Risk Factors and Multidimensional Assessment of Long Coronavirus Disease Fatigue: A Nested Case-Control Study.

BACKGROUND: Fatigue is the most prevalent and debilitating long-COVID (coronavirus disease) symptom; however, risk factors and pathophysiology of this condition remain unknown. We assessed risk factors for long-COVID fatigue and explored its possible pathophysiology. METHODS: This was a nested case-control study in a COVID recovery clinic. Individuals with (cases) and without (controls) significant fatigue were included. We performed a multidimensional assessment evaluating various parameters, including pulmonary function tests and cardiopulmonary exercise testing, and implemented multivariable logistic regression to assess risk factors for significant long-COVID fatigue. RESULTS: A total of 141 individuals were included. The mean age was 47 (SD: 13) years; 115 (82%) were recovering from mild coronavirus disease 2019 (COVID-19). Mean time for evaluation was 8 months following COVID-19. Sixty-six (47%) individuals were classified with significant long-COVID fatigue. They had a significantly higher number of children, lower proportion of hypothyroidism, higher proportion of sore throat during acute illness, higher proportions of long-COVID symptoms, and of physical limitation in daily activities. Individuals with long-COVID fatigue also had poorer sleep quality and higher degree of depression. They had significantly lower heart rate [153.52 (22.64) vs 163.52 (18.53); P = .038] and oxygen consumption per kilogram [27.69 (7.52) vs 30.71 (7.52); P = .036] at peak exercise. The 2 independent risk factors for fatigue identified in multivariable analysis were peak exercise heart rate (OR: .79 per 10 beats/minute; 95% CI: .65-.96; P = .019) and long-COVID memory impairment (OR: 3.76; 95% CI: 1.57-9.01; P = .003). CONCLUSIONS: Long-COVID fatigue may be related to autonomic dysfunction, impaired cognition, and decreased mood. This may suggest a limbic-vagal pathophysiology. CLINICAL TRIALS REGISTRATION: NCT04851561.

A possible increased risk of metamizole-associated neutropenia among COVID-19 patients.

Metamizole is commonly used as analgesic and antipyretic drug. The use of metamizole is prohibited in several countries due to its rare side effect of neutropenia and even agranulocytosis. Among the many symptoms of COVID-19, fever and diffuse pain predominant and therefore it can be assumed that metamizole may be widely used in the current epidemic period. So far, there have been no reports on the safety of metamizole in COVID-19 patients. We describe a series of 3 patients who developed severe neutropenia under metamizole treatment, raising a concern of a possible increased risk of this side effect among COVID-19 patients.

An Early Unexpected Immune Thrombotic Thrombocytopenic Purpura Relapse Associated with SARS-CoV-2 Infection: A Case Report and Literature Review.

SARS-CoV-2 has been reported as a possible triggering factor for the development of several autoimmune diseases and inflammatory dysregulation. Here, we present a case report of a woman with a history of systemic lupus erythematosus and antiphospholipid syndrome, presenting with concurrent COVID-19 infection and immune thrombotic thrombocytopenic purpura (TTP). The patient was treated with plasma exchange, steroids, and caplacizumab with initial good response to therapy. The course of both TTP and COVID-19 disease was mild. However, after ADAMTS-13 activity was normalized, the patient experienced an early unexpected TTP relapse manifested by intravascular hemolysis with stable platelet counts requiring further treatment. Only 3 cases of COVID-19 associated TTP were reported in the literature thus far. We summarize the literature and suggest that COVID-19 could act as a trigger for TTP, with good outcomes if recognized and treated early.

The association of crown-rump length discrepancy with birthweight discordance in spontaneous versus assisted conception dichorionic twins.

OBJECTIVE: This study aimed to compare the associations of crown-rump length (CRL) discrepancy with birthweight discordance in spontaneous versus vitro fertilization (IVF) conceived dichorionic twin pregnancies. METHOD: A computerized retrospective study of women referred to our ultrasonographic unit for nuchal translucency examination between January 1997 and December 2011. The study group was subdivided into twins conceived after IVF, non-IVF fertility treatment and spontaneously conceived twins. Birthweight discordance was defined as a difference of birthweights of >20%. RESULTS: A total of 688 dichorionic twin pregnancies were included, all of them ending in live birth of both twins. IVF-conceived pregnancies were associated with a significant increased risk of extreme birthweight discordance compared with spontaneous-conceived twin pregnancies (OR = 2.3; CI = 1.4-3.8, P < 0.001). A significant correlation was found between CRL discrepancy and birthweight discordance in spontaneous-conceived pregnancies (r = 0.15, P < 0.05). In contrast, there was no significant correlation between CRL discrepancy and birthweight discordance in both IVF and fertility treatment-conceived pregnancies. CONCLUSION: Because birthweight discordance in IVF-conceived twins did not correlate with CRL discrepancy, we assume that it emerges later in pregnancy, maybe related to maternal underplaying complications, for which IVF was indicated in the first place.

A real-life setting evaluation of the effect of remdesivir on viral load in COVID-19 patients admitted to a large tertiary centre in Israel.

OBJECTIVES: The effectiveness of remdesivir, a Food and Drug Administration-approved drug for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been repeatedly questioned during the current coronavirus disease 2019 (COVID-19) pandemic. Most of the recently reported studies were randomized controlled multicentre clinical trials. Our goal was to test the efficiency of remdesivir in reducing nasopharyngeal viral load and hospitalization length in a real-life setting in patients admitted to a large tertiary centre in Israel. METHODS: A total of 142 COVID-19 patients found to have at least three reported SARS-CoV-2 quantitative RT-PCR tests during hospitalization were selected for this study. Of these, 29 patients received remdesivir, while the remaining non-treated 113 patients served as controls. RESULTS: Among the tested parameters, the control and remdesivir groups differed significantly only in the intubation rates. Remdesivir treatment did not significantly affect nasopharyngeal viral load, as determined by comparing the differences between the first and last cycle threshold values of the SARS-CoV-2 quantitative RT-PCR tests performed during hospitalization (cycle threshold 7.07 ± 6.85 vs. 7.08 ± 7.27, p 0.977 in the control and treated groups, respectively). Remdesivir treatment shortened hospitalization length by less than a day compared with non-treated controls and by 3.1 days when non-intubated patients from both groups were compared. These differences, however, were not statistically significant, possibly because of the small size of the remdesivir group. DISCUSSION: Remdesivir was not associated with nasopharyngeal viral load changes, but our study had a significant disease severity baseline imbalance and was not powered to detect viral load or clinical differences.

Secondary bacterial infection in COVID-19 patients is a stronger predictor for death compared to influenza patients.

Secondary bacterial infections are a potentially fatal complication of influenza infection. We aimed to define the impact of secondary bacterial infections on the clinical course and mortality in coronavirus disease 2019 (COVID-19) patients by comparison with influenza patients. COVID-19 (n = 642) and influenza (n = 742) patients, admitted to a large tertiary center in Israel and for whom blood or sputum culture had been taken were selected for this study. Bacterial culture results, clinical parameters, and death rates were compared. COVID-19 patients had higher rates of bacterial infections than influenza patients (12.6% vs. 8.7%). Notably, the time from admission to bacterial growth was longer in COVID-19 compared to influenza patients (4 (1-8) vs. 1 (1-3) days). Late infections (> 48 h after admission) with gram-positive bacteria were more common in COVID-19 patients (28% vs. 9.5%). Secondary infection was associated with a higher risk of death in both patient groups 2.7-fold (1.22-5.83) for COVID-19, and 3.09-fold (1.11-7.38) for Influenza). The association with death remained significant upon adjustment to age and clinical parameters in COVID-19 but not in influenza infection. Secondary bacterial infection is a notable complication associated with worse outcomes in COVID-19 than influenza patients. Careful surveillance and prompt antibiotic treatment may benefit selected patients.

Intranasal gonadotropin-releasing hormone agonist (GnRHa) for luteal-phase support following GnRHa triggering, a novel approach to avoid ovarian hyperstimulation syndrome in high responders.

OBJECTIVE: To study whether intranasal GnRH agonist (GnRHa) can be effectively used for luteal support in high-responder patients undergoing fresh-embryo transfer after ovulation induction with the use of GnRHa. DESIGN: Retrospective cohort study. SETTING: Private fertility clinic. PATIENT(S): Forty-six high-responder patients were administered a GnRHa ovulation trigger to avoid ovarian hyperstimulation syndrome (OHSS), followed by 2 weeks of daily intranasal GnRHa (nafarelin) for luteal-phase support. No additional progesterone supplementation was administrated. INTERVENTION(S): Intranasal GnRHa for luteal-phase support. MAIN OUTCOME MEASURE(S): The primary outcome was ongoing clinical pregnancy rate. RESULT(S): High median progesterone levels were measured at midluteal phase and on the day of the first positive pregnancy test (190 nmol/L on both measures). We obtained 24 (52.1%) ongoing clinical pregnancies. None of the patients developed OHSS. CONCLUSION(S): Intranasal GnRHa is effective in achieving luteal-phase support in high-responder patients triggered with GnRHa and avoiding OHSS.