We screened the database of the French National reference centre for meningococci and Haemophilus influenzae (NRCMHi) for biologically confirmed IMD cases (meningococci detected by culture and/or from a normally sterile site) and compared data for the period between 01 January and 15 May of 2019 and 2020. Meningococcal isolates are sent to the NRCMHi for full typing (MLST and WGS) as part of the mandatory reporting of IMD (9). A total of 305 cases of IMD were received at the NRCMHi for the two studied periods (176 in 2019 and 129 in 2020). The number of cases in 2020 decreased in 2020 compared to that of 2019 without any change in the vaccination strategies. This decrease occurred mainly during the lockdown period (16 March 2020-15 May 2020) with 23 IMD cases during the lockdown period in 2020 and 69 IMD cases during the same period in 2019 (P=0.0008). The number of IMD cases did not significantly differ between 2019 and 2020 before the period 16 March-15 May (Figure). Moreover, the decrease seems to mainly involve IMD cases due to serogroups B and C but not IMD due to serogroup Y and other unusual serogroups or non-serogroupable isolates which did not decreased significantly and which proportions increased during the lockdown 2020 (Figure). A special attention was drawn to IMD cases due to serogroup W that was continuing to increase in 2020 before the lockdown. The emergence of highly transmissible and hyperinvasive serogroup W isolates of the clonal complex CC11 in France as in other countries in Europe was reported since 2013 (10, 11). The serogroup W isolates showed a sharp decrease during the lockdown (3 cases in 2020 during the lockdown versus 22 cases during the corresponding period of 2019; P=0.001). Moreover, The decrease contrasted with the increasing number of IMD cases due to serogroup W before the lockdown period in 2020 compared to the same period in 2019 (31 cases before the lockdown in 2020 versus 19 cases for the corresponding period in 2019, P=0.01). The decrease during the lockdown involved mainly the highly transmissible and hyperinvasive isolates belonging to the clonal complex CC11(11).
The MLST typing data were obtained for 288 cases (94% of all IMD cases of this report; 167 for 2019 and 121 for 2020). The distribution of genetic lineages differed mainly during the lockdown period in 2020 compared to the same period in 2019 with lower proportion (although not significantly), of hyperinvasive genetic lineages in 2020 during the lockdown period (45% in 2020 versus 65% for the same period in 2019). This proportion did not differ outside the period corresponding to the lockdown for the two years (Figure). The genotypes that did not changed or even increased in 2020 were CC23 and the isolates belonging to the unassigned clonal complexes (UA). These isolates were frequently of serogroup Y (Supplementary Table). Indeed, IMD due to serogroup Y is frequently observed in elderly and associated with flu and respiratory manifestations such as bacteremic pneumonia (4, 12). Secondary invasive meningococcal infections were reported to occur 7 to 10 days after flu infections (4, 6). Interestingly, sepsis was also observed as a common complication during COVID-19 and occurred at a median of 9.0 days (7.0–13.0) after illness onset although the bacterial aetiology was not explored (8). We therefore explored whether IMD (detectable meningococci in a normally sterile site) was more frequently detected in association with respiratory presentations since the emergence of SARS CoV-2. We screened the NRCMHi database for IMD cases that were associated with “pneumonia” or “bronchopneumonia” as clinical manifestations. A total of 25 cases were detected (7 in 2019 and 18 in 2020 representing 4% and 14% of all cases respectively; P=0.005). Several of the 2020 IMD cases were preceded by clinically suspected SARS-CoV-2 infection (Supplementary Table).. These cases were not reported elsewhere.
Age and sex distributions did not differ significantly during this period for the two years for IMD cases without respiratory manifestations (Table). However, the age distribution differed significantly when respiratory presentations were present compared to cases without respiratory manifestations for each year. Indeed, median ages for IMD cases without respiratory manifestations were 21.1 and 20.5 for 2019 and 2020 respectively (Table). These median ages for IMD cases with respiratory manifestations were 82.2 (P=0.016) and 70.7 (P<0.0001) for the two years respectively) (Table). It is noteworthy that more male were present among cases with respiratory manifestations in 2020 compared to 2019 (Table). Serogroup distribution also differed for cases with respiratory manifestations compared to cases without respiratory presentations. The proportions of serogroups W and Y isolates were significantly higher among IMD cases with respiratory presentations (Table) in both 2019 and 2020 underlining the role of these isolates in respiratory forms of IMD (4, 6). These isolates (in particular serogroup W isolates) belonged mainly to non hyperinvasive genetic lineages (Figure and Supplementary Table).
The lockdown seems to have reduced inter-human meningococcal transmission that was associated with significantly lower number of “usual” IMD cases compared to the corresponding reference period of 2019. This decrease involved hyperinvasive but not the non-hyperinvasive isolates further underlying that the former may show higher transmission rates. Moreover, clinical forms with respiratory manifestations seem to increase on the basis of the non-hyperinvasive isolates that may be carried for longer period although of lower virulence. Our data suggest that the increase in these respiratory forms of IMD was concomitant with the COVID-19 pandemic and was mainly observed among elderly. More investigations are required to explore whether these data reveal an enhanced susceptibility to IMD that may be directly linked to the SARS-CoV-2 infections (13). An additional interference between COVID-19 and IMD may originate from the use anti-complement drugs that are explored to control COVID-19 by lowering complement mediated pro-inflammatory response (14). These drugs such as anti-complement compounded 5 (C5) are known to increase the risk for IMD (15).