key: cord-0953943-63409v8v authors: Duggal, Priya; Penson, Tristan; Manley, Hannah N.; Vergara, Candelaria; Munday, Rebecca M.; Duchen, Dylan; Linton, Elizabeth A.; Zurn, Amber; Keruly, Jeanne C.; Mehta, Shruti H.; Thomas, David L. title: Post‐sequelae symptoms and comorbidities after COVID‐19 date: 2022-01-31 journal: J Med Virol DOI: 10.1002/jmv.27586 sha: 58a1ab40dd104a2233a2c521c8912b9128393889 doc_id: 953943 cord_uid: 63409v8v The frequency, severity, and forms of symptoms months after coronavirus 2019 (COVID‐19) are poorly understood, especially in community settings. To better understand and characterize symptoms months after community‐based COVID‐19, a retrospective cohort analysis was conducted. Three hundred and twenty‐eight consecutive persons with a positive test for SARS‐CoV‐2 in the Johns Hopkins Health System, Maryland, March−May 2020, were selected for the study. Symptom occurrence and severity were measured through questionnaires. Of 328 persons evaluated, a median of 242 days (109−478 days) from the initial positive SARS‐CoV‐2 test, 33.2% reported not being fully recovered and 4.9% reported symptoms that constrained daily activities. Compared to those who reported being fully recovered, those with post‐acute sequelae were more likely to report a prior history of heart attack (p < 0.01). Among those reporting long‐term symptoms, men and women were equally represented (men = 34.8%, women = 34.6%), but only women reported symptoms that constrained daily activities, and 56% of them were caregivers. The types of new or persistent symptoms varied, and for many, included a deviation from prior COVID‐19 health, such as being less able to exercise, walk, concentrate, or breathe. A limitation is that self‐report of symptoms might be biased and/or caused by factors other than COVID‐19. Overall, even in a community setting, symptoms may persist months after COVID‐19 reducing daily activities including caring for dependents. The 328 cases (59% women) had a mean age of 47.6 years (range, 19−87 years) ( onset was true both for those with symptoms but were functional (3−6 months = 9%, 6−9 months = 50%, 9+ months = 36%) and for those with symptoms that limited daily activities, (3−6 months = 12.5%, 6−9 months = 44%, 9+ months = 44%). The types of new or persistent symptoms reported varied considerably in form and severity post-infection, and no single symptom was present in the majority of those recovering. The principal differences before the diagnosis of COVID-19 across the three groups were that those with persistent symptoms were more likely to report an antecedent heart attack (p < 0.01). received COVID-19 specific treatments (i.e., convalescent plasma, remdesivir) (n < 5) to evaluate recovery impact. Interestingly, all of those with significantly limiting symptoms were women (n = 16) and 56% were responsible for the care of another person (Table 1) . Some additional differences were evident among those with persistent symptoms. Compared to the 109 who were symptomatic but still able to perform daily roles (functional), the 16 individuals with post-acute symptoms that were limiting were more likely to report an inability to walk long distances (25% vs. 5.5%, p = 0.007) or walk-upstairs (31% vs. 6%, p = 0.002) and to report new heart problems (12.5% vs. 2% p = 0.02) ( Table 3a) . As they self-selected COVID-19 research instead of being contacted consecutively from a list testing SARS-CoV-2 positive, we separately analyzed an additional 179 individuals who participated in the Johns Hopkins HOPE Registry. Those in the HOPE Registry who continued to experience symptoms reported initially experiencing nearly all the presenting symptoms more often than those whose symptoms had resolved (Tables 2b and 3b ). Shortness of breath and pressure/tightness in the chest was a presenting symptom across both studies in those that reported symptoms but limited function. In this study, persistent symptoms were reported by 40% of the study participants a median of 8 months (242 days) after SARS-CoV-2 infection, a majority of whom remained outpatients. No single organ system was uniformly affected, with symptoms ranging from neurocognitive to respiratory and musculoskeletal. However, many reported a clear, persistent decline from their pre-COVID-19 health condition with 4.9% reporting severe limitations in performing daily activities. Interestingly, the prevalence of persistent symptoms did not appreciably decline with time from infection onset, even for those whose symptoms were so severe as to limit their daily activities. This finding underscores the importance of efforts to prevent SARS-CoV-2 infections and research to understand and combat the long-term morbidity. Our findings are consistent with another study that has systematically characterized the spectrum of symptoms in an ambulatory setting. 3 Interestingly, we did not detect differences in post-SARS-CoV-2 sequalae by age. However, there was a distinct sex difference, with women having more severe post-acute symptom persistence than men. Other sex differences have been described with SARS-CoV-2, including T A B L E 3a Frequency and type of persistent or new symptoms post-SARS-CoV-2 infection in those who have not fully recovered a lower anti-SARS-CoV-2 antibody titers 6 or loss of antibodies. 7 The significance of this finding is underscored in view of the disproportionate burden of dependent care born by women, as reported by half of those with significant functional limitations in our study. In this study, there were two sources of patients: those we con- These consecutive case series participants reported fewer overall presenting and persistent symptoms as compared to those who entered our study by contacting the Johns Hopkins HOPE Registry. It's likely that those who experience persistent symptoms and limitations on their daily function may be more motivated to seek out related research and report their symptoms. It is also notable that other studies have used different instruments to assess symptoms after COVID-19. For example, O'Connor and coworkers used accepted psychometric measures to characterize the COVID-19 Yorkshire Rehabilitation Scale. 8 The apparent types and severity of post-COVID-19 symptoms might differ based on the instruments used. That used in the present study is available online (Supporting Information Data). In summary, up to 15 months after SARS-CoV-2 infection, persistent symptoms are common in ambulatory and hospitalized patients. More research is needed to understand why only some persons fully recover and to promote more rapid recovery among others. Research electronic data capture (REDCap)-a metadata-driven methodology and workflow process for providing translational research informatics support The REDCap consortium: building an international community of software platform partners Sequelae in adults at 6 months after COVID-19 infection Persistent symptoms in patients after acute COVID-19 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection Durability of SARS-CoV-2-specific IgG responses in saliva for up to 8 months after infection. medRxiv The COVID-19 Yorkshire Rehabilitation Scale (C19-YRS): application and psychometric analysis in a post-COVID-19 syndrome cohort The authors declare that there are no conflict of interests.