Coronavirus (Covid-19)

Tongue, nasal, and mid-turbinate swabs to detect SARS-CoV-2 were collected by 530 outpatients before a health care worker collected nasopharyngeal swabs from these patients. Both the mid-turbinate and the nasal samples collected by the patients themselves may be clinically acceptable, with estimated sensitivities above 90%.

NVX-CoV2373 is a vaccine containing a full-length stabilized recombinant spike protein trimer that is administered in two doses 3 weeks apart along with a saponin-based adjuvant. In a randomized trial, approximately 20,000 participants received the vaccine and 10,000 a placebo. Vaccine efficacy against infection was 90%, and reactogenicity was similar to that of other Covid-19 vaccines.

During a surge in cases of Covid-19 in Israel, a rapid deployment of BNT162b2 booster injections was initiated in long-term care facilities over a 3-week period in July. When infection rates were increasing in the general population, rates in long-term care facilities decreased by 71%, and hospitalization rates fell by 80%.

Among 843,208 participants in Israel who were 50 years of age or older and had received two doses of the BNT162b2 vaccine at least 5 months earlier, those who received a booster had 90% lower mortality due to Covid-19 than those who did not receive a booster. The study period was 54 days; adverse effects were not recorded.

In a study involving 4.7 million fully vaccinated persons in Israel, the rate of confirmed Covid-19 was lower among those who received a booster than among those who did not by a factor of approximately 10. Among participants 60 years of age or older, the rate of severe illness was lower by a factor of 17.9 and the rate of death by a factor of 14.7.

In nursing homes, the lowest quartile of staff vaccination rates in counties in the highest quartile of prevalence of Covid-19 was associated with 1.56 additional cases per 100 beds among residents, 1.50 additional cases per 100 beds among staff, and 0.19 additional Covid-19–related deaths of residents per 100 beds relative to the highest quartile of staff vaccination rates in the same county.

Neutralization assays of SARS-CoV-2 pseudoviruses expressing wild-type, omicron, or a synthetic resistant spike protein in plasma drawn from 47 people over time showed much lower omicron neutralization than Wuhan-hu-1 neutralization after two doses of an mRNA vaccine. However, samples from persons vaccinated after recovery from Covid-19 and those who received a booster vaccine had high levels of omicron neutralization.

Oral outpatient treatment for Covid-19 is needed. In this phase 3, double-blind, randomized, controlled trial, molnupiravir, a small-molecule antiviral, was studied in unvaccinated patients with less than 5 days of Covid-19 illness. By day 29, hospitalization for progression of Covid-19 was lower with molnupiravir (6.8%) than with placebo (9.7%).

This phase 3, placebo-controlled platform trial evaluated a single infusion of casirivimab and imdevimab (REGEN-COV) at 2400-mg and 1200-mg doses in outpatients with acute SARS-CoV-2 infection. The incidence of Covid-19–related hospitalization was lower and recovery was faster among patients who received the antibody combination than among those who received placebo.

Platelet-activating antibodies can develop after adenoviral vector vaccination against Covid-19, leading to a potentially fatal procoagulant state. In an analysis involving 35 patients with these antibodies, platelet activation declined in nearly every patient within 12 weeks, despite the persistence of positivity on ELISA, and 5 patients received additional vaccination without sequelae.

The phenotypes of VITT were defined in 220 patients in the United Kingdom who presented a median of 14 days after the first ChAdOx1 nCoV-19 vaccination. Half had cerebral venous sinus thrombosis, a third of whom also had intracranial hemorrhage. Mortality was 22%. Intravenous immune globulin may reverse VITT.

A group of 11 patients had elements of VITT (thrombocytopenia, high d-dimer levels, and positivity for anti-PF4 antibodies) associated with severe headache but no other evidence of thrombosis during the period after ChAdOx1 nCoV-19 vaccination. Four of the patients went on to have thromboses and intracerebral hemorrhage, which suggests that the findings are a VITT prodrome.

The mu variant of SARS-CoV-2 was 10.6 times as resistant to neutralization by serum samples obtained from persons who had recovered from Covid-19 as the B.1 lineage virus and 9.1 times as resistant to neutralization by serum samples from persons who had received the BNT162b2 vaccine.

A resurgence of Covid-19 in mid-June prompted an examination of Covid-19 immunity as a function of month of vaccination in Israel. Data on confirmed infection and severe disease among fully vaccinated persons were collected from July 11 to 31, 2021. Relative and absolute rates of infection and severe disease increased with time since the second vaccine dose in all age groups.

In a test-negative, case–control study involving more than 900,000 participants in Qatar, vaccine effectiveness peaked at 77.5% in the first month after the second dose. The effectiveness fell thereafter to as low as 20% in months 5 through 7 after vaccination, but protection against serious Covid-19 remained greater than 90% for at least 6 months.

A third dose of the BNT162b2 vaccine was administered to 23 volunteers 8 to 9 months after the second dose, and the immune response was assessed. Local reactions were similar to those seen after the second dose. One month after the third dose, neutralization titers were 5 to 7 times as high as those before the third dose, and neutralization extended to the delta variant.

In a longitudinal study involving nearly 4000 health care workers in Israel who had received two doses of BNT162b2 vaccine, levels of spike-binding IgG and neutralizing antibody decreased and did so to a greater extent in men, persons 65 years of age or older, and persons with immunosuppression. Obese persons had higher levels of antibody than nonobese persons.

B-cell and T-cell responses were measured to assess the stability and duration of vaccine-induced immunity. Responses to BNT162b2 and mRNA-1273 peaked early and declined over 6 to 8 months. The response to Ad26.CoV2.S reached a lower peak but continued without evidence of notable decline for 8 months. Response levels correlating with protection have not yet been defined.

The effectiveness of the BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines was assessed from May through August 2021. Initial protection was high, but there was a modest waning after the delta variant surged and public health mitigation policies changed. Protection against hospitalization remained high.

A SARS-CoV-2 surveillance program conducted by the National Basketball Association identified 173 newly infected persons. The viral kinetics were systematically studied and are described.

In a trial of mRNA-1273 or placebo involving 3700 adolescents 12 to 17 years of age, two doses of vaccine stimulated high levels of neutralizing antibodies, with a side-effect profile similar to that seen in other age groups. The incidence of Covid-19 in the unvaccinated group was too low to gauge protection, but Covid-19 did not develop in any vaccinated participants.

This randomized trial of the BNT162b2 vaccine involved 2260 adolescents 12 to 15 years of age. Similar levels of antibody to SARS-CoV-2 were elicited in the 12-to-15-year-old participants and in 16-to-25-year-old participants in a parallel trial. Among participants with no evidence of previous infection, no cases of Covid-19 were diagnosed in vaccine recipients, as compared with 16 cases in placebo recipients.

The rare florid local reactions to Covid-19 vaccines bear gross and microscopic similarity to previously reported cutaneous basophil hypersensitivity reactions to injection of rabbit serum proteins and keyhole limpet hemocyanin in humans.

In a multinational, observer-blinded, randomized trial involving 44,165 participants 16 years of age or older and 2264 participants 12 to 15 years of age, the efficacy of the BNT162b2 vaccine was 91% against Covid-19 and 97% against severe disease through 6 months of follow-up. In South Africa, where the beta variant was widespread, vaccine efficacy was 100%. Late toxic effects from the vaccine were not observed.

In a test-negative case–control study involving 1482 vaccinated health care workers and 3449 controls, the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines were 88.8% and 96.3% effective, respectively, at preventing symptomatic Covid-19. Efficacy was similar in subgroups according to age (<50 or ≥50 years), racial and ethnic groups, underlying conditions, and various levels of patient contact.

An analysis of surveillance data on inpatients younger than 21 years of age who had multisystem inflammatory syndrome in children and were hospitalized between March 15 and October 31, 2020, showed that initial treatment with IVIG plus glucocorticoids was associated with a lower risk of cardiovascular dysfunction and a lower incidence of adjunctive therapy use than IVIG alone.