Solicited local and systemic adverse events were predominantly mild to moderate and transient. These events occurred more frequently among NVX-CoV2373 recipients than among placebo recipients (any local adverse event, 58.0% and 21.1%, respectively, after dose 1 and 78.9% and 21.7% after dose 2; any systemic adverse event, 47.7% and 40.0%, respectively, after dose 1 and 69.5% and 35.9% after dose 2).
Figure 4.
Solicited Local and Systemic Adverse Events (Safety Analysis Population).
After each dose, the most frequently reported solicited local adverse events were tenderness and injection-site pain. The median duration of these events was 2 days or less (Table S11). Severe (grade ≥3) local reactions were infrequent overall but were more common among NVX-CoV2373 recipients than among placebo recipients, particularly after dose 2 (1.1% of NVX-CoV2373 recipients and <1% of placebo recipients after dose 1 and 6.7% and <1%, respectively, after dose 2) (
Figure 4 and Table S10).
The most common solicited systemic adverse events were headache, myalgia, fatigue, and malaise, which were detected more frequently among NVX-CoV2373 recipients and after the second injection and lasted for a median duration of 1 day or less (Table S13). Fever of any severity was rare (<1%) and was similarly distributed in the vaccine and placebo groups after each dose. Severe systemic reactions were more common among NVX-CoV2373 recipients, particularly after dose 2 (2.4% of NVX-CoV2373 recipients and 2.1% of placebo recipients after dose 1 and 12.1% and 2.1%, respectively, after dose 2) (
Figure 4 and Table S12), but they were less frequent than has been reported for other Covid-19 vaccines.
2
In this preliminary safety “snapshot,” unsolicited adverse events were slightly more frequent among NVX-CoV2373 recipients than among placebo recipients (16.3% and 14.8%, respectively), although the imbalance appeared to include duplicate reporting by investigators of reactogenicity that had also been derived from participant-reported outcomes. The frequencies of medically attended adverse events, serious adverse events, severe adverse events, adverse events of special interest related to Covid-19, and potential immune-mediated medical conditions were balanced between the two groups (Table S9). No episodes of anaphylaxis, no evidence of vaccine-associated enhanced Covid-19, and no events that triggered prespecified pause rules were observed. No episodes of the Guillain–Barré syndrome
20 and no imbalance in myocarditis or pericarditis
21 or in vaccine-induced immune thrombosis with thrombocytopenia
22 were observed during the relatively short safety follow-up period reported here (Tables S14 through S16). All-cause mortality was balanced: nine deaths occurred among NVX-CoV2373 recipients (0.5%), and five occurred among placebo recipients (0.5%)
https://www.nejm.org/doi/full/10.1056/NEJMoa2116185