Is recurrence possible in coronavirus disease 2019 (COVID-19)? Case series and systematic review of literature

Abstract

Can a patient diagnosed with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) be infected again? This question is still unsolved. We tried to analyze local and literature cases with a positive respiratory swab after recovery. We collected data from symptomatic patients diagnosed with SARS-CoV-2 infection in the Italian Umbria Region that, after recovery, were again positive for SARS-CoV-2 in respiratory tract specimens. Samples were also assessed for infectivity in vitro. A systematic review of similar cases reported in the literature was performed. The study population was composed of 9 patients during a 4-month study period. Among the new positive samples, six were inoculated in Vero-E6 cells and showed no growth and negative molecular test in culture supernatants. All patients were positive for IgG against SARS-CoV-2 nucleoprotein and/or S protein. Conducting a review of the literature, 1350 similar cases have been found. The presumptive reactivation occurred in 34.5 days on average (standard deviation, SD, 18.7 days) after COVID-19 onset, when the 5.6% of patients presented fever and the 27.6% symptoms. The outcome was favorable in 96.7% of patients, while the 1.1% of them were still hospitalized at the time of data collection and the 2.1% died. Several hypotheses have been formulated to explain new positive respiratory samples after confirmed negativity. According to this study, the phenomenon seems to be due to the prolonged detection of SARS-CoV-2 RNA traces in respiratory samples of recovered patients. The failure of the virus to replicate in vitro suggests its inability to replicate in vivo.

A systematic review on the recurrence of SARS-CoV-2 virus: frequency, risk factors, and possible explanations

“…Within the first admission, considering 1064 patients, the majority of re-positive cases ( n = 987; 92.7%) were asymptomatic or had mild to moderate symptoms [ 1 , 3 , 13 , 14 , 16 , 17 , 19 , 21–24 , 26–28 , 30–33 , 36–45 , 47 , 48 , 50–52 , 54 , 56 , 58 , 59 , 61 , 62 , 64–67 , 69–73 , 75 , 77 ], but some of them had severe or critical disease ( n = 77, 7.3%) [ 1 , 13 , 18 , 21 , 23 , 24 , 27 , 30 , 31 , 35 , 36 , 39 , 42 , 43 , 46 , 49 , 55 , 60 , 63 , 68 , 74 ]. To compare the severity of disease during the first and second courses of illness in re-positive patients, 57 studies including 858 re-positive patients, it was reported that the disease severity decreased or remained unchanged in 835 cases (97.3%) [ 13 , 15–20 , 23 , 24 , 26 , 28–31 , 33 , 36–48 , 50 , 52–54 , 58–61 , 65–68 , 70 , 71 , …”

Neurological Sequelae in Patients with COVID-19: A Histopathological Perspective

“…ACE2 is also a key regulator of the renin–angiotensin–aldosterone system (RAAS). SARS-CoV-2 can cause an ACE/ACE2 balance disruption and RAAS activation, which eventually leads to disease progression, especially in patients with comorbidities, such as hypertension, diabetes mellitus, and cardiovascular diseases [ 8 ].…”

Diagnostic SARS-CoV-2 Cycle Threshold Value Predicts Disease Severity, Survival, and Six-Month Sequelae in COVID-19 Symptomatic Patients

“…Further to the recognized risk factors for severity, the initial prognostic workup of persons infected by SARS-CoV-2 would also benefit from viral biomarkers able to predict COVID-19 evolution. In this regard, it is a current matter of debate whether SARS-CoV-2 viral load is an impactful factor in determining disease outcomes [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. Previous evidence from SARS-CoV and influenza suggests that the higher the initial viral load, the worse the clinical evolution [ 18 , 19 ].…”

“…Previous evidence from SARS-CoV and influenza suggests that the higher the initial viral load, the worse the clinical evolution [ 18 , 19 ]. To date, few studies have investigated the relationships among SARS-CoV-2 viral load (usually measured by the proxy PCR cycle threshold value, Ct), and mortality, disease progression, and overall severity [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 17 ]. Current data point towards a plausible positive correlation between the amount of detected virus and the degree of SARS-CoV-2 pneumonia severity, hypoxemia intensity, risk of death, as well as of hematological, biochemical, and inflammatory alterations [ 6 , 9 , 10 , 11 , 12 , 17 , 20 , 21 ].…”