RESUMO
ObjectiveTo investigate temporal trends, severe outcomes, and rebound among systemic autoimmune rheumatic disease (SARD) patients according to outpatient SARS-CoV-2 treatment. MethodsWe performed a retrospective cohort study investigating outpatient SARS-CoV-2 treatments among SARD patients at Mass General Brigham (23/Jan/2022-30/May/2022). We identified SARS-CoV-2 infection by positive PCR or antigen test (index date=first positive test) and SARDs using diagnosis codes and immunomodulator prescription. Outpatient treatments were confirmed by medical record review. The primary outcome was hospitalization or death within 30 days following the index date. COVID-19 rebound was defined as documentation of negative then newly-positive SARS-CoV-2 tests. The association of any vs. no outpatient treatment with hospitalization/death was assessed using multivariable logistic regression. ResultsWe analyzed 704 SARD patients with COVID-19 (mean age 58.4 years, 76% female, 49% with rheumatoid arthritis). Treatment as outpatient increased over calendar time (p<0.001). A total of 426(61%) received outpatient treatment: 307(44%) with nirmatrelvir/ritonavir, 105(15%) with monoclonal antibodies, 5(0.7%) with molnupiravir, 3(0.4%) with outpatient remdesivir, and 6(0.9%) with combinations. There were 9/426 (2.1%) hospitalizations/deaths among those treated as outpatient compared to 49/278 (17.6%) among those with no outpatient treatment (adjusted odds ratio [aOR] 0.12, 0.05 to 0.25). 25/318 (8%) of patients who received oral outpatient treatment had documented COVID-19 rebound. ConclusionOutpatient treatment was strongly associated with lower odds of severe COVID-19 compared to no outpatient treatment. At least 8% of SARD patients experienced COVID-19 rebound. These findings highlight the importance of outpatient COVID-19 treatment for SARD patients and the need for further research on rebound. KEY MESSAGES What is already known on this topic?O_LIPrevious studies suggest that monoclonal antibodies are an effective outpatient treatment option for patients at high-risk of severe COVID-19, including those with systemic autoimmune rheumatic diseases (SARDs). C_LIO_LINirmatrelvir/ritonavir and molnupiravir are recently-authorized effective oral outpatient SARS-CoV-2 treatment options, but clinical trials were performed among the general population, mostly among unvaccinated and prior to Omicron viral variants. C_LIO_LIOral outpatient SARS-CoV-2 treatments may result in COVID-19 rebound, characterized by newly-positive COVID-19 testing and recurrent symptoms, but no studies have investigated rebound prevalence among SARD patients. C_LI What this study adds?O_LIThis is one of the first studies investigating outpatient SARS-CoV-2 treatments among SARD patients that includes oral options and quantifies the prevalence of COVID-19 rebound. C_LIO_LIOutpatient treatment was associated with 88% reduced odds of severe COVID-19 compared to no treatment. C_LIO_LIAt least 8% of SARDs receiving oral outpatient treatment experienced COVID-19 rebound. C_LI How this study might affect research, practice, or policy?O_LIThese results should encourage clinicians to prescribe and SARD patients to seek prompt outpatient COVID-19 treatment. C_LIO_LIThis research provides an early estimate of the prevalence of COVID-19 rebound after oral outpatient treatment to quantify this risk to clinicians and SARD patients and encourage future research. C_LI
RESUMO
Beyond the unpredictable acute illness caused by SARS-CoV-2, one-fifth of infections unpredictably result in long-term persistence of symptoms despite the apparent clearance of infection. Insights into the mechanisms that underlie post-acute sequelae of COVID-19 (PASC) will be critical for the prevention and clinical management of long-term complications of COVID-19. Several hypotheses have been proposed that may account for the development of PASC, including persistence of virus or the dysregulation of immunity. Among the immunological changes noted in PASC, alterations in humoral immunity have been observed in some patient subsets. To begin to determine whether SARS-CoV-2 or other pathogen specific humoral immune responses evolve uniquely in PASC, we performed comprehensive antibody profiling against SARS-CoV-2 and a panel of endemic pathogens or routine vaccine antigens using Systems Serology in a cohort of patients with pre-existing rheumatic disease who either developed or did not develop PASC. A distinct humoral immune response was observed in individuals with PASC. Specifically, individuals with PASC harbored less inflamed and weaker Fc{gamma} receptor binding anti-SARS-CoV-2 antibodies and a significantly expanded and more inflamed antibody response against endemic Coronavirus OC43. Individuals with PASC, further, generated more avid IgM responses and developed an expanded inflammatory OC43 S2-specific Fc-receptor binding response, linked to cross reactivity across SARS-CoV-2 and common coronaviruses. These findings implicate previous common Coronavirus imprinting as a marker for the development of PASC. One Sentence SummaryThrough high dimensional humoral immune profiling we uncovered the potential importance of previous common Coronavirus imprinting as a novel marker and potential mechanism of an endotype of PASC.
RESUMO
ObjectivesTo investigate temporal trends in incidence and severity of COVID-19 among patients with systemic autoimmune rheumatic diseases (SARDs) from the first wave through the Omicron wave. MethodsWe conducted a retrospective cohort study investigating COVID-19 outcomes among SARD patients systematically identified to have confirmed COVID-19 from March 1, 2020 to January 31, 2022 at a large healthcare system in Massachusetts. We tabulated COVID-19 counts of total and severe cases (hospitalizations or deaths) and compared the proportion with severe COVID-19 by calendar period and by vaccination status. We used logistic regression to estimate the ORs for severe COVID-19 for each period compared to the early COVID-19 period (reference group). ResultsWe identified 1449 SARD patients with COVID-19 (mean age 58.4 years, 75.2% female, 33.9% rheumatoid arthritis). There were 399 (27.5%) cases of severe COVID-19. The proportion of severe COVID-19 outcomes declined over calendar time (p for trend <0.001); 45.6% of cases were severe in the early COVID-19 period (March 1-June 30, 2020) vs. 14.7% in the Omicron wave (December 17, 2021-January 31, 2022; adjusted odds ratio 0.29, 95%CI 0.19-0.43). A higher proportion of those unvaccinated were severe compared to not severe cases (78.4% vs. 59.5%). ConclusionsThe proportion of SARD patients with severe COVID-19 has diminished since early in the pandemic, particularly during the most recent time periods, including the Omicron wave. Advances in prevention, diagnosis, and treatment of COVID-19 may have improved outcomes among SARD patients. KEY MESSAGESO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIPatients with systemic autoimmune rheumatic diseases (SARDs) may be at increased risk for severe COVID-19, defined as hospitalization or death. C_LIO_LIPrevious studies of SARD patients suggested improving COVID-19 outcomes over calendar time, but most were performed prior to the wide availability of COVID-19 vaccines or the Omicron wave that was characterized by high infectivity. C_LI What does this study add?O_LIThe proportion of SARD patients with severe COVID-19 outcomes was lower over calendar time C_LIO_LIThe adjusted odds ratio of severe COVID-19 in the Omicron wave was 0.29 (95%CI 0.19-0.43) compared to early COVID-19 period. C_LIO_LIThe absolute number of severe COVID-19 cases during the peak of the Omicron variant wave was similar to the peaks of other waves. C_LIO_LISARD patients with severe vs. not severe COVID-19 were more likely to be unvaccinated. C_LI How might this impact on clinical practice or future developments?O_LIThese findings suggest that advances in COVID-19 prevention, diagnosis, and treatment have contributed to improved outcomes among SARD patients over calendar time. C_LIO_LIFuture studies should extend findings into future viral variants and consider the roles of waning immunity after vaccination or natural infection among SARD patients who may still be vulnerable to severe COVID-19. C_LI
