute the clinician to better deal with the patients like this.

The association of non-severe COVID-19 infection and progression to frailty among robust older veterans.

BACKGROUND: Studies have shown that frailty was increased in hospitalized COVID-19 patients. However, it is not clear whether non-severe COVID-19 increases the risk for pre-frailty and frailty development. Our study aimed to determine the risk of developing frailty and pre-frailty in robust veterans who contracted non-severe COVID-19. METHODS: We conducted a retrospective cohort study to assess the association of SARS-CoV-2 infection with the development of pre-frailty and frailty status among robust U.S. veterans using VA COVID-19 Shared Data Resource. We included patients 55 years and older who had at least one SARS-CoV-2 testing between March 15, 2020, and November 30, 2020, had been active patients in the past 12 months, and had a VA frailty index of zero (robust status) at the time of testing. Cox proportional hazard model was used to assess the association between COVID-19 infection and developing frailty or pre-frailty and frailty. We also assessed the association by patients' age groups, sex, and race. FINDINGS: We identified 82070 veterans mean age 68.3 ± 7.8, 74738 (91.1%) male, 53899 (65.7%) white, 7557 (9.2%) with mild COVID-19 infection. Over the follow up period of 36 months, testing positive for COVID-19 was associated with a 66% increase in the hazard of becoming frail (adjusted HR = 1.66, 95%CI: 1.32-2.08), and a 68% increase in the hazard of becoming pre-frail (adjusted HR = 1.68, 95%CI: 1.45-1.94). Among male patients, mild COVID-19 infection was associated with a 54% increase in the hazard of becoming frail (adjusted HR = 1.54, 95% CI: 1.21-1.96), while among female patients there was a 330% increase (adjusted HR = 4.30, 95% CI: 2.13-8.64). CONCLUSIONS AND RELEVANCE: Non-severe COVID-19 infection that occurred in robust older adults increased the risk of developing frailty. Further multi-center prospective cohort studies evaluating the mechanism of action and clinical trials of treatment options for post-COVID frailty are indicated in Veterans to support clinical care.

Impact and prevalence of comorbidities and complications on the severity of COVID-19 in association with age, gender, obesity, and pre-existing smoking: A meta-analysis.

Background: COVID-19 patients usually present multiple comorbidities and complications associated with severe forms of SARS-CoV-2 infection. This study aimed to assess the risk factors and prevalence of comorbidities and complications contributing to the severity of COVID-19. Methods: This meta-analysis was performed according to PRISMA guidelines. We searched various databases, including PubMed, Google Scholar, and Scopus (between 2020 and 2023), for eligible studies for this meta-analysis. Results: Thirty-three studies were eligible, including 85,812 patients, of which 36 % (30,634/85,812) had severe disease, whereas 64 % (55,178/85,812) had non-severe disease. Severe cases were potentially correlated with the following factors: gender (male) (odd ratio (OR) = 1.52, 95 % CI: 1.34-1.73), advanced age (OR = 3.06, 95 % CI: 2.18-4.40) pre-existing smoking (OR = 1.33, 95 % CI: 1.01-1.75), obesity (OR = 2.11, 95 % CI: 1.47-3.04), diabetes (OR = 1.81, 95 % CI: 1.35-2.43), hypertension (OR = 2.22, 95 % CI: 1.72-2.87), coronary heart disease (OR = 2.17, 95 % CI: 1.42-3.31), CKD (OR = 2.27, 95 % CI: 1.26-4.06), COPD (OR = 1.95, 95 % CI: 1.22-3.09), malignancy (OR = 1.63, 95 % CI: 1.07-2.49) and cerebrovascular disease (OR = 2.76, 95 % CI: 1.63-4.62). All these comorbidities were significantly higher in the severe COVID-19 group compared with the non-severe COVID-19 group. In addition, the most severe complications were associated with shock (OR = 28.08, 95 % CI: 3.49-226.03), ARDS (OR = 13.09, 95 % CI: 5.87-29.18), AKI (OR = 16.91, 95 % CI: 1.87-152.45) and arrhythmia (OR = 7.47, 95 % CI: 2.96-18.83). However, these complications were the most likely to prevent recovery in patients with severe affections compared with non-severe affection groups. Conclusion: All the comorbidities and complications listed above are more likely to cause severe forms of COVID-19 in some patients and hinder recovery. They are therefore risk factors to be controlled to minimize the undesirable effects of the disease.

Efficacy of combined COVID-19 convalescent plasma with oral RNA-dependent RNA polymerase inhibitor treatment versus neutralizing monoclonal antibody therapy in COVID-19 outpatients: a multi-center, non-inferiority, open-label randomized controlled trial (PlasMab).

IMPORTANCE: This pivotal study reveals that high neutralizing titer COVID-19 convalescent plasma therapy (CPT) combined with favipiravir (FPV) is non-inferior to sotrovimab in preventing hospitalization and severe outcomes in outpatients with mild-to-moderate COVID-19 and high-risk comorbidities. It underscores the potential of CPT-FPV as a viable alternative to neutralizing monoclonal antibodies like sotrovimab, especially amid emerging variants with spike protein mutations. The study's unique approach, comparing a monoclonal antibody with CPT, demonstrates the efficacy of early intervention using high neutralizing antibody titer CPT, even in populations with a significant proportion of elderly patients. These findings are crucial, considering the alternative treatment challenges, especially in resource-limited countries, posed by the rapidly mutating SARS-CoV-2 virus and the need for adaptable therapeutic strategies.

Antibiotic prescribing trends in the US during the first 11 months of the COVID-19 pandemic.

BACKGROUND: The study aims to compare antibiotic prescribing trends for U.S. COVID-19 patients, categorized by disease severity, and non-COVID-19 population with similar symptoms during 2019-2020 pandemic. METHODS: A retrospective observational cohort design using Symphony Health (January-November 2020). Sample population included about 13.3 million patients with at least one prescription claim ±6 months from date of diagnosis of COVID-19 or COVID-19 like symptom. Cohorts were categorized based on diagnosis codes; COVID-19 positive cohorts 1 to 3 with severe, mild, and no symptoms, respectively and non-COVID-19 cohorts 4 and 5 with severe and mild symptoms, respectively. Descriptive statistics were calculated for demographic characteristics and acute antibiotic utilization (≤7 days) including total number of antibiotics, weekly rate of prescribing, and proportion of fills in three "appropriateness" categories (always appropriate, potentially appropriate, never appropriate). RESULTS: Three cohorts with a positive COVID-19 diagnosis code constituted a total of about 1.8 million patients (13.53%). About 22.79% of COVID-19 positive groups had severe symptoms, 24.43% had moderate symptoms and the majority, 52.78%, had no symptoms. In the analytical sample of 13 million, about 4.2 million antibiotic prescriptions were prescribed to 2.5 million patients (19%) within 7 days of the first diagnosis of either COVID-19 or COVID-19-like symptoms. Within the COVID-19 positive cohorts, about 11% received an antibiotic prescription, while the non-COVID-19 cohorts, about 19.70% received an antibiotic. Among patients with antibiotic prescriptions, about 37.01% were prescribed an antibiotic "appropriately", 39.46% were prescribed a "potentially appropriate" antibiotic and about 22.64% received an "inappropriate" antibiotic. Among patients prescribed antibiotics, azithromycin was the most common, ranging from 21.80 to 44.80% for each cohort. CONCLUSIONS: Although the overall proportion of COVID-19 patients receiving antibiotics was much lower than non-COVID-19 patients, the findings suggest use of antibiotics persisted despite guidelines against widespread use, particularly for patients with moderate and mild COVID-19 symptoms.

Late pulmonary embolism in a patient with non-severe COVID-19: case report, value of antithrombotic prophylaxis and literature review.

Since the onset of the COVID-19 pandemic, several small cohorts have reported the recurrent occurrence of venous thromboembolic disease (VTE), particulary pulmonary embolism, in serious patients hospitalized in intensive care units. We report the case of a patient who presented a minor COVID-19 infection treated on an outpatient basis with good clinical resolution. She developed a pulmonary embolism three weeks after the onset of symptoms. When she was admitted to the emergency room, the two real time reverse transcription polymerase chain reactions (RT-PCRs) performed were negative, moreover the anti-SARS-CoV-2 Immunoglobulin Gs (IgGs) serological test was positive and the chest scanner without and with injection of contrast product showed specific images of COVID-19 with intermediate pulmonary embolism according to the classification of the European society of cardiology (ESC). This observation is interesting since there are not many studies which address the question of the occurrence of late pulmonary embolism in patients with non-severe COVID-19 and raises the discussion on the criteria for the initiation of thromboembolic prophylaxis treatment at the first diagnosis of the disease and duration of that treatment.

Efficacy Evaluation of Early, Low-Dose, Short-Term Corticosteroids in Adults Hospitalized with Non-Severe COVID-19 Pneumonia: A Retrospective Cohort Study.

OBJECTIVES: This study aimed to observe the efficacy of corticosteroids in non-severe COVID-19 pneumonia. METHODS: A retrospective study based on propensity score matching was designed to explore the effects of corticosteroids. Primary outcomes included the rate of patients who developed severe disease and mortality. Secondary outcomes included duration of fever, virus clearance time, length of hospital stay, and the use of antibiotics. RESULTS: A total of 475 patients with non-severe COVID-19 pneumonia were enrolled, 55 patients received early, low-dose, and short-term corticosteroids therapy, 420 patients received non-corticosteroids therapy. Compared to the non-corticosteroids group, there was a prolonged duration of fever (median 5 vs 3 days, p < 0.001), virus clearance time (median 18 vs 11 days, p < 0.001), and length of hospital stay (median 23 vs 15 days, p < 0.001) in the corticosteroids group. The percentages of antibiotics therapy (89.1% vs 23.6%, p < 0.001), use of at least two antibiotics (38.2% vs 12.7%, p = 0.002), and antifungal therapy (7.3% vs 0, p = 0.042) were higher in the corticosteroids group than those in the non-corticosteroids group. Compared to the non-corticosteroids group, more patients developed severe disease (12.7% vs 1.8%, p = 0.028) in the corticosteroids group. There was no significant difference between the two groups in mortality (1.8% vs 0, p = 0.315). CONCLUSION: In adult patients with non-severe COVID-19 pneumonia, early, low-dose, and short-term corticosteroids therapy was associated with worse clinical outcomes.