Decline in the number of patients with meningitis in German hospitals during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: In 2020, a wide range of hygiene measures was implemented to mitigate infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In consequence, pulmonary infections due to other respiratory pathogens also decreased. Here, we evaluated the number of bacterial and viral meningitis and encephalitis cases during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In a multicentre retrospective analysis of data from January 2016 until December 2020, numbers of patients diagnosed with bacterial meningitis and other types of CNS infections (such as viral meningitis and encephalitis) at 26 German hospitals were studied. Furthermore, the number of common meningitis-preceding ear-nose-throat infections (sinusitis, mastoiditis and otitis media) was evaluated. RESULTS: Compared to the previous years, the total number of patients diagnosed with pneumococcal meningitis was reduced (n = 64 patients/year in 2020 vs. n = 87 to 120 patients/year between 2016 and 2019, all p < 0.05). Additionally, the total number of patients diagnosed with otolaryngological infections was significantly lower (n = 1181 patients/year in 2020 vs. n = 1525 to 1754 patients/year between 2016 and 2019, all p < 0.001). We also observed a decline in viral meningitis and especially enterovirus meningitis (n = 25 patients/year in 2020 vs. n = 97 to 181 patients/year between 2016 and 2019, all p < 0.001). DISCUSSION: This multicentre retrospective analysis demonstrates a decline in the number of patients treated for viral and pneumococcal meningitis as well as otolaryngological infections in 2020 compared to previous years. Since the latter often precedes pneumococcal meningitis, this may point to the significance of the direct spread of pneumococci from an otolaryngological focus such as mastoiditis to the brain as one important pathophysiological route in the development of pneumococcal meningitis.

Association Between SARS-CoV-2 Infection and Immune-Mediated Myopathy in Patients Who Have Died.

Importance: Myalgia, increased levels of creatine kinase, and persistent muscle weakness have been reported in patients with COVID-19. Objective: To study skeletal muscle and myocardial inflammation in patients with COVID-19 who had died. Design, Setting, and Participants: This case-control autopsy series was conducted in a university hospital as a multidisciplinary postmortem investigation. Patients with COVID-19 or other critical illnesses who had died between March 2020 and February 2021 and on whom an autopsy was performed were included. Individuals for whom informed consent to autopsy was available and the postmortem interval was less than 6 days were randomly selected. Individuals who were infected with SARS-CoV-2 per polymerase chain reaction test results and had clinical features suggestive of COVID-19 were compared with individuals with negative SARS-CoV-2 polymerase chain reaction test results and an absence of clinical features suggestive of COVID-19. Main Outcomes and Measures: Inflammation of skeletal muscle tissue was assessed by quantification of immune cell infiltrates, expression of major histocompatibility complex (MHC) class I and class II antigens on the sarcolemma, and a blinded evaluation on a visual analog scale ranging from absence of pathology to the most pronounced pathology. Inflammation of cardiac muscles was assessed by quantification of immune cell infiltrates. Results: Forty-three patients with COVID-19 (median [interquartile range] age, 72 [16] years; 31 men [72%]) and 11 patients with diseases other than COVID-19 (median [interquartile range] age, 71 [5] years; 7 men [64%]) were included. Skeletal muscle samples from the patients who died with COVID-19 showed a higher overall pathology score (mean [SD], 3.4 [1.8] vs 1.5 [1.0]; 95% CI, 0-3; P < .001) and a higher inflammation score (mean [SD], 3.5 [2.1] vs 1.0 [0.6]; 95% CI, 0-4; P < .001). Relevant expression of MHC class I antigens on the sarcolemma was present in 23 of 42 specimens from patients with COVID-19 (55%) and upregulation of MHC class II antigens in 7 of 42 specimens from patients with COVID-19 (17%), but neither were found in any of the controls. Increased numbers of natural killer cells (median [interquartile range], 8 [8] vs 3 [4] cells per 10 high-power fields; 95% CI, 1-10 cells per 10 high-power fields; P < .001) were found. Skeletal muscles showed more inflammatory features than cardiac muscles, and inflammation was most pronounced in patients with COVID-19 with chronic courses. In some muscle specimens, SARS-CoV-2 RNA was detected by reverse transcription-polymerase chain reaction, but no evidence for a direct viral infection of myofibers was found by immunohistochemistry and electron microscopy. Conclusions and Relevance: In this case-control study of patients who had died with and without COVID-19, most individuals with severe COVID-19 showed signs of myositis ranging from mild to severe. Inflammation of skeletal muscles was associated with the duration of illness and was more pronounced than cardiac inflammation. Detection of viral load was low or negative in most skeletal and cardiac muscles and probably attributable to circulating viral RNA rather than genuine infection of myocytes. This suggests that SARS-CoV-2 may be associated with a postinfectious, immune-mediated myopathy.

Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19.

The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease. Moreover, thromboembolic events throughout the body, including in the CNS, have been described. Given the neurological symptoms observed in a large majority of individuals with COVID-19, SARS-CoV-2 penetrance of the CNS is likely. By various means, we demonstrate the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain. Furthermore, we describe the morphological changes associated with infection such as thromboembolic ischemic infarction of the CNS and present evidence of SARS-CoV-2 neurotropism. SARS-CoV-2 can enter the nervous system by crossing the neural-mucosal interface in olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue, including delicate olfactory and sensory nerve endings. Subsequently, SARS-CoV-2 appears to follow neuroanatomical structures, penetrating defined neuroanatomical areas including the primary respiratory and cardiovascular control center in the medulla oblongata.