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25 October

Today it’s Sunday, October 25. This is another bad-news-day. The weather is bad. The infection numbers are worrisomely increasing although the winter is still to come. The D614G variant doesn’t care (see below). Despite this, the shopping malls overflow, luring out thousands of thoughtless people. It has never been so essential to buy lingerie on Sundays. Friends and colleagues have been diagnosed with SARS-CoV-2 during the last week. The German health minister, a reasonable guy, is infected. Emre Can and Serge Gnabry, two German National soccer players, are infected. The Giro d’Italia peloton went on strike. The father (> 80 years of age) of a friend was admitted to hospital yesterday, suffering from COVID-19. The tsunami has arrived. There is no treatment, no vaccine. The immediate future is dark. If you woke up this morning in a bad or slightly depressed mood, don’t read our Top 10 today. Come back tomorrow.

Epidemiology

Mallapaty S. Why COVID outbreaks look set to worsen this winter. Nature News, October 23, 2020. Full-text: https://doi.org/10.1038/d41586-020-02972-4

It’s too soon to say whether COVID is seasonal like the flu — but where clusters aren’t under control, infections will continue to swell. Smriti Mallapaty explains how a small seasonal effect will probably contribute to bigger outbreaks in winter. Difficult months ahead.

Rafiei Y, Mello MM. The Missing Piece — SARS-CoV-2 Testing and School Reopening. October 21, 2020. Full-text: https://doi.org/10.1056/NEJMp2028209

Many health authorities (including the CDC) still recommend against screening testing in schools, citing constraints on testing capacity and the unavailability of real-world studies of its effectiveness. They focus on screening for COVID-19 symptoms. In this important viewpoint, Yasmin Rafiei and Michelle M. Mello explain why this will not work. They believe that increasing routine screening using rapid tests in schools should rank among the most urgent national priorities. Nevertheless, the testing-related challenges are immense (financial, logistics etc.). See above.

Immunology

Yang OO, Ibarrondo FJ. Loss of Anti-SARS-CoV-2 Antibodies in Mild Covid-19. Reply. N Engl J Med. 2020 Oct 22;383(17):1697-1698. PubMed: https://pubmed.gov/32966713. Full-text: https://doi.org/10.1056/NEJMc2027051

Still a controversy about anti-SARS-CoV-2 antibody decay. Some groups found a marked decline while others obtained conflicting results that suggest stability over time. Several factors probably explain these apparent contradictions (heterogeneous populations studied but mainly different methods). Would you mind coming to an agreement, please? The authors here (see the second reply) believe they’re right (decay). They think that they have the better method. If so, this would be bad news by raising questions about the likelihood of natural herd immunity and whether a vaccine can give more prolonged responses.

Transmission

Hou YJ, Chiba S, Halfmann P, et al. SARS-CoV-2 D614G Variant Exhibits Enhanced Replication ex vivo and Earlier Transmission in vivo. bioRxiv. 2020 Sep 29:2020.09.28.317685. PubMed: https://pubmed.gov/33024969. Full-text: https://doi.org/10.1101/2020.09.28.317685.

This is a pre-print and not a peer reviewed paper. However, this milestone work from Ralph Baric and colleagues (among the leading labs world-wide) probably provides the explanation for the exploding numbers. The D614G substitution in the S protein is now the most prevalent SARS-CoV-2 strain circulating globally. Engineering SARS-CoV-2 variants harboring the D614G substitution, the Baric group shows that the D614G variant replicates more efficiency in primary human proximal airway epithelial cells and is more fit than wildtype virus in competition studies. Infection of human ACE2 transgenic mice and Syrian hamsters with the wildtype or D614G viruses produced similar titers in respiratory tissue and pulmonary disease. However, the D614G variant exhibited significantly faster droplet transmission between hamsters than the WT virus, early after infection. No more doubts that the SARS-CoV2 D614G substitution enhances infectivity, replication fitness, and early transmission. Phantastic work, but probably the worst news during the last months. Expect this paper to published in Nature or Science.

Murphy N, Boland M, Bambury N, et al. A large national outbreak of COVID-19 linked to air travel, Ireland, summer 2020. Euro Surveill 2020;25(42):pii=2001624. Full-text: https://doi.org/10.2807/1560-7917.ES.2020.25.42.2001624

Honestly, if you had seen this selection of seats, wouldn’t you have felt safe? This was a 7.5 h flight into Ireland, with a passenger occupancy of 17% (49/283 seats). Astonishingly, the flight-associated attack rate was 9.8–17.8%, leading to 13 cases (in flight-transmission was proven by 99% homology across the virus genome in five cases travelling from three different continents). A mask was worn during the flight by nine cases, not worn by one (a child), and unknown for three. Spread to 46 non-flight cases occurred country-wide. No need to explain why this is bad news.

Pringle JC, Leikauskas J, Ransom-Kelley S, et al. COVID-19 in a Correctional Facility Employee Following Multiple Brief Exposures to Persons with COVID-19 — Vermont, July–August 2020. MMWR Morb Mortal Wkly Rep. ePub: 21 October 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6943e1

On August 11, 2020, a young male correctional officer was found to be infected. Some days earlier, he had multiple brief encounters with six infected incarcerated or detained persons (IDPs). Other infection routes were ruled out. Why is this of interest? Because detailed video surveillance footage was available! It showed that the officer had no close contact (being within 6 feet of infectious persons for ≥15 consecutive minutes) but numerous brief (approximately 1-minute) encounters. During his 8-hour shift, he was within 6 feet of an infectious IDP an estimated 22 times while the cell door was open, for an estimated 17 total minutes of cumulative exposure. IDPs wore microfiber cloth masks during most interactions with the correctional officer that occurred outside a cell; however, during several encounters IDPs did not wear masks. During all interactions, the correctional officer wore a microfiber cloth mask, gown, and eye protection (goggles). He also wore gloves during most interactions. This is bad news because we can’t rely on definitions of “close contacts”.

Collateral damage

Wathelet M, Duhem S, Vaiva G, et al. Factors Associated With Mental Health Disorders Among University Students in France Confined During the COVID-19 Pandemic. JAMA Netw Open October 23, 2020. 2020;3(10):e2025591. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.25591

This nation-wide survey study of 69,054 students from France who experienced quarantine found high prevalence rates of severe self-reported mental health symptoms, including suicidal thoughts (11%), severe distress (22%), high level of perceived stress (25%), severe depression (16%), and high level of anxiety (28%). Among risk factors identified, female or nonbinary gender, problems with income or housing, history of psychiatric follow-up, symptoms compatible with COVID-19, social isolation, and low quality of information received were associated with altered mental health. Main limitation is that the population represented only 4.3% of students contacted and that self-selection bias may have altered the results. However, they are suffering.

Treatment

Agarwal A, Mukherjee A, Kumar G, Chatterjee P, Bhatnagar T, Malhotra P; PLACID Trial Collaborators. Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial). BMJ. 2020 Oct 22;371:m3939. PubMed: https://pubmed.gov/33093056. Full-text: https://doi.org/10.1136/bmj.m3939

Convalescent plasma (giving neutralizing antibodies of people who made it through SARS-CoV-2 infection) has been one of the biggest hopes. This open label randomized controlled trial (RCT; the largest to date with results) investigated the effectiveness of CP in adults with moderate COVID-19 in 39 public and private hospitals across India. In total, 235 patients were assigned to two doses of 200 mL CP and 229 to best standard of care only (control arm). Progression to severe disease or all-cause mortality at 28 days after enrolment occurred in 44 (19%) participants receiving CP and in 41 (18%) in the control arm. Moreover, CP treatment did not show anti-inflammatory properties and there were no difference between patients with or without neutralizing antibodies at baseline (who had produced their own antibodies or not). The main limitation: The authors did not measure the antibody titers in CP before transfusion because validated, reliable commercial tests were not available when the trial started. Let’s hope that low antibody titers were the reason for the lack of efficacy.

Pathak EB. Convalescent plasma is ineffective for covid-19. BMJ. 2020 Oct 22;371:m4072. PubMed: https://pubmed.gov/33093025. Full-text: https://doi.org/10.1136/bmj.m4072

A strong statement, after all (and some thoughts on how to deal with the bad results of the PLACID trial).

Chowdhury JF, Moores LK, Connors JM. Anticoagulation in Hospitalized Patients with Covid-19. N Engl J Med. 2020 Oct 22;383(17):1675-1678. PubMed: https://pubmed.gov/33085867. Full-text: https://doi.org/10.1056/NEJMclde2028217

The case of a 78-year-old man with hypertension and hyperlipidemia who was brought to the emergency department 48 hours ago. Now that the patient’s condition has worsened, with progressive hypoxemia, elevated inflammatory markers, and an increase in d-dimer level, it is to decide whether a) the prophylactic doses of anticoagulants should be maintained or whether b) they should be replaced by an increased dose (and if so, what agent). Lisa Moores says a), Jean Connors says b). Both have good arguments. This is bad news, because after 9 months, we still don’t know what to do.

Well, you are still here? Brave. See you tomorrow. We will find a way through this.

Top 10: October 25