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  Conference on Retroviruses
and Opportunistic Infections
February 12-16, 2022
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Long COVID Definition - Cardiac Rhythm Upsets, Diabetes, GU Symptoms Emerge as Persistent COVID Problems
  2022 CROI, February 12-16 and 22-24, 2022
Mark Mascolini
Cardiac dysrhythmia, diabetes, fatigue, anosmia (loss of smell), genitourinary (GU) disorders, and other conditions emerged as persistent problems after the initial month of COVID-19 infection in a 98,000-person comparison of people with or without COVID in the Kaiser Permanente Mid-Atlantic States healthcare system [1]. Identifying such conditions is a first step in defining postacute sequelae of SARS-CoV-2 infection (PASC), also called Long COVID.
Researchers define PASC as new or persistent COVID-related symptoms following convalescence or the 30 days after diagnosis. PASC symptoms, conditions, and timeline remain incompletely defined. A cluster of 2022 CROI studies addressed PASC, or Long COVID, including this one from the Kaiser Permanente Mid-Atlantic States healthcare system.
The Kaiser team considered four types of diagnoses:
1. Prevalent diagnoses: Diagnoses in the 4 years before COVID diagnosis that could be exacerbated by COVID but are not part of PASC.
2. Diagnoses during COVID: Diagnoses within 30 days after a positive COVID test.
3. Persistent diagnoses: Diagnoses within 30 days of COVID diagnosis that persist into the post-COVID period (30 to 120 days after a positive COVID test.
4. Incident diagnoses: New diagnoses more than 30 days after a positive COVID test and not seen in the 4 years before or the 30 days after a positive COVID test.
The researchers selected Kaiser members at least 18 years old who had a positive or negative SARS-CoV-2 RT-PCR between January 1, 2020 and December 31, 2021. They defined three diagnostic periods:
1. Prevalent: 4 years before the RT-PCR test
2. Acute/persistent: 0 to 30 days after RT-PCR and persistent through the following 30 to 120 days
3. Incident/late: newly arising 30 to 120 days after RT-PCR
The Kaiser team matched RT-PCR-positive people to RT-PCR-negative people by month of test, age group, race, sex, and medical center. To identify “conditions of focus” that distinguished COVID-positive from -negative people, they figured risk ratios (RR) and 95% confidence intervals (CI). This exercise yielded a list of conditions that qualified as potential PASC conditions of focus, arranged in order of incidence (with persistence percentage in parentheses):
- Abdominal pain (0.70%)
- Gastrointestinal disease (1.60%)
- Other nervous system disorders (0.90%)
- Nonspecific chest pain (1.40%)
- Conditions associated with dizziness or vertigo (0.90%)
- Malaise or fatigue (1.00%)
- Other lower respiratory disease (4.50%)
- Anxiety disorder (0.90%)
- Mental health (0.60%)
- Cardiac dysrhythmias (1.20%)
- Nausea and vomiting (0.30%)
- Other nutritional, endocrine, and metabolic disorders (0.20%)
- Fluid and electrolyte disorders (0.90%)
- Anosmia (loss of sense of smell) (0.05%)
- Respiratory failure or insufficiency, respiratory arrest (2.70%)
The investigators successfully matched 28,118 RT-PCR-positive COVID cases with 70,293 RT-PCR-negative controls. Women made up about 57% of each group; about 12% were 65 or older, and about 28% were 50 to 64. Blacks made up about 40% of each group, Hispanics about 22%, and whites about 20%. The most frequent comorbidities were diabetes (18.7% of cases, 16.4% of controls), chronic kidney disease (3.0% of cases, 3.3% of controls), and tumor (2.6% of cases, 3.7% of controls); 0.8% in each group had HIV infection.
Among COVID-positive people, 4.1% had an acute/persistent condition of focus, compared with 2.5% of COVID-negative controls, yielding a 60% higher risk in the COVID group (RR 1.60, 95% CI 1.49 to 1.72). In contrast, percentage of people with any condition differed hardly at all between the COVID-positive and -negative groups: 20.4% and 22.1%. Acute/persistent conditions significantly more frequent in the COVID group were:
- Cardiac dysrhythmia (RR 1.90)
- Diabetes (RR 1.96)
- Fluid and electrolyte disorders (RR 1.96)
- Malaise and fatigue (RR 2.89)
- Nonspecific chest pain (RR 2.39)
- Other lower respiratory disease (RR 2.51)
The COVID group also had a higher rate of incident/late conditions of focus than the non-COVID controls, 13.6% vs 12.1%, to yield a 12% higher risk (RR1.12, 95% CI 1.08 to 1.16). Incident/late conditions significantly more frequent in the COVID group were:
- Anosmia (RR 3.88)
- Cardiac dysrhythmias (RR 1.25)
- Diabetes (RR 1.20)
- Genitourinary symptoms and ill-defined conditions (RR 1.21)
- Malaise and fatigue (RR 1.60)
- Nonspecific chest pain (RR 1.39)
The Kaiser team proposed that identified conditions of focus occur more frequently in people with than without COVID, for up to 120 days after diagnosis. These conditions may help guide a definition of PASC: cardiac dysrhythmias, diabetes, malaise/fatigue, respiratory disease, genitourinary symptoms, nonspecific chest pain, anosmia, and fluid and electrolyte disorders. The investigators see a need for more work to clarify persistence beyond 120 days and symptom severity.
1. Horberg MA, Watson ES, Jefferson CR, et al. Post-acute sequelae of SARS-CoV-2: clinical condition comparison in a matched cohort. 2022 CROI, February 12-16 and 22-24, 2022. Abstract 98.