Major Update 2: Antibody Response and Risk for Reinfection After SARS-CoV-2 Infection-Final Update of a Living, Rapid Review.

BACKGROUND: The durability of the antibody response after SARS-CoV-2 infection and the role of antibodies in protection against reinfection are unclear. PURPOSE: To synthesize evidence on the SARS-CoV-2 antibody response and reinfection risk with a focus on gaps identified in our prior reports. DATA SOURCES: MEDLINE (Ovid), EMBASE, CINAHL, World Health Organization Research Database, and reference lists from 16 December 2021 through 8 July 2022, with surveillance through 22 August 2022. STUDY SELECTION: English-language, cohort studies evaluating IgG antibody duration at least 12 months after SARS-CoV-2 infection, the antibody response among immunocompromised adults, predictors of nonseroconversion, and reinfection risk. DATA EXTRACTION: Two investigators sequentially extracted study data and rated quality. DATA SYNTHESIS: Most adults had IgG antibodies after SARS-CoV-2 infection at time points greater than 12 months (low strength of evidence [SoE]). Although most immunocompromised adults develop antibodies, the overall proportion with antibodies is lower compared with immunocompetent adults (moderate SoE for organ transplant patients and low SoE for patients with cancer or HIV). Prior infection provided substantial, sustained protection against symptomatic reinfection with the Delta variant (high SoE) and reduced the risk for severe disease due to Omicron variants (moderate SoE). Prior infection was less protective against reinfection with Omicron overall (moderate SoE), but protection from earlier variants waned rapidly (low SoE). LIMITATION: Single review for abstract screening and sequential review for study selection, data abstraction, and quality assessment. CONCLUSION: Evidence for a sustained antibody response to SARS-CoV-2 infection is considerable for both Delta and Omicron variants. Prior infection protected against reinfection with both variants, but, for Omicron, protection was weaker and waned rapidly. This information may have limited clinical applicability as new variants emerge. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42020207098).

Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults

BACKGROUND: The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in COVID-19 disease susceptibility, severity, and treatment is unclear. PURPOSE: To evaluate, on an ongoing basis, whether use of ACEIs or ARBs either increases risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or is associated with worse COVID-19 disease outcomes, and to assess the efficacy of these medications for COVID-19 treatment. DATA SOURCES: MEDLINE (Ovid) and Cochrane Database of Systematic Reviews from 2003 to 4 May 2020, with planned ongoing surveillance for 1 year; the World Health Organization database of COVID-19 publications and medRxiv.org through 17 April 2020; and ClinicalTrials.gov to 24 April 2020, with planned ongoing surveillance. STUDY SELECTION: Observational studies and trials in adults that examined associations and effects of ACEIs or ARBs on risk for SARS-CoV-2 infection and COVID-19 disease severity and mortality. DATA EXTRACTION: Single-reviewer abstraction confirmed by another reviewer, independent evaluation by 2 reviewers of study quality, and collective assessment of certainty of evidence. DATA SYNTHESIS: Two retrospective cohort studies found that ACEI and ARB use was not associated with a higher likelihood of receiving a positive SARS-CoV-2 test result, and 1 case-control study found no association with COVID-19 illness in a large community (moderate-certainty evidence). Fourteen observational studies, involving a total of 23 565 adults with COVID-19, showed consistent evidence that neither medication was associated with more severe COVID-19 illness (high-certainty evidence). Four registered randomized trials plan to evaluate ACEIs and ARBs for treatment of COVID-19. LIMITATION: Half the studies were small and did not adjust for important confounding variables. CONCLUSION: High-certainty evidence suggests that ACEI or ARB use is not associated with more severe COVID-19 disease, and moderate-certainty evidence suggests no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain. PRIMARY FUNDING SOURCE: None. (PROSPERO: registration number pending).

Antibody Response After SARS-CoV-2 Infection and Implications for Immunity : A Rapid Living Review.

BACKGROUND: The clinical significance of the antibody response after SARS-CoV-2 infection remains unclear. PURPOSE: To synthesize evidence on the prevalence, levels, and durability of detectable antibodies after SARS-CoV-2 infection and whether antibodies to SARS-CoV-2 confer natural immunity. DATA SOURCES: MEDLINE (Ovid), Embase, CINAHL, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, World Health Organization global literature database, and Covid19reviews.org from 1 January through 15 December 2020, limited to peer-reviewed publications available in English. STUDY SELECTION: Primary studies characterizing the prevalence, levels, and duration of antibodies in adults with SARS-CoV-2 infection confirmed by reverse transcriptase polymerase chain reaction (RT-PCR); reinfection incidence; and unintended consequences of antibody testing. DATA EXTRACTION: Two investigators sequentially extracted study data and rated quality. DATA SYNTHESIS: Moderate-strength evidence suggests that most adults develop detectable levels of IgM and IgG antibodies after infection with SARS-CoV-2 and that IgG levels peak approximately 25 days after symptom onset and may remain detectable for at least 120 days. Moderate-strength evidence suggests that IgM levels peak at approximately 20 days and then decline. Low-strength evidence suggests that most adults generate neutralizing antibodies, which may persist for several months like IgG. Low-strength evidence also suggests that older age, greater disease severity, and presence of symptoms may be associated with higher antibody levels. Some adults do not develop antibodies after SARS-CoV-2 infection for reasons that are unclear. LIMITATIONS: Most studies were small and had methodological limitations; studies used immunoassays of variable accuracy. CONCLUSION: Most adults with SARS-CoV-2 infection confirmed by RT-PCR develop antibodies. Levels of IgM peak early in the disease course and then decline, whereas IgG peaks later and may remain detectable for at least 120 days. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42020207098).

Racial and Ethnic Disparities in COVID-19-Related Infections, Hospitalizations, and Deaths : A Systematic Review.

BACKGROUND: Data suggest that the effects of coronavirus disease 2019 (COVID-19) differ among U.S. racial/ethnic groups. PURPOSE: To evaluate racial/ethnic disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and COVID-19 outcomes, factors contributing to disparities, and interventions to reduce them. DATA SOURCES: English-language articles in MEDLINE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, searched from inception through 31 August 2020. Gray literature sources were searched through 2 November 2020. STUDY SELECTION: Observational studies examining SARS-CoV-2 infections, hospitalizations, or deaths by race/ethnicity in U.S. settings. DATA EXTRACTION: Single-reviewer abstraction confirmed by a second reviewer; independent dual-reviewer assessment of quality and strength of evidence. DATA SYNTHESIS: 37 mostly fair-quality cohort and cross-sectional studies, 15 mostly good-quality ecological studies, and data from the Centers for Disease Control and Prevention and APM Research Lab were included. African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection, hospitalization, and COVID-19-related mortality compared with non-Hispanic White populations, but not higher case-fatality rates (mostly reported as in-hospital mortality) (moderate- to high-strength evidence). Asian populations experience similar outcomes to non-Hispanic White populations (low-strength evidence). Outcomes for other racial/ethnic groups have been insufficiently studied. Health care access and exposure factors may underlie the observed disparities more than susceptibility due to comorbid conditions (low-strength evidence). LIMITATIONS: Selection bias, missing race/ethnicity data, and incomplete outcome assessments in cohort and cross-sectional studies must be considered. In addition, adjustment for key demographic covariates was lacking in ecological studies. CONCLUSION: African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection and COVID-19-related mortality but similar rates of case fatality. Differences in health care access and exposure risk may be driving higher infection and mortality rates. PRIMARY FUNDING SOURCE: Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development. (PROSPERO: CRD42020187078).

Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults

BACKGROUND: The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in COVID-19 disease susceptibility, severity, and treatment is unclear. PURPOSE: To evaluate, on an ongoing basis, whether use of ACEIs or ARBs either increases risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or is associated with worse COVID-19 disease outcomes, and to assess the efficacy of these medications for COVID-19 treatment. DATA SOURCES: MEDLINE (Ovid) and Cochrane Database of Systematic Reviews from 2003 to 4 May 2020, with planned ongoing surveillance for 1 year; the World Health Organization database of COVID-19 publications and medRxiv.org through 17 April 2020; and ClinicalTrials.gov to 24 April 2020, with planned ongoing surveillance. STUDY SELECTION: Observational studies and trials in adults that examined associations and effects of ACEIs or ARBs on risk for SARS-CoV-2 infection and COVID-19 disease severity and mortality. DATA EXTRACTION: Single-reviewer abstraction confirmed by another reviewer, independent evaluation by 2 reviewers of study quality, and collective assessment of certainty of evidence. DATA SYNTHESIS: Two retrospective cohort studies found that ACEI and ARB use was not associated with a higher likelihood of receiving a positive SARS-CoV-2 test result, and 1 case-control study found no association with COVID-19 illness in a large community (moderate-certainty evidence). Fourteen observational studies, involving a total of 23 565 adults with COVID-19, showed consistent evidence that neither medication was associated with more severe COVID-19 illness (high-certainty evidence). Four registered randomized trials plan to evaluate ACEIs and ARBs for treatment of COVID-19. LIMITATION: Half the studies were small and did not adjust for important confounding variables. CONCLUSION: High-certainty evidence suggests that ACEI or ARB use is not associated with more severe COVID-19 disease, and moderate-certainty evidence suggests no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain. PRIMARY FUNDING SOURCE: None. (PROSPERO: registration number pending).

Antithrombotic Therapies in COVID-19 Disease: a Systematic Review.

BACKGROUND: Infection with coronavirus SARS-CoV-2, causing COVID-19 disease, leads to inflammation and a prothrombotic state. OBJECTIVE: This rapid systematic review aims to synthesize evidence on thromboembolism incidence and outcomes with antithrombotic therapies in COVID-19. DATA SOURCES: We searched MEDLINE (Ovid), Cochrane Rapid Reviews, PROSPERO, and the WHO COVID-19 Database from January 1, 2003, to April 22, 2020, for studies meeting pre-specified inclusion criteria. STUDY SELECTION, DATA EXTRACTION, AND SYNTHESIS: One investigator identified articles for inclusion, abstracted data, and performed quality assessment, with second reviewer checking. RESULTS: Incidence of thromboembolism among hospitalized patients with COVID-19 ranged from 25 to 53% in 4 retrospective series. We identified 3 studies (1 retrospective cohort study, 1 prospective uncontrolled observational study, and 1 case series) examining outcomes among COVID-19 patients who received antithrombotic therapies. These studies all included different interventions (thromboprophylaxis with unfractionated heparin (UFH) or low molecular-weight heparin (LMWH); an intensive thromboprophylaxis protocol with LMWH, antithrombin, and clopidogrel; and salvage therapy with tissue plasminogen activator and heparin). These studies are overall poor quality due to methodological limitations including unclear patient selection protocols, lack of reporting or adjustment for patient baseline characteristics, inadequate duration of follow-up, and partial reporting of outcomes. CONCLUSIONS: New evidence on thromboembolism in COVID-19 does not warrant a change in current guidance on thromboprophylaxis among hospitalized patients. Prospective trials of antithrombotic treatment strategies among patients with COVID-19 are urgently needed.