Cross-sectional case-control studies (Blue)
Read on for our pick of COVID-19-related cross-sectional case control studies from the scientific press for February 2023:
- Persistent COVID-19 Symptoms at 6 Months After Onset and the Role of Vaccination Before or After SARS-CoV-2 Infection
- Evaluation of immunological responses to third COVID-19 vaccine among people treated with sphingosine receptor-1 modulators and anti-CD20 therapy
- Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study
Persistent COVID-19 Symptoms at 6 Months After Onset and the Role of Vaccination Before or After SARS-CoV-2 Infection
The objective of this study was to identify characteristics associated with persistent post-COVID-19 symptoms and to describe post-COVID-19 medical encounters. This cohort study used data from the Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases With Pandemic Potential (EPICC) study implemented in the US military health system (MHS); MHS beneficiaries aged 18 years or older who tested positive for SARS-CoV-2 from February 28, 2020, through December 31, 2021, were analyzed, with 1-year follow-up. The outcomes analyzed included survey-reported symptoms through 6 months after SARS-CoV-2 infection and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis categories reported in medical records 6 months following SARS-CoV-2 infection vs 3 months before infection.
More than half of the 1832 participants in these analyses were aged 18 to 44 years (1226 [66.9%]; mean [SD] age, 40.5 [13.7] years), were male (1118 [61.0%]), were unvaccinated at the time of their infection (1413 [77.1%]), and had no comorbidities (1290 [70.4%]). A total of 728 participants (39.7%) had illness that lasted 28 days or longer (28-89 days: 364 [19.9%]; ≥90 days: 364 [19.9%]). Participants who were unvaccinated prior to infection (risk ratio [RR], 1.39; 95% CI, 1.04-1.85), reported moderate (RR, 1.80; 95% CI, 1.47-2.22) or severe (RR, 2.25; 95% CI, 1.80-2.81) initial illnesses, had more hospitalized days (RR per each day of hospitalization, 1.02; 95% CI, 1.00-1.03), and had a Charlson Comorbidity Index score of 5 or greater (RR, 1.55; 95% CI, 1.01-2.37) were more likely to report 28 or more days of symptoms. Among unvaccinated participants, postinfection vaccination was associated with a 41% lower risk of reporting symptoms at 6 months (RR, 0.59; 95% CI, 0.40-0.89). Participants had higher risk of pulmonary (RR, 2.00; 95% CI, 1.40-2.84), diabetes (RR, 1.46; 95% CI, 1.00-2.13), neurological (RR, 1.29; 95% CI, 1.02-1.64), and mental health-related medical encounters (RR, 1.28; 95% CI, 1.01-1.62) at 6 months after symptom onset than at baseline (before SARS-CoV-2 infection). The authors concluded that in this cohort study, more severe acute illness, a higher Charlson Comorbidity Index score, and being unvaccinated were associated with a higher risk of reporting COVID-19 symptoms lasting 28 days or more. Participants with COVID-19 were more likely to seek medical care for diabetes, pulmonary, neurological, and mental health-related illness for at least 6 months after onset compared with their pre-COVID baseline health care use patterns. These findings may inform the risk-benefit ratio of COVID-19 vaccination policy.
Richard SA, Pollett SD, Fries AC, Berjohn CM, Maves RC, Lalani T, Smith AG, Mody RM, Ganesan A, Colombo RE, Lindholm DA, Morris MJ, Huprikar N, Colombo CJ, Madar C, Jones M, Larson DT, Bazan SE, Mende K, Saunders D, Livezey J, Lanteri CA, Scher AI, Byrne C, Rusiecki J, Ewers E, Epsi NJ, Rozman JS, English C, Simons MP, Tribble DR, Agan BK, Burgess TH; Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases With Pandemic Potential (EPICC) COVID-19 Cohort Study Group. Persistent COVID-19 Symptoms at 6 Months After Onset and the Role of Vaccination Before or After SARS-CoV-2 Infection. JAMA Netw Open. 2023 Jan 3;6(1):e2251360. doi: 10.1001/jamanetworkopen.2022.51360.
Evaluation of immunological responses to third COVID-19 vaccine among people treated with sphingosine receptor-1 modulators and anti-CD20 therapy
People living with multiple sclerosis (MS) and other disorders treated with immunomodulatory therapies remain concerned about suboptimal responses to coronavirus disease 2019 (COVID-19) vaccines. Important questions persist regarding immunological response to third vaccines, particularly with respect to newer virus variants. The objective of this observational study was to evaluate humoral and cellular immune responses to a third COVID-19 vaccine dose in people on anti-CD20 therapy and sphingosine 1-phosphate receptor (S1PR) modulators, including Omicron-specific assays.
The immunological responses to third COVID-19 vaccine dose in participants treated with anti-CD20 agents, S1PR modulators, and healthy controls was evaluated. Neutralizing antibodies against USA-WA1/2020 (WA1) and B.1.1.529 (BA.1) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were measured before and after third vaccine. Groups were compared by one-way ANOVA with Tukey multiple comparisons. Cellular responses to spike peptide pools generated from WA1 and BA.1 were evaluated. Pre-post comparisons were made by Wilcoxon paired t-tests, inter-cohort comparisons by Mann-Whitney t-test. This cohort includes 25 participants on anti-CD20 therapy, 12 on S1PR modulators, and 14 healthy controls. Among those on anti-CD20 therapy, neutralizing antibodies to WA1 were significantly reduced compared to healthy controls (ID50% GM post-vaccination of 8.1 ± 2.8 in anti-CD20 therapy group vs 452.6 ± 8.442 healthy controls, P < 0.0001) and neutralizing antibodies to BA.1 were below the threshold of detection nearly universally. However, cellular responses, including to Omicron-specific peptides, were not significantly different from controls. Among those on S1PR modulators, neutralizing antibodies to WA1 were detected in a minority, and only 3/12 had neutralizing antibodies just at the limit of detection to BA.1. Cellular responses to Spike antigen in those on S1PR modulators were reduced by a factor of 100 compared to controls (median 0.0008% vs. 0.08%, p < 0.001) and were not significantly “boosted” by a third injection. The authors concluded that participants on anti-CD20 and S1PR modulator therapies had impaired antibody neutralization capacity, particularly to BA.1, even after a third vaccine. T cell responses were not affected by anti-CD20 therapies but were nearly abrogated by S1PR modulators.
Katz Sand I, Gnjatic S, Krammer F, Tuballes K, Carreño JM, Satyanarayan S, Filomena S, Staker E, Tcheou J, Miller A, Fabian M, Safi N, Nichols J, Patel J, Krieger S, Tankou S, Horng S, Klineova S, Beck E, Merad M, Lublin F. Evaluation of immunological responses to third COVID-19 vaccine among people treated with sphingosine receptor-1 modulators and anti-CD20 therapy. Mult Scler Relat Disord. 2022 Dec 28;70:104486. doi: 10.1016/j.msard.2022.104486.
Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study
The objective of this retrospective nationwide cohort study was to determine the clinical sequelae of long covid for a year after infection in patients with mild disease and to evaluate its association with age, sex, SARS-CoV-2 variants, and vaccination status. 1 913 234 Maccabi Healthcare Services members of all ages who did a polymerase chain reaction test for SARS-CoV-2 between 1 March 2020 and 1 October 2021 were included. The main outcome measures were: the risk of an evidence based list of 70 reported long covid outcomes in unvaccinated patients infected with SARS-CoV-2 matched to uninfected people, adjusted for age and sex and stratified by SARS-CoV-2 variants, and risk in patients with a breakthrough SARS-CoV-2 infection compared with unvaccinated infected controls. Risks were compared using hazard ratios and risk differences per 10 000 patients measured during the early (30-180 days) and late (180-360 days) time periods after infection. Covid-19 infection was significantly associated with increased risks in early and late periods for anosmia and dysgeusia (hazard ratio 4.59 (95% confidence interval 3.63 to 5.80), risk difference 19.6 (95% confidence interval 16.9 to 22.4) in early period; 2.96 (2.29 to 3.82), 11.0 (8.5 to 13.6) in late period), cognitive impairment (1.85 (1.58 to 2.17), 12.8, (9.6 to 16.1); 1.69 (1.45 to 1.96), 13.3 (9.4 to 17.3)), dyspnoea (1.79 (1.68 to 1.90), 85.7 (76.9 to 94.5); 1.30 (1.22 to 1.38), 35.4 (26.3 to 44.6)), weakness (1.78 (1.69 to 1.88), 108.5, 98.4 to 118.6; 1.30 (1.22 to 1.37), 50.2 (39.4 to 61.1)), and palpitations (1.49 (1.35 to 1.64), 22.1 (16.8 to 27.4); 1.16 (1.05 to 1.27), 8.3 (2.4 to 14.1)) and with significant but lower excess risk for streptococcal tonsillitis and dizziness. Hair loss, chest pain, cough, myalgia, and respiratory disorders were significantly increased only during the early phase. Male and female patients showed minor differences, and children had fewer outcomes than adults during the early phase of covid-19, which mostly resolved in the late period. Findings remained consistent across SARS-CoV-2 variants. Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnoea and similar risk for other outcomes compared with unvaccinated infected patients. The authors concluded that this nationwide study suggests that patients with mild covid-19 are at risk for a small number of health outcomes, most of which are resolved within a year from diagnosis.
Mizrahi B, Sudry T, Flaks-Manov N, Yehezkelli Y, Kalkstein N, Akiva P, Ekka-Zohar A, Ben David SS, Lerner U, Bivas-Benita M, Greenfeld S. Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study. BMJ. 2023 Jan 11;380:e072529. doi: 10.1136/bmj-2022-072529.
