Objective Most SARS‐CoV‐2‐infected individuals never require hospitalization. However, some develop prolonged symptoms. We sought to characterize the spectrum of neurologic manifestations in non‐hospitalized Covid‐19 “long haulers”. Methods This is a prospective study of the first 100 consecutive patients (50 SARS‐CoV‐2 laboratory‐positive (SARS‐CoV‐2+) and 50 laboratory‐negative (SARS‐CoV‐2‐) individuals) presenting to our Neuro‐Covid‐19 clinic between May and November 2020. Due to early pandemic testing limitations, patients were included if they met Infectious Diseases Society of America symptoms of Covid‐19, were never hospitalized for pneumonia or hypoxemia, and had neurologic symptoms lasting over 6 weeks. We recorded the frequency of neurologic symptoms and analyzed patient‐reported quality of life measures and standardized cognitive assessments. Results Mean age was 43.2 ± 11.3 years, 70% were female, and 48% were evaluated in televisits. The most frequent comorbidities were depression/anxiety (42%) and autoimmune disease (16%). The main neurologic manifestations were: “brain fog” (81%), headache (68%), numbness/tingling (60%), dysgeusia (59%), anosmia (55%), and myalgias (55%), with only anosmia being more frequent in SARS‐CoV‐2+ than SARS‐CoV‐2‐ patients (37/50 [74%] vs. 18/50 [36%]; p < 0.001). Moreover, 85% also experienced fatigue. There was no correlation between time from disease onset and subjective impression of recovery. Both groups exhibited impaired quality of life in cognitive and fatigue domains. SARS‐CoV‐2+ patients performed worse in attention and working memory cognitive tasks compared to a demographic‐matched US population (T‐score 41.5 [37, 48.25] and 43 [37.5, 48.75], respectively; both p < 0.01). Interpretation Non‐hospitalized Covid‐19 “long haulers” experience prominent and persistent “brain fog” and fatigue that affect their cognition and quality of life.

Objective: Covid-19 can involve multiple organs including the nervous system. We sought to characterize the neurologic manifestations, their risk factors, and associated outcomes in hospitalized patients with Covid-19. Methods: We examined neurologic manifestations in 509 consecutive patients admitted with confirmed Covid-19 within a hospital network in Chicago, Illinois. We compared the severity of Covid-19 and outcomes in patients with and without neurologic manifestations. We also identified independent predictors of any neurologic manifestations, encephalopathy, and functional outcome using binary logistic regression. Results: Neurologic manifestations were present at Covid-19 onset in 215 (42.2%), at hospitalization in 319 (62.7%), and at any time during the disease course in 419 patients (82.3%). The most frequent neurologic manifestations were myalgias (44.8%), headaches (37.7%), encephalopathy (31.8%), dizziness (29.7%), dysgeusia (15.9%), and anosmia (11.4%). Strokes, movement disorders, motor and sensory deficits, ataxia, and seizures were uncommon (0.2 to 1.4% of patients each). Severe respiratory disease requiring mechanical ventilation occurred in 134 patients (26.3%). Independent risk factors for developing any neurologic manifestation were severe Covid-19 (OR 4.02; 95% CI 2.04-8.89; P < 0.001) and younger age (OR 0.982; 95% CI 0.968-0.996; P = 0.014). Of all patients, 362 (71.1%) had a favorable functional outcome at discharge (modified Rankin Scale 0-2). However, encephalopathy was independently associated with worse functional outcome (OR 0.22; 95% CI 0.11-0.42; P < 0.001) and higher mortality within 30 days of hospitalization (35 [21.7%] vs. 11 [3.2%] patients; P < 0.001). Interpretation: Neurologic manifestations occur in most hospitalized Covid-19 patients. Encephalopathy was associated with increased morbidity and mortality, independent of respiratory disease severity.

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Objective We characterized the evolution of neurologic symptoms and self‐perceived recovery of non‐hospitalized COVID‐19 “long haulers” 6–9 months after their initial Neuro‐COVID‐19 clinic evaluation. Methods In this follow‐up study on the first 100 patients, 50 SARS‐CoV‐2 laboratory‐positive (SARS‐CoV‐2 + ), and 50 laboratory‐negative (SARS‐CoV‐2 − ), evaluated at our Neuro‐COVID‐19 clinic between May and November 2020, patients completed phone questionnaires on their neurologic symptoms, subjective impression of recovery and quality of life. Results Of 52 patients who completed the study (27 SARS‐CoV‐2 + , 25 SARS‐CoV‐2 − ) a median 14.8 (range 11–18) months after symptom onset, mean age was 42.8 years, 73% were female, and 77% were vaccinated for SARS‐CoV‐2. Overall, there was no significant change in the frequency of most neurologic symptoms between first and follow‐up evaluations, including “brain fog” (81 vs. 71%), numbness/tingling (69 vs. 65%), headache (67 vs. 54%), dizziness (50 vs. 54%), blurred vision (34 vs. 44%), tinnitus (33 vs. 42%), and fatigue (87 vs. 81%). However, dysgeusia and anosmia decreased overall (63 vs. 27%, 58 vs. 21%, both p < 0.001). Conversely, heart rate and blood pressure variation (35 vs. 56%, p = 0.01) and gastrointestinal symptoms (27 vs. 48%, p = 0.04) increased at follow‐up. Patients reported improvements in their recovery, cognitive function, and fatigue, but quality of life measures remained lower than the US normative population ( p < 0.001). SARS‐CoV‐2 vaccination did not have a positive or detrimental impact on cognitive function or fatigue. Interpretation Non‐hospitalized COVID‐19 “long haulers” continue to experience neurologic symptoms, fatigue, and compromised quality of life 14.8 months after initial infection.

The clinical observation that a laparoscopic cholecystectomy is a minimally invasive operation has not been demonstrated on a biochemical basis. Interleukin-6, a known endogenous pyrogen and hepatocyte-stimulating protein, correlates with the significance of surgical trauma. Utilizing the IL-6 immunoassay, we studied this biochemical parameter of trauma to compare its response in laparoscopic vs open cholecystectomy. Sixteen patients who underwent only laparoscopic cholecystectomy showed peak IL-6 concentrations of 51 pg/ml (22-86) vs a peak IL-6 concentration of 124 pg/ml (56-225) for open cholecystectomy. Six additional patients who underwent an ERCP followed by laparoscopic cholecystectomy showed a dramatic rise in peak IL-6 concentration to 315 pg/ml (15-634). These results biochemically confirm the true minimal invasiveness of laparoscopic cholecystectomy. The findings in the ERCP-followed-by-laparoscopic-cholecystectomy group support the theory that two invasive procedures in close proximity may prime the cytokine system in its response to surgical trauma.