The Manual is compiling some of the most significant news items regarding COVID-19 to help people stay up to date.
News items compiled by Richard B. Lynn, MD.
February 14, 2022
Vitamin D and severity of COVID-19 infection
A retrospective study published February 3, 2022 in PLOS ONE looked at all patients admitted to a medical center in Israel between April 7, 2020 and February 4, 2021 who had positive polymerase chain reaction (PCR) tests for SARS-CoV-2 (COVID-19). Of the 1176 patients with a positive PCR test, 253 had a previous 25-hydroxyvitamin D (25(OH)D) level measured 14 to 730 days prior to the positive PCR test. A lower vitamin D level, defined as < 20 ng/mL, was more common in patients with severe or critical disease (87.4%) than in patients with mild or moderate disease (34.3%; p < 0.001). Patients with vitamin D deficiency (<20 ng/mL) were 14 times more likely to have severe or critical disease than patients with 25(OH)D ≥ 40 ng/mL (odds ratio [OR], 14; 95% confidence interval [CI], 4 to 51; p < 0.001). Pre-infection deficiency of vitamin D was associated with increased disease severity and mortality due to COVID-19. The authors suggested further study to determine whether vitamin D supplementation for vitamin D-deficient individuals in the community will impact the severity of future COVID-19 episodes.
February 2, 2022
Early factors anticipate post-acute sequelae of COVID-19
Post-acute sequelae of COVID-19 (PASC, also known as long COVID or long-haul COVID) describes long-term symptoms experienced weeks to months after primary infection with SARS-CoV-2, the virus that causes COVID-19. PASC is a common problem and represents an emerging global crisis. However, risk factors for PASC and their biological associations are poorly understood. A study published in the journal Cell in January 2022, reported on a longitudinal investigation of 309 COVID-19 patients from initial diagnosis (T1), through acute disease (T2), to convalescence (T3) 2 to 3 months after onset of initial symptoms. At T3, symptoms included fatigue (52% of participants), cough (25%), and anosmia/dysguesia (18%).
The study integrated clinical data with patient-reported symptoms and identified 4 PASC-anticipating risk factors at the time of initial COVID-19 diagnosis:
Different patterns of these risk factors and autoantibodies correlated with different PASC symptoms. Most PASC factors are detectable at the time COVID-19 is diagnosed, emphasizing the importance of making sure to identify them early. Future studies involving a greater number of patients for longer duration will be needed to learn the predictive value of these risk factors.
January 20, 2022
Multisystem inflammatory syndrome in children (MIS-C)
Multisystem inflammatory syndrome in children (MIS-C) is a rare but important complication of COVID-19. Although most children with COVID-19 have mild or no symptoms, some children can have severe illness. The current increase in the number of children with COVID-19 being admitted to hospitals in the US makes MIS-C even more important. The CDC established a national reporting platform to gather epidemiologic and clinical data from patients suspected of having MIS-C. An analysis of this database was published in April 2021 in JAMA Pediatrics.
The analysis included 1733 patients with MIS-C. Findings of note were that 57.6% were male and 71.3% were Hispanic or Black. More than half reported gastrointestinal symptoms, rash, or conjunctival hyperemia. Major clinical findings were hypotension or shock (54%), cardiac dysfunction (31%), pericardial effusion (23.4%), myocarditis (17.3%), and coronary artery dilatation or aneurysms (16.5%). Overall, 58.2% were admitted to the intensive care unit, and 24 patients died. Of note, patients aged 18 to 20 were more likely to have myocarditis (30.9%), pneumonia (36.4%), and acute respiratory distress syndrome (18.2%). The first 2 MIS-C peaks followed COVID-19 peaks by 2 to 5 weeks. This finding suggests that MIS-C is due to a delayed immunologic response to SARS-CoV-2 infection.
January 4, 2022
Omicron severity in the UK
A report by the UK Health Security Agency (UKHSA) regarding COVID-19 variants published on December 31, 2021 provided insight into the severity of Omicron cases compared to Delta cases. The analysis included 528,176 Omicron cases and 573,012 Delta cases occurring between November 22 and December 26, 2021. The analysis included COVID-19 cases with sequenced or genotyped variant or based on S-gene negativity/positivity that presented to emergency care or were admitted to the hospital within 14 days of specimen date (data as of Dec. 29, 2021). The risk of presentation to emergency care or hospital admission with Omicron was approximately half of that for Delta. The risk of hospitalization alone with Omicron was one-third of that for Delta. These preliminary data may be affected by delays in reporting hospitalization. Overall, the data suggest that infection with Omicron causes less severe disease than infection with Delta in the individual patient. The report emphasizes that this may not result in a lower burden on hospitals given the higher transmission rate with Omicron.
The analysis evaluated possible risk factors for hospital admission, including vaccination status. Researchers found that the risk of being admitted to hospital for Omicron cases was 65% lower for patients who had received 2 doses of a vaccine and 81% lower for those who had received 3 doses of vaccine compared to those who were unvaccinated (including those < 28 days since their first vaccine dose).
December 7, 2021
Omicron variant has unique insertion mutation
Seven coronaviruses are known to cause disease in humans. Four are seasonal coronaviruses that most frequently cause symptoms of the common cold. Three cause much more severe, and sometimes fatal, respiratory infections (SARS, MERS, COVID-19).
The Omicron variant of SARS-CoV-2 (the virus that causes COVID-19) has 37 mutations in the spike protein, including 30 substitution mutations, 6 deletion mutations, and one insertion mutation (ins214EPE). Researchers from Nference, a firm based in Cambridge Mass, have searched the GISAID database, which includes information on the 5.4 million SARS-CoV-2 genomes covering 1523 lineages of the virus. Their results have been posted on the OSFPREPRINT website.
The investigators found that the substitution and deletion mutations have appeared in previous SARS-CoV-2 lineages. However, the insertion mutation in the Omicron variant (ins214EPE) has not been observed in any SARS-CoV-2 lineage other than Omicron. Importantly, this insertion mutation has been observed in a seasonal coronavirus (HCoV-229E). The authors postulate that this mutation in Omicron may have arisen in a patient coinfected with both the SARS-CoV-2 virus and HCOV-229E.
November 10, 2021
BNT162b3 COVID-19 vaccine in children 5 to 11 years old
The data from the clinical study on the Pfizer-BioNTech COVID-19 vaccine (mRNA) in children 5 to 11 years of age was published in the New England Journal of Medicine on November 9, 2021. In June 2021, a total of 2,316 children 5 to 11 years of age were screened for inclusion, and 2,285 underwent randomization across 81 sites in the United States, Spain, Finland, and Poland. 1,517 children were randomly assigned to receive the Pfizer vaccine and 751 were assigned to receive placebo.
Adverse reactions were generally mild to moderate, lasting 1 to 2 days. Injection-site pain was the most common local reaction, occurring in about 74% of vaccine recipients. Fatigue and headache were the most frequently reported systemic reactions. Frequency of fatigue and headache was similar among vaccine and placebo recipients after the first dose. Fatigue and headache were more frequent among vaccine recipients than among placebo recipients after the second dose.
A significant immunological response was achieved by 99.2% of participants 1 month after the second dose (same immunological response rate as in vaccine recipients 16 to 25 years of age). There were 3 cases of COVID-19 (with onset 7 days or more after the second dose) among vaccine recipients and 16 among placebo recipients; the observed vaccine efficacy was 90.7% (95% CI, 67.7 to 98.3). No cases of severe COVID-19 or multisystem inflammatory syndrome were reported.
October 28, 2021
Myocarditis after BNT162b2 mRNA COVID-19 vaccine in Israel
The Israeli data on myocarditis after vaccination for COVID-19 was published in the New England Journal of Medicine on October 6, 2021. The study retrospectively reviewed data obtained from December 20, 2020 to May 31, 2021, regarding all cases of myocarditis reported to the Israeli Ministry of Health active surveillance system. By May 31, 2021, approximately 5.1 million Israelis (of 9.3 million Israeli residents) had received two doses of the COVID-19 BNT162b2 mRNA vaccine.
There were 283 cases of myocarditis reported. These cases included 142 among vaccinated persons within 21 days after the first dose or 30 days after the second dose, 40 among vaccinated persons not in proximity to vaccination, and 101 among unvaccinated persons. Of the 142 cases occurring after vaccination, the clinical presentation was judged to be mild in 95%; one fulminant case was fatal. Of 136 persons with definite or probable myocarditis, 19 presented after the first dose of vaccine and 117 after the second dose.
Comparison of the incidence of myocarditis between vaccinated and unvaccinated persons was 2.35 (95% CI, 1.10 to 5.02). This result was driven mainly by the findings for males in younger age groups. The rate ratio was highest in male recipients between the ages of 16 and 19 years (8.96; 95% CI, 4.50 to 17.83), with a ratio of 1 in 6637.
As compared with the expected incidence based on historical data, the standardized incidence ratio was 5.34 (95% CI, 4.48 to 6.40) and was highest after the second dose in male recipients between the ages of 16 and 19 years (13.60; 95% CI, 9.30 to 19.20).
The authors concluded that the incidence of myocarditis was low but increased particularly after the receipt of the second dose of the Pfizer vaccine among young male recipients. The clinical presentation of myocarditis after vaccination was usually mild.
October 13, 2021
Residual symptoms seven months after COVID-19 in people treated as outpatients
Symptomatic people who tested positive for COVID-19 at the Geneva University Hospitals in Switzerland from March 18 to May 15, 2020, were contacted again at 30 to 45 days and 7 to 9 months from diagnosis and asked about symptoms consistent with COVID-19. This study was published in the Annals of Internal Medicine in September 2021. The follow-up at 7 to 9 months after COVID-19 diagnosis was completed by 410 patients, of whom 39.0% reported residual symptoms. Fatigue (20.7%) was the most common symptom reported, followed by loss of taste or smell (16.8%), shortness of breath (11.7%), and headache (10.0%). The authors concluded that about a third of persons with mild to moderate, acute COVID-19 in an outpatient setting have long-term symptoms at 7 to 9 months.
September 27, 2021
The recent approval in the US of a third (booster) dose of the BNT162b2 messenger RNA vaccine (Pfizer–BioNTech) was based in part on the experience in Israel. In Israel, the administration of a third (booster) dose of the Pfizer vaccine was approved on July 30, 2021, for persons who were 60 years of age or older and who had received a second dose of vaccine at least 5 months earlier. A study published in the New England Journal of Medicine on September 15, 2021, reported on data collected from July 30 through August 31, 2021, regarding 1,137,804 Israeli residents who were 60 years of age or older and had been fully vaccinated (received two doses of the Pfizer vaccine) at least 5 months earlier. The rate of confirmed COVID-19 and the rate of severe illness were compared between those who had received a booster injection at least 12 days earlier and those who had not received a booster injection. The results showed that at least 12 days after the booster dose, the rate of confirmed infection was lower in the booster group than in the non-booster group by a factor of 11.3, and the rate of severe illness was lower by a factor of 19.5. The study concluded that the rates of confirmed COVID-19 and severe illness were substantially lower among those who received a booster (third) dose of the Pfizer vaccine.